This document discusses treatment of chronic kidney disease (CKD). It aims to slow progression to end-stage renal disease (ESRD) and prepare for ESRD. The most effective treatment is controlling blood pressure with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs), which work by blocking the renin-angiotensin-aldosterone system (RAAS). Glycemic control in diabetes also seems to slow progression. While other potential treatments target various pathways and processes, more research is still needed due to the limited proven effective therapies currently available to treat CKD.
Review Of Strategies To Enhance Outcomes For Patients With Type 2 DiabetsRhonda Greenapple
The document reviews strategies to improve outcomes for patients with type 2 diabetes from a payer's perspective. It discusses how diabetes results in significant health issues and costs, with complications including cardiovascular disease. While treatments exist, many patients struggle with adherence and face economic barriers. The article evaluates initiatives to enhance adherence and outcomes, such as consumer-driven plans, wellness programs, and value-based insurance, finding that combinations of strategies across multiple modalities may be most effective at improving health and reducing costs. Additional innovative programs are needed to meaningfully change patient outcomes and maximize cost-effectiveness for payers.
ICN VIctoria: John Botha on Critical Care Renal FailureGerard Fennessy
Professor John Botha from Frankston Hospital in Melbourne talks at the April 2014 Victorian Intensive Care Network meeting on Renal Failure in Critical Care
This randomized controlled trial compared pentoxifylline to prednisolone for treating severe alcoholic hepatitis. 68 patients received either pentoxifylline (Group I) or prednisolone (Group II) for 28 days, followed by tapering of prednisolone over 7 weeks in Group II. Group I had lower mortality (5 deaths) compared to Group II (12 deaths) at 3 months. Group II also had more cases of hepatorenal syndrome. Pentoxifylline was associated with lower MELD scores. Higher baseline Maddrey scores predicted increased mortality. The study concluded that pentoxifylline had reduced mortality and improved risk profile compared to prednisolone for severe alcoholic hepatitis.
This document summarizes the evidence linking sugar intake to cardiovascular disease risk. It finds relatively consistent evidence that markers of sugar intake are associated with risk factors for cardiovascular disease and the disease itself. In contrast, the evidence linking saturated fat and salt to cardiovascular outcomes is weaker. The document also reviews the history of dietary guidelines focusing on fat and sugar, and how views have changed over time regarding sugar's role in disease risk.
Ueda 2016 diabetes mellitus and heart failure - yahia kishkueda2015
Diabetes and heart failure have a bidirectional relationship where each condition can lead to or worsen the other. Over 60% of asymptomatic type 2 diabetes patients have left ventricular diastolic dysfunction. The prevalence of heart failure is higher in diabetics and increases with age. Diabetes increases the risk of heart failure through hypertension, coronary artery disease, diabetic nephropathy and cardiomyopathy. Intensive glucose control can help prevent microvascular complications but does not significantly reduce cardiovascular events. Several diabetes medications need to be used cautiously in heart failure patients. Both conditions are serious with high mortality rates so treatment must target overall improvement.
Certain diabetes drugs may increase the risk of heart failure in patients by 14%, according to a study of 95,000 patients. The risk was directly associated with the type of drug used, as some drugs carried a higher risk than others or standard care. While some drugs increased the risk, intensive weight loss strategies showed a trend toward lower heart failure risk. The study also found that for every 1 kilogram of weight gain linked to a diabetes drug, there was a 7% higher risk of associated heart failure. The results could change how high-risk diabetes patients are managed going forward.
Dr Vivek Baliga - Chronic Disease Management In Heart Failure And DiabetesDr Vivek Baliga
Dr Vivek Baliga, Consultant Internal Medicine at Baliga Diagnostics discusses the management of 2 common problems in medical practice - heart failure and type 2 diabetes, including the link between the two. For more articles for patients, visit http://heartsense.in/author/dr-vivek-baliga-b/. For scientific articles and short reviews, visit http://drvivekbaliga.net/
Clozapine-induced myocarditis and pericarditis [Case Report]Zahiruddin Othman
This document summarizes a case study of a 50-year-old man who developed myocarditis and pericarditis after starting treatment with clozapine. 17 days after beginning clozapine, the man experienced tachycardia, low blood pressure, and fever. Tests found elevated cardiac enzymes and ECG changes indicative of myocarditis and pericarditis. His symptoms improved after stopping clozapine treatment. The study concludes that older age and concomitant sodium valproate treatment may increase the risk of clozapine-induced cardiac side effects. Medical professionals should investigate potential cardiac complications in patients who recently started clozapine and experience new symptoms like tachycardia, low blood pressure, and fever.
Review Of Strategies To Enhance Outcomes For Patients With Type 2 DiabetsRhonda Greenapple
The document reviews strategies to improve outcomes for patients with type 2 diabetes from a payer's perspective. It discusses how diabetes results in significant health issues and costs, with complications including cardiovascular disease. While treatments exist, many patients struggle with adherence and face economic barriers. The article evaluates initiatives to enhance adherence and outcomes, such as consumer-driven plans, wellness programs, and value-based insurance, finding that combinations of strategies across multiple modalities may be most effective at improving health and reducing costs. Additional innovative programs are needed to meaningfully change patient outcomes and maximize cost-effectiveness for payers.
ICN VIctoria: John Botha on Critical Care Renal FailureGerard Fennessy
Professor John Botha from Frankston Hospital in Melbourne talks at the April 2014 Victorian Intensive Care Network meeting on Renal Failure in Critical Care
This randomized controlled trial compared pentoxifylline to prednisolone for treating severe alcoholic hepatitis. 68 patients received either pentoxifylline (Group I) or prednisolone (Group II) for 28 days, followed by tapering of prednisolone over 7 weeks in Group II. Group I had lower mortality (5 deaths) compared to Group II (12 deaths) at 3 months. Group II also had more cases of hepatorenal syndrome. Pentoxifylline was associated with lower MELD scores. Higher baseline Maddrey scores predicted increased mortality. The study concluded that pentoxifylline had reduced mortality and improved risk profile compared to prednisolone for severe alcoholic hepatitis.
This document summarizes the evidence linking sugar intake to cardiovascular disease risk. It finds relatively consistent evidence that markers of sugar intake are associated with risk factors for cardiovascular disease and the disease itself. In contrast, the evidence linking saturated fat and salt to cardiovascular outcomes is weaker. The document also reviews the history of dietary guidelines focusing on fat and sugar, and how views have changed over time regarding sugar's role in disease risk.
Ueda 2016 diabetes mellitus and heart failure - yahia kishkueda2015
Diabetes and heart failure have a bidirectional relationship where each condition can lead to or worsen the other. Over 60% of asymptomatic type 2 diabetes patients have left ventricular diastolic dysfunction. The prevalence of heart failure is higher in diabetics and increases with age. Diabetes increases the risk of heart failure through hypertension, coronary artery disease, diabetic nephropathy and cardiomyopathy. Intensive glucose control can help prevent microvascular complications but does not significantly reduce cardiovascular events. Several diabetes medications need to be used cautiously in heart failure patients. Both conditions are serious with high mortality rates so treatment must target overall improvement.
Certain diabetes drugs may increase the risk of heart failure in patients by 14%, according to a study of 95,000 patients. The risk was directly associated with the type of drug used, as some drugs carried a higher risk than others or standard care. While some drugs increased the risk, intensive weight loss strategies showed a trend toward lower heart failure risk. The study also found that for every 1 kilogram of weight gain linked to a diabetes drug, there was a 7% higher risk of associated heart failure. The results could change how high-risk diabetes patients are managed going forward.
Dr Vivek Baliga - Chronic Disease Management In Heart Failure And DiabetesDr Vivek Baliga
Dr Vivek Baliga, Consultant Internal Medicine at Baliga Diagnostics discusses the management of 2 common problems in medical practice - heart failure and type 2 diabetes, including the link between the two. For more articles for patients, visit http://heartsense.in/author/dr-vivek-baliga-b/. For scientific articles and short reviews, visit http://drvivekbaliga.net/
Clozapine-induced myocarditis and pericarditis [Case Report]Zahiruddin Othman
This document summarizes a case study of a 50-year-old man who developed myocarditis and pericarditis after starting treatment with clozapine. 17 days after beginning clozapine, the man experienced tachycardia, low blood pressure, and fever. Tests found elevated cardiac enzymes and ECG changes indicative of myocarditis and pericarditis. His symptoms improved after stopping clozapine treatment. The study concludes that older age and concomitant sodium valproate treatment may increase the risk of clozapine-induced cardiac side effects. Medical professionals should investigate potential cardiac complications in patients who recently started clozapine and experience new symptoms like tachycardia, low blood pressure, and fever.
1) Diabetic nephropathy is a kidney disease caused by damage from uncontrolled diabetes, often accompanied by high blood pressure. It involves thickening and scarring of the kidney's filtering units called glomeruli.
2) The trial drug formula, containing herbs like Berberis vulgaris and Solanum nigrum, improved creatinine clearance in 65.71% of patients with mild to moderate renal impairment after 120 days. For patients with severe impairment, a slower response was seen.
3) The formulation acts as a renal function modulator through vasodilation and improved blood flow. It is recommended for early stages of diabetic nephropathy and was found to be an effective and affordable
1) The document discusses the results of the NAVIGATOR study which examined the effects of the drugs nateglinide and valsartan on the development of diabetes and cardiovascular disease in high-risk patients.
2) The study found that neither drug reduced the two primary cardiovascular outcomes. The only positive result was a small reduction in incident diabetes with valsartan.
3) The study does not provide strong evidence that lowering post-prandial glycemia prevents diabetes or reduces cardiovascular disease, as nateglinide had little effect despite increasing hypoglycemia risk. Valsartan was also a weak preventer of diabetes and did not lower cardiovascular events.
Diabetic cardiomyopathy refers to myocardial disease in diabetic subjects that cannot be ascribed to hypertension, coronary artery disease (CAD), or any other known cardiac disease. Key aspects discussed include the high prevalence of heart failure in diabetic patients, pathophysiological changes such as hypertrophy and fibrosis, and risk factors like hyperglycemia and hypertension. Management involves tight control of blood pressure and blood glucose, as well as medications like angiotensin-converting enzyme inhibitors, beta blockers, and aldosterone receptor antagonists which have been shown to improve outcomes. Aggressive modification of cardiovascular risk factors is important in the management of diabetic cardiomyopathy.
This document discusses various pharmacologic interventions for congestive heart failure, cardiomyopathy, and valve disease. It describes the mechanisms of action, therapeutic effects, adverse effects and nursing implications of several classes of heart failure medications including: ACE inhibitors, angiotensin receptor blockers, beta blockers, loop diuretics, thiazide diuretics, potassium sparing diuretics, nitrates, digoxin, milrinone, morphine, nesiritide, sacubitril/valsartan, and ivabradine. The document provides details on specific drugs within each class and how they are used to treat symptoms and improve outcomes for patients with heart failure.
Viral hepatitis is an infection that causes liver inflammation and damage. Inflammation is swelling that occurs when tissues of the body become injured or infected. Inflammation can damage organs. Researchers have discovered several different viruses link that cause hepatitis, including hepatitis A, B, C, D, and E.
Three randomized trials evaluated the effects of treating secondary hyperparathyroidism (SHPT) with bioactive vitamin D on bone mineral density in patients with pre-dialysis chronic kidney disease. The trials showed weak evidence that treatment improved bone mineral density based on small sample sizes of 62 patients total. However, the trials did not require baseline SHPT and did not follow published treatment guidelines. No randomized controlled trials evaluated the effects of treating SHPT on fractures, cardiovascular events, or mortality. Larger trials are needed to determine the potential benefits and harms of treating SHPT in pre-dialysis chronic kidney disease.
The HOPE-3 trial evaluated the effects of combination therapy with rosuvastatin, candesartan, and hydrochlorothiazide versus placebo in over 12,000 individuals without cardiovascular disease but at intermediate risk. It found that the combination therapy lowered blood pressure and LDL cholesterol more than placebo and reduced the risk of cardiovascular events like heart attack and stroke by 29% over 5.6 years of follow up. However, the combination therapy also increased adverse effects like muscle pain compared to placebo.
Diabetic cardiomyopathy is characterized by ventricular dysfunction that occurs independently of coronary artery disease or hypertension. Hyperglycemia causes structural and functional damage to cardiac myocytes through increased advanced glycation end products and oxidative stress that impair calcium handling. Other risk factors include insulin resistance, dyslipidemia, hypertension, and obesity. Over time, these factors can lead to myocardial fibrosis and decreased systolic and diastolic function. Strict control of blood sugar and associated cardiovascular risk factors is important to prevent and manage diabetic cardiomyopathy.
The FIGARO-DKD trial found that:
1) Finerenone significantly reduced the risk of the primary cardiovascular outcome (composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure) by 13% compared to placebo in patients with chronic kidney disease and type 2 diabetes.
2) The cardiovascular benefit was primarily driven by a reduction in hospitalization for heart failure despite excluding patients with symptomatic heart failure with reduced ejection fraction.
3) Finerenone did not significantly reduce the risk of a sustained 40% decline in eGFR but did trend toward improving the clinically accepted outcome of a sustained 57% decline in eGFR compared to placebo.
Running head illness and disease managementillness and disearyan532920
Chronic kidney disease is a debilitating disease that affects many organ systems and is associated with high risks of cardiovascular disease and early death. It has numerous comorbidities such as diabetes, hypertension, heart disease, and impacts patients' quality of life through disability and high medical costs. About 10% of the global population is affected by CKD, and it is a leading cause of death worldwide. Goals for improving CKD include reducing the disease burden through early detection and treatment of risk factors like diabetes and hypertension.
The association between type ii diabetes mellitus and hypertension a case reportpharmaindexing
This case report describes a 53-year old female patient with a history of ischemic heart disease and hypertension who presented with symptoms of hyperglycemia and was diagnosed with type 2 diabetes. The patient's random blood sugar was 449 mg/dl and blood pressure was 164/88 mm Hg. The case report examines the relationship between the patient's type 2 diabetes and existing hypertension and the management of both conditions. The patient was prescribed metformin, insulin aspart, enalapril, and candesartan to control her blood glucose levels, blood pressure, and reduce cardiac risk factors according to clinical guidelines.
This document discusses guidelines for glycemic control in patients with diabetes and chronic kidney disease. It recommends monitoring HbA1c levels twice per year and targeting levels between 6.5-8%. Clinical trials showed that intensive glycemic control can reduce kidney disease progression but may increase mortality risk if targets are too low. The document also discusses guidelines for blood pressure control and the renoprotective effects of blocking the renin-angiotensin system with ACE inhibitors or ARBs. Combination therapy with an ACE inhibitor and ARB or adding an MRA may provide additional benefits but also increase risks like hyperkalemia.
Diabetic nephropathy considered one of the most common complications of DM. This presentation answer the question are some diabetic patient immune to diabetic nephroapthy
The document provides information about Cushing syndrome including its definition, causes, signs and symptoms, diagnostic methods, complications, treatment options, nursing management, and prognosis. Cushing syndrome is defined as prolonged exposure to high levels of cortisol and can be caused by tumors or medications. Signs include high blood pressure, abdominal obesity, and skin changes. Diagnosis involves tests to check cortisol levels. Treatment may involve medications, surgery, or lifestyle changes and nursing care aims to manage symptoms and prevent complications.
Non diabetic renal disease with or without diabetic nephropathy dr.amgad el-...FarragBahbah
This document discusses non-diabetic renal disease in diabetic patients. It begins by describing diabetic nephropathy and its characteristics. It then discusses the prevalence of proteinuria in type 1 and type 2 diabetes. Several case studies are presented showing patients with atypical presentations for diabetic nephropathy who were found to have non-diabetic renal diseases like lupus nephritis or focal segmental glomerulosclerosis instead. The document emphasizes that a renal biopsy can identify these non-diabetic diseases and lead to improved outcomes versus assuming diabetic nephropathy. It reviews several studies finding prevalence rates of non-diabetic renal disease in diabetics ranging from 17-85% depending on biopsy criteria
This document discusses ways to protect the kidney in patients with diabetes. It summarizes that diabetic kidney disease (DKD) is a common complication of diabetes and the leading cause of end-stage renal disease. The stages of DKD range from microalbuminuria to proteinuria to declining kidney function. The progression of DKD to chronic kidney disease can be delayed through strict control of blood pressure, cholesterol, diet, education, and use of ACE inhibitors or ARBs which help preserve kidney function.
Yoga is a non-invasive and cost effective therapeutic intervention that works at the Psychological and physical level. This is effective in reduction of BP, heart rate, inflammatory markers and in patients with chronic kidney disease. Hypertension and diabetes are the most common risk factors in CKD where Yogic lifestyle helps in maintaining the blood pressure, sugar and lipid levels, reduction in oxidative stress, sympathetic tone, stress and pain associated with CKD.
Modern modalities for management of diabetes dr mahir jallo gulf medical univ...Mahir Khalil Ibrahim Jallo
This document discusses modern modalities for managing diabetes. It begins by defining the main types of diabetes - type 1, type 2, and gestational diabetes. It then discusses diabetes complications and treatments, including various classes of oral medications and insulins to manage blood glucose levels. Newer classes of medications that work by different mechanisms, such as DPP-4 inhibitors and SGLT2 inhibitors, are also covered. The document emphasizes the importance of a multifactorial treatment approach to diabetes management.
This document provides an overview of diabetic kidney disease (DKD). It discusses the epidemiology, pathophysiology, clinical presentation, diagnosis, treatment, and evidence related to DKD. Some key points include: DKD is the leading cause of kidney failure worldwide; hyperglycemia is the primary factor in its development; it can present with or without albuminuria; treatment involves glycemic control, blood pressure control, and RAAS inhibitors; landmark trials such as RENAAL and IDNT showed renoprotective effects of ACEIs and ARBs; and recent trials demonstrate kidney and cardiovascular benefits of SGLT2 inhibitors in DKD patients.
This document discusses the benefits of Ketosteril, an alpha keto analog supplement for chronic kidney disease (CKD) patients. It summarizes that Ketosteril can replace essential amino acids while minimizing nitrogen waste, delay the need for dialysis, and improve nutritional status for CKD patients on protein-restricted diets. Information on Ketosteril's manufacturer, Fresenius Kabi, a global healthcare company based in Germany, is also provided to assure the quality of the product.
This document discusses the management of diabetic nephropathy. It begins with defining diabetic nephropathy as a clinical syndrome characterized by persistent albuminuria, progressive decline in glomerular filtration rate, elevated blood pressure, worse glycemic control, hypertension, and genetic predisposition. It then outlines the typical progression of diabetic kidney disease and reviews risk factors. Current treatment strategies are aimed at strict glycemic control, blood pressure control, reducing proteinuria, and preserving renal function through ACE inhibitors, ARBs, and lifestyle modifications like weight loss and smoking cessation. Newer treatments continue to be explored, but therapeutic intervention works best when begun early and glycemia, blood pressure, and proteinuria are well controlled.
1) Diabetic nephropathy is a kidney disease caused by damage from uncontrolled diabetes, often accompanied by high blood pressure. It involves thickening and scarring of the kidney's filtering units called glomeruli.
2) The trial drug formula, containing herbs like Berberis vulgaris and Solanum nigrum, improved creatinine clearance in 65.71% of patients with mild to moderate renal impairment after 120 days. For patients with severe impairment, a slower response was seen.
3) The formulation acts as a renal function modulator through vasodilation and improved blood flow. It is recommended for early stages of diabetic nephropathy and was found to be an effective and affordable
1) The document discusses the results of the NAVIGATOR study which examined the effects of the drugs nateglinide and valsartan on the development of diabetes and cardiovascular disease in high-risk patients.
2) The study found that neither drug reduced the two primary cardiovascular outcomes. The only positive result was a small reduction in incident diabetes with valsartan.
3) The study does not provide strong evidence that lowering post-prandial glycemia prevents diabetes or reduces cardiovascular disease, as nateglinide had little effect despite increasing hypoglycemia risk. Valsartan was also a weak preventer of diabetes and did not lower cardiovascular events.
Diabetic cardiomyopathy refers to myocardial disease in diabetic subjects that cannot be ascribed to hypertension, coronary artery disease (CAD), or any other known cardiac disease. Key aspects discussed include the high prevalence of heart failure in diabetic patients, pathophysiological changes such as hypertrophy and fibrosis, and risk factors like hyperglycemia and hypertension. Management involves tight control of blood pressure and blood glucose, as well as medications like angiotensin-converting enzyme inhibitors, beta blockers, and aldosterone receptor antagonists which have been shown to improve outcomes. Aggressive modification of cardiovascular risk factors is important in the management of diabetic cardiomyopathy.
This document discusses various pharmacologic interventions for congestive heart failure, cardiomyopathy, and valve disease. It describes the mechanisms of action, therapeutic effects, adverse effects and nursing implications of several classes of heart failure medications including: ACE inhibitors, angiotensin receptor blockers, beta blockers, loop diuretics, thiazide diuretics, potassium sparing diuretics, nitrates, digoxin, milrinone, morphine, nesiritide, sacubitril/valsartan, and ivabradine. The document provides details on specific drugs within each class and how they are used to treat symptoms and improve outcomes for patients with heart failure.
Viral hepatitis is an infection that causes liver inflammation and damage. Inflammation is swelling that occurs when tissues of the body become injured or infected. Inflammation can damage organs. Researchers have discovered several different viruses link that cause hepatitis, including hepatitis A, B, C, D, and E.
Three randomized trials evaluated the effects of treating secondary hyperparathyroidism (SHPT) with bioactive vitamin D on bone mineral density in patients with pre-dialysis chronic kidney disease. The trials showed weak evidence that treatment improved bone mineral density based on small sample sizes of 62 patients total. However, the trials did not require baseline SHPT and did not follow published treatment guidelines. No randomized controlled trials evaluated the effects of treating SHPT on fractures, cardiovascular events, or mortality. Larger trials are needed to determine the potential benefits and harms of treating SHPT in pre-dialysis chronic kidney disease.
The HOPE-3 trial evaluated the effects of combination therapy with rosuvastatin, candesartan, and hydrochlorothiazide versus placebo in over 12,000 individuals without cardiovascular disease but at intermediate risk. It found that the combination therapy lowered blood pressure and LDL cholesterol more than placebo and reduced the risk of cardiovascular events like heart attack and stroke by 29% over 5.6 years of follow up. However, the combination therapy also increased adverse effects like muscle pain compared to placebo.
Diabetic cardiomyopathy is characterized by ventricular dysfunction that occurs independently of coronary artery disease or hypertension. Hyperglycemia causes structural and functional damage to cardiac myocytes through increased advanced glycation end products and oxidative stress that impair calcium handling. Other risk factors include insulin resistance, dyslipidemia, hypertension, and obesity. Over time, these factors can lead to myocardial fibrosis and decreased systolic and diastolic function. Strict control of blood sugar and associated cardiovascular risk factors is important to prevent and manage diabetic cardiomyopathy.
The FIGARO-DKD trial found that:
1) Finerenone significantly reduced the risk of the primary cardiovascular outcome (composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure) by 13% compared to placebo in patients with chronic kidney disease and type 2 diabetes.
2) The cardiovascular benefit was primarily driven by a reduction in hospitalization for heart failure despite excluding patients with symptomatic heart failure with reduced ejection fraction.
3) Finerenone did not significantly reduce the risk of a sustained 40% decline in eGFR but did trend toward improving the clinically accepted outcome of a sustained 57% decline in eGFR compared to placebo.
Running head illness and disease managementillness and disearyan532920
Chronic kidney disease is a debilitating disease that affects many organ systems and is associated with high risks of cardiovascular disease and early death. It has numerous comorbidities such as diabetes, hypertension, heart disease, and impacts patients' quality of life through disability and high medical costs. About 10% of the global population is affected by CKD, and it is a leading cause of death worldwide. Goals for improving CKD include reducing the disease burden through early detection and treatment of risk factors like diabetes and hypertension.
The association between type ii diabetes mellitus and hypertension a case reportpharmaindexing
This case report describes a 53-year old female patient with a history of ischemic heart disease and hypertension who presented with symptoms of hyperglycemia and was diagnosed with type 2 diabetes. The patient's random blood sugar was 449 mg/dl and blood pressure was 164/88 mm Hg. The case report examines the relationship between the patient's type 2 diabetes and existing hypertension and the management of both conditions. The patient was prescribed metformin, insulin aspart, enalapril, and candesartan to control her blood glucose levels, blood pressure, and reduce cardiac risk factors according to clinical guidelines.
This document discusses guidelines for glycemic control in patients with diabetes and chronic kidney disease. It recommends monitoring HbA1c levels twice per year and targeting levels between 6.5-8%. Clinical trials showed that intensive glycemic control can reduce kidney disease progression but may increase mortality risk if targets are too low. The document also discusses guidelines for blood pressure control and the renoprotective effects of blocking the renin-angiotensin system with ACE inhibitors or ARBs. Combination therapy with an ACE inhibitor and ARB or adding an MRA may provide additional benefits but also increase risks like hyperkalemia.
Diabetic nephropathy considered one of the most common complications of DM. This presentation answer the question are some diabetic patient immune to diabetic nephroapthy
The document provides information about Cushing syndrome including its definition, causes, signs and symptoms, diagnostic methods, complications, treatment options, nursing management, and prognosis. Cushing syndrome is defined as prolonged exposure to high levels of cortisol and can be caused by tumors or medications. Signs include high blood pressure, abdominal obesity, and skin changes. Diagnosis involves tests to check cortisol levels. Treatment may involve medications, surgery, or lifestyle changes and nursing care aims to manage symptoms and prevent complications.
Non diabetic renal disease with or without diabetic nephropathy dr.amgad el-...FarragBahbah
This document discusses non-diabetic renal disease in diabetic patients. It begins by describing diabetic nephropathy and its characteristics. It then discusses the prevalence of proteinuria in type 1 and type 2 diabetes. Several case studies are presented showing patients with atypical presentations for diabetic nephropathy who were found to have non-diabetic renal diseases like lupus nephritis or focal segmental glomerulosclerosis instead. The document emphasizes that a renal biopsy can identify these non-diabetic diseases and lead to improved outcomes versus assuming diabetic nephropathy. It reviews several studies finding prevalence rates of non-diabetic renal disease in diabetics ranging from 17-85% depending on biopsy criteria
This document discusses ways to protect the kidney in patients with diabetes. It summarizes that diabetic kidney disease (DKD) is a common complication of diabetes and the leading cause of end-stage renal disease. The stages of DKD range from microalbuminuria to proteinuria to declining kidney function. The progression of DKD to chronic kidney disease can be delayed through strict control of blood pressure, cholesterol, diet, education, and use of ACE inhibitors or ARBs which help preserve kidney function.
Yoga is a non-invasive and cost effective therapeutic intervention that works at the Psychological and physical level. This is effective in reduction of BP, heart rate, inflammatory markers and in patients with chronic kidney disease. Hypertension and diabetes are the most common risk factors in CKD where Yogic lifestyle helps in maintaining the blood pressure, sugar and lipid levels, reduction in oxidative stress, sympathetic tone, stress and pain associated with CKD.
Modern modalities for management of diabetes dr mahir jallo gulf medical univ...Mahir Khalil Ibrahim Jallo
This document discusses modern modalities for managing diabetes. It begins by defining the main types of diabetes - type 1, type 2, and gestational diabetes. It then discusses diabetes complications and treatments, including various classes of oral medications and insulins to manage blood glucose levels. Newer classes of medications that work by different mechanisms, such as DPP-4 inhibitors and SGLT2 inhibitors, are also covered. The document emphasizes the importance of a multifactorial treatment approach to diabetes management.
This document provides an overview of diabetic kidney disease (DKD). It discusses the epidemiology, pathophysiology, clinical presentation, diagnosis, treatment, and evidence related to DKD. Some key points include: DKD is the leading cause of kidney failure worldwide; hyperglycemia is the primary factor in its development; it can present with or without albuminuria; treatment involves glycemic control, blood pressure control, and RAAS inhibitors; landmark trials such as RENAAL and IDNT showed renoprotective effects of ACEIs and ARBs; and recent trials demonstrate kidney and cardiovascular benefits of SGLT2 inhibitors in DKD patients.
This document discusses the benefits of Ketosteril, an alpha keto analog supplement for chronic kidney disease (CKD) patients. It summarizes that Ketosteril can replace essential amino acids while minimizing nitrogen waste, delay the need for dialysis, and improve nutritional status for CKD patients on protein-restricted diets. Information on Ketosteril's manufacturer, Fresenius Kabi, a global healthcare company based in Germany, is also provided to assure the quality of the product.
This document discusses the management of diabetic nephropathy. It begins with defining diabetic nephropathy as a clinical syndrome characterized by persistent albuminuria, progressive decline in glomerular filtration rate, elevated blood pressure, worse glycemic control, hypertension, and genetic predisposition. It then outlines the typical progression of diabetic kidney disease and reviews risk factors. Current treatment strategies are aimed at strict glycemic control, blood pressure control, reducing proteinuria, and preserving renal function through ACE inhibitors, ARBs, and lifestyle modifications like weight loss and smoking cessation. Newer treatments continue to be explored, but therapeutic intervention works best when begun early and glycemia, blood pressure, and proteinuria are well controlled.
This document presents standards of care for diabetes established by the American Diabetes Association (ADA). It discusses:
1) Classification of diabetes into four types: type 1, type 2, other specific types, and gestational diabetes.
2) Diagnosis of diabetes based on plasma glucose criteria or A1C levels, with a revised grading system to evaluate evidence supporting each recommendation.
3) Screening, diagnostic, and treatment recommendations to improve health outcomes for patients with diabetes.
This document presents standards of care for diabetes established by the American Diabetes Association (ADA). It discusses:
1) Classification of diabetes into four types: type 1, type 2, other specific types, and gestational diabetes.
2) Diagnosis of diabetes based on plasma glucose criteria or A1C levels, with a revised grading system to evaluate evidence supporting each recommendation.
3) Screening, diagnostic, and treatment recommendations to improve health outcomes for patients with diabetes.
This document discusses the challenges of managing diabetes in patients with chronic kidney disease (CKD). It notes that diabetes is a leading cause of CKD progression and that CKD increases mortality risk in diabetes patients. Managing glucose levels in CKD patients is difficult due to risks of hypoglycemia from insulin clearance issues and need to adjust oral medications for kidney function. The CARMELINA trial demonstrated the renal safety of the DPP-4 inhibitor linagliptin in high cardio-renal risk patients, showing no increase in sustained decrease in eGFR or other renal outcomes compared to placebo over 2 years.
2023 Definitions, phenotypes, and subphenotypes in AKI.pdfJesusPlanelles
The document discusses the need to reclassify acute kidney injury (AKI) to facilitate more targeted and individualized treatment approaches.
Current AKI definitions focus only on functional changes like rises in creatinine, which detect injury too late for early intervention. The document proposes reclassifying AKI based on causal phenotype and subphenotypes defined by biomarkers that reveal specific injury pathways.
Precisely defining AKI phenotypes by cause, such as ischemia or nephrotoxins, and subphenotypes by activated pathophysiological mechanisms, could help triage patients to tailored therapies in a precision medicine approach, rather than just providing supportive care for the broad AKI syndrome.
This document provides guidelines for the classification, diagnosis, and testing of diabetes and pre-diabetes. It discusses:
1) The classification of diabetes into types 1, 2, gestational, and other specific types.
2) Current diagnostic criteria including A1C, fasting plasma glucose, and oral glucose tolerance tests.
3) Recommendations for testing asymptomatic individuals for pre-diabetes and type 2 diabetes based on risk factors.
This document discusses chronic kidney disease (CKD), including its pathophysiology, risk factors, and treatment strategies to slow progression. It notes that CKD progression involves both hemodynamic and non-hemodynamic mechanisms, such as activation of the renin-angiotensin-aldosterone system leading to inflammation and fibrosis. Blocking the RAAS through ACE inhibitors, ARBs, and blood pressure control has been shown to slow CKD progression by reducing proteinuria, glomerular hypertension, and inflammation. The document reviews several landmark clinical trials that established the renoprotective effects of RAAS inhibition in diabetic and non-diabetic kidney diseases.
Diabetic kidney disease remains a major global health problem. Recent research has provided insights into the pathophysiology and has identified new diagnostic and therapeutic approaches. Several large clinical trials have shown that sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists, mineralocorticoid receptor antagonists, and endothelin receptor antagonists can reduce kidney disease progression and cardiovascular events in patients with diabetes and kidney disease. Ongoing trials are further evaluating combination therapies and the benefits of these agents in non-diabetic kidney disease and heart failure.
This document provides an overview of chronic kidney disease (CKD). It begins by defining CKD and different stages of kidney disease severity. Major risk factors for CKD progression include diabetes and hypertension. Early detection and treatment can slow CKD progression and improve outcomes. Treatment focuses on controlling blood pressure and glucose, with ACE inhibitors/ARBs shown to protect kidney function. Lifestyle changes like diet and exercise are also important for management.
End of life care in heart failure - a framework for implementationNHS Improvement
End of life care in heart failure - A framework for implementation
This joint publication with the End of Life Care Team, highlights how an end of life care service can best accommodate the specific needs of heart failure patients. The framework takes each step of the end of life pathway and suggests the heart failure specific care that a patient and their carers need and how it can be delivered in the community, the hospice environment or in secondary care.
(Published June 2010).
This document provides guidelines for screening, monitoring, classifying severity, and treating diabetic macular edema (DME). It recommends annual screening of diabetic patients aged 15+ for retinopathy and treating any sight-threatening cases found. For DME treatment, it discusses traditional laser photocoagulation as well as newer options like intravitreal corticosteroids and anti-VEGF drugs. Intravitreal injections of anti-VEGF agents are considered first-line therapy for center-involving DME, with laser as an option for non-center cases or if thickening persists after anti-VEGF treatment. Strict control of modifiable risk factors like glycemia, blood pressure, and lipids can also help prevent
The document discusses chronic kidney disease (CKD), including its definition, stages, diagnosis, prevalence, costs, and treatment options such as renal replacement therapy. CKD is common and often occurs alongside other conditions like cardiovascular disease or diabetes. While usually asymptomatic, CKD can be detected through simple tests and treating it can prevent progression and complications. However, it often goes unrecognized until later stages.
Diabetic Nephropathy;Physiotherapy approach, a case reportenweluntaobed
Diabetic nephropathy is a complication of diabetes that results in chronic kidney disease. It is caused by damage to the glomeruli of the kidneys from hyperglycemia. It can progress to kidney failure if not controlled. The presentation includes edema, hypertension, reduced kidney function. Management involves controlling blood sugar and pressure with medications like ACE inhibitors. Prognosis depends on stage of disease and risk factors present, with proteinuria indicating higher mortality risk. Physiotherapy can help reduce pain and swelling and improve function for patients with diabetic nephropathy.
1. The document provides information on chronic kidney disease (CKD) management in primary care, including screening, evaluation, goals of care, and complications.
2. It emphasizes the primary care provider's important role in early CKD detection through testing at-risk patients, managing blood pressure and diabetes, and referring to nephrology as appropriate.
3. A collaborative care model between primary care and nephrology can improve outcomes through coordinated management and addressing patient safety issues in CKD.
1. The document provides information on chronic kidney disease (CKD) management in primary care, including screening, evaluation, goals of care, and complications.
2. It emphasizes the primary care provider's important role in early CKD detection through testing at-risk patients, managing blood pressure and diabetes, and referring to nephrology as appropriate.
3. A collaborative care model between primary care and nephrology can improve outcomes through coordinated management and addressing patient safety issues in CKD.
cardiorenal syndrome and its characteristics and complications and causes.pptxArunDeva8
This study analyzed the risk factors and outcomes of acute cardiorenal syndrome (CRS-1) in 460 patients admitted with acute coronary syndrome or acute decompensated heart failure at a tertiary care center in South India. 34% of patients developed CRS-1, defined as acute kidney injury resulting from acute worsening of cardiac function. Risk factors for CRS-1 included diabetes, chronic kidney disease, lower ejection fraction, and higher levels of cardiac biomarkers. Patients with CRS-1 required more intensive care interventions and had higher in-hospital mortality of 20.2% compared to 7.8% in patients without CRS-1. Early detection and multidisciplinary management can help provide better outcomes for patients with
Chronic Kidney Disease: An Update (Part II) provides information on:
1. The pathophysiology, signs and symptoms, disease progression, and treatment interventions for chronic kidney disease.
2. Treatment strategies for chronic kidney disease including screening for risk factors, slowing disease progression through treatment of comorbid conditions, and preparing for renal replacement therapies like dialysis and transplant as kidney function declines.
3. The role of controlling cardiovascular risk factors like blood pressure, cholesterol, and blood sugar in treating chronic kidney disease and preventing associated complications like cardiovascular disease. Intensive treatment can help slow kidney disease progression.
Similar to Manejo de la erc. review actualizada (20)
Este documento resume la uropatía obstructiva, incluyendo sus causas más comunes, su fisiopatología y efectos en los riñones superior e inferior, el tiempo de recuperación de los riñones después de la obstrucción, los métodos de diagnóstico y tratamiento.
El documento habla sobre la urolitiasis o formación de cálculos renales. Señala que la incidencia es mayor en hombres que en mujeres y que la recurrencia a los 5 años es entre 35-50%. Explica que el síntoma principal es el cólico renal y que la litotricia es el tratamiento más usado para cálculos menores a 2 cm. Finalmente, indica que aumentar el consumo de líquidos a 2L/día reduce la recurrencia de cálculos.
Este documento describe los mecanismos de acción y usos clínicos de los diuréticos. Explica cómo los diuréticos modifican la excreción de sodio y otros iones para lograr un balance negativo de agua, ya sea a través de diuréticos natriuréticos o alterando la osmolaridad. También analiza los efectos hemodinámicos de los diuréticos y su uso en el manejo de edemas y en pacientes con enfermedad renal crónica.
Este documento describe la producción científica peruana sobre diabetes mellitus tipo 2 y nefropatía diabética. Se encontraron 22 artículos que abordaron temas como la prevalencia de diabetes, el manejo clínico de pacientes diabéticos, el diagnóstico y factores de riesgo de nefropatía diabética. Los estudios mostraron que la prevalencia de diabetes varía según la región del país, siendo mayor en la costa. Muchos pacientes diabéticos tienen un control inadecuado de la glucemia y la
Este documento describe varios métodos para evaluar la función renal, incluyendo la tasa de filtración glomerular, creatinina, urea, clearencia de creatinina, beta trace protein, cistatina C, y las fórmulas Cockcroft-Gault y CKD-EPI. Ningún método es perfecto, pero las fórmulas CKD-EPI que usan creatinina o cistatina C son las más precisas para estimar la tasa de filtración glomerular.
Este documento resume los principales métodos de diagnóstico por imágenes en nefrología, incluyendo radiografía, ultrasonografía, tomografía computarizada, resonancia magnética y medicina nuclear. Describe las aplicaciones y ventajas de cada técnica para evaluar la anatomía y función renal.
La glomerulonefritis rápidamente progresiva (GNRP) es una enfermedad renal que causa una rápida pérdida de la función renal. Existen tres tipos principales de GNRP que se distinguen por sus hallazgos de inmunofluorescencia. El tratamiento depende del tipo y la etiología subyacente, e incluye corticoides e inmunosupresores. Los factores pronósticos asociados con un peor pronóstico renal incluyen niveles más altos de creatinina al inicio y dependencia inicial de diá
El documento resume las directrices para el diagnóstico y tratamiento de la enfermedad renal crónica por parte de médicos internistas. Resalta la importancia de despistar la enfermedad mediante la medición de albuminuria y el cálculo de la tasa de filtración glomerular, así como identificar y controlar factores de riesgo como la hipertensión y diabetes. También discute objetivos terapéuticos y opciones de medicamentos, y enfatiza la necesidad de derivar pacientes a nefrólogos cuando sea necesario.
Este estudio encontró que la investigación científica entre residentes de nefrología en Perú es deficiente. Se encuestó a 40 médicos residentes y recién egresados, de los cuales el 67.5% nunca realizó investigación durante su residencia. Ninguno publicó sus trabajos de investigación. Casi todos consideraron que sus sedes hospitalarias no promueven adecuadamente la investigación. El estudio concluye que se requieren estrategias para mejorar la formación en investigación durante la residencia de nefrología en Perú.
Este estudio evaluó la tasa de abandono de la terapia de hemodiálisis en 190 pacientes del Hospital Nacional 2 de Mayo en Perú. Se encontró que 44.21% de los pacientes abandonaron la terapia de hemodiálisis, posiblemente debido a la falta de cupos disponibles. El abandono de la terapia de hemodiálisis se asoció con un diagnóstico de inicio de diálisis en los últimos 6 meses. Los autores concluyen que la frecuencia de abandono de la terapia de hemodiálisis es
El documento discute las indicaciones para iniciar, no iniciar o descontinuar la diálisis. Señala que aunque la diálisis mejora marcadores a corto plazo, no todos los pacientes se benefician en términos de mortalidad o calidad de vida. Estudios muestran que la mortalidad es alta en pacientes en diálisis y que algunos pacientes se arrepienten de haberla iniciado. El documento concluye que la decisión de diálisis debe ser individualizada considerando factores como pronóstico, comorbilidades,
El documento describe la nefropatía diabética, sus factores de riesgo, manifestaciones clínicas, fisiopatología, tratamiento y recomendaciones para prevenir y controlar la progresión de la enfermedad. Explica que la nefropatía diabética es la principal causa de enfermedad renal en el mundo y que su control requiere optimizar los niveles de glucosa y presión arterial a través de medicamentos como IECA o ARA2. También enfatiza la importancia de detectarla tempranamente mediante la evaluación de la
La tesis analiza la figura del héroe mítico en el anime Los Caballeros del Zodiaco y cómo esto genera interés. Explora cómo la serie presenta a los caballeros como héroes arquetípicos que luchan por la justicia, similares a héroes míticos griegos. El estudiante Manuel Salinas Villa presenta esta tesis bajo la asesoría del Dr. Julio Amador Bech para obtener el título de Licenciado en Ciencias de la Comunicación con especialidad en Producción en el año 2008 en la Facultad de Ciencias Políticas
Este documento describe la hipoakalemia, incluyendo su epidemiología, clasificación, metabolismo, distribución y excreción del potasio. También cubre las manifestaciones clínicas, el diagnóstico, el tratamiento y el manejo de la hipoakalemia. La hipoakalemia se define como un nivel de potasio sérico menor a 3.5 meq/l y puede ser leve, moderada o severa. El principal mecanismo regulador del potasio es la bomba de sodio-potasio, y la reposición del potasio
Este estudio evaluó las características clínicas e histológicas de 27 pacientes con glomerulonefritis rápidamente progresiva (GNRP) atendidos en un hospital general en Lima, Perú entre 1998 y 2008. La mayoría de los pacientes fueron mujeres con una edad promedio de 33 años. Más de la mitad presentaron hipertensión arterial y síndromes nefríticos o nefróticos. Histológicamente, más del 70% de los glomérulos mostraron crecientes, predominando los epiteliales. Las caus
El estudio encontró que más de las tres cuartas partes de los pacientes diabéticos llegaron a consulta con albuminuria. El análisis multivariado mostró que la albuminuria se asoció con el sexo femenino (OR 3,721) y con estadios avanzados de enfermedad renal crónica (OR 1,926).
Este documento discute el síndrome nefrótico, incluyendo su definición, fisiopatología, complicaciones, diagnóstico etiológico y tratamiento. Explica que la proteinuria en el síndrome nefrótico se debe a alteraciones en la barrera de filtración glomerular y sus componentes. También describe las principales causas del síndrome nefrótico y el enfoque para evaluar la etiología y complicaciones en los pacientes.
La nefritis lúpica es la afectación renal más común en el lupus eritematoso sistémico. Afecta principalmente a mujeres latinas y afroamericanas entre 16-55 años. El diagnóstico se realiza mediante biopsia renal que muestra depósitos de complejos inmunes que activan el complemento y causan inflamación y daño renal. El tratamiento incluye corticoides e inmunosupresores con el objetivo de lograr remisión renal y prevenir recaídas y enfermedad renal en etapa terminal.
Este documento describe la injuria renal aguda (IRA), incluyendo su definición, diagnóstico, etapas, epidemiología, prevención y terapias de reemplazo renal. Resume las principales causas de IRA en unidades de cuidados intensivos y países en desarrollo. Ofrece recomendaciones para la prevención y tratamiento de IRA, incluyendo el uso de fluidos y medicamentos. Finalmente, analiza el pronóstico de los pacientes con IRA y los resultados de un estudio sobre las características clínicas de pacientes con IRA en diális
Este documento discute la hiponatremia, una condición médica común que se presenta en alrededor del 20-25% de pacientes hospitalizados. La hiponatremia se asocia con un mayor riesgo de mortalidad y puede deberse a cambios en la concentración de agua más que de sodio. El documento proporciona guías para diagnosticar la hiponatremia evaluando la gravedad, cronicidad, osmolaridad y volemia. También discute las estrategias para tratar la hiponatremia, incluyendo la
Adhd Medication Shortage Uk - trinexpharmacy.comreignlana06
The UK is currently facing a Adhd Medication Shortage Uk, which has left many patients and their families grappling with uncertainty and frustration. ADHD, or Attention Deficit Hyperactivity Disorder, is a chronic condition that requires consistent medication to manage effectively. This shortage has highlighted the critical role these medications play in the daily lives of those affected by ADHD. Contact : +1 (747) 209 – 3649 E-mail : sales@trinexpharmacy.com
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Travel vaccination in Manchester offers comprehensive immunization services for individuals planning international trips. Expert healthcare providers administer vaccines tailored to your destination, ensuring you stay protected against various diseases. Conveniently located clinics and flexible appointment options make it easy to get the necessary shots before your journey. Stay healthy and travel with confidence by getting vaccinated in Manchester. Visit us: www.nxhealthcare.co.uk
These lecture slides, by Dr Sidra Arshad, offer a simplified look into the mechanisms involved in the regulation of respiration:
Learning objectives:
1. Describe the organisation of respiratory center
2. Describe the nervous control of inspiration and respiratory rhythm
3. Describe the functions of the dorsal and respiratory groups of neurons
4. Describe the influences of the Pneumotaxic and Apneustic centers
5. Explain the role of Hering-Breur inflation reflex in regulation of inspiration
6. Explain the role of central chemoreceptors in regulation of respiration
7. Explain the role of peripheral chemoreceptors in regulation of respiration
8. Explain the regulation of respiration during exercise
9. Integrate the respiratory regulatory mechanisms
10. Describe the Cheyne-Stokes breathing
Study Resources:
1. Chapter 42, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 36, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 13, Human Physiology by Lauralee Sherwood, 9th edition
Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
- Video recording of this lecture in English language: https://youtu.be/Pt1nA32sdHQ
- Video recording of this lecture in Arabic language: https://youtu.be/uFdc9F0rlP0
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Does Over-Masturbation Contribute to Chronic Prostatitis.pptxwalterHu5
In some case, your chronic prostatitis may be related to over-masturbation. Generally, natural medicine Diuretic and Anti-inflammatory Pill can help mee get a cure.
Rasamanikya is a excellent preparation in the field of Rasashastra, it is used in various Kushtha Roga, Shwasa, Vicharchika, Bhagandara, Vatarakta, and Phiranga Roga. In this article Preparation& Comparative analytical profile for both Formulationon i.e Rasamanikya prepared by Kushmanda swarasa & Churnodhaka Shodita Haratala. The study aims to provide insights into the comparative efficacy and analytical aspects of these formulations for enhanced therapeutic outcomes.
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
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Promoting Wellbeing - Applied Social Psychology - Psychology SuperNotes
Manejo de la erc. review actualizada
1. http://www.kidney-international.org review
& 2012 International Society of Nephrology
Treatment of chronic kidney disease
Jeffrey M. Turner1, Carolyn Bauer1, Matthew K. Abramowitz1, Michal L. Melamed1 and
Thomas H. Hostetter2
1
Nephrology Division, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA and 2Nephrology Division,
Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
Treatment of chronic kidney disease (CKD) can slow its Treatment of chronic kidney disease (CKD) aims to slow
progression to end-stage renal disease (ESRD). However, progression to end-stage renal disease (ESRD) and to prepare
the therapies remain limited. Blood pressure control using for ESRD. Because the symptoms of chronically progressive
angiotensin-converting enzyme (ACE) inhibitors or renal failure develop slowly, therapy of CKD is usually directed
angiotensin II receptor blockers (ARBs) has the greatest at an asymptomatic condition detected only by laboratory
weight of evidence. Glycemic control in diabetes seems testing. The task is also made more difficult as it usually
likely to retard progression. Several metabolic disturbances represents a late attempt at prevention. That is, the major
of CKD may prove to be useful therapeutic targets but causes of ESRD, hypertension, and type 2 diabetes can
have been insufficiently tested. These include acidosis, themselves be avoided to some degree by primary preventive
hyperphosphatemia, and vitamin D deficiency. Drugs aimed measures such as diet, weight control, and exercise. Further-
at other potentially damaging systems and processes, more, once hypertension or diabetes are manifest, their renal
including endothelin, fibrosis, oxidation, and advanced complications can be mitigated by secondary prevention efforts
glycation end products, are at various stages of development. aimed at blood pressure and glycemic control. Thus, treatment
In addition to the paucity of proven effective therapies, the of CKD often represents an example of tertiary prevention in
incomplete application of existing treatments, the education populations who have failed the first lines of prevention but
of patients about their disease, and the transition to ESRD who are still relatively asymptomatic. These features make
care remain major practical barriers to better outcomes. CKD therapy a formidable task in practice. However, over
Kidney International (2012) 81, 351–362; doi:10.1038/ki.2011.380; the past 20 years, some effective treatments of CKD have
published online 14 December 2011 developed. These can delay and, in some cases, prevent ESRD.
KEYWORDS: chronic kidney disease; chronic renal disease; chronic renal The notion of CKD as a single entity with generic therapy
insufficiency is a simplification but a useful one. Admittedly, some forms
of CKD, especially inflammatory and autoimmune ones,
require special treatments. However, even these approaches
are usually applied in addition to those used for the most
common hypertensive and diabetic causes. Viewing CKD as a
single process rests both on the effectiveness of therapy across
a range of primary diseases and on the data, suggesting that
final common physiological pathways underlie the progres-
sion of CKD irrespective of initiating insult.1–3
Cardiovascular disease (CVD) is now well known to be
common and often fatal in people with CKD.4,5 Hence,
careful attention to reducing traditional CVD risk factors in
CKD is of great importance. Nevertheless, delay of ESRD
remains a primary goal of CKD therapy simply because
specific treatments to avoid CVD in this population do not
currently exist. Standard methods of CVD prevention should
be assiduously applied in CKD. Similarly, people with CKD
should receive health maintenance applicable to the general
population such as cancer screening and vaccinations.
Correspondence: Thomas H. Hostetter, Nephrology Division, Department of
Medicine, Case Western Reserve University, School of Medicine, 11100 Euclid
The definition of CKD has itself received considerable
Avenue, Cleveland, Ohio 44106, USA. attention. The most important consequence of the definition
E-mail: thomas.hostetter@uhhospitals.org is its implications for therapy of an individual patient.
Received 6 April 2011; revised 29 August 2011; accepted 30 August Current treatment options are broadly initiated across CKD
2011; published online 14 December 2011 populations because they are relatively inexpensive and safe.
Kidney International (2012) 81, 351–362 351
2. review JM Turner et al.: Treatment of CKD
Given the low potential risk for individuals treated with these reduce this capillary hypertension by both reducing arterial
medications, and the absence of sophisticated prognostic perfusion pressure and relaxation of the efferent arteriole, the
tools, extended debate of CKD definitions is largely unimpor- dominant site of AngII action.1,7 Relief from this excessive
tant for clinical practice. If more toxic or expensive therapies capillary pressure likely prevents mesangial cell proliferation
are forthcoming, or when better markers of progression and matrix production, as well as podocyte loss.1
develop, then the definition may need refinement. At present, Subsequent to the description of beneficial hemodynamic
we regard the simple definition of CKD as an estimated effects, investigators began to describe the RAAS as a
glomerular filtration rate (eGFR) of o60 ml/min per 1.73 m2 proinflammatory and profibrotic mediator. AngII activates
and/or persistent albuminuria 430 mg of urinary albumin NF-kB (nuclear factor k-light-chain-enhancer of activated B
per gram of urinary creatinine as adequate. cells), upregulates adhesion molecules, and may directly
stimulate proliferation of lymphocytes.21,22 The net result of
RENIN–ANGIOTENSIN–ALDOSTERONE SYSTEM these actions is a local inflammatory environment in areas
Angiotensin-converting enzyme (ACE) inhibitors were the where AngII is in high concentration, namely the kidney.
first treatment shown to be effective in slowing the AngII may also foster fibrosis via interactions with transform-
progression of diabetic nephropathy in 1993 by Lewis ing growth factor-b (TGF-b) and the induction of extracellular
et al.6 The work followed on animal studies by several matrix proteins such as type I procollagen, fibronectin, and
laboratories, most notably that of Barry Brenner in the collagen type IV.23 In addition, animal models have implicated
1980s.7 ACE inhibitors and angiotensin II receptor blockers aldosterone to be directly involved with mechanisms of
(ARBs) are standard drugs for primary hypertension. endothelial dysfunction, inflammation, and fibrosis.24 Table 1
However, they are each especially effective in slowing the gives a more complete list of the proposed inflammatory
progressive decay of GFR in CKD.6,8–11 Diabetic nephropathy mechanisms mediated by the RAAS. Using ACE inhibitors and
has been the disease state most studied with these agents. In ARBs to quell these hostile attacks in the kidney is likely an
both diabetes mellitus type 1 and type 2, slowing the rate of important factor in slowing the progression of CKD.
progressive renal injury with renin–angiotensin–aldosterone As ACE inhibitors and ARBs each slow progression
system (RAAS) inhibition has been intimately associated individually, the question has arisen as to whether the
with the stabilization or reduction of proteinuria.6,11 These combination would provide additional advantage. This issue
findings have been demonstrated in patients with micro- has not been definitively settled. One early report of the
albuminura and macroalbuminuria.6,12,13 In nondiabetic COOPERATE trial claimed that the combination was super-
renal diseases, the data for the benefits of RAAS inhibition ior to the individual drugs.25 However, these results and their
on progression of CKD are strongest in those patients with analyses have been brought into question and retracted.26,27
proteinuria 41000 mg/day according to a recent meta- These events make any conclusions drawn from the
analysis.14 The AASK trial further supports this in African COOPERATE trial invalid. An analysis of a study designed
Americans with hypertensive nephropathy.15 The benefit of to examine cardiovascular end points in subjects with
RAAS inhibition in subjects with nondiabetic kidney disease cardiovascular disease but generally good renal function
without proteinuria is less clear. In certain disease states such (the ONTARGET study) found lesser proteinuria with
as autosomal dominant polycystic kidney disease, there may be combination ACE inhibitor and ARB therapy, but no benefit
little to no benefit from ACE inhibitors and ARBs despite in terms of preventing a decline in GFR.28 This study raises a
measurable reductions in proteinuria.16 This is a current topic couple of interesting findings. First, the relationship between
of investigation in the HALT PKD trial.17 The exact nature of improved proteinuria and worsening GFR contributes
the relationship between proteinuria and progressive renal further reason to question the significance of reduced
injury remains a topic of debate.18 It may be misleading to albumin excretion as a meaningful clinical outcome. Second,
interpret reductions in albuminuria as a surrogate for the lack of improved renal end points in those receiving dual
improved renal function. Although some authors argue that therapy questions the validity of this treatment strategy for
experimental evidence suggests that proteinuria has direct slowing CKD progression. A high burden of renal vascular
toxic effects, currently there is no consensus that the available atherosclerosis in the participating subjects may have
evidence clearly establishes a cause and effect role.19,20 For this contributed to these results, and it remains unclear whether
reason, the significance of the antiproteinuric properties of these findings can be directly applied to broader populations
ACE inhibitors and ARBs is unclear. with renal dysfunction. Currently, several trials are underway
On the contrary, there are two widely accepted mechan- to address this, but at present there are no firm data to
isms by which ACE inhibitors and ARBs are understood to be support the use of combination therapy.17,29
beneficial agents in CKD: hemodynamic/antihypertensive Aldosterone contributes along with AngII to the adverse
actions and anti-inflammatory/antifibrotic actions. Their actions of the RAAS in progressive CKD. Recognition of the
reduction of angiotensin II (AngII) levels (and subsequent deleterious effects of aldosterone has led to attempts to
reduction in aldosterone levels) is central to both of these selectively block it by using the mineralocorticoid receptor
pathways. In many animal models of CKD, glomerular blockers.30 A large number of studies in experimental animals
capillary pressures are elevated. ACE inhibitors and ARBs have supported this approach. Several trials in human
352 Kidney International (2012) 81, 351–362
3. JM Turner et al.: Treatment of CKD review
Table 1 | Reported nonhemodynamic effects of renin–angiotensin–aldosterone system
Mechanism Comment Mediator
Stimulation of NF-kB A transcription factor resulting in a cascade of cytokines and other AngII,
proinflammatory factors AngIII, AngIV
Stimulation of ETs-1 A mediator of vascular inflammation with T-cell and macrophage/ AngII
monocyte recruitment
Adhesion molecules Facilitates adhesion of inflammatory cells to capillary walls AngII
Vascular cellular adhesion molecule 1
Intracellular adhesion molecule 1
Integrins
Cell proliferation Enhances structural renal damage and fibrosis AngII/Aldo
Mesangial cells
Glomerular endothelial cells
Fibroblasts
Apoptosis As opposed to cellular proliferation, under certain circumstances, AngII
AngII instead induces apoptosis; how this is regulated is unclear
Increased TGF-b expression An important protein that results in cascading effects central to AngII/Renin
inflammation and fibrosis
Increased connective tissue growth factor Can occur by direct stimulation by AngII or via TGF-b upregulation AngII
Increased ECM products Result in ECM accumulation and are pivotal factors that contribute AngII
Type I procollagen to fibrosis
Fibronectin
Collagen type IV
Increased metalloproteinase inhibitors Also results in ECM accumulation due to decreased turnover AngII
Plasminogen activator inhibitor-1
Tissue inhibitor of matrix metalloproteinases
Ac-SDKP hydrolysis Increases fibrosis and inflammatory cell infiltration ACE
Reactive oxygen species Leads to cellular damage Aldo
MAPK activation Contributes to mesangial injury and renal fibrosis AngII/Aldo
Abbreviations: ACE, angiotensin-converting enzyme; Ac-SDKP, N-acetyl-seryl-aspartyl-lysyl-proline; Aldo, aldosterone; Ang, angiotensin; ECM, extracellular matrix;
ETs-1, endothelins-1; MAPK, mitogen-activated protein kinase; NF-kB, nuclear factor k-light-chain-enhancer of activated B cells; TGF-b, transforming growth factor-b.
subjects with CKD have shown a reduction in proteinuria glomerular capillary pressure affected by antihypertensive
when aldosterone blockade was added to an ACE inhibitor or medications dictate their beneficial effects. However, the
ARB.30–33 However, there is not yet a large enough trial to optimal target arterial pressure in CKD is largely a matter
assess the effects on decline in GFR. Moreover, hyperkalemia of opinion. Current guidelines suggest a target of
is more frequent. Thus, there are no sufficient data to o130/80 mm Hg for patients with CKD, a more stringent
recommend the addition of aldosterone blockade to standard control than the 140/90 mm Hg recommended for the general
therapy in CKD. population. A recent meta-analysis was performed to
Inhibition of renin is yet another means of interrupting specifically address this question.36 The study included
the RAAS. Addition of a renin inhibitor to an ARB reduced results from 2272 subjects with nondiabetic renal disease
proteinuria in diabetic nephropathy.34 The diminution of involved in the MDRD, AASK, and REIN-2 trials. Overall, no
proteinuria was with little if any further reduction in blood benefits in renal outcomes, cardiovascular outcomes, or
pressure, and no additional side effects were noted with the death were obtained in patients with CKD who were treated
combination. A larger and longer trial is underway to test the to a goal blood pressure of 125–130/75–80 mm Hg as
value of renin inhibitor addition to ACE inhibitors or ARBs compared with 140/90 mm Hg. From subgroup analysis,
using cardiovascular and renal end points.35 proteinuria did appear to be an effect modifier. Participants
In summary, blockade of the RAAS with ACE inhibitors with daily proteinuria 4300 mg in the AASK trial and
or ARBs has proven effective in retarding progression of 41000 mg in the MDRD trial did show a benefit. The
CKD. Studies are ongoing to assess the value of interrupting ACCORD trial in type 2 diabetes compared a goal systolic
the pathway simultaneously at multiple sites, but such blood pressure of 140 mm Hg with one of 120 mm Hg and
approaches have, at this time, not been proven more effective found no overall benefit to the lower goal.37 Albuminuria was
than the use of ACE inhibitors or ARBs and have not been less with the lower pressure but eGFR was also lower at the
adequately assessed for safety. end of the study in this group. However, the trial did not
target people with CKD, and on average the starting eGFRs
BLOOD PRESSURE were 490 ml/min per 1.73 m2 and albumin excretion less
Although there is a considerable amount of overlap when than the microalbumuria level. Whether a goal of 120 mm Hg
considering the beneficial effects of RAAS inhibition and systolic pressure is desirable in the CKD population is
blood pressure control, it is important to appreciate them as unknown but is a question to be addressed by the SPRINT
two separate treatment targets. The reductions in arterial and trial, which will recruit a large fraction of subjects with CKD.
Kidney International (2012) 81, 351–362 353
4. review JM Turner et al.: Treatment of CKD
Until we have these results, the present guideline of ammonia with complement component, C3.49,50 Bicarbonate
130/80 mm Hg seems reasonable, especially for those patients supplementation reduced injury in some but not all rat
with higher amounts of proteinuria. models tested.51–53
If first-line therapy with an ACE inhibitor or ARB fails to An analysis of the relation of serum bicarbonate to
achieve the target of 130/80, and often it will not, the choice progression of renal disease in a data set including over 5000
of the second agent is also largely a matter of opinion. outpatients found that low serum bicarbonate level was strongly
Addition of a diuretic has physiological appeal. In short-term associated with subsequent progression of kidney disease.54
studies, the addition of a thiazide diuretic to an ARB showed Obviously, this strong association does not prove a causal
additional reduction of proteinuria in CKD, possibly relationship, and a clinical trial is needed to determine whether
suggesting further renal protection.38 Often it is said that amelioration of acidosis would lessen progression. Kovesdy
thiazide diuretics lose potency in later stages of CKD et al.55 have recently reported that lower serum bicarbonate was
compared with loop diuretics. There is little evidence for associated with mortality in a cohort with CKD.
this contention.39 Many people with CKD will require more Several relatively small trials of the effects of bicarbonate
than the combination of a diuretic and ACE inhibitor or supplementation on renal disease progression have been
ARB to reach target blood pressures. Further choices are recently reported. The first trial was randomized, but not
similarly not based on long-term studies of progression, blinded or placebo controlled, and studied people with
but b-blockers, calcium channel blockers, and/or central advanced CKD.56 It comprised 129 subjects with estimated
sympatholytic agents are satisfactory. creatinine clearance (CrCl) of o30 ml/min who were rando-
Targeting blood pressure o130/80 mm Hg is recom- mized to receive either sodium bicarbonate or continuation
mended, but will often require two or more drugs. of usual care. The treated group received an average of
14 mEq/day of bicarbonate. The most striking result was a
GLYCEMIC CONTROL IN DIABETES 6.5% vs. 33% incidence in ESRD over a 2-year follow-up,
Glycemic control reduces the progression of renal disease as treated vs. control, respectively. Another trial studied subjects
judged by the mitigation of increasing albuminuria in both with relatively high eGFR (B75 ml/min) and assigned 40
type 1 and type 2 diabetes.40–43 For example, in the DCCT, in subjects each to sodium bicarbonate supplementation, sodium
type 1 diabetes, strict glycemic control compared with usual chloride supplementation, or nothing.57 Sodium bicarbonate at
control lessened the progression from microalbuminuria a dose of 0.5 mEq per kg body weight per day was associated
(30–299 mg albumin per g creatinine) to macroalbuminuria with fewer subjects developing more advanced disease over
(4300 mg albumin per g creatinine). Similarly, in the 5 years (o60 ml/min). The rate of decline in eGFR was
ACCORD trial, transitions to microalbuminuria and macro- significantly less in those receiving sodium bicarbonate as
albuminuria were diminished by stringent glycemic control. compared with those receiving sodium chloride or placebo.
However, the incidence of ESRD was not different between Interestingly, urinary endothelin excretion declined with
levels of glycemic control in ACCORD or ADVANCE, another bicarbonate treatment. In an uncontrolled trial comparing
study of glycemic control in type 2 diabetes, and the incidence 30 patients with eGFR o60 ml/min given sodium citrate for 24
of ESRD has been low in follow-ups to DCCT.42–44 months with 29 CKD patients not treated with alkali, eGFR was
No large-scale studies have specifically tested the higher at the end of the study in the treated group.58 An effect
benefits of glycemic control in diabetic CKD with GFR of of alkali on progression of kidney disease in these patients may
o60 ml/min per 1.73 m2 or macroalbuminuria. Thus, have been mediated by a reduction in endothelin secretion.
although attention to glucose control seems to afford renal More recent data suggest that treatment with alkali in CKD
protection, this has been gauged largely by changes in patients reduces both endothelin and aldosterone secretion.59
albuminuria. Evidence that glucose control can forestall Thus, the effects of alkali supplementation on the
ESRD in people with established diabetic CKD is lacking. The progression of renal disease have been tested only in small
exact best level of glycemic control is uncertain. Because of studies with less than optimal design but with encouraging
overall mortality risks with very stringent glycemic control, results. Present guidelines suggest treating patients with alkali
current guidelines call for hemoglobin A1c levels of o7.0%. when serum bicarbonate level decreases to o22 mEq/l.
At present, maintaining hemoglobin A1c of p7.0% remains Although this is opinion based, the available human data
reasonable for people with established diabetic CKD. and the prior animal studies raise the possibility that such
treatment could retard progression.
METABOLIC DERANGEMENTS OF CKD
Acid base Phosphate
Although the acidosis of CKD results from decreased renal Recent evidence suggests that fibroblast growth factor-23, a
ammoniagenesis, ammonia production per residual GFR in phosphaturic hormone, increases early in CKD to maintain
patients and per residual nephron in animals actually rises as phosphorous balance.60 Regardless of this, without inter-
CKD progresses.45–48 Data in rat models of renal disease have vention, hyperphosphatemia regularly appears as CKD
suggested that excess ammoniagenesis per residual nephron progresses. Control of hyperphosphatemia with dietary
causes tubulointerstitial injury because of the interaction of restriction and phosphate binders have long been mainstays
354 Kidney International (2012) 81, 351–362
5. JM Turner et al.: Treatment of CKD review
of therapy directed at preventing bone disease. However, vitamin D should mitigate secondary hyperparathyroidism,
animal studies more than 30 years ago also suggested that but whether this slows progression of CKD or lessens CVD is
hyperphosphatemia hastened progression to ESRD by causing uncertain. In principle, targeted suppression of PTH with a
calcium–phosphate crystal deposition within the renal inter- calcimimetic would be an attractive means of testing the role
stitium.61 More recent observational studies have found that of PTH in extraosseous sequelae of CKD. However, to date,
elevated phosphate associates with more rapid decline in eGFR, the role of PTH in such events is untested.
and also that separately it associates with CVD in CKD as well
as the general population.62–67 In parallel to this, additional Uric acid
studies have also linked elevated serum fibroblast growth Epidemiological studies have often found an association
factor-23 with a greater risk for progression of CKD.68,69 between hyperuricemia and CVD.76–78 The basis for this
In recent years, the proposed pathogenetic mechanisms association is uncertain. However, over the past several years,
for extraosseous toxicity have grown to suggest a role for hypertension has been ascribed to hyperuricemia based
hyperphosphatemia in vascular and cardiac calcifications, largely on animal studies, but human studies are few.76
both of which are common in advanced CKD. These One study of newly diagnosed hypertensive adolescents
calcifications may be mediated through hormonal reactions found that lowering uric acid with allopurinol reduced blood
to phosphate such as the phosphatonins and cellular pressure.79
transformations of vascular smooth muscle cells to those With regard to CKD, hyperuricemia predictably appears as
with more bone phenotypes.70 In any case, interventional GFR declines. Furthermore, uric acid is clearly toxic to the
trials to test the efficacy of phosphate-lowering strategies for kidney in very high concentrations as in tumor lysis. Whether
either slowing CKD progression or preventing CVD are more modest elevations of uric acid are detrimental is more
lacking. Thus, phosphate control when used in CKD must be controversial. Observational studies have found modest
based on data for ameliorating bone outcomes, which are associations of hyperuricemia with decline in renal func-
themselves modest, or at best opinion based on animal and tion.80 One small randomized but unblinded trial involved 25
epidemiologic work. Further trials are needed. patients with mixed causes of CKD. Subjects were assigned to
receive either allopurinol or conventional treatment.81 The
Vitamin D investigators succeeded in lowering uric acid, but in this
Deficiency of 1,25-dihydroxyvitamin D may be expected with study blood pressure was not affected. The serum creatinine
advancing CKD, as the kidney is the site of its synthesis. tended to remain lower in the allopurinol-treated group, but
However, low levels of its precursor 25-hydroxyvitamin D have was not statistically different from that in the control group.
been linked epidemiologically to more rapid progression of A combined end point of incident ESRD and 40% rise in
CKD.71 The physiological actions of vitamin D are multiple creatinine was significantly greater in the untreated group. A
and extend well beyond its classic effects on calcium, second randomized control study involving 113 patients,
phosphate, and bone.72 For example, vitamin D suppresses again with mixed causes of CKD, also showed a favorable
renin secretion, and this action has been proposed as beneficial effect induced by allopurinol.82 In this study, those receiving
in CKD.73 There are no long-term trials of vitamin D allopurinol had a mean eGFR increase of 1.3 ml/min per
supplementation in progressive renal disease using the 1.73 m2 over a period of 24 months. This was a statistically
strongest outcomes such as reduction of GFR or incidence of significant difference when compared with the mean eGFR
ESRD. However, in the VITAL study, a synthetic vitamin D decrease of 3.3 ml/min per 1.73 m2 observed in the control
analog, paricalcitol, did lower albuminuria in subjects with group. These findings occurred independent of any differ-
diabetic nephropathy.74 In this study, reduced albuminuria was ences in blood pressure between the two groups. These
associated with a decrease in blood pressure and an increase in studies, although suggestive, are not sufficiently robust to
eGFR, suggesting that vitamin D–mediated renin suppression recommend allopurinol as a means of slowing progression.
may have been the major contributing mechanism. Clearly, Larger studies might be warranted except that allopurinol has
clinical trials are needed to test the effect of vitamin D on hard a rather high risk for allergic reactions that can be severe. If
outcomes, and especially to test inexpensive forms such as better alternatives for uric acid–lowering drugs were available,
nutritional vitamin D, cholecalciferol. then larger trials would be attractive.
Parathyroid hormone Anemia
Secondary hyperparathyroidism also regularly attends pro- Several studies have tested the efficacy and safety of therapy
gressive CKD and is at least partly a consequence of of anemia with erythropoietin congeners in CKD before
hyperphosphatemia and vitamin D deficiency. Elevated dialysis.83 The largest and most persuasive study TREAT
PTH levels have also been suggested as toxic even beyond randomized 4038 subjects with CKD due to type 2 diabetes
their capacity to induce bone loss.75 However, an analysis of to a target hemoglobin of 13 g/dl, or placebo with
published literature found that the evidence for links between darbepoieten rescue if the level dropped below 9 g/dl.84 The
parathyroid hormone (PTH) and CVD or mortality was baseline eGFR was B35 ml/min per 1.73 m2 for each of
poor.66 The usual recommendations for phosphate and the two groups. Except for more strokes in the higher
Kidney International (2012) 81, 351–362 355
6. review JM Turner et al.: Treatment of CKD
hemoglobin group, there were no differences in cardiovas- frequently found in sclerotic regions of glomeruli, as well as
cular or renal outcomes between the two groups. Approxi- areas of interstitial fibrosis.92 In addition, mesangial cell
mately 16% of the subjects in each group developed ESRD proliferation may also be directly stimulated by low-density
over the 4 years of study. Thus, maintaining hemoglobin lipoproteins and triglyceride-rich lipoproteins.93
levels at 13 g/dl is unwarranted. The lower hemoglobin group Experimental studies in animals and observational data in
had an average level of 10.6 g/dl but received more humans support the hypothesis that lipids contribute directly
transfusions. The optimal level is not clear. Current guide- to renal injury and progression of CKD. Rats fed high-
lines call for levels between 10 and 12 g/dl in ESRD, and this cholesterol diets were found to have greater amounts of
also seems reasonable for patients with CKD predialysis. glomerulosclerosis and tubulointerstitial damage compared
However, lower levels might be equally good, but in practice with those fed standard diets.94,95
a small percentage of CKD patients require treatment for In humans, a number of epidemiological studies have
severe anemia before ESRD. suggested that elevated cholesterol and triglyceride levels
are associated with a more rapid progression of renal
Dietary protein dysfunction.96–98
Dietary protein restriction was one of the earliest therapeutic Given this, lipid-lowering therapy to slow the progression
maneuvers used in CKD. In addition to contributing to of CKD has generated a great deal of interest in the nephro-
alterations in phosphorous, metabolic acidosis, and uric acid logy community. Although a number of different classes of
as described previously, other proposed mechanisms for these medications have been studied, the pertinent data
renal injury from increased dietary intake include altered revolve around HMG-CoA (3-hydroxy-3-methyl-glutaryl-
hemodynamics, leading to glomerular hyperfiltration, and CoA) reductase inhibitors (statins). This class of medication
reduced cytokine-mediated fibrosis.85,86 Protein restriction seems to offer a potential benefit not just by way of
does seem to ameliorate some of the symptoms of advanced decreasing the lipoprotein burden within tissues, but also
CKD, and many animal studies showed that it reduced renal by way of their additional anti-inflammatory affects. In
injury.87 However, clinical trials have been less clear as to its animal studies, statin therapy has been shown to reduce
efficacy in slowing progression. A large analysis of the macrophage recruitment into the glomerulus, limit expres-
available clinical trial literature concluded that low-protein sion of inflammatory factors including chemokines, cyto-
diets reduced the incidence of ESRD in nondiabetic kines, and adhesion molecules, and decrease fibrosis and
patients.88 Because of varying study designs, this review mesangial cell expansion.99 These beneficial effects have been
could not define an optimal level of intake. Properly seen across a number of disease models including diabetic
constructed and monitored protein restriction can be safe.87 nephropathy, focal glomerulosclerosis, cyclosporine nephro-
Probably because successful and safe protein restriction toxicity, and chronic allograft dysfunction.100–103
requires much effort for physicians, dieticians, and patients, Data in human trials supporting the benefits of statin
it is not sedulously practiced. Provided that malnutrition is therapy for slowing the progression of CKD have been less
avoided and the burden is acceptable to the individual convincing. In a meta-analysis of 39,704 patients from 27
patient, a target of 0.8 g of protein per kg body weight per randomized, controlled, and crossover studies, treatment
day seems reasonable. However, careful monitoring of with statins resulted in a small but statistically significant
nutritional status and attentive dietary care is needed if favorable effect on yearly decline in eGFR (1.22 ml/min/year
protein restriction is attempted. slower in statin recipients as compared with placebo).104 In a
subgroup analysis, those patients with cardiovascular disease
LIPID-LOWERING THERAPY were the most likely to benefit, whereas those with diabetes or
Abnormal lipid metabolism often accompanies renal dys- hypertensive nephropathy or glomerulonephritis were not
function. Although hyperlipidemia does not in itself seem found to have a statistically significant benefit. The GREACE
to cause primary renal disease, it may contribute to the study evaluated the effects of a structured care algorithm for
progression of CKD. The hypothesis of lipid nephrotoxicity titrating atorvastatin to reach the low-density lipoprotein
was first generated by Moorhead et al.89 in 1982. The level of o100 mg/dl vs. usual care in the secondary
proposed mechanisms parallel the injury events that lead to prevention of major cardiac events. A post hoc analysis
atherosclerosis in other vascular beds. In the presence of evaluated the effects of statin therapy on change in renal
lipids, mesangial cells are stimulated to recruit macrophages function. For those patients who received atorvastatin as part
through the production of chemokines.90 Activated mesan- of the structured care group the CrCl increased by 12%, and
gial cells and accumulated macrophages subsequently release for those who received various statins as part of the usual care
oxygen radical species that lead to oxidized low-density group the CrCl increased by 4.9%. In contrast, those who did
lipoproteins. These oxidized low-density lipoproteins have not receive any statins had a decrease in CrCl of 5.2%. These
been shown to stimulate proinflammatory and profibrotic results represent the largest benefit of any trial to date;
cytokines.91 A likely integral component to this process is the however, it is important to keep in mind that the study
phagocytosis of lipoproteins by macrophages and mesangial design and the fact that this was a post hoc analysis invites
cells to produce foam cells. As evidence for this, foam cells are certain bias. Another meta-analysis of 15 studies including
356 Kidney International (2012) 81, 351–362
7. JM Turner et al.: Treatment of CKD review
1384 subjects found that those treated with statins were more 3.8 ml/min per 1.73 m2 over 54 weeks. A 2400 mg dose
likely to have reductions in albuminuria or proteinuria; group was also included; however, a significant dropout rate
however, no hard clinical outcomes were reported.105 occurred in these subjects and no significant change in
The recently completed Study of Heart and Renal eGFR as compared with placebo was found. Interestingly,
Protection (SHARP) is the largest randomized controlled inflammatory biomarker levels were highly correlated with
trial to date to study the effects of statin therapy on baseline eGFR in this study. No significant changes in
progression of CKD.106 The study involved over 9438 biomarker levels occurred as a result of treatment with
participants, 6382 of whom had CKD and were not on pirfenidone. Overall, these results are promising, and it will
hemodialysis. Comparing those who received simvastain be interesting to see whether larger studies continue to show
20 mg plus ezetimibe 10 mg with those who received placebo, a benefit for using this medication to treat diabetic
there was no difference in the risk of those with CKD to nephropathy.
progress to ESRD. Although the study did suggest that lipid-
lowering medications are beneficial in predialysis CKD Bardoxolone methyl
patients to prevent major cardiovascular events, this is the Bardoxolone methyl is the first member of a new antioxidant
strongest evidence to date to demonstrate a lack of benefit in inflammation modulator drug class. Bardoxolone methyl and
slowing CKD progression with these agents. Thus, despite a other antioxidant inflammation modulators activate nuclear
reasonably conceived hypothesis, and supporting experimen- factor-erythroid 2-related factor 2, a transcription factor that
tal evidence in animal studies, current human data do not controls over 250 cytoprotective proteins.114 The net result is
convincingly show a significant benefit from statins for an inhibition of immune-mediated inflammation at the
altering the disease course of CKD. tissue level, which may protect against end-organ damage.
Results from a recently completed phase IIb clinical trial
SELECTED NEW THERAPIES reported that bardoxolone methyl has a positive effect on the
Pirfenidone progression of diabetic nephropathy.115 In this multicenter,
Pirfenidone is a synthetic molecule with antifibrotic proper- randomized, controlled trial sponsored by the manufacturer
ties that has emerged as a promising oral treatment for CKD. of the drug, 227 adults with diabetes mellitus type 2 and
Although the exact mechanism of action is unknown, the moderate-to-severe CKD (eGFR 20–45 ml/min per 1.73 m2)
effects of pirfenidone seem to be mediated through were randomized to receive either bardoxolone methyl or
interruptions in the TGF-b pathway.107 Mesangial cell placebo. Almost all of the patients were receiving either an
cultures treated with pirfenidone have shown a reduction ACE inhibitor or an ARB and had well-controlled serum
of TGF-b production, antagonism of TGF-b signaling, glucose and blood pressure levels. Over the course of 24
inhibition of TGF-b-induced reactive oxygen species genera- weeks, patients receiving 25, 75, or 150 mg of bardoxolone
tion, and a reduction of TGF-b-mediated matrix production. methyl all had statistically significant increases in mean eGFR
In a murine model of diabetic nephropathy, pirfenidone as compared with those receiving placebo (between-group
significantly reduced mesangial matrix expansion indepen- differences in eGFR were 8.2, 11.4, and 10.4 ml/min per
dent of alterations in albuminuria or blood glucose levels.107 1.73 m2, respectively). Continued follow-up found that these
Similar findings have been found in rat models of post- benefits persisted over 52 weeks. Surprisingly, improvements
adaptive focal segmental glomerulosclerosis.108 in GFR were seen as early as 4 weeks, and this suggests some
Clinical trials have shown encouraging results for the use skepticism about whether the improved GFR was truly a
of pirfenidone in the treatment of various nonrenal result of reduced inflammation and sustainable changes in
fibrotic diseases including cirrhosis, multiple sclerosis, and kidney structure or was a more temporary change resulting in
pulmonary fibrosis.109–111 Specific to kidney disease, an improved GFR due to altered hemodynamics. Also raising
open-label, observational study of 18 subjects with focal concern was the increase in frequency of adverse events such
segmental glomerulosclerosis and a mean baseline GFR of as muscle spasms, nausea, hypomagnesemia, and decreased
26 ml/min per 1.73 m2 compared the change in GFR during appetite seen in those receiving bardoxolone methyl. The
a 12-month baseline period with a subsequent 12-month suggestion that this drug may actually improve GFR in
treatment period with pirfenidone.112 Although the GFR patients with diabetic nephropathy is intriguing; however,
declined throughout both periods in all patients, the more long-term studies with larger groups are needed to
median monthly GFR decline rate was significantly less validate its effects.
during the treatment period as compared with the baseline
period (À0.45 vs. À0.61 ml/min per 1.73 m2; Po0.01). A Endothelin-1 antagonism
phase II randomized controlled trial involving 77 partici- Endothelins are a group of related peptides with powerful
pants with diabetic nephropathy (eGFR 20 to 75 ml/min per vasoconstrictor properties. Endothelin-1 (ET-1) is the
1.73 m2) was recently completed.113 The subjects receiving a predominant isoform in the human kidney and acts on a
1200 mg dose of pirfenidone not only had a significant wide distribution of receptors throughout the renal vascu-
benefit with regard to change in eGFR as compared with lature and collecting system.116 ET-1 contributes to renal
placebo, but also actually had a mean increase in eGFR of dysfunction through multiple mechanisms including arterial
Kidney International (2012) 81, 351–362 357
8. review JM Turner et al.: Treatment of CKD
vasoconstriction, glomerular hypertension, increased protei- metformin, more specific agents for inhibition of AGE
nuria, and interstitial fibrosis. formation or AGE receptor blockade have been developed
ET-1 blockade has been studied as a potential treatment and studied. A number of these agents have shown potential
strategy for CKD. Animal studies have demonstrated to treat CKD in animal studies.124–129 Aminoguanidine was
elevations of ET-1 after subtotal nephrectomy.117 Treatment the first AGE inhibitor to be studied in humans. Although
with ET-1 antagonist in these models has shown not only proteinuria was decreased in type 1 diabetics during a phase
reductions in proteinuria, but also improvements in III trial, no significant improvement on the progression to
CrCl.117,118 These promising findings provided proof of overt nephropathy was found.130 This study was terminated
concept and have led to human trials. In one study, early because of safety concerns and apparent lack of efficacy.
antagonism of the endothelin type A receptor (ETa) Pyridoxamine is a vitamin B6 derivative. Phase II studies in
improved renal blood flow and reduced renal vascular subjects with diabetes mellitus type 1 and type 2 demon-
resistance in subjects with CKD.119 However, results from a strated it to be well tolerated and showed a statistically
large, multicenter, randomized, controlled trial have raised significant slower decrease in creatinine over 24 weeks.131
serious questions about the safety of these agents. The study Other agents in this class have been used in human studies as
compared the efficacy of avosentan with placebo for well; however, their specific benefit on renal outcomes has
treatment of CKD progression in subjects with diabetic not yet been evaluated.132,133 These medications have not yet
nephropathy.120 After a median follow-up of only 4 months, proven clear efficacy for treatment of CKD, but given the
the trial was prematurely terminated owing to an excess of promising experimental data, there are likely to be more
cardiovascular events in the avosentan-treated group. It is clinical trials to come in the near future.
noteworthy that those in the treatment group did have
significantly less proteinuria, but there was no difference in DELIVERY OF CKD CARE
the primary composite end point of time to doubling of Patients with CKD have many challenges including manage-
serum creatinine, ESRD, or death. A more recent trial tested ment of multiple medications, major changes in diet, and
another ETa antagonist, atrasentan, in 89 subjects with surgery for dialysis access months before any symptoms of
diabetic nephropathy.121 Reported to be more selective for kidney failure occur. Multidisciplinary CKD programs use
the ETa receptor than the ETb receptor as compared with the patient education, nutrition resources, and guideline-driven
previously mentioned avosentan, it was felt that atrasentan nephrology care to achieve the goals of decreasing cardio-
would result in fewer safety concerns. In this study, all vascular morbidity, slowing the progression of renal disease,
patients were already receiving a RAAS blocking agent. No and improving the transition to dialysis or transplant. These
difference in albumin excretion was found with a 0.25 mg programs are heterogeneous between different practices but
dose group; however, 0.75 and 1.75 mg dose groups did result often include a subset of nephrologists, physician assistants
in a significant reduction. The most common side effect was or nurse practitioners, nurses, social workers, dieticians, and
peripheral edema, and this was only significantly more pharmacists. Many of the services that are included in these
frequent in the 1.75 mg dose group. This study provides some programs such as social workers, nutrition counseling,
suggestion that both ETa receptor selectivity and dose may be nursing care, and pharmacist interventions are not paid for
important with regard to the safety profile of these by standard fee-for-service payments; therefore, there is a
medications. Whether reductions in albumin excretion will large need to prove that these interventions are clinically
translate into improvements in more robust renal outcomes effective as well as cost effective. There is growing literature
is unclear. Until additional studies address this, and more that shows that multidisciplinary programs can decrease
evidence becomes available to clearly support the safety of hospitalizations, improve arterial–venous access placement
endothelin antagonists, it remains questionable whether these before hemodialysis, and decrease mortality both before and
agents will become a viable treatment option for CKD. after the initiation of dialysis.
Using evidence-based guidelines has been shown to
INHIBITORS OF ADVANCED GLYCATION END PRODUCTS improve outcomes of patients with CKD. One study by
Advanced glycation end products (AGEs) form from the Snyder and Collins134 demonstrated that adherence to the
nonenzymatic glycation of proteins by glucose and its Kidney Disease Outcomes Quality Initiative preventive
metabolites. AGEs facilitate cellular damage by directly health-care guidelines decreased atherosclerotic heart disease.
modifying cellular proteins and altering their function or These authors found that the more preventive measures used
by binding to specific AGE receptors that induce a broad per year, including two creatinine measurements, lipid
range of cellular responses leading to injury. While implicated measurement, calcium–phosphorus measurement, PTH mea-
as a major pathogenic mechanism in diabetic nephropathy, surement, HbA1c measurement, and influenza vaccine,
AGEs also contribute to kidney injury in other forms of decreased the risk of atherosclerotic heart disease in a high-
nondiabetic renal disease and aging.122 The use of direct risk Medicare cohort with CKD. Guideline-driven care in a
therapeutics that disrupt the AGE/AGE receptor axis is a multidisciplinary program is often implemented by a
developing treatment strategy.123 In addition to common physician extender. Lee et al.135 showed that a nurse
therapies such as RAAS inhibitors, statins, aspirin, and practitioner using guideline-directed care was more effective
358 Kidney International (2012) 81, 351–362
9. JM Turner et al.: Treatment of CKD review
in decreasing hospitalizations after initiation of dialysis. They Access to a nephrologist for 41 year before dialysis
also had a substantial increase in patients starting dialysis initiation has been shown to decrease mortality for patients
with an arterial–venous access in 5 years; 62% had with CKD.143,144 Multidisciplinary care has also been shown
arterial–venous access in the nurse practitioner group to decrease mortality both before and after the initiation of
compared with 20% in a renal hypertension clinic.135 dialysis. Two studies compared outcomes of patients who
Several other studies also showed decreased hospitaliza- initiated hemodialysis and found that those patients who had
tion rates and improved arterial–venous access using a been followed up in a multidisciplinary program before
multidisciplinary model. Cohorts of patients who had dialysis starts had lower mortality rates.145,146 Hemmelgarn
attended multidisciplinary programs in California, Canada, et al.147 compared a predialysis cohort of patients who had
and Taiwan showed dialysis starts with increased number of multidisciplinary care to a cohort of propensity-matched
functioning arterial–venous accesses, and with either de- controls and found significantly decreased mortality rates in
creased number of inpatient days or decreased number of the patients exposed to the multidisciplinary intervention.
hospitalizations.136–138 Decreased hospitalizations by out- Multidisciplinary care has been shown to improve
patient dialysis starts and the use of arterial–venous access outcomes in patients with CKD and is likely cost effective.
achieved by multidisciplinary programs also result in health- However, most of the evidence is from small cohorts and not
care savings. According to the USRDS (United States Renal randomized controlled trials. In addition, there is likely a
Data System) database, the inpatient cost per member per publication bias with only centers that have positive
month for dialysis initiation ranges from $9846 for Medicare outcomes publishing their data. These programs likely
recipients up to $22,841 for patients with commercial improve care in this patient population, and more rigorous
insurance; this could be greatly reduced by increasing study is needed to demonstrate their benefit and ability to
outpatient dialysis starts.139 A functional arterial–venous decrease costs.
fistula is associated with a difference of approximately $3000
dollars per patient per year compared with a hemocatheter, CONCLUSIONS
and the total yearly dialysis expenditure for a patient with a The increasing use of treatments to attenuate progressive
hemocatheter averages $90,110 compared with $64,701 for a CKD, most notably glycemic control in diabetic CKD and
patient with a fistula.139 Proponents of multidisciplinary blood pressure treatment with ACE inhibitors and ARBs in
programs maintain that the cost savings of these programs almost all forms of CKD, have coincided with a plateau in the
outweigh the personnel and increased health-care utilization incidence of ESRD in the United States over the past few
costs. A study in Taiwan found that the patients in the years.139 This is a very welcome change after decades of
interdisciplinary program studied for 6 months before increasing incidence and is likely related to the use of these
dialysis initiation had a mean cost of $1200 per patient less treatment options. However, a stable rate of incidence at over
than those patients who had seen a nephrologist only.138 100,000 people per year is not good enough, and the field has
Patient education and multidisciplinary care through not seen a truly new therapy for slowing progression in over a
different models have decreased both the rate of kidney decade.
disease progression and the rate of reaching ESRD. A Organized multidisciplinary clinics seem to be an effective
randomized controlled trial demonstrated that one 90-min means to apply the tools we have. However, these tools are far
educational session with a follow-up phone call every 3 weeks from perfect. One can consider a clinical trial as something
significantly decreased the time to dialysis by B3 months in akin to such a clinic, and subjects in the trials taking ACE
patients expected to start dialysis within 6–18 months.140 inhibitors or ARBs still progressed, although more slowly
Richards et al.141 studied a cohort of patients with eGFRs than subjects on the comparators. If a better result than a
o30 ml/min in a primary care program in England who had stable incidence of ESRD is to be achieved, then new
access to a nurse, patient education, medication manage- therapies are needed. Obviously, basic research will be
ment, and dietary advice. They found that the program critical. Although beyond the scope of this review, recent
significantly decreased the rate of fall of eGFR, and the findings such as the deleterious reactivation of the role of
impact was greatest in those patients whose eGFR was falling NOTCH pathway in CKD and the discovery of APOL 1
the fastest, 45 ml/min in the 9 months before the study. The (apolipoprotein L, 1) polymorphisms conferring risk for focal
positive impact of multidisciplinary programs has also been segmental sclerosis are strong examples of such basic research
demonstrated in patients with higher eGFRs, those between with potential drug targets.148,149 New reliable markers of
30 and 59 ml/min. A study in a health maintenance renal disease that would allow faster, smaller, and therefore
organization population found that the rate of eGFR decline less expensive trials are highly desirable. Finally, testing of
was less in patients who enrolled in an interdisciplinary care relatively simple and cheap approaches such as bicarbonate
model compared with historical controls.142 Given that the and nutritional vitamin D that will not be supported by the
average cost per patient per year for hemodialysis, peritoneal pharmaceutical industry seems overdue.
dialysis, and transplant is $77,506, $57,639, and $26,668,
respectively, delaying ESRD would likely result in a DISCLOSURE
considerable cost savings.139 All the authors declared no competing interests.
Kidney International (2012) 81, 351–362 359
10. review JM Turner et al.: Treatment of CKD
REFERENCES 26. Kunz R, Wolbers M, Glass T et al. The COOPERATE trial: a letter of
1. Hostetter TH. Hyperfiltration and glomerulosclerosis. Semin Nephrol concern. Lancet 2008; 371: 1575–1576.
2003; 23: 194–199. 27. Bidani A. Controversy about COOPERATE ABPM trial data. Am J Nephrol
2. Zandi-Nejad K, Brenner BM. Strategies to retard the progression of 2006; 26: 629, 632; author reply 629–632.
chronic kidney disease. Med Clin North Am 2005; 89: 489–509. 28. Mann JF, Schmieder RE, McQueen M et al. Renal outcomes with
3. Remuzzi G, Benigni A, Remuzzi A. Mechanisms of progression and telmisartan, ramipril, or both, in people at high vascular risk (the
regression of renal lesions of chronic nephropathies and diabetes. J Clin ONTARGET study): a multicentre, randomised, double-blind, controlled
Invest 2006; 116: 288–296. trial. Lancet 2008; 372: 547–553.
4. Go AS, Chertow GM, Fan D et al. Chronic kidney disease and the risks of 29. Fried LF, Duckworth W, Zhang JH et al. Design of combination
death, cardiovascular events, and hospitalization. N Engl J Med 2004; angiotensin receptor blocker and angiotensin-converting enzyme
351: 1296–1305. inhibitor for treatment of diabetic nephropathy (VA NEPHRON-D). Clin J
5. van der Velde M, Matsushita K, Coresh J et al. Lower estimated Am Soc Nephrol 2009; 4: 361–368.
glomerular filtration rate and higher albuminuria are associated with all- 30. Ponda MP, Hostetter TH. Aldosterone antagonism in chronic kidney
cause and cardiovascular mortality. A collaborative meta-analysis of disease. Clin J Am Soc Nephrol 2006; 1: 668–677.
high-risk population cohorts. Kidney Int 2011; 79: 1341–1352. 31. Bomback AS, Kshirsagar AV, Amamoo MA et al. Change in proteinuria
6. Lewis EJ, Hunsicker LG, Bain RP et al. The effect of angiotensin- after adding aldosterone blockers to ACE inhibitors or angiotensin
converting-enzyme inhibition on diabetic nephropathy. The receptor blockers in CKD: a systematic review. Am J Kidney Dis 2008; 51:
Collaborative Study Group. N Engl J Med 1993; 329: 1456–1462. 199–211.
7. Zatz R, Anderson S, Meyer TW et al. Lowering of arterial blood pressure 32. Navaneethan SD, Nigwekar SU, Sehgal AR et al. Aldosterone antagonists
limits glomerular sclerosis in rats with renal ablation and in experimental for preventing the progression of chronic kidney disease. Cochrane
diabetes. Kidney Int Suppl 1987; 20: S123–S129. Database Syst Rev 2009: CD007004.
8. Jafar TH, Schmid CH, Landa M et al. Angiotensin-converting enzyme 33. Mehdi UF, Adams-Huet B, Raskin P et al. Addition of angiotensin
inhibitors and progression of nondiabetic renal disease. A meta-analysis receptor blockade or mineralocorticoid antagonism to maximal
of patient-level data. Ann Intern Med 2001; 135: 73–87. angiotensin-converting enzyme inhibition in diabetic nephropathy.
9. Lewis EJ, Hunsicker LG, Clarke WR et al. Renoprotective effect of the J Am Soc Nephrol 2009; 20: 2641–2650.
angiotensin-receptor antagonist irbesartan in patients with 34. Parving HH, Persson F, Lewis JB et al. Aliskiren combined with losartan in
nephropathy due to type 2 diabetes. N Engl J Med 2001; 345: 851–860. type 2 diabetes and nephropathy. N Engl J Med 2008; 358: 2433–2446.
10. The GISEN Group (Gruppo Italiano di Studi Epidemiologici in 35. Parving HH, Brenner BM, McMurray JJ et al. Aliskiren Trial in Type 2
Nefrologia). Randomised placebo-controlled trial of effect of ramipril on Diabetes Using Cardio-Renal Endpoints (ALTITUDE): rationale and study
decline in glomerular filtration rate and risk of terminal renal failure in design. Nephrol Dial Transplant 2009; 24: 1663–1671.
proteinuric, non-diabetic nephropathy. Lancet 1997; 349: 1857–1863. 36. Upadhyay A, Earley A, Haynes SM et al. Systematic review: blood
11. Brenner BM, Cooper ME, de Zeeuw D et al. Effects of losartan on renal pressure target in chronic kidney disease and proteinuria as an effect
and cardiovascular outcomes in patients with type 2 diabetes and modifier. Ann Intern Med 2011; 154: 541–548.
nephropathy. N Engl J Med 2001; 345: 861–869. 37. Cushman WC, Evans GW, Byington RP et al. Effects of intensive blood-
12. Ravid M, Lang R, Rachmani R et al. Long-term renoprotective effect of pressure control in type 2 diabetes mellitus. N Engl J Med 362:
angiotensin-converting enzyme inhibition in non-insulin-dependent 1575–1585.
diabetes mellitus. A 7-year follow-up study. Arch Intern Med 1996; 156: 38. Vogt L, Waanders F, Boomsma F et al. Effects of dietary sodium and
286–289. hydrochlorothiazide on the antiproteinuric efficacy of losartan. J Am Soc
13. Captopril reduces the risk of nephropathy in IDDM patients with Nephrol 2008; 19: 999–1007.
microalbuminuria. The Microalbuminuria Captopril Study Group. 39. Dussol B, Moussi-Frances J, Morange S et al. A randomized trial of
Diabetologia 1996; 39: 587–593. furosemide vs hydrochlorothiazide in patients with chronic renal failure
14. Jafar TH, Stark PC, Schmid CH et al. Progression of chronic kidney
and hypertension. Nephrol Dial Transplant 2005; 20: 349–353.
disease: the role of blood pressure control, proteinuria, and angiotensin- 40. The Diabetes Control and Complications (DCCT) Research Group. Effect
converting enzyme inhibition: a patient-level meta-analysis. Ann Intern
of intensive therapy on the development and progression of diabetic
Med 2003; 139: 244–252.
nephropathy in the Diabetes Control and Complications Trial. Kidney Int
15. Appel LJ, Wright Jr JT, Greene T et al. Intensive blood-pressure control in
1995; 47: 1703–1720.
hypertensive chronic kidney disease. N Engl J Med 2010; 363: 918–929.
41. Bilous R. Microvascular disease: what does the UKPDS tell us about
16. Jafar TH, Stark PC, Schmid CH et al. The effect of angiotensin-converting-
diabetic nephropathy? Diabet Med 2008; 25(Suppl 2): 25–29.
enzyme inhibitors on progression of advanced polycystic kidney
42. Ismail-Beigi F, Craven T, Banerji MA et al. Effect of intensive treatment of
disease. Kidney Int 2005; 67: 265–271.
hyperglycaemia on microvascular outcomes in type 2 diabetes: an
17. Chapman AB. Approaches to testing new treatments in autosomal
analysis of the ACCORD randomised trial. Lancet 376: 419–430.
dominant polycystic kidney disease: insights from the CRISP and HALT-
43. Patel A, MacMahon S, Chalmers J et al. Intensive blood glucose control
PKD studies. Clin J Am Soc Nephrol 2008; 3: 1197–1204.
18. Glassock RJ. Debate: CON position. Should microalbuminuria ever be and vascular outcomes in patients with type 2 diabetes. N Engl J Med
considered as a renal endpoint in any clinical trial? Am J Nephrol 2010; 2008; 358: 2560–2572.
31: 462–465; discussion 466–467. 44. de Boer IH, Rue TC, Cleary PA et al. Long-term Renal Outcomes of
19. Zoja C, Morigi M, Remuzzi G. Proteinuria and phenotypic change of Patients With Type 1 Diabetes Mellitus and Microalbuminuria: An
proximal tubular cells. J Am Soc Nephrol 2003; 14(Suppl 1): S36–S41. Analysis of the Diabetes Control and Complications Trial/Epidemiology
20. Abbate M, Zoja C, Remuzzi G. How does proteinuria cause progressive of Diabetes Interventions and Complications Cohort. Arch Intern Med
renal damage? J Am Soc Nephrol 2006; 17: 2974–2984. 171: 412–420.
21. Ruster C, Wolf G. Renin-angiotensin-aldosterone system and progression 45. Van Slyke DD, Linder GC, Hiller A et al. The excretion of ammonia and
of renal disease. J Am Soc Nephrol 2006; 17: 2985–2991. titratable acid in nephritis. J Clin Invest 1926; 2: 255–288.
22. Sowers JR, Whaley-Connell A, Epstein M. Narrative review: the emerging 46. Simpson DP. Control of hydrogen ion homeostasis and renal acidosis.
clinical implications of the role of aldosterone in the metabolic Medicine (Baltimore) 1971; 50: 503–541.
syndrome and resistant hypertension. Ann Intern Med 2009; 150: 47. Simon E, Martin D, Buerkert J. Contribution of individual superficial
776–783. nephron segments to ammonium handling in chronic metabolic
23. Ruster C, Wolf G. Renin-angiotensin-aldosterone system and progression acidosis in the rat. Evidence for ammonia disequilibrium in the renal
of renal disease. J Am Soc Nephrol 2006; 17: 2985–2991. cortex. J Clin Invest 1985; 76: 855–864.
24. Nishiyama A, Abe Y. Molecular mechanisms and therapeutic strategies 48. Schoolwerth AC, Sandler RS, Hoffman PM et al. Effects of nephron
of chronic renal injury: renoprotective effects of aldosterone blockade. reduction and dietary protein content on renal ammoniagenesis in the
J Pharmacol Sci 2006; 100: 9–16. rat. Kidney Int 1975; 7: 397–404.
25. Nakao N, Yoshimura A, Morita H et al. Combination treatment of 49. Nath KA, Hostetter MK, Hostetter TH. Pathophysiology of chronic
angiotensin-II receptor blocker and angiotensin-converting-enzyme tubulo-interstitial disease in rats. Interactions of dietary acid load,
inhibitor in non-diabetic renal disease (COOPERATE): a randomised ammonia, and complement component C3. J Clin Invest 1985; 76:
controlled trial. Lancet 2003; 361: 117–124. 667–675.
360 Kidney International (2012) 81, 351–362
11. JM Turner et al.: Treatment of CKD review
50. Tolins JP, Hostetter MK, Hostetter TH. Hypokalemic nephropathy in the 76. Feig DI, Kang DH, Johnson RJ. Uric acid and cardiovascular risk. N Engl J
rat. Role of ammonia in chronic tubular injury. J Clin Invest 1987; 79: Med 2008; 359: 1811–1821.
1447–1458. 77. Wen CP, David Cheng TY, Chan HT et al. Is high serum uric acid a risk
51. Torres VE, Cowley Jr BD, Branden MG et al. Long-term ammonium marker or a target for treatment? Examination of its independent effect
chloride or sodium bicarbonate treatment in two models of polycystic in a large cohort with low cardiovascular risk. Am J Kidney Dis 56:
kidney disease. Exp Nephrol 2001; 9: 171–180. 273–288.
52. Throssell D, Brown J, Harris KP et al. Metabolic acidosis does not 78. Tangri N, Weiner DE. Uric acid, CKD, and cardiovascular disease:
contribute to chronic renal injury in the rat. Clin Sci (Lond) 1995; 89: confounders, culprits, and circles. Am J Kidney Dis 56: 247–250.
643–650. 79. Feig DI, Soletsky B, Johnson RJ. Effect of allopurinol on blood pressure of
53. Throssell D, Harris KP, Bevington A et al. Renal effects of metabolic adolescents with newly diagnosed essential hypertension: a randomized
acidosis in the normal rat. Nephron 1996; 73: 450–455. trial. Jama 2008; 300: 924–932.
54. Shah SN, Abramowitz M, Hostetter TH et al. Serum bicarbonate levels 80. Obermayr RP, Temml C, Gutjahr G et al. Elevated uric acid increases the
and the progression of kidney disease: a cohort study. Am J Kidney Dis risk for kidney disease. J Am Soc Nephrol 2008; 19: 2407–2413.
2009; 54: 270–277. 81. Siu YP, Leung KT, Tong MK et al. Use of allopurinol in slowing the
55. Kovesdy CP, Anderson JE, Kalantar-Zadeh K. Association of serum progression of renal disease through its ability to lower serum uric acid
bicarbonate levels with mortality in patients with non-dialysis- level. Am J Kidney Dis 2006; 47: 51–59.
dependent CKD. Nephrol Dial Transplant 2009; 24: 1232–1237. 82. Goicoechea M, de Vinuesa SG, Verdalles U et al. Effect of allopurinol in
56. de Brito-Ashurst I, Varagunam M, Raftery MJ et al. Bicarbonate chronic kidney disease progression and cardiovascular risk. Clin J Am Soc
supplementation slows progression of CKD and improves nutritional Nephrol 2010; 5: 1388–1393.
status. J Am Soc Nephrol 2009; 20: 2075–2084. 83. Parfrey PS. Critical appraisal of randomized controlled trials of anemia
57. Mahajan A, Simoni J, Sheather SJ et al. Daily oral sodium bicarbonate correction in patients with renal failure. Curr Opin Nephrol Hypertens 20:
preserves glomerular filtration rate by slowing its decline in early 177–181.
hypertensive nephropathy. Kidney Int 2010; 78: 303–309. 84. Pfeffer MA, Burdmann EA, Chen CY et al. A trial of darbepoetin alfa in
58. Phisitkul S, Khanna A, Simoni J et al. Amelioration of metabolic acidosis type 2 diabetes and chronic kidney disease. N Engl J Med 2009; 361:
in patients with low GFR reduced kidney endothelin production and 2019–2032.
kidney injury, and better preserved GFR. Kidney Int 2010; 77: 617–623. 85. Woods LL. Mechanisms of renal hemodynamic regulation in response to
59. Wesson DE, Simoni J, Broglio K et al. Acid retention accompanies protein feeding. Kidney Int 1993; 44: 659–675.
reduced GFR in humans and increases plasma levels of endothelin and 86. Nakamura T, Fukui M, Ebihara I et al. Low protein diet blunts the rise in
aldosterone. Am J Physiol Renal Physiol 2011; 300: F830–F837. glomerular gene expression in focal glomerulosclerosis. Kidney Int 1994;
60. Wolf M. Forging forward with 10 burning questions on FGF23 in kidney
45: 1593–1605.
disease. J Am Soc Nephrol 2010; 21: 1427–1435. 87. Curhan GC, Mitch WE In: Brenner BM (ed). The Kidney, 8th edn. Saunders:
61. Alfrey AC. The role of abnormal phosphorus metabolism in the
Philadelphia, PA, 2008, pp 1817–1847.
progression of chronic kidney disease and metastatic calcification.
88. Fouque D, Laville M. Low protein diets for chronic kidney disease in non
Kidney Int Suppl 2004; 66: S13–S17.
diabetic adults. Cochrane Database Syst Rev 2009: CD001892.
62. Foley RN. Phosphate levels and cardiovascular disease in the general
89. Moorhead JF, Chan MK, El-Nahas M et al. Lipid nephrotoxicity in chronic
population. Clin J Am Soc Nephrol 2009; 4: 1136–1139.
progressive glomerular and tubulo-interstitial disease. Lancet 1982; 2:
63. Levin A, Djurdjev O, Beaulieu M et al. Variability and risk factors for
1309–1311.
kidney disease progression and death following attainment of stage 4
90. Rovin BH, Tan LC. LDL stimulates mesangial fibronectin production and
CKD in a referred cohort. Am J Kidney Dis 2008; 52: 661–671.
chemoattractant expression. Kidney Int 1993; 43: 218–225.
64. Tonelli M, Curhan G, Pfeffer M et al. Relation between alkaline
91. Keane WF. The role of lipids in renal disease: future challenges. Kidney
phosphatase, serum phosphate, and all-cause or cardiovascular
Int Suppl 2000; 75: S27–S31.
mortality. Circulation 2009; 120: 1784–1792.
92. Magil AB. Interstitial foam cells and oxidized lipoprotein in human
65. Eddington H, Hoefield R, Sinha S et al. Serum phosphate and mortality in
glomerular disease. Mod Pathol 1999; 12: 33–40.
patients with chronic kidney disease. Clin J Am Soc Nephrol 5:
93. Nishida Y, Oda H, Yorioka N. Effect of lipoproteins on mesangial cell
2251–2257.
66. Palmer SC, Hayen A, Macaskill P et al. Serum levels of phosphorus, proliferation. Kidney Int Suppl 1999; 71: S51–S53.
parathyroid hormone, and calcium and risks of death and cardiovascular 94. Kasiske BL, O0 Donnell MP, Schmitz PG et al. Renal injury of diet-induced
disease in individuals with chronic kidney disease: a systematic review hypercholesterolemia in rats. Kidney Int 1990; 37: 880–891.
and meta-analysis. Jama 305: 1119–1127. 95. Guijarro C, Kasiske BL, Kim Y et al. Early glomerular changes in rats with
67. Bellasi A, Mandreoli M, Baldrati L et al. Chronic kidney disease dietary-induced hypercholesterolemia. Am J Kidney Dis 1995; 26:
progression and outcome according to serum phosphorus in mild-to- 152–161.
moderate kidney dysfunction. Clin J Am Soc Nephrol 2011; 6: 883–891. 96. Ravid M, Brosh D, Ravid-Safran D et al. Main risk factors for nephropathy
68. Titan SM, Zatz R, Graciolli FG et al. FGF-23 as a predictor of renal in type 2 diabetes mellitus are plasma cholesterol levels, mean blood
outcome in diabetic nephropathy. Clin J Am Soc Nephrol 2011; 6: pressure, and hyperglycemia. Arch Intern Med 1998; 158: 998–1004.
241–247. 97. Schaeffner ES, Kurth T, Curhan GC et al. Cholesterol and the risk of renal
69. Fliser D, Kollerits B, Neyer U et al. Fibroblast growth factor 23 (FGF23) dysfunction in apparently healthy men. J Am Soc Nephrol 2003; 14:
predicts progression of chronic kidney disease: the Mild to Moderate 2084–2091.
Kidney Disease (MMKD) Study. J Am Soc Nephrol 2007; 18: 2600–2608. 98. Appel GB, Radhakrishnan J, Avram MM et al. Analysis of metabolic
70. Hruska KA, Mathew S, Lund RJ et al. The pathogenesis of vascular parameters as predictors of risk in the RENAAL study. Diabetes Care
calcification in the chronic kidney disease mineral bone disorder: the 2003; 26: 1402–1407.
links between bone and the vasculature. Semin Nephrol 2009; 29: 99. Fried LF. Effects of HMG-CoA reductase inhibitors (statins) on
156–165. progression of kidney disease. Kidney Int 2008; 74: 571–576.
71. Melamed ML, Astor B, Michos ED et al. 25-hydroxyvitamin D levels, race, 100. Ota T, Takamura T, Ando H et al. Preventive effect of cerivastatin on
and the progression of kidney disease. J Am Soc Nephrol 2009; 20: diabetic nephropathy through suppression of glomerular macrophage
2631–2639. recruitment in a rat model. Diabetologia 2003; 46: 843–851.
72. Gal-Moscovici A, Sprague SM. Use of vitamin D in chronic kidney disease 101. Kasiske BL, O0 Donnell MP, Cleary MP et al. Treatment of hyperlipidemia
patients. Kidney Int 78: 146–151. reduces glomerular injury in obese Zucker rats. Kidney Int 1988; 33:
73. Zhang Y, Kong J, Deb DK et al. Vitamin D receptor attenuates renal 667–672.
fibrosis by suppressing the renin-angiotensin system. J Am Soc Nephrol 102. Li C, Lim SW, Choi BS et al. Inhibitory effect of pravastatin on
21: 966–973. transforming growth factor beta1-inducible gene h3 expression in a rat
74. de Zeeuw D, Agarwal R, Amdahl M et al. Selective vitamin D receptor model of chronic cyclosporine nephropathy. Am J Nephrol 2005; 25:
activation with paricalcitol for reduction of albuminuria in patients with 611–620.
type 2 diabetes (VITAL study): a randomised controlled trial. Lancet 376: 103. Zhang W, Liu M, Wu Y et al. Protective effects of atorvastatin on chronic
1543–1551. allograft nephropathy in rats. J Surg Res 2007; 143: 428–436.
75. Rodriguez M, Lorenzo V. Parathyroid hormone, a uremic toxin. Semin 104. Sandhu S, Wiebe N, Fried LF et al. Statins for improving renal outcomes:
Dial 2009; 22: 363–368. a meta-analysis. J Am Soc Nephrol 2006; 17: 2006–2016.
Kidney International (2012) 81, 351–362 361
12. review JM Turner et al.: Treatment of CKD
105. Douglas K, O0 Malley PG, Jackson JL. Meta-analysis: the effect of statins 128. Wilkinson-Berka JL, Kelly DJ, Koerner SM et al. ALT-946 and
on albuminuria. Ann Intern Med 2006; 145: 117–124. aminoguanidine, inhibitors of advanced glycation, improve severe
106. Baigent C, Landray MJ, Reith C et al. The effects of lowering LDL nephropathy in the diabetic transgenic (mREN-2)27 rat. Diabetes 2002;
cholesterol with simvastatin plus ezetimibe in patients with chronic 51: 3283–3289.
kidney disease (Study of Heart and Renal Protection): a randomised 129. Figarola JL, Loera S, Weng Y et al. LR-90 prevents dyslipidaemia and
placebo-controlled trial. Lancet 2011; 377: 2181–2192. diabetic nephropathy in the Zucker diabetic fatty rat. Diabetologia 2008;
107. RamachandraRao SP, Zhu Y, Ravasi T et al. Pirfenidone is renoprotective 51: 882–891.
in diabetic kidney disease. J Am Soc Nephrol 2009; 20: 1765–1775. 130. Bolton WK, Cattran DC, Williams ME et al. Randomized trial of an
108. Shimizu T, Fukagawa M, Kuroda T et al. Pirfenidone prevents collagen inhibitor of formation of advanced glycation end products in diabetic
accumulation in the remnant kidney in rats with partial nephrectomy. nephropathy. Am J Nephrol 2004; 24: 32–40.
Kidney International Supplement 1997; 63: S239–S243. 131. Williams ME, Bolton WK, Khalifah RG et al. Effects of pyridoxamine in
109. Walker JE, Giri SN, Margolin SB. A double-blind, randomized, controlled combined phase 2 studies of patients with type 1 and type 2 diabetes
study of oral pirfenidone for treatment of secondary progressive and overt nephropathy. Am J Nephrol 2007; 27: 605–614.
multiple sclerosis. Mult Scler 2005; 11: 149–158. 132. Stirban A, Negrean M, Stratmann B et al. Benfotiamine prevents macro-
110. Armendariz-Borunda J, Islas-Carbajal MC, Meza-Garcia E et al. A pilot and microvascular endothelial dysfunction and oxidative stress
study in patients with established advanced liver fibrosis using following a meal rich in advanced glycation end products in individuals
pirfenidone. Gut 2006; 55: 1663–1665. with type 2 diabetes. Diabetes Care 2006; 29: 2064–2071.
111. Azuma A, Nukiwa T, Tsuboi E et al. Double-blind, placebo-controlled trial 133. Little WC, Zile MR, Kitzman DW et al. The effect of alagebrium chloride
of pirfenidone in patients with idiopathic pulmonary fibrosis. Am J Respir (ALT-711), a novel glucose cross-link breaker, in the treatment of elderly
Crit Care Med 2005; 171: 1040–1047. patients with diastolic heart failure. J Card Fail 2005; 11: 191–195.
112. Cho ME, Smith DC, Branton MH et al. Pirfenidone slows renal function 134. Snyder JJ, Collins AJ. Association of preventive health care with
decline in patients with focal segmental glomerulosclerosis. Clin J Am atherosclerotic heart disease and mortality in CKD. J Am Soc Nephrol
Soc Nephrol 2007; 2: 906–913. 2009; 20: 1614–1622.
113. Sharma K, Ix JH, Mathew AV et al. Pirfenidone for diabetic nephropathy. 135. Lee W, Campoy S, Smits G et al. Effectiveness of a chronic kidney disease
J Am Soc Nephrol 2011; 22: 1144–1151. clinic in achieving K/DOQI guideline targets at initiation of dialysis–a
114. Sporn MB, Liby KT, Yore MM et al. New synthetic triterpenoids: potent single-centre experience. Nephrol Dial Transplant 2007; 22: 833–838.
agents for prevention and treatment of tissue injury caused by 136. Yeoh HH, Tiquia HS, Abcar AC et al. Impact of predialysis care on clinical
inflammatory and oxidative stress. J Nat Prod 2011; 74: 537–545. outcomes. Hemodial Int 2003; 7: 338–341.
115. Pergola PE, Raskin P, Toto RD et al. Bardoxolone methyl and kidney 137. Levin A, Lewis M, Mortiboy P et al. Multidisciplinary predialysis
function in CKD with type 2 diabetes. N Engl J Med 2011; 365: programs: quantification and limitations of their impact on patient
327–336. outcomes in two Canadian settings. Am J Kidney Dis 1997; 29: 533–540.
116. Dhaun N, Goddard J, Webb DJ. The endothelin system and its 138. Wei SY, Chang YY, Mau LW et al. Chronic kidney disease care program
antagonism in chronic kidney disease. J Am Soc Nephrol 2006; 17: improves quality of pre-end-stage renal disease care and reduces
943–955. medical costs. Nephrology (Carlton) 2010; 15: 108–115.
117. Brochu E, Lacasse S, Moreau C et al. Endothelin ET(A) receptor blockade 139. U.S. Renal Data System. USRDS 2009 Annual Data Report: Atlas of End-
prevents the progression of renal failure and hypertension in uraemic Stage Renal Disease in the United States. National Institutes of Health,
rats. Nephrol Dial Transplant 1999; 14: 1881–1888. National Institute of Diabetes and Digestive and Kidney Diseases:
118. Wolf SC, Brehm BR, Gaschler F et al. Protective effects of endothelin Bethesda, MD, 2009.
antagonists in chronic renal failure. Nephrol Dial Transplant 1999; 140. Devins GM, Mendelssohn DC, Barre PE et al. Predialysis
14(Suppl 4): 29–30. psychoeducational intervention and coping styles influence time to
119. Goddard J, Johnston NR, Hand MF et al. Endothelin-A receptor dialysis in chronic kidney disease. Am J Kidney Dis 2003; 42: 693–703.
antagonism reduces blood pressure and increases renal blood flow in 141. Richards N, Harris K, Whitfield M et al. Primary care-based disease
hypertensive patients with chronic renal failure: a comparison of management of chronic kidney disease (CKD), based on estimated
selective and combined endothelin receptor blockade. Circulation 2004; glomerular filtration rate (eGFR) reporting, improves patient outcomes.
109: 1186–1193. Nephrol Dial Transplant 2008; 23: 549–555.
120. Mann JF, Green D, Jamerson K et al. Avosentan for overt diabetic 142. Bayliss EA, Bhardwaja B, Ross C et al. Multidisciplinary team care may
nephropathy. J Am Soc Nephrol 2010; 21: 527–535. slow the rate of decline in renal function. Clin J Am Soc Nephrol 2011.
121. Kohan DE, Pritchett Y, Molitch M et al. Addition of atrasentan to renin- 143. Stack AG. Impact of timing of nephrology referral and pre-ESRD care on
angiotensin system blockade reduces albuminuria in diabetic mortality risk among new ESRD patients in the United States. Am J
nephropathy. J Am Soc Nephrol 2011; 22: 763–772. Kidney Dis 2003; 41: 310–318.
122. Tanji N, Markowitz GS, Fu C et al. Expression of advanced glycation end 144. Chen SC, Hwang SJ, Tsai JC et al. Early nephrology referral is associated
products and their cellular receptor RAGE in diabetic nephropathy and with prolonged survival in hemodialysis patients even after exclusion of
nondiabetic renal disease. J Am Soc Nephrol 2000; 11: 1656–1666. lead-time bias. Am J Med Sci 2010; 339: 123–126.
123. Daroux M, Prevost G, Maillard-Lefebvre H et al. Advanced glycation end- 145. Curtis BM, Ravani P, Malberti F et al. The short- and long-term impact of
products: implications for diabetic and non-diabetic nephropathies. multi-disciplinary clinics in addition to standard nephrology care on
Diabetes Metab 2010; 36: 1–10. patient outcomes. Nephrol Dial Transplant 2005; 20: 147–154.
124. Izuhara Y, Nangaku M, Takizawa S et al. A novel class of advanced 146. Goldstein M, Yassa T, Dacouris N et al. Multidisciplinary predialysis care
glycation inhibitors ameliorates renal and cardiovascular damage in and morbidity and mortality of patients on dialysis. Am J Kidney Dis
experimental rat models. Nephrol Dial Transplant 2008; 23: 497–509. 2004; 44: 706–714.
125. Brownlee M, Vlassara H, Kooney A et al. Aminoguanidine prevents 147. Hemmelgarn BR, Manns BJ, Zhang J et al. Association between
diabetes-induced arterial wall protein cross-linking. Science 1986; 232: multidisciplinary care and survival for elderly patients with chronic
1629–1632. kidney disease. J Am Soc Nephrol 2007; 18: 993–999.
126. Degenhardt TP, Alderson NL, Arrington DD et al. Pyridoxamine inhibits 148. Bielesz B, Sirin Y, Si H et al. Epithelial Notch signaling regulates
early renal disease and dyslipidemia in the streptozotocin-diabetic rat. interstitial fibrosis development in the kidneys of mice and humans.
Kidney Int 2002; 61: 939–950. J Clin Invest 2010; 120: 4040–4054.
127. Babaei-Jadidi R, Karachalias N, Ahmed N et al. Prevention of incipient 149. Genovese G, Friedman DJ, Ross MD et al. Association of trypanolytic
diabetic nephropathy by high-dose thiamine and benfotiamine. ApoL1 variants with kidney disease in African Americans. Science 2010;
Diabetes 2003; 52: 2110–2120. 329: 841–845.
362 Kidney International (2012) 81, 351–362