- Acute kidney injury (AKI) is characterized by a rapid decline in kidney function and is associated with increased short and long-term mortality. AKI diagnosis relies on changes in serum creatinine and urine output.
- Risk factors for AKI include older age, chronic kidney disease, comorbidities like diabetes and heart disease, as well as exposures to sepsis, surgery, nephrotoxins and shock. Causes of AKI include pre-renal, intrinsic renal and post-renal factors.
- Prevention strategies focus on identifying at-risk patients, optimizing volume status, and discontinuing or avoiding nephrotoxins. Treatment involves correcting hypovolemia, discontinuing
This document discusses chronic kidney disease (CKD) and summarizes 6 case studies of CKD clinics. It finds that while CKD was traditionally defined by end-stage renal disease, treating earlier CKD stages can prevent progression to kidney failure. The case studies show different models of CKD care, from academic medical centers to private nephrology practices. Successful clinics utilize guidelines, coordinate with primary doctors, and conduct community outreach for education and early referrals. Barriers to CKD care include late referrals, lack of guidelines implementation, and financial challenges of preventative care.
The document is a clinical practice guideline for acute kidney injury (AKI) published by Kidney Disease: Improving Global Outcomes (KDIGO) in 2012. It contains recommendations on defining and classifying AKI, evaluating patients at risk, preventing AKI, treating AKI with renal replacement therapy, and managing specific causes of AKI like contrast-induced nephropathy. The guideline includes sections on introduction and methodology, definition of AKI, prevention and general treatment of AKI, contrast-induced AKI, and dialysis interventions. It provides tables summarizing recommendation statements and clinical practice recommendations supported by evidence reviews.
Ngal ,cystatin c versus creatinine clearence asMoustafa Rezk
This document discusses biomarkers for acute kidney injury (AKI), specifically NGAL and cystatin C. It provides background on the definition and classification of AKI, limitations of creatinine as a biomarker, and the need for earlier detection. It summarizes studies showing NGAL and cystatin C can increase within hours after cardiac surgery or injury, earlier than rises in creatinine. These biomarkers may allow for earlier diagnosis and intervention to prevent further kidney damage.
The document summarizes chronic kidney disease (CKD) and its management. It defines CKD and outlines the new classification system. It discusses evaluating kidney function through estimated GFR and albuminuria. It covers managing CKD progression through blood pressure control, RAAS interruption, glycemic control, and treating complications like anemia. It recommends lowering protein intake in later stages and salt intake. Overall, the document provides clinical practice guidelines for defining, evaluating, and managing CKD and its progression and complications.
1) The document discusses a Phase 3 clinical trial investigating the effects of the ASK1 inhibitor selonsertib (SEL) in patients with diabetic kidney disease (DKD).
2) The trial did not meet its primary endpoint of a 50% improvement in eGFR from baseline to week 48. However, exploratory analyses found SEL induced acute but reversible eGFR declines followed by stabilization or improvement in eGFR slope over time.
3) Adverse events including acute kidney injury and fluid overload were similar between SEL and placebo groups. The study was limited by its short duration and data issues from two sites.
Based on the clinical information provided:
- Metastatic pancreatic cancer being treated with chemotherapy
- New onset nephrotic range proteinuria, hematuria, hypertension, edema
- Dysmorphic RBCs and granular casts on urine microscopy
The most likely histological finding on renal biopsy would be:
Amyloidosis. This constellation of findings is classic for amyloidosis-associated nephrotic syndrome in the setting of an underlying plasma cell dyscrasia or malignancy. Cellular crescents and endocapillary proliferation would be unusual in this case. Mesangial hypercellularity alone is nonspecific and does not fit with the clinical picture.
Pentoxyfilline in Diabetic Renal Disease and Renal TransplantationChristos Argyropoulos
Pentoxifylline may reduce proteinuria in patients with diabetic kidney disease, according to a meta-analysis of 10 randomized controlled trials. The analysis found that pentoxifylline led to a statistically significant decline in proteinuria compared to standard renin-angiotensin system blockade alone, with an effect size similar to full-dose ACE inhibitors. However, the included studies had small sample sizes and short durations. Pentoxifylline did not significantly affect glomerular filtration rate, blood pressure, or adverse effects. Larger and longer term studies are still needed to determine if pentoxifylline can delay kidney function decline in diabetic kidney disease.
This document discusses chronic kidney disease (CKD) and strategies to retard its progression. It covers CKD epidemiology and risk factors like hypertension, diabetes, metabolic acidosis, sleep quality, uric acid levels, antibiotic use, gut microbiome, herbal remedies, nutrition, exercise, and weight management. Later sections discuss roles of primary care providers, predicting disease course, and virtual learning through the ESNT Virtual Academy. The overall goal is to review current knowledge on modifiable factors that impact CKD progression and identify opportunities for improved prevention and management of kidney disease.
This document discusses chronic kidney disease (CKD) and summarizes 6 case studies of CKD clinics. It finds that while CKD was traditionally defined by end-stage renal disease, treating earlier CKD stages can prevent progression to kidney failure. The case studies show different models of CKD care, from academic medical centers to private nephrology practices. Successful clinics utilize guidelines, coordinate with primary doctors, and conduct community outreach for education and early referrals. Barriers to CKD care include late referrals, lack of guidelines implementation, and financial challenges of preventative care.
The document is a clinical practice guideline for acute kidney injury (AKI) published by Kidney Disease: Improving Global Outcomes (KDIGO) in 2012. It contains recommendations on defining and classifying AKI, evaluating patients at risk, preventing AKI, treating AKI with renal replacement therapy, and managing specific causes of AKI like contrast-induced nephropathy. The guideline includes sections on introduction and methodology, definition of AKI, prevention and general treatment of AKI, contrast-induced AKI, and dialysis interventions. It provides tables summarizing recommendation statements and clinical practice recommendations supported by evidence reviews.
Ngal ,cystatin c versus creatinine clearence asMoustafa Rezk
This document discusses biomarkers for acute kidney injury (AKI), specifically NGAL and cystatin C. It provides background on the definition and classification of AKI, limitations of creatinine as a biomarker, and the need for earlier detection. It summarizes studies showing NGAL and cystatin C can increase within hours after cardiac surgery or injury, earlier than rises in creatinine. These biomarkers may allow for earlier diagnosis and intervention to prevent further kidney damage.
The document summarizes chronic kidney disease (CKD) and its management. It defines CKD and outlines the new classification system. It discusses evaluating kidney function through estimated GFR and albuminuria. It covers managing CKD progression through blood pressure control, RAAS interruption, glycemic control, and treating complications like anemia. It recommends lowering protein intake in later stages and salt intake. Overall, the document provides clinical practice guidelines for defining, evaluating, and managing CKD and its progression and complications.
1) The document discusses a Phase 3 clinical trial investigating the effects of the ASK1 inhibitor selonsertib (SEL) in patients with diabetic kidney disease (DKD).
2) The trial did not meet its primary endpoint of a 50% improvement in eGFR from baseline to week 48. However, exploratory analyses found SEL induced acute but reversible eGFR declines followed by stabilization or improvement in eGFR slope over time.
3) Adverse events including acute kidney injury and fluid overload were similar between SEL and placebo groups. The study was limited by its short duration and data issues from two sites.
Based on the clinical information provided:
- Metastatic pancreatic cancer being treated with chemotherapy
- New onset nephrotic range proteinuria, hematuria, hypertension, edema
- Dysmorphic RBCs and granular casts on urine microscopy
The most likely histological finding on renal biopsy would be:
Amyloidosis. This constellation of findings is classic for amyloidosis-associated nephrotic syndrome in the setting of an underlying plasma cell dyscrasia or malignancy. Cellular crescents and endocapillary proliferation would be unusual in this case. Mesangial hypercellularity alone is nonspecific and does not fit with the clinical picture.
Pentoxyfilline in Diabetic Renal Disease and Renal TransplantationChristos Argyropoulos
Pentoxifylline may reduce proteinuria in patients with diabetic kidney disease, according to a meta-analysis of 10 randomized controlled trials. The analysis found that pentoxifylline led to a statistically significant decline in proteinuria compared to standard renin-angiotensin system blockade alone, with an effect size similar to full-dose ACE inhibitors. However, the included studies had small sample sizes and short durations. Pentoxifylline did not significantly affect glomerular filtration rate, blood pressure, or adverse effects. Larger and longer term studies are still needed to determine if pentoxifylline can delay kidney function decline in diabetic kidney disease.
This document discusses chronic kidney disease (CKD) and strategies to retard its progression. It covers CKD epidemiology and risk factors like hypertension, diabetes, metabolic acidosis, sleep quality, uric acid levels, antibiotic use, gut microbiome, herbal remedies, nutrition, exercise, and weight management. Later sections discuss roles of primary care providers, predicting disease course, and virtual learning through the ESNT Virtual Academy. The overall goal is to review current knowledge on modifiable factors that impact CKD progression and identify opportunities for improved prevention and management of kidney disease.
This document discusses the role of glyptins (DPP-4 inhibitors) in the management of type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). It notes that T2DM is a leading cause of CKD globally and that strict glycemic control is important for treating diabetic nephropathy. However, patients with CKD are at higher risk of hypoglycemia from antidiabetic medications. The document examines whether glyptins may be renoprotective and safer to use in CKD patients compared to other drugs due to their low risk of hypoglycemia. It reviews studies on the use of sitagliptin and other glyptins in T2
This study compared outcomes of steroid withdrawal versus continued steroid therapy in kidney and heart transplant recipients. Over 1500 patients were enrolled from 1994-2002 and followed for 5-6 years on average. Results showed that steroid withdrawal led to superior patient and graft survival rates compared to controls continuing steroids. Steroid withdrawal also reduced risks of complications like osteoporosis and cataracts. However, it was associated with a small increased risk of acute rejection episodes. Overall, the study suggests that steroid withdrawal after 6 months is safe and effective for transplant recipients.
World Kidney Day was established to raise awareness of chronic kidney disease (CKD) and encourage detection and prevention programs. CKD affects over 20 million Americans and is a major cause of death worldwide. While kidney failure requiring dialysis has increased, CKD is often preventable or treatable through control of diabetes, hypertension, and obesity. World Kidney Day aims to educate the public and healthcare professionals about CKD risks and signs through collaborative events around the world each March.
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
1) The document discusses microRNAs (miRNAs) and their role in kidney development, function, and disease.
2) miRNAs act as master regulators of gene expression and are involved in pathways like TGF-beta that are important in renal fibrosis.
3) Circulating and urinary miRNAs show potential as biomarkers for acute and chronic kidney diseases, helping to address the need for better markers of disease risk and progression.
Bariatric surgery, especially malabsorptive procedures like Roux-en-Y gastric bypass, significantly increases the risk of kidney stones compared to obese controls. The risk is highest with malabsorptive procedures and correlates with the degree of fat malabsorption and enteric hyperoxaluria. However, bariatric surgery does not appear to increase the risk of chronic kidney disease. Further research is still needed to fully understand the mechanisms by which bariatric surgery leads to hyperoxaluria and kidney stone formation.
This document provides guidelines for the detection, prevention and management of kidney disease in people with diabetes. It aims to standardize screening approaches and improve diagnosis and management to reduce progression to end-stage renal disease. Key points covered include definitions of microalbuminuria and nephropathy, prevalence of chronic kidney disease in diabetes populations, screening recommendations including annual urine testing for albumin/protein starting at age 12, and the relationship between reduced kidney function and mortality risk. The goal is a collaborative approach between primary care, diabetes specialists and nephrology to manage renal complications of diabetes.
ABSTRACT- Background: Viral hepatitis B and C can lead to the end stage liver disease and diabetes mellitus is also
a life-long chronic disease. Simultaneous presences of both of these conditions lead to synergistic detrimental outcome.
So identification of diabetes mellitus at the initial evaluation of a patient having chronic hepatitis B and C is essential.
Materials and methods: This study was designed as a retrospective single center cross-sectional study. The association
of viral hepatitis B and C with diabetes mellitus was investigated at the Liver Centre Dhaka, Bangladesh for a period of
12 years. HBsAg was tested for hepatitis B virus infection and anti-HCV for hepatitis C virus infection. Demographic
profile and biochemical data were retrieved from records.
Results: A total of 29425 cases were analyzed in the study [median age 31(19–95) years, 24615(84%) males]. HBsAg
positive were 27475 and hepatitis C were 1950. Patients with hepatitis C were older than hepatitis B (p<0.001).
Although previous history of jaundice was similar in both infections but history of blood transfusion was more common
among hepatitis C patients (p<0.001). Analyzing different conditions of liver disease, it was observed that hepatitis B
virus infection was highly responsible for acute hepatitis than hepatitis C (10.7% vs 1.1%) (p<0.001). Chronic hepatitis
was similar in rate (73.3% vs 59.9%). But in both conditions of cirrhosis of liver like compensated and decompensated
states, hepatitis C virus was significantly responsible than the hepatitis B virus 24.7% vs 9.6% (p<0.001) and 14.3% vs
6.4% (p<0.001) respectively. The most significant finding was very higher rate of diabetes among hepatitis C which
was 22.6% while only 1.8% among hepatitis B virus infection (p<0.001).
Conclusion: Hepatitis C virus was highly related with the presence of diabetes than hepatitis B.
Key-words- Diabetes mellitus, Prevalence, Hepatitis B virus, Hepatitis C virus
A limited presentation about a) age related renal functional changes b) management of CKD, including advance care planning and transplantation referral c) management of potentially risky drugs in the elderly with CKD (NOACs)
This document discusses relative blood volume (RBV) monitoring and its potential applications in dialysis. It provides an overview of RBV monitoring principles, compartmental fluid shifts, and RBV profiles in relation to intradialytic hypotension. While RBV monitoring shows promise for fluid management and blood pressure control, evidence from studies is mixed. The largest study to date found RBV monitoring increased mortality and hospitalizations. Further research is still needed to fully understand the clinical utility and appropriate applications of RBV monitoring.
Background and Aim: Many studies have found association between Red Cell Distribution Width (RDW) values and hypertension, dipping pattern, and end-organ damage. RDW values are affected by blood vitamin B12, iron, and folic acid levels, parameters that were not assessed in the previous studies. The aim of our study was to evaluate the relation between RDW and hypertension, dipper pattern, and end-organ damage independently from vitamin B12, folic acid, and ferritin levels in newly diagnosed hypertensive patients.
Slidedeck of the presentation I gave during the East by Southwest conference, co-organized by the Division of Nephrology (UNM) and the Renal and Electrolyte Division (UPMC)
This document discusses uric acid metabolism and its role in health and disease. It covers normal uric acid levels, foods and substances that can affect levels, and the pathways of purine breakdown. It then examines abnormal uric acid metabolism and how this can lead to hyperuricemia and conditions like gout, kidney stones, and chronic kidney disease. It reviews the evidence that chronic hyperuricemia is an independent risk factor for hypertension, cardiovascular disease, and kidney disease. Treatment of asymptomatic hyperuricemia is debated, with some guidelines recommending treatment to prevent non-gout related diseases.
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.
Gpc manejo de enfermedades glomerulares-kdigo-2021WilliamBarrera34
This document provides clinical practice guidelines for the management of glomerular diseases published by KDIGO (Kidney Disease: Improving Global Outcomes) in 2021. It includes 11 chapters covering various glomerular diseases and recommendations for their evaluation and treatment. Key recommendations are presented in figures and tables throughout. Evaluation of evidence and grading of recommendations follows standardized processes. The guidelines aim to provide an evidence-based framework to guide clinical decision-making for glomerular diseases.
This document discusses diabetes and kidney disease. It notes that diabetes is a worldwide epidemic that is increasing prevalence, especially in India. Diabetes is now the leading cause of end-stage kidney disease globally. Up to 40% of patients with diabetes will develop some form of kidney damage. The natural history of diabetic nephropathy is described, from early microalbuminuria to later macroalbuminuria and declining kidney function. Treatment focuses on glycemic control, blood pressure control, and blocking the renin-angiotensin system to slow disease progression. However, reductions in progression have been modest with current therapies.
This document discusses glucose control in renal transplant patients. It presents a case of new onset diabetes after transplant and reviews the pharmacology of immunosuppressants like calcineurin inhibitors that can cause glucose dysregulation. It also discusses the current recommendations for glucose control during and after transplant, including managing new onset diabetes after transplant through diagnosis and treatment approaches. Risk factors for developing new onset diabetes after transplant are examined, as well as the impacts of hyperglycemia on kidney transplant outcomes.
Assessment Outcomes Dyslipidaemia in Dialysis PatientAI Publications
Background: Chronic kidney disease is defined as the presence, for more than three months, of changes in the structure or function of the kidneys, secondary to a progressive decline in the number of nephrons, with a consequent deterioration in health resulting from the inability of the kidneys to perform their excretory functions, softener, and metabolism. Chronic kidney disease (CKD) is a clinical condition caused by the progressive and progressive loss of kidney function. Chronic kidney disease is not only implicated by the gradual deterioration of quality of life and life expectancy when it progresses to more advanced stages but also by the increase in cardiovascular morbidity and mortality, which is the leading cause of death in these patients. Aim: This paper aims to assess the outcomes of dyslipidemia in a dialysis patient. Patients and method: In this study, a descriptive cross-sectional study was applied to study the Assessment Outcomes of Dyslipidemia in Dialysis Patients in Iraq from 4th January 2021 to 7th August 2022. Data were collected for 150 patients in different hospitals in Iraq, where the patients were divided into two groups, the first group of patients, which included DIALYSIS PATIENTS, which included 80, and the second group, the control group, which included patients, which include 70 patients. Results and discussions: collected 150 cases distributed according to dialysis patients (80) and controls (70); the most frequent ages in this study ranged from 40-49 years old 34 (42.5%) patients group, 33 (47.14%) control group with a statistical difference of 0.0831. In this study was evaluated the Outcomes of dyslipidemia in a dialysis patient. Imbalances were found in levels of dyslipidemia which LDL 5.12±3.4 of the patients' group, as for the control group 2.1±3.3-HDL 2.43±2.4 of the patients' group, 1.4±1.5 for the control group, TRIGLYCERIDE 1.75±1.8 of patients group, 0.55±0.43 for the control group with A statistically significant relationship were found between dyslipidemia levels and outcomes in the group of patients at P value < 0.05.
This document discusses the role of glyptins (DPP-4 inhibitors) in the management of type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). It notes that T2DM is a leading cause of CKD globally and that strict glycemic control is important for treating diabetic nephropathy. However, patients with CKD are at higher risk of hypoglycemia from antidiabetic medications. The document examines whether glyptins may be renoprotective and safer to use in CKD patients compared to other drugs due to their low risk of hypoglycemia. It reviews studies on the use of sitagliptin and other glyptins in T2
This study compared outcomes of steroid withdrawal versus continued steroid therapy in kidney and heart transplant recipients. Over 1500 patients were enrolled from 1994-2002 and followed for 5-6 years on average. Results showed that steroid withdrawal led to superior patient and graft survival rates compared to controls continuing steroids. Steroid withdrawal also reduced risks of complications like osteoporosis and cataracts. However, it was associated with a small increased risk of acute rejection episodes. Overall, the study suggests that steroid withdrawal after 6 months is safe and effective for transplant recipients.
World Kidney Day was established to raise awareness of chronic kidney disease (CKD) and encourage detection and prevention programs. CKD affects over 20 million Americans and is a major cause of death worldwide. While kidney failure requiring dialysis has increased, CKD is often preventable or treatable through control of diabetes, hypertension, and obesity. World Kidney Day aims to educate the public and healthcare professionals about CKD risks and signs through collaborative events around the world each March.
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
1) The document discusses microRNAs (miRNAs) and their role in kidney development, function, and disease.
2) miRNAs act as master regulators of gene expression and are involved in pathways like TGF-beta that are important in renal fibrosis.
3) Circulating and urinary miRNAs show potential as biomarkers for acute and chronic kidney diseases, helping to address the need for better markers of disease risk and progression.
Bariatric surgery, especially malabsorptive procedures like Roux-en-Y gastric bypass, significantly increases the risk of kidney stones compared to obese controls. The risk is highest with malabsorptive procedures and correlates with the degree of fat malabsorption and enteric hyperoxaluria. However, bariatric surgery does not appear to increase the risk of chronic kidney disease. Further research is still needed to fully understand the mechanisms by which bariatric surgery leads to hyperoxaluria and kidney stone formation.
This document provides guidelines for the detection, prevention and management of kidney disease in people with diabetes. It aims to standardize screening approaches and improve diagnosis and management to reduce progression to end-stage renal disease. Key points covered include definitions of microalbuminuria and nephropathy, prevalence of chronic kidney disease in diabetes populations, screening recommendations including annual urine testing for albumin/protein starting at age 12, and the relationship between reduced kidney function and mortality risk. The goal is a collaborative approach between primary care, diabetes specialists and nephrology to manage renal complications of diabetes.
ABSTRACT- Background: Viral hepatitis B and C can lead to the end stage liver disease and diabetes mellitus is also
a life-long chronic disease. Simultaneous presences of both of these conditions lead to synergistic detrimental outcome.
So identification of diabetes mellitus at the initial evaluation of a patient having chronic hepatitis B and C is essential.
Materials and methods: This study was designed as a retrospective single center cross-sectional study. The association
of viral hepatitis B and C with diabetes mellitus was investigated at the Liver Centre Dhaka, Bangladesh for a period of
12 years. HBsAg was tested for hepatitis B virus infection and anti-HCV for hepatitis C virus infection. Demographic
profile and biochemical data were retrieved from records.
Results: A total of 29425 cases were analyzed in the study [median age 31(19–95) years, 24615(84%) males]. HBsAg
positive were 27475 and hepatitis C were 1950. Patients with hepatitis C were older than hepatitis B (p<0.001).
Although previous history of jaundice was similar in both infections but history of blood transfusion was more common
among hepatitis C patients (p<0.001). Analyzing different conditions of liver disease, it was observed that hepatitis B
virus infection was highly responsible for acute hepatitis than hepatitis C (10.7% vs 1.1%) (p<0.001). Chronic hepatitis
was similar in rate (73.3% vs 59.9%). But in both conditions of cirrhosis of liver like compensated and decompensated
states, hepatitis C virus was significantly responsible than the hepatitis B virus 24.7% vs 9.6% (p<0.001) and 14.3% vs
6.4% (p<0.001) respectively. The most significant finding was very higher rate of diabetes among hepatitis C which
was 22.6% while only 1.8% among hepatitis B virus infection (p<0.001).
Conclusion: Hepatitis C virus was highly related with the presence of diabetes than hepatitis B.
Key-words- Diabetes mellitus, Prevalence, Hepatitis B virus, Hepatitis C virus
A limited presentation about a) age related renal functional changes b) management of CKD, including advance care planning and transplantation referral c) management of potentially risky drugs in the elderly with CKD (NOACs)
This document discusses relative blood volume (RBV) monitoring and its potential applications in dialysis. It provides an overview of RBV monitoring principles, compartmental fluid shifts, and RBV profiles in relation to intradialytic hypotension. While RBV monitoring shows promise for fluid management and blood pressure control, evidence from studies is mixed. The largest study to date found RBV monitoring increased mortality and hospitalizations. Further research is still needed to fully understand the clinical utility and appropriate applications of RBV monitoring.
Background and Aim: Many studies have found association between Red Cell Distribution Width (RDW) values and hypertension, dipping pattern, and end-organ damage. RDW values are affected by blood vitamin B12, iron, and folic acid levels, parameters that were not assessed in the previous studies. The aim of our study was to evaluate the relation between RDW and hypertension, dipper pattern, and end-organ damage independently from vitamin B12, folic acid, and ferritin levels in newly diagnosed hypertensive patients.
Slidedeck of the presentation I gave during the East by Southwest conference, co-organized by the Division of Nephrology (UNM) and the Renal and Electrolyte Division (UPMC)
This document discusses uric acid metabolism and its role in health and disease. It covers normal uric acid levels, foods and substances that can affect levels, and the pathways of purine breakdown. It then examines abnormal uric acid metabolism and how this can lead to hyperuricemia and conditions like gout, kidney stones, and chronic kidney disease. It reviews the evidence that chronic hyperuricemia is an independent risk factor for hypertension, cardiovascular disease, and kidney disease. Treatment of asymptomatic hyperuricemia is debated, with some guidelines recommending treatment to prevent non-gout related diseases.
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.
Gpc manejo de enfermedades glomerulares-kdigo-2021WilliamBarrera34
This document provides clinical practice guidelines for the management of glomerular diseases published by KDIGO (Kidney Disease: Improving Global Outcomes) in 2021. It includes 11 chapters covering various glomerular diseases and recommendations for their evaluation and treatment. Key recommendations are presented in figures and tables throughout. Evaluation of evidence and grading of recommendations follows standardized processes. The guidelines aim to provide an evidence-based framework to guide clinical decision-making for glomerular diseases.
This document discusses diabetes and kidney disease. It notes that diabetes is a worldwide epidemic that is increasing prevalence, especially in India. Diabetes is now the leading cause of end-stage kidney disease globally. Up to 40% of patients with diabetes will develop some form of kidney damage. The natural history of diabetic nephropathy is described, from early microalbuminuria to later macroalbuminuria and declining kidney function. Treatment focuses on glycemic control, blood pressure control, and blocking the renin-angiotensin system to slow disease progression. However, reductions in progression have been modest with current therapies.
This document discusses glucose control in renal transplant patients. It presents a case of new onset diabetes after transplant and reviews the pharmacology of immunosuppressants like calcineurin inhibitors that can cause glucose dysregulation. It also discusses the current recommendations for glucose control during and after transplant, including managing new onset diabetes after transplant through diagnosis and treatment approaches. Risk factors for developing new onset diabetes after transplant are examined, as well as the impacts of hyperglycemia on kidney transplant outcomes.
Assessment Outcomes Dyslipidaemia in Dialysis PatientAI Publications
Background: Chronic kidney disease is defined as the presence, for more than three months, of changes in the structure or function of the kidneys, secondary to a progressive decline in the number of nephrons, with a consequent deterioration in health resulting from the inability of the kidneys to perform their excretory functions, softener, and metabolism. Chronic kidney disease (CKD) is a clinical condition caused by the progressive and progressive loss of kidney function. Chronic kidney disease is not only implicated by the gradual deterioration of quality of life and life expectancy when it progresses to more advanced stages but also by the increase in cardiovascular morbidity and mortality, which is the leading cause of death in these patients. Aim: This paper aims to assess the outcomes of dyslipidemia in a dialysis patient. Patients and method: In this study, a descriptive cross-sectional study was applied to study the Assessment Outcomes of Dyslipidemia in Dialysis Patients in Iraq from 4th January 2021 to 7th August 2022. Data were collected for 150 patients in different hospitals in Iraq, where the patients were divided into two groups, the first group of patients, which included DIALYSIS PATIENTS, which included 80, and the second group, the control group, which included patients, which include 70 patients. Results and discussions: collected 150 cases distributed according to dialysis patients (80) and controls (70); the most frequent ages in this study ranged from 40-49 years old 34 (42.5%) patients group, 33 (47.14%) control group with a statistical difference of 0.0831. In this study was evaluated the Outcomes of dyslipidemia in a dialysis patient. Imbalances were found in levels of dyslipidemia which LDL 5.12±3.4 of the patients' group, as for the control group 2.1±3.3-HDL 2.43±2.4 of the patients' group, 1.4±1.5 for the control group, TRIGLYCERIDE 1.75±1.8 of patients group, 0.55±0.43 for the control group with A statistically significant relationship were found between dyslipidemia levels and outcomes in the group of patients at P value < 0.05.
Hepatorenal Syndrome (HRS) poses a unique challenge to liver failure patients. The key pathophysiologic feature of HRS includes a marked reduction in renal blood fl ow that is caused by intense vasoconstriction of the renal circulation counteracting the pathologic systemic and splanchnic arterial vasodilation. The diagnosis of HRS requires a reduction in the glomerular filtration rate and exclusion of other causes of renal failure. Novel biomarkers including cystatin C, neutrophil gelatinase associated lipocalin (NGAL), IL-8 and liver-type fatty acid binding protein (L-FABP) have been proven to be useful for predicting HRS. All existing treatments can only be considered supportive. Other potential therapeutic options such as selectively targeting renal vasodilation are promising. Currently, liver transplant isthe only treatment that improves long-term survival.
An ensemble multi-model technique for predicting chronic kidney diseaseIJECEIAES
Chronic Kidney Disease (CKD) is a type of lifelong kidney disease that leads to the gradual loss of kidney function over time; the main function of the kidney is to filter the wastein the human body. When the kidney malfunctions, the wastes accumulate in our body leading to complete failure. Machine learning algorithms can be used in prediction of the kidney disease at early stages by analyzing the symptoms. The aim of this paper is to propose an ensemble learning technique for predicting Chronic Kidney Disease (CKD). We propose a new hybrid classifier called as ABC4.5, which is ensemble learning for predicting Chronic Kidney Disease (CKD). The proposed hybrid classifier is compared with the machine learning classifiers such as Support Vector Machine (SVM), Decision Tree (DT), C4.5, Particle Swarm Optimized Multi Layer Perceptron (PSO-MLP). The proposed classifier accurately predicts the occurrences of kidney disease by analysis various medical factors. The work comprises of two stages, the first stage consists of obtaining weak decision tree classifiers from C4.5 and in the second stage, the weak classifiers are added to the weighted sum to represent the final output for improved performance of the classifier.
Chronic kidney disease (CKD) affects 8-16% of the global population and is often underdiagnosed. Defined as a glomerular filtration rate below 60 mL/min/1.73 m2 or markers of kidney damage for over 3 months, CKD is most commonly caused by diabetes and hypertension. Primary care clinicians play an important role in screening for CKD through routine testing of serum creatinine and urine albumin-to-creatinine ratio, diagnosing and staging CKD based on GFR and albuminuria levels, and managing CKD through controlling risk factors, treating complications, and referring high-risk patients to nephrologists. Appropriate screening, diagnosis and management
This document discusses the management of acute kidney injury (AKI). It defines AKI and outlines its diagnosis and evaluation. AKI is common in hospitalized patients and associated with increased short- and long-term mortality. When present, determining the underlying cause is important as some causes are reversible. Prevention focuses on optimizing volume status and avoiding nephrotoxic drugs. Currently there are no approved pharmacotherapies for treating AKI, and the optimal timing of renal replacement therapy is unclear. Recent evidence suggests AKI increases risk for chronic kidney disease and future kidney injury.
This document provides an overview of acute kidney injury (AKI) management. It discusses that AKI is common in hospitalized patients and associated with increased morbidity and mortality. When AKI is present, the underlying cause should be promptly investigated, with attention to potentially reversible causes. Measures to prevent AKI include optimizing volume status and avoiding nephrotoxic medications. Currently there are no approved targeted pharmacotherapies for treating AKI, and the optimal timing of renal replacement therapy is unclear.
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 discusses recent advances in acute kidney injury (AKI). It summarizes that novel biomarkers like cystatin C and NGAL are being studied to detect AKI earlier than serum creatinine. Intravenous fluids are beneficial for preventing contrast-induced AKI while N-acetylcysteine is less established. Diuretics help treat acute decompensated heart failure. Combination therapy with midodrine, octreotide, and albumin provides an alternative to terlipressin for hepatorenal syndrome. Fluid resuscitation in AKI patients requires caution, as overly aggressive use increases mortality risk. AKI may increase risk of chronic kidney disease, so monitoring patients with a history of AKI is important
Chronic kidney disease (CKD) is a global public health problem
worldwide. The worldwide prevalence of CKD has increased in
various countries such as the U.S. (13.1%), Taiwan (9.8-11.9%),
Norway (10.2%), Japan (12.9-15.1%) China (3.2-11.3%), Korea (7.2- 13.7%), Thailand (8.45-16.3%), Singapore (3.2-18.6%), and Australia(11.2%)
This document provides clinical practice guidelines for acute kidney injury (AKI) from the UK Renal Association. It summarizes the definition and staging systems for AKI from ADQI, AKIN and KDIGO to standardize classification. AKI has significant prevalence in hospitalized patients and poor outcomes, with mortality ranging from 10-80% depending on severity and presence of multiorgan failure. Prevention and early recognition of AKI is important. The guidelines cover areas like assessment, prevention, management, renal replacement therapy modalities and prescriptions, and timing of treatment. Improving education of healthcare professionals about AKI is emphasized.
This document discusses the diagnosis and management of acute kidney injury (AKI) in the intensive care unit (ICU). It defines AKI and outlines biomarkers that can help identify it earlier than creatinine. Common causes of AKI in the ICU include sepsis, major surgery, low cardiac output, and medications. The document reviews risk factors for developing AKI and strategies for preventing it, such as fluid management and avoiding nephrotoxins. It discusses general management of established AKI including nutrition, anticoagulation, and dialysis. The impact of renal replacement therapy on outcomes is also addressed.
This document provides an overview of chronic kidney disease (CKD). It defines CKD as kidney damage or decreased kidney function lasting at least 3 months. The global prevalence of CKD is estimated to be 13.4% with higher rates in certain regions like eastern Uganda. Common causes include diabetes, hypertension, and glomerulonephritis. Later stages of CKD can cause complications like fluid overload, hyperkalemia, and metabolic acidosis which require management approaches like dietary modifications and medications. The document discusses evaluating and managing CKD and its associated risks and complications.
Chronic Renal Failure (CRF), a progressive, irreversible deterioration in renal function in which the body’s ability to sustain
metabolic and fluid and electrolyte balance fails, resulting in uremia or azotemia, is a global public health problem that tends to
take dimensions of epidemic and has severe impact on quality of patient’s life. Chronic kidney diseases represent a noteworthy
health problem across the globe with CRF. The clear-cut prevalence of CRF worldwide was obscure due to the clinical
continuum ranging from indolent, asymptomatic to complete renal decompensation. Thus, continual inputs through a series
of research considering various conventional and certain earlier techniques in background, along this thrust medical area, led
an emerging and medically most precise technique, namely, Electro-homeopathic therapy that has been currently in practice
by a number of practitioners in India revealing fascinating outcome without any significant post therapeutic physiological
and/or biochemical side effect as well as risk factor. The efficacy of the Electro-homoeopathy treatment for chronic kidney
disease has been successfully monitored over a period of 30-60 and 30-80 days, respectively, in the case of GFR and renal
lithiasis, based on improvement in the subjective parameters and blood investigations. Nevertheless, paralysis of bladder
cases was cured within 30 to 60 days of treatment. The outcome of this overview provides new insights into developing and
establishing more and more advanced account of Electro-Homeopathic system for accurate diagnosis enlightening specific
root cause/origin (Etiology) and smooth-running management of ‘Chronic Renal Failure’ as well as its manifestation.
This document provides clinical practice guidelines for the management of Acute Kidney Injury (AKI). It discusses the definition and staging systems for AKI, epidemiology and outcomes. Prevention, management, treatment facilities and timing of renal replacement therapy are covered. Guidelines are provided on choice of renal replacement modality, dialyser membranes, vascular access, anticoagulation, and prescription of renal replacement therapy. There is a lack of evidence to guide optimal care and timing of renal replacement therapy. The document aims to standardize care and improve outcomes of patients with AKI.
Neutrophil gelatinase-associated lipocalin (NGAL) is a protein biomarker that shows promise for the early detection of acute kidney injury (AKI). NGAL levels rise rapidly in the urine and blood within 2 hours of kidney injury. Measurement of NGAL may help diagnose AKI earlier than the current method of measuring creatinine levels, allowing for more timely treatment. NGAL also appears to play a protective role in the kidney by reducing cell death and increasing cell regeneration after injury. Large clinical studies are still needed but NGAL testing may eventually be useful for early AKI detection in high-risk hospital patients.
Evaluate of the Physical Performance of Patients Undergoing HemodialysisAhmed Alkhaqani
This study aimed to measure the physical performance of 62 patients undergoing hemodialysis using the Short Physical Performance Battery (SPPB) scale. The study found that the patients' physical performance was below predicted levels at baseline and deteriorated further over three assessments spaced four weeks apart. The results indicated poor physical performance in patients with chronic kidney disease undergoing hemodialysis. This was related to low physical activity levels in this patient population rather than demographic or clinical factors.
Although there has been much high-quality research conducted in this field in recent years, preventing CSA-AKI by avoiding renal insults remains the mainstay of management. Biomarkers have the potential to diagnose CSA-AKI at an earlier stage, but efficacious interventions to treat established CSA-AKI remain elusive. Off-pump coronary artery bypass may be associated with a lower risk of CSA-AKI compared to on-pump procedures, but this has not been shown to impact long-term renal or clinical outcomes.
Renal disorders can cause complications like chronic kidney disease (CKD) that increase risks during dental procedures and surgery. Patients with CKD are more likely to experience bleeding due to platelet and blood vessel dysfunction, and also have increased risk of infection. They may also develop dental problems such as periodontal disease, tooth discoloration and loss of enamel. When undergoing surgery, CKD patients are at higher risk of complications including bleeding, infections, cardiovascular and thrombotic events due to changes in fluid, electrolyte and acid-base balance as well as altered drug metabolism and clearance. Careful preoperative evaluation and management involving nephrologists can help reduce these perioperative risks.
This document summarizes key information about chronic kidney disease (CKD) and cardiovascular disease (CVD). It notes that patients with CKD should be considered at the highest risk for CVD. Lower estimated glomerular filtration rate (eGFR) is associated with higher risks of coronary disease and CVD mortality. The risks of all-cause mortality are significantly higher across all levels of eGFR and proteinuria for patients with early diabetic kidney disease compared to those without. Heart failure hospitalization risk increases as kidney function declines. The development of macroalbuminuria in diabetes patients heralds a rapid decline in glomerular filtration rate. Timely protection and maintenance of kidney function can reduce CVD risks.
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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
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12. Comprehend the vectorial analysis of the normal ECG
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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
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- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
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Acute kidney injury from diagnosis to prevention and treatment strategies
1. Journal of
Clinical Medicine
Review
Acute Kidney Injury: From Diagnosis to Prevention
and Treatment Strategies
Joana Gameiro * , José Agapito Fonseca , Cristina Outerelo and José António Lopes
Department of Medicine, Division of Nephrology and Renal Transplantation, Centro Hospitalar Lisboa Norte,
EPE, Av. Prof. Egas Moniz, 1649-035 Lisboa, Portugal; jose.nuno.agapito@gmail.com (J.A.F.);
cristinaouterelo@gmail.com (C.O.); jalopes93@hotmail.com (J.A.L.)
* Correspondence: joana.estrelagameiro@gmail.com; Tel.: +351-21-780-5000
Received: 23 April 2020; Accepted: 25 May 2020; Published: 2 June 2020
Abstract: Acute kidney injury (AKI) is characterized by an acute decrease in renal function that
can be multifactorial in its origin and is associated with complex pathophysiological mechanisms.
In the short term, AKI is associated with an increased length of hospital stay, health care costs,
and in-hospital mortality, and its impact extends into the long term, with AKI being associated with
increased risks of cardiovascular events, progression to chronic kidney disease (CKD), and long-term
mortality. Given the impact of the prognosis of AKI, it is important to recognize at-risk patients and
improve preventive, diagnostic, and therapy strategies. The authors provide a comprehensive review
on available diagnostic, preventive, and treatment strategies for AKI.
Keywords: acute kidney injury; prevention; diagnosis; treatment
1. Introduction
Acute kidney injury (AKI) is a frequent diagnosis with an incidence that varies from 5.0% to 7.5%
in hospitalized patients and that reaches up to 50–60% in critically ill patients [1–6]. AKI is characterized
by an acute decrease in renal function that can be multifactorial in its origin and is associated with
complex pathophysiological mechanisms [1,7].
In the short term, AKI is associated with an increased length of hospital stay, health care costs,
and in-hospital mortality, and its impact extends into the long term, with AKI being associated with
increased risks of cardiovascular events, progression to chronic kidney disease (CKD), and long-term
mortality [8].
The incidence of AKI has increased in the past few decades, which might reflect the impact
of the increased recognition of this diagnosis and improvements in patient care, namely through
improvements in dialytic care, the availability of less nephrotoxic drugs, and a decrease in the
use of dopamine and diuretics [1,9]. Mortality rates have declined in critically ill patients with
AKI, but mortality rates are still significantly high and increase with AKI severity, specifically in
dialysis-requiring AKI [6,9–11].
AKI survivors are at increased risk of developing CKD, which defined by the persistence of kidney
disease for a period of more than 90 days [8]. Additionally, investigators now consider that AKI and
CKD are part of a disease continuum instead of separate entities [8]. Indeed, the term acute kidney
disease (AKD) has been recently proposed to define the continuing pathological processes and adverse
events developing after AKI [12].
AKD is defined as an acute or subacute damage and/or a loss of kidney function for a duration of
between 7 and 90 days after exposure to an AKI-initiating event [12]. This highlights the importance of
renal recovery, as recovery within 48 h is typically associated with the rapid reversal of AKI, as well as
the impact of AKD on pre-existing CKD in increasing the risk for kidney disease progression [12].
J. Clin. Med. 2020, 9, 1704; doi:10.3390/jcm9061704 www.mdpi.com/journal/jcm
2. J. Clin. Med. 2020, 9, 1704 2 of 21
Given the impact of the prognosis of AKI, it is important to enhance the recognition of at-risk
patients and to improve preventive, diagnostic, and therapeutic strategies. The authors provide a
comprehensive literature review on available preventive and therapeutic strategies for AKI.
2. Diagnosis of AKI
The currently widespread AKI classification was developed by the Kidney Disease Improving
Global Outcomes (KDIGO) work group in 2012 and defines AKI as an increase in the serum creatinine
(SCr) level to at least 0.3 mg/dL within 48 h, an increase in SCr to more than 1.5 times the baseline
(which is known or presumed to have occurred within the prior 7 days), or a urine output (UO)
decrease to less than 0.5 mL/kg/h for 6 h [13]. This classification also stratifies different stages of AKI
severity and provides criteria that could be applied in clinical activity and investigation [14] (Table 1).
Table 1. Kidney Disease Improving Global Outcomes (KDIGO) classification.
Stage SCr UO
1
Increase in SCr ≥ 0.3 mg/dL (≥26.5 µmol/L) or
increase in SCr ≥ 150% to 200% (1.5 to 1.9X)
0.5 mL/kg/h (6 h)
2 Increase in SCr 200% to 300% (2 to 2.9X) 0.5 mL/kg/h (12 h)
3
Increase in SCr 300% (≥3X) or Increase in
SCr to ≥4 mg/dL (≥353.6 µmol/L) or initiation
of renal replacement therapy
0.3 mL/kg/h (24 h) or anuria (12 h)
SCr: serum creatinine; UO: urine output.
The current definition relies on SCr and UO, which are imperfect markers with significant
limitations, namely that these do not account for the duration or cause of AKI [15]. SCr is an insensitive
marker because it is altered by factors affecting its production (age, gender, diet, muscle mass,
and sepsis), dilution (fluid administration), elimination (previous renal dysfunction), and secretion
(medications). Thus, SCr cannot be used as an accurate estimate of glomerular filtration rate (GFR)
in the non-steady state, and it underestimates the degree of dysfunction due to reduced muscle
mass, increased catabolism, or positive fluid balance in critical patients. Additionally, it often takes
two-to-three days before SCr is elevated after a renal insult when renal injury occurs in the setting of
appropriate renal reserve, meaning that other nephrons increase function to compensate for injured
nephrons, and so SCr may not change despite actual structural damage [16,17].
Though UO is an early marker for AKI, it also relies on patient’s volemic and hemodynamic status
and the use of diuretics, and so it is difficult to assess without a urinary catheter and its usefulness
relies on an hourly assessment that is time consuming [15,17,18].
Recently, potential urinary and serum biomarkers of AKI have been identified, namely cystatin-C,
neutrophil gelatinase associated lipocalin (NGAL), N-acetyl-glucosaminidase (NAG), kidney injury
molecule 1 (KIM-1), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin 18 (IL-18), liver-type fatty
acid-binding protein (L-FABP), calprotectin, urine angiotensinogen (AGT), urine microRNAs, insulin-like
growth factor-binding protein 7 (IGFBP7), and tissue inhibitor of metalloproteinases-2 (TIMP-2) [19–29].
Both NGAL and IGFBP7 with TIMP-2 are the most promising markers that have been validated in
multiple settings. However, their increased cost and a lack of substantial evidence of improvement of
outcomes are important limitations for their widespread clinical use [30,31].
These markers reflect different stages of the pathophysiology of AKI, so, the use of a panel of
several biomarkers covering different phases of this syndrome might provide a better early diagnostic
tool for AKI, as well as providing targets for future treatments [27,28,30,32–35].
3. Risk factors for AKI
Both patient susceptibilities and exposures are risk factors for AKI [11,36,37] (Table 2).
3. J. Clin. Med. 2020, 9, 1704 3 of 21
Patient age is an important non-modifiable risk factor, as the loss of renal reserve and the
physiologic decline of GFR may place older patients at risk for AKI [38–42].
CKD patients possess a loss of autoregulation, abnormal vasodilation, susceptibility to
antihypertensive agents, and nephrotoxins, and the side effects of medication contribute to the
development of AKI [42]. Moreover, AKI and CKD have been described as interconnected syndromes
because AKI leads to the worsening of CKD and CKD predisposes one to AKI [42,43]. CKD also limits
renal recovery after AKI [44].
Patient comorbidities such as diabetes mellitus, hypertension, cardiovascular disease, chronic
liver disease, and chronic obstructive pulmonary disease have also been identified as important AKI
predictors [11,13,36,37,40,45,46]. Given the increasing incidence of HIV-infected patients in past few
decades, HIV infection is also a risk factor that predisposes patients to AKI [47,48].
Exposure to sepsis, surgery, nephrotoxins, and shock are specific modifiable factors that contribute
to AKI [1,13]. Indeed, large cohort studies focusing on critically ill patients have reported that the two
most important causes of AKI are sepsis and surgery [6,49].
Additionally, recent research has reported that other factors like hyperuricemia, hypoalbuminemia,
obesity, anemia, and hyperglycemia have been associated with an increased risk of AKI [49–69].
Table 2. Risk factors for acute kidney injury (AKI).
AKI Risk Factors
Older age Shock
Diabetes Sepsis
Hypertension Nephrotoxins
Chronic kidney disease (NSAIDs, ARB, ACEi, contrast)
Cardiovascular disease Surgery
Chronic liver disease Hyperuricemia
Chronic obstructive pulmonary disease Hypoalbuminemia
HIV infection Hyperglycemia
Obesity Anemia
ACEi: angiotensin-converting enzyme inhibitor; ARB: angiotensin receptor blocker; NSAID: nonsteroidal
anti-inflammatory drugs.
4. Causes and Assessment of AKI
AKI is a complex syndrome involving numerous pathophysiological processes that include
pre-renal AKI, acute tubular necrosis, acute interstitial nephritis, acute glomerular diseases, and acute
obstructive nephropathy [54].
These causes can be systematized into three groups, namely prerenal AKI, which accounts for up
to 60% of cases and results from the functional adaptation to hypoperfusion of structurally normal
kidneys; intrinsic renal AKI, which results from structural damage to any component of the renal
parenchyma and accounts for up to 40% of cases; and, less frequently, postrenal AKI, which results
from urinary tract obstruction [55,56]. The causes are summarized in Table 3.
Essentially, the majority of causes of AKI are actually not renal-specific because the kidneys are highly
sensitive to any systemic upset [55]. Indeed, the most common causes being septic shock, post major
surgery, cardiogenic shock, and hypovolemia highlight this fact [57].
Most cases are multifactorial, and, following the inciting event causing kidney injury, numerous
pathophysiologic pathways occur, including hemodynamic instability, microcirculatory dysfunction,
tubular cell injury, tubular obstruction, renal congestion, microvascular thrombi, endothelial dysfunction,
and inflammation [55,56,58–60].
The assessment of the cause of AKI must include a careful history, including medications and
exposures, as well as a thorough physical examination. The assessment of fluid status and the presence
of signs and symptoms of acute or chronic heart failure, infection, and urinary tract obstruction must
be included in a first approach [54,61].
4. J. Clin. Med. 2020, 9, 1704 4 of 21
Table 3. Causes of AKI.
Causes of AKI
Pre-renal Intrinsic Post-renal
- Hypovolemia
Hemorrhage
Volume depletion
Renal fluid loss (over-diuresis)
Third space (burns, peritonitis,
muscle trauma
- Tubular
Renal ischemia
(shock, surgery, hemorrhage, trauma,
bacteremia, pancreatitis, pregnancy)
Nephrotoxic drugs
(antibiotics, antineoplastic drugs,
contrast media, organic solvents,
anesthetic drugs, heavy metals)
Endogenous toxins
(myoglobin, hemoglobin, uric acid)
- Extrarenal obstruction
Prostate hypertrophy
Improperly placed catheter
Bladder, prostate or cervical cancer
Retroperitoneal fibrosis
- Impaired cardiac function
Congestive heart failure
Acute myocardial infarction
Massive pulmonary embolism
- Glomerular
Post-infectious glomerulonephritis
Lupus nephritis
IgA glomerulonephritis
Infective endocarditis
Goodpasture syndrome
Wegener disease
- Systemic vasodilatation
Anti-hypertensive medications
Gram negative bacteremia
Cirrhosis
Anaphylaxis
- Interstitial
Infections
(bacterial, viral)
Medications(antibiotics, diuretics,
NSAIDs, anti-ulcer agents) - Intrarenal obstruction
Nephrolithiasis
Blood clots
Papillary necrosis
Drugs (acyclovir, methotrexate)
- Increased vascular resistance
Anesthesia
Surgery
Hepatorenal syndrome
NSAID medications
Drugs that cause renal
vasoconstriction (cyclosporine,
ARB, ACEi)
- Vascular
Large vessels
(bilateral renal artery stenosis,
bilateral renal vein thrombosis)
Small vessels
(vasculitis, malignant hypertension,
atherosclerotic or thrombotic emboli,
hemolytic uremic syndrome,
thrombotic thrombocytopenic
purpura)
IgA: Immunoglobulin A.
Laboratory evaluation should comprise SCr, urea, electrolytes, complete blood count, liver function
tests, glucose level, bone profile, urine analysis, and microscopic examination, and a renal ultrasound
must be performed to exclude obstruction. Urine output should be measured. A chest x-ray can provide
evidence of a potential cause, such as pneumonia or vasculitis, but it can also prove useful in volume
overload evaluation [54,61].
Less frequent causes of AKI such as vasculitis, glomerulopathy, and hemolytic uremic syndrome
should be considered in the presence of fever, rash, joint pains, pulmonary infiltrates, abnormal urine
analysis, thrombocytopenia, and hemolytic anemia when significant dehydration, hypotension,
nephrotoxins, and obstruction have been excluded [54,61]. Thus, the determination of the cause
of AKI must be completed with an assessment of antineutrophil cytoplasmic antibodies (ANCA),
anti-glomerular basement membrane antibodies (anti-GBM), antinuclear antibodies (ANA), anti-double
stranded DNA (anti-dsDNA) antibodies, complement factors, rheumatoid factor, antistreptolysin O titer
(ASOT), cryoglobulins, serum electrophoresis, immunoglobulins, serum free light chains, hepatitis,
and HIV serology [54,61] (Table 4).
5. J. Clin. Med. 2020, 9, 1704 5 of 21
Table 4. Preventive and treatment strategies for AKI.
Prevention of Acute Kidney Injury
Identify high-risk patients
Kidney health assessment in high risk patients
CKD history
blood pressure assessment
SCr level
urine dipstick
medication list
Every 12 months
30 days before exposure to AKI risk
2–3 days after exposure to AKI risk
Discontinue and/or avoid nephrotoxins Optimize hemodynamic and volume status
Treatment of Acute Kidney Injury
Correction of Hypovolemia
Individualized fluid therapy
Avoid positive fluid balance
Isotonic Saline
Albumin
Vasopressor support (MAP 65 mmHg)
Noradrenaline
Vasopressin
Terlipressin
Discontinue nephrotoxins and Adjust drugs to renal function
NSAIDs
ARBs, ACEis
Contrast
Metformin
Aminoglycosides
Vancomycin
Absolute indications for RRT
Severe/refractory hyperkalemia
Severe/refractory, metabolic acidosis
Refractory volume overload
Clinical complications of uremia (encephalopathy, pericarditis or neuropathy)
Investigate and Treat Acute Kidney Injury Cause
SCr, Urea, Electrolytes ANCA antibodies, anti-GBM antibodies, ANA antibodies, anti-dsDNA antibodies
Complete blood count, Liver function tests, Glucose level, Bone profile complement factors, rheumatoid factor, ASOT, cryoglobulins
Urine analysis and microscopic examination serum electrophoresis, immunoglobulins, serum free light chains
Renal ultrasound
hepatitis and HIV serology
Chest X-ray
Follow-up after Acute Kidney Injury
Nephrology referral within 3 months after AKI episode
SCr, urea, and proteinuria
Medication reconciliation
Education on nephrotoxic avoidance
Strategies to prevent CKD progression
ANA: antinuclear antibodies; ANCA: antineutrophil cytoplasmic antibodies; anti-GBM: anti-glomerular basement
membrane; anti-dsDNA: anti-double stranded DNA; ARB: angiotensin receptor blocker; ASOT: antistreptolysin
O titer; CKD: chronic kidney disease; RRT: renal replacement therapy.
5. Treatment of AKI
The therapeutic strategies for AKI based on the KDIGO guidelines and bundles of care are limited
and mostly supportive [13].
The clinical approach should begin by hemodynamic stabilization, the early identification of
complications of AKI, the identification of its cause, and its treatment [62]. Hemodynamic stabilization
is of critical significance because autoregulation mechanisms are impaired in AKI [63].
Particular attention should be given to medications with renal toxicity, which should be
discontinued, and dose adjustment according to renal function to avoid underdosing or adverse
effects [62,64]. Additionally, in septic patients, prompt initiation of antibiotics is crucial [65].
It is important to rapidly identify and treat other complications in the therapeutic approach for
the patient with AKI, such as hyperkalemia, metabolic acidosis, anemia, and fluid overload [13].
During the course of AKI, it is also recommended to prevent infection and start stress-ulcer
prophylaxis [13].
5.1. Fluid Therapy
Fluid balance should be individualized, although the optimal fluid to this effect is undetermined.
The titration of fluids is complex and requires the careful monitoring of patient’s volemia [63].
Hypovolemia reduces renal blood flow, but AKI patients are also at risk for volume overload [55].
Furthermore, a positive fluid balance is independently associated with increased mortality in AKI
6. J. Clin. Med. 2020, 9, 1704 6 of 21
patients and contributes to worse outcomes in critically ill patients [66–68]. Goal-directed therapy
guided by the assessment of fluid responsiveness appears to be associated with better outcomes [69,70].
Different types of fluids have different mechanisms of action. While colloids, such as albumin or
starches, rely on oncotic gradients and selectively expand the extracellular space, crystalloids—namely
saline, Ringer’s lactate or PlasmaLyte—equilibrate across intravascular and extravascular spaces [63,71].
Albumin appears to be relatively safe, but a consistent survival advantage compared with
crystalloids has not been demonstrated [72–74]. The Saline Versus Albumin Fluid Evaluation (SAFE)
trial reported that there was no renal or mortality benefit in patients who received albumin, but less
total volume was required for resuscitation, which could be attractive in reducing positive fluid
balance [72]. Furthermore, in the Colloids Versus Crystalloids for the Resuscitation of the Critically Ill
(CRISTAL) trial, there was a decrease in need for mechanical ventilation, the need for vasopressors,
and the mortality at 90-days in patients who received colloids [75].
Thus, albumin may prove important when large volumes of fluids are anticipated. Indeed, the recent
Surviving Sepsis Campaign recommendations state that when patients require substantial amounts of
crystalloids, albumin might be additionally used [76]. Still, there are no data supporting the routine use of
colloids for volume resuscitation [77].
The administration of albumin in combination with terlipressin is also beneficial in specific conditions,
such as cirrhotic patients and cardiac surgery patients with hypoalbuminemia in which the preoperative
administration of albumin reduces the risk of postoperative AKI [78,79]. Nevertheless, caution must be
taken in patients with traumatic brain injury, in which albumin has been associated with an increased
mortality risk and should be avoided [72]. Some concerns have been raised on the use of hyperoncotic
albumin in septic shock patients who are volume depleted and have increased vascular permeability, as it
might increase AKI risk by promoting intracellular dehydration to expand volume [80,81].
Large randomized trials have reported higher incidences of AKI in patients treated with starches,
which appears to be due to osmotic nephrosis with proximal tubule vacuolization and swelling. [63,82,83]
The use of starches should thus be avoided [82].
There are less data concerning the use of gelatins and AKI, though observational data suggest
these might contribute to AKI due to osmotic nephrosis [84]. Therefore, the use of gelatins is also not
recommended in AKI [13,63].
Saline is the most frequently used crystalloid in critically ill patients [63,85]. Nevertheless,
the administration of large volumes can cause hyperchloremia and metabolic acidosis. Hyperchloremia can
lead to renal vasoconstriction and a consequent reduction in glomerular filtration [71,86].
Studies comparing different types of crystalloids in critically ill patients at risk of AKI have
demonstrated conflicting results [85–89]. Yunos reported that a chloride-restrictive strategy was
associated with a significant decrease in the incidence of AKI in critically ill patients [88]. The Saline
versus PlasmaLyte for intensive care unit (ICU) Fluid Therapy (SPLIT) trial did not find differences in
the rates of AKI or mortality in a population of mostly postoperative patients who received modest
volumes for resuscitation [90,91]. In the Isotonic Solutions and Major Adverse Renal Events Trial
(SMART) and in the Saline against Lactated Ringer’s or PlasmaLyte in the Emergency Department
(SALT-ED), trial there were reductions in adverse kidney outcomes within 30 days in patients who
received buffered solutions [85,92]. Though it is theorized that AKI occurs due to hyperchloremia only
when large volumes are administered, a recent study of critically ill patients receiving large volumes of
fluid did not demonstrate an association between chloride load and AKI risk after adjusting for disease
severity [93]. Thus, saline remains the preferred solution for volume resuscitation, though chloride
concentrations should be monitored [13,55,62].
5.2. Vasopressor Drugs
After volume resuscitation, vasopressor support should be considered to maintain renal perfusion
in order to avoid positive fluid balance. In patients with AKI, the median blood pressure target should
be higher than 65 mmHg to ensure accurate renal perfusion [13,94–96].
7. J. Clin. Med. 2020, 9, 1704 7 of 21
In vasodilatory states, noradrenaline is the recommended first-line vasopressor [76,97].
Noradrenaline improves microcirculatory flow by increasing perfusion pressure above the autoregulation
threshold in hypotensive patients, but in high doses, it can cause a decrease in the flow by excessive
vasoconstriction [98]. Thus, the current recommendations suggest to administer the lowest dose to
achieve the blood pressure target and keep adequate perfusion parameters [98].
Vasopressin and terlipressin are effective alternatives for raising blood pressure, though their
benefit on kidney function or mortality comparing to noradrenaline has not been demonstrated [99–102].
Angiotensin II has shown promising results on patient outcomes in recent studies, namely by improving
survival and renal function recovery [103]. Nevertheless, further studies are still required to recommend
the routine use of angiotensin II.
In contrary to previous beliefs, there is no evidence for a “renal dose” dopamine in AKI management,
because there is no association between dopamine use in AKI and improvement in survival or renal
function [104–107]. Fenoldopam has a similar hemodynamic renal effect to that oe low-dose dopamine
and had been demonstrated to decrease systemic vascular resistance whilst increasing renal blood flow to
the kidney [108,109]. Despite promising studies, there has been no conclusive evidence of the beneficial
effect of fenoldopam in the management of AKI, and further investigation is warranted [110,111].
5.3. Diuretics
The use of diuretics is only recommended to manage fluid overload and electrolyte disturbances
in AKI [13,112]. Based on pathophysiology studies, it was previously thought that loop diuretics
might protect the loop of Henle from ischemia by decreasing its workload [112]. This has never
been confirmed, and, on the contrary, it has been demonstrated that furosemide is not associated
with clinical benefits in preventing AKI, decreasing the need for renal replacement therapy (RRT),
renal recovery, or decreasing in-hospital mortality [113–115]. It is important to note that certain studies
have associated the use of loop diuretics with an increased risk of mortality, which might be related to
the delay in appropriate RRT start [112,115,116]. Additionally, a loop diuretic used in high doses may
cause ototoxicity [112]. Therefore, the KDIGO guidelines do not recommend the use of diuretics to
prevent AKI [13].
5.4. Drug Nephrotoxicity
Drug nephrotoxicity has been associated with 20–40% of AKI causes and can reach up to 60% in
elderly patients [117,118]. Patients with underlying AKI or CKD, sepsis, acute or chronic liver failure,
acute or chronic heart failure, pulmonary hypertension, malignancies, and exposure surgery are at
increased risk for drug-induced nephrotoxicity [117].
The mechanisms of drug-induced nephrotoxicity are diverse and vary with different drug
classes. (Table 3). Drugs can induce not only direct toxicity due to tubular injury, interstitial nephritis,
glomerular injury, or obstructive nephropathy but also indirect nephrotoxicity associated with a
decrease in renal blood flow [119]. Furthermore, drug-induced nephrotoxicity results from the
combination of innate drug toxicity, altered renal hemodynamics, previous renal disease, and altered
drug pharmacokinetics in critical illness [119,120].
Due to the associated reduced glomerular pressure, patients exposed to nonsteroidal anti-inflammatory
drugs (NSAIDs), renin–angiotensin–aldosterone system blockers, high-dose systemic vasoconstrictors, or
calcineurin inhibitors are at high-risk to develop prerenal AKI in the setting of altered systemic and renal
hemodynamics or fluid loss; these also increase the risk for acute tubular injury [117].
Acutetubularnecrosis(ATN)isdose-dependentandisthemostcommonformofdrug-inducedAKIin
the hospital setting [121]. The most common drugs associated with ATN are aminoglycosides, vancomycin,
radiocontrast media, cisplatin, amphotericin B, foscarnet, and osmotically active agents [117,121].
Acute interstitial nephritis (AIN) causes up to 10% of AKI cases. AIN is an idiosyncratic
reaction that is not dose-dependent [117,120]. Antimicrobials such as b-lactams, sulfa-based drugs and
8. J. Clin. Med. 2020, 9, 1704 8 of 21
quinolones, anti-ulcer agents, anti-convulsants, and diuretics are the most common drugs associated
with AIN [117,118,122].
Post-renal AKI due to crystal-induced luminal obstruction can occur in patients exposed to
acyclovir, sulfa-based medications, ciprofloxacin, and methotrexate [121]. Less frequently, drug-induced
glomerular disease can result from the administration of hydralazine, propylthiouracil, allopurinol,
and penicillamine, all of which have been associated with development of ANCA vasculitis, mitomycin
C, oral contraceptive agents, calcineurin inhibitors, antineoplastic agents, ticlopidine, and quinine, all
of which can cause thrombotic microangiopathy [121].
Therefore, the prescription of drugs must be carefully considered to minimize toxicity. The KDIGO
guidelines recommend the early discontinuation of potential nephrotoxic drugs, the avoidance of
radiocontrast and other nephrotoxic drugs, and drug dose monitoring [13].
5.5. Other Therapeutic Strategies
Remote ischemic preconditioning is a technique that induces multiple short cycles of ischemia and
reperfusion by cuff inflation [123]. This has been tested as a possible method to protect the kidneys from
ischemia reperfusion injury, although there is conflicting evidence regarding the results in reducing
AKI or mortality, and it is not recommended in clinical practice [124–128].
Levosimendan has both vasodilatory and inotropic actions [129]. It might improve kidney function
by improving cardiac function but also through afferent arteriolar vasodilatation, though this benefit
remains debatable [130]. In a recent meta-analysis, the use of levosimendan was associated with a
decrease in AKI incidence and mortality in cardiac surgery patients, proving its potential use [131].
Several new potential therapeutic targets for AKI are currently being investigated and entering
clinical trials. These include pathways involved in inflammation, fibrosis, mitochondrial function,
oxidative stress, and hemodynamics. Though promising, further clinical trials are still required.
ReltecimodisapeptideantagonistofCD28(co-stimulatoryreceptor)thatactsasanimmunomodulator
and has been demonstrated to attenuate the systemic inflammatory response and decrease organ
dysfunction in necrotizing soft tissue infections [132,133].
Due to the fact that active vitamin D has anti-proliferative and pro-differentiation actions, it might
be that lower levels of vitamin D contribute to AKI [134,135]. Indeed, critically ill patients with vitamin
D deficiencies have been reported to have higher rates of AKI and further progression to CKD [135–137].
Calcifediol and calcitriol are still under investigation as possible treatments in early AKI [138–140].
Alkaline phosphatase is an enzyme expressed along the proximal tubule and has the ability to
reduce renal inflammation. The use of human recombinant alkaline phosphatase has been investigated
in clinical trials as a potential anti-inflammatory drug that could attenuate kidney injury or promote
renal regeneration [141–143]. A recent trial reported that, despite not affecting short-term kidney
function, there was a long-term benefit in kidney function [144].
Teprasiran is under investigation as an apoptosis inhibitor and has had promising results in
patients undergoing cardiac surgery at risk for AKI by demonstrating a reduction in major adverse
kidney events at 90 days [145,146].
Intensive investigation in this area reflects the fact that, to date, there are no established
pharmacotherapies for AKI. The most important measures to be applied in clinical practice remain the
hemodynamic monitoring and administration of fluids and vasopressors, the eviction and avoidance of
nephrotoxins, and the treatment of AKI complications (Table 4).
5.6. Renal Replacement Therapy
Conventional criteria for initiation of RRT in AKI are anuria, severe/refractory hyperkalemia,
severe/refractory metabolic acidosis, refractory volume overload, severe azotemia, or clinical complications
of uremia such as encephalopathy, pericarditis, or neuropathy [147,148].
There are different modalities of RRT that can be provided in cases of severe AKI, namely intermittent
hemodialysis (HD), continuous RRT (CRRT), slow low-efficiency dialysis (SLED), or peritoneal dialysis
9. J. Clin. Med. 2020, 9, 1704 9 of 21
(PD) [149]. Continuous RRT (CRRT) is the most common form of renal support provided to critically
ill patients because it provides better volume control and acid–base and electrolyte correction while
maintaining hemodynamic stability [147,148]. Though there is no sustained evidence reporting a difference
inmortalitybetweentheuseDH,SLED,orCRRTinAKIpatients, thereisatendencyforearlierrenalrecovery
and decreased progression to CKD with CRRT use [150,151]. The KDIGO guidelines recommend the use
of CRRT and HD as complementary therapies, although CRRT should be favored in hemodynamically
unstable patients and in patients with increased intracranial pressure [13]. Ultimately, the choice between
RRT modalities relies on patient clinical status, resource availability, and local expertise [149].
RRT is essential to maintain volume, electrolyte, acid-base, and uremic solute homeostasis in AKI
patients. It is also theorized that RRT can modulate inflammation, which might prove crucial in septic
patients, though this remains uncertain [147,152]. Nonetheless, RRT requires central venous dialysis
catheter insertion, the exposure of blood to an extracorporeal circuit, and anticoagulation, and it can be
associated with hemodynamic instability, which may contribute to delayed kidney recovery [147,152].
The timing to start RRT remains controversial. According to the KDIGO guidelines, RRT should
be started when life-threatening changes in fluid, electrolyte, and acid-base balances exist, and it is
recommended to consider the broader clinical context and trends of laboratory values when making
the decision to start RRT [13]. It is also non-consensual if RRT can change patient outcomes or is merely
a surrogate for the critical illness on patient outcomes [153–156].
Recent randomized clinical trials have evaluated the optimal timing to start RRT in critically ill
AKI patients. The heterogeneity in definitions of timing and criteria has contributed to lack of a strong
recommendation [153,154].
The Early Versus Late Initiation of RRT (ELAIN) was a single-center trial of 231 critically ill,
mostly surgical AKI patients. In this study, Zarbock et al. defined the early group as starting RRT
within 8 h of fulfilling KDIGO stage 2 AKI and elevated plasma NGAL levels, and they defined the
delayed group as starting RRT within 12 h of developing KDIGO stage 3 AKI or in the presence of an
absolute indication [157]. The early RRT group was associated with 15% less mortality, greater RRT
independence, and less hospitalization days than the delayed RRT group. However, the delayed group
included 9% of patients who did not start RRT due to the recovery of kidney function [157].
In contrast, in the Artificial Kidney Initiation in Kidney Injury (AKIKI) multicenter trial of
620 critically ill AKI patients, an early RRT start did not decrease mortality, with no differences noted
in hospital stays and renal recovery, and the delayed group had greater RRT-free days and fewer
incidences of catheter-related infections [158]. In this study, early RRT was defined as starting RRT
within 6 h of fulfilling KDIGO stage 3 AKI, and delayed RRT was defined as RRT start only in response
to the development of absolute indications. Additionally, only 51% in the delayed group started
RRT [158].
Considering the contrasting results of these studies, another multicenter trial was conducted in
488 patients with septic shock and severe AKI; this was entitled Initiation of Dialysis Early versus Late
in the Intensive Care Unit (IDEAL-ICU) [159]. In this study, Barbar et al. defined the early group as
RRT start within 12 h of achieving the failure stage of the RIFLE (Risk, Injury, Failure, Loss of kidney
function, and End-stage kidney disease) classification without life-threatening AKI complications,
and they defined the delayed group as starting RRT after a delay of 48 h of achieving the failure stage
of the RIFLE classification. The results of the IDEAL-ICU trial were consistent with AKIKI and also
demonstrated no significant difference in mortality between groups [159].
Only the ELAIN trial provided evidence that suggested the benefit of an early RRT start,
which has not been verified in most recent studies. Several factors might have contributed to this
conflicting evidence.
Firstly, the population studied, the AKI diagnostic criteria, and the definition of timing in each
study were different. The ELAIN trial included a mixed ICU population but was mostly surgical
patients, whereas the AKIKI and IDEAL trials included medical ICU patients with a higher proportion
of sepsis. The ELAIN trial also included a significantly higher proportion of CKD patients (with a
10. J. Clin. Med. 2020, 9, 1704 10 of 21
glomerular filtration rate of higher than 30 mL/min/1.73 m2) than the AKIKI and IDEAL trials
(41% vs. 10% and 15%, respectively). Patients enrolled in the AKIKI and IDEAL trials were at least
stage 3 KDIGO or failure on the RIFLE classification, while this was only the case for patients in
the delayed group in the ELAIN trial. Thus, the inclusion of less severe patients in the ELAIN trial
might have beneficially influenced the outcome. Interestingly, patients in the ELAIN trial received
delayed RRT at a significantly earlier point than the delayed group in the AKIKI and IDEAL trials
(25.5 vs. 57 and 51.5 h, respectively).
Secondly, RRT modalities were different in these trials. All patients in the ELAIN trial were
started on continuous RRT, and a combination of continuous and intermittent RRT techniques were
prescribed in the AKIKI and IDEAL trials. Therefore, the disparities between RRT modalities might
have influenced the hemodynamic assessment, treatment, and outcome of these patients.
Finally, a lower proportion of patients in the delayed group of the AKIKI and IDEAL trials initiated
RRT than the delayed group of the ELAIN trial (51% and 62% vs. 91%, respectively). This suggests
that a conservative approach to RRT start in response to persistent AKI or complications might be
acceptable, as several patients with KDIGO stage 3 recovered renal function and ultimately did not
require RRT.
The results of the ongoing Standard Versus Accelerated Initiation of Dialysis in Acute Kidney
Injury (STARRT-AKI) and AKIKI 2 multicenter trials are highly anticipated in order to provide a more
definitive answer to the problem of optimal timing for RRT start [160,161].
The timing of initiation has only been assessed in critically ill and the post-surgical settings, [162,163]
and the inconsistent results have led to a perpetuation of the traditional recommendations of RRT start.
6. Prevention of AKI
In the absence of effective therapeutic interventions on established AKI and due to its significant
on morbidity and mortality, we can only rely on AKI prevention and early diagnosis to reduce its
incidence and detrimental consequences.
On the other hand, it could be argued that risk assessment is futile because it is unclear which
interventions for high-risk patients should be implemented and whether these interventions are
actually effective.
However, recent studies have suggested that the risk stratification of patients for AKI can allow
for the employment of effective intervention and reduce the incidence of AKI, although there has been
no evidence of benefit for long-term renal outcomes [164–166].
The recent Acute Disease Quality Initiative (ADQI) conference on “Quality Improvement for AKI”
proposed that the range of care in AKI should be a continuum from risk assessment and prevention in
the community setting, to AKI prevention in the hospital, to optimizing AKI management, and finally
to the surveillance of AKD and the prevention of recurrent AKI and progression to CKD [167].
At least 50% of AKI episodes are believed to begin in the community setting, so health care
professionals should identify at-risk patients (Table 2) and implement preventive interventions to
decrease the incidence of AKI [168–170].
High-risk patients for AKI should have a kidney health assessment (KHA) every 12 months, at least
30 days before exposure and two-to-three days after exposure that carries AKI risk in order to define
and modify their risk profile [167,171]. The KHA must include AKI and CKD history, blood pressure
assessment, SCr level, urine dipstick, and medication list [167].
After an acute exposure to an AKI inciting event, namely nephrotoxic medications, radiocontrast,
surgery, or acute disease, medications should be adjusted, further nephrotoxic exposures should be
minimized, and AKI occurrence and its complications should be monitored [167].
At hospital admission, patients should also be screened for AKI risk [13,169,172]. In high-risk
patients, the early correction of modifiable risk factors should be considered in order to prevent AKI
occurrence [64,167,173].
11. J. Clin. Med. 2020, 9, 1704 11 of 21
The gold-standard of AKI prevention remains the optimization of hemodynamic and volume
status, medication review such as the cessation of angiotensin-converting enzyme inhibitor/angiotensin
receptor blocker (ACEi/ARB) and metformin, and the minimization of nephrotoxic exposure [13,174].
7. Follow-Up after AKI
For patients with AKI, the main goal should be the recovery to baseline kidney function in the
shortest period of time in order to reduce duration and disease severity, thus highlighting the role of
early diagnosis and prompt management [62,167,175].
To date, there remains no standardized AKI or AKD follow-up care, but several studies have
reported low rates of nephrology follow-up after AKI across different settings. [176,177]. In the United
States Renal Data System annual report of 2015, only 19% of patients had a nephrology follow-up at
12 months after an AKI hospitalization [178]. In another study, only 4% of patients were referred to a
nephrologist at three months and only 9% at one year, though the mortality rate during this period
was 22% [179].
The benefit of nephrology referral is uncertain, however, recent studies have suggested that in
high-risk patients, an early nephrology referral may improve survival. Indeed, Harel et al. reported
that only 41% of AKI patients had a nephrology follow-up and that this was associated with a 24%
mortality reduction in two years of follow-up [180].
Determining which patients are at higher risk for CKD development after AKI is crucial.
Risk factors for CKD after AKI include the severity, duration, and recurrence of AKI; the timing of
renal recovery; advanced age; lower baseline renal function; diabetes mellitus; hypertension; chronic
heart failure; hypoalbuminemia; proteinuria; chronic liver disease; and a higher Charlson comorbidity
index [181].
The KDIGO guidelines and the ADQI consensus recommend that after an episode of AKI,
patients should be followed by a nephrologist at least three months after the episode in order
to assess kidney recovery and/or progression to CKD or progressive CKD [13,167]. The follow-up
evaluation should include kidney function and proteinuria to assess prognosis and outcome, medication
reconciliation, patient education to nephrotoxic avoidance, and the employment of strategies to prevent
CKD progression [167].
Further research is warranted to identify high-risk patients, define timing for nephrology follow-up,
and to develop strategies to improve patient outcomes.
8. Conclusions
Currently, there are no established pharmacotherapies for AKI. Treatment strategies for AKI
comprise hemodynamic stabilization, the eviction of nephrotoxins, and the treatment of AKI
complications. The gold-standard of AKI prevention includes identifying at-risk patients, optimizing
hemodynamic and volume statuses, reviewing medication, and minimizing nephrotoxic exposure.
Considering the significant prognostic impact of AKI, it is crucial to focus further research on AKI
prevention and therapy.
Author Contributions: The authors participated as follows: J.G. drafted the article, J.A.F. participated in the
literature review of data, C.O. revised the article, and J.A.L. revised the article and approved the final version to be
submitted for publication. All authors have read and agreed to the published version of the manuscript.
Funding: There was no funding for this study.
Conflicts of Interest: The authors declare no conflict of interest.
References
1. Susantitaphong, P.; Cruz, D.N.; Cerda, J.; Abulfaraj, M.; Alqahtani, F.; Koulouridis, I.; Jaber, B.L. Acute Kidney
Injury Advisory Group of the American Society of Nephrology. World Incidence of AKI: A Meta-Analysis.
Clin. J. Am. Soc. Nephrol. 2013, 8, 1482–1493. [CrossRef]
12. J. Clin. Med. 2020, 9, 1704 12 of 21
2. Lameire, N.; Van Biesen, W.; Vanholder, R. The changing epidemiology of acute renal failure. Nat. Clin.
Pract. Nephrol. 2006, 2, 364–377. [CrossRef]
3. Rodrigues, F.B.; Bruetto, R.G.; Torres, U.S.; Otaviano, A.P.; Zanetta, D.M.T.; Burdmann, E.A. Incidence and
Mortality of Acute Kidney Injury after Myocardial Infarction: A Comparison between KDIGO and RIFLE
Criteria. PLoS ONE 2013, 8, e69998. [CrossRef] [PubMed]
4. Luo, X.; Jiang, L.; Du, B.; Wen, Y.; Wang, M.; Xi, X. A comparison of different diagnostic criteria of acute
kidney injury in critically ill patients. Crit. Care 2014, 18, R144. [CrossRef] [PubMed]
5. Fujii, T.; Uchino, S.; Takinami, M.; Bellomo, R. Validation of the Kidney Disease Improving Global Outcomes
Criteria for AKI and Comparison of Three Criteria in Hospitalized Patients. Clin. J. Am. Soc. Nephrol. 2014, 9,
848–854. [CrossRef]
6. Bagshaw, S.M.; George, C.; Bellomo, R. Changes in the incidence and outcome for early acute kidney injury
in a cohort of Australian intensive care units. Crit. Care 2007, 11, R68. [CrossRef] [PubMed]
7. Hoste, E.A.J.; Kellum, J.A.; Selby, N.M.; Zarbock, A.; Palevsky, P.M.; Bagshaw, S.M.; Goldstein, S.L.; Cerdá, J.;
Chawla, L.S. Global epidemiology and outcomes of acute kidney injury. Nat. Rev. Nephrol. 2018, 14, 607–625.
[CrossRef] [PubMed]
8. Chertow, G.M.; Burdick, E.; Honour, M.; Bonventre, J.V.; Bates, D.W. Acute Kidney Injury, Mortality, Length of
Stay, and Costs in Hospitalized Patients. J. Am. Soc. Nephrol. 2005, 16, 3365–3370. [CrossRef]
9. Hsu, R.K.; McCulloch, C.E.; Dudley, R.A.; Lo, L.J.; Hsu, C. Temporal Changes in Incidence of Dialysis-Requiring
AKI. J. Am. Soc. Nephrol. 2012, 24, 37–42. [CrossRef]
10. Bellomo, R. The epidemiology of acute renal failure: 1975 versus 2005. Curr. Opin. Crit. Care 2006, 12,
557–560. [CrossRef]
11. Cruz, D.N.; Ronco, C. Acute kidney injury in the intensive care unit: Current trends in incidence and outcome.
Crit. Care 2007, 11, 149. [CrossRef] [PubMed]
12. Bagshaw, S.M.; George, C.; Bellomo, R. Early acute kidney injury and sepsis: A multicentre evaluation.
Crit. Care 2008, 12, R47. [CrossRef] [PubMed]
13. Khwaja, A. KDIGO Clinical Practice Guidelines for Acute Kidney Injury. Nephron 2012, 120, c179–c184.
[CrossRef] [PubMed]
14. Gameiro, J.; Agapito Fonseca, J.; Jorge, S.; Lopes, J.A. Acute Kidney Injury Definition and Diagnosis:
A Narrative Review. J. Clin. Med. 2018, 7, 307. [CrossRef] [PubMed]
15. Chawla, L.S.; Bellomo, R.; Bihorac, A.; Goldstein, S.L.; Siew, E.D.; Bagshaw, S.M.; Bittleman, D.; Cruz, D.;
Endre, Z.; Fitzgerald, R.L.; et al. Acute kidney disease and renal recovery: Consensus report of the Acute
Disease Quality Initiative (ADQI) 16 Workgroup. Nat. Rev. Nephrol. 2017, 13, 241–257. [CrossRef]
16. Moledina, D.G.; Parikh, C.R. Phenotyping of Acute Kidney Injury: Beyond Serum Creatinine. Semin. Nephrol.
2018, 38, 3–11. [CrossRef]
17. Waikar, S.S.; Betensky, R.A.; Emerson, S.C.; Bonventre, J.V. Imperfect Gold Standards for Kidney Injury
Biomarker Evaluation. J. Am. Soc. Nephrol. 2011, 23, 13–21. [CrossRef]
18. Thomas, M.E.; Blaine, C.; Dawnay, A.; Devonald, M.A.; Ftouh, S.; Laing, C.; Latchem, S.; Lewington, A.;
Milford, D.V.; Ostermann, M. The definition of acute kidney injury and its use in practice. Kidney Int. 2015, 87,
62–73. [CrossRef]
19. Macedo, E.; Malhotra, R.; Claure-Del Granado, R.; Fedullo, P.; Mehta, R.L. Defining urine output criterion for
acute kidney injury in critically ill patients. Nephrol. Dial. Transplant. 2010, 26, 509–515. [CrossRef]
20. Schinstock, C.A.; Semret, M.H.; Wagner, S.J.; Borland, T.M.; Bryant, S.C.; Kashani, K.B.; Larson, T.S.; Lieske, J.C.
Urinalysis is more specific and urinary neutrophil gelatinase-associated lipocalin is more sensitive for early
detection of acute kidney injury. Nephrol. Dial. Transplant. 2012, 28, 1175–1185. [CrossRef]
21. Parikh, C.R.; Mishra, J.; Thiessen-Philbrook, H.; Dursun, B.; Ma, Q.; Kelly, C.; Dent, C.; Devarajan, P.;
Edelstein, C.L. Urinary IL-18 is an early predictive biomarker of acute kidney injury after cardiac surgery.
Kidney Int. 2006, 70, 199–203. [CrossRef] [PubMed]
22. Di Somma, S.; Magrini, L.; De Berardinis, B.; Marino, R.; Ferri, E.; Moscatelli, P.; Ballarino, P.; Carpinteri, G.;
Noto, P.; Gliozzo, B.; et al. Additive value of blood neutrophil gelatinase-associated lipocalin to clinical
judgement in acute kidney injury diagnosis and mortality prediction in patients hospitalized from the
emergency department. Crit. Care 2013, 17, R29. [CrossRef]
13. J. Clin. Med. 2020, 9, 1704 13 of 21
23. Bennett, M.; Dent, C.L.; Ma, Q.; Dastrala, S.; Grenier, F.; Workman, R.; Syed, H.; Ali, S.; Barasch, J.; Devarajan, P.
Urine NGAL Predicts Severity of Acute Kidney Injury After Cardiac Surgery: A Prospective Study. Clin. J.
Am. Soc. Nephrol. 2008, 3, 665–673. [CrossRef] [PubMed]
24. Hall, I.E.; Yarlagadda, S.G.; Coca, S.G.; Wang, Z.; Doshi, M.; Devarajan, P.; Han, W.K.; Marcus, R.J.;
Parikh, C.R. IL-18 and Urinary NGAL Predict Dialysis and Graft Recovery after Kidney Transplantation.
J. Am. Soc. Nephrol. 2009, 21, 189–197. [CrossRef] [PubMed]
25. Jia, H.-M.; Huang, L.-F.; Zheng, Y.; Li, W.-X. Diagnostic value of urinary tissue inhibitor of metalloproteinase-2
and insulin-like growth factor binding protein 7 for acute kidney injury: A meta-analysis. Crit. Care 2017, 21.
[CrossRef]
26. Bargnoux, A.-S.; Piéroni, L.; Cristol, J.-P. Analytical study of a new turbidimetric assay for urinary neutrophil
gelatinase-associated lipocalin (NGAL) determination. Clin. Chem. Lab. Med. 2013, 51. [CrossRef]
27. Westhoff, J.H.; Tönshoff, B.; Waldherr, S.; Pöschl, J.; Teufel, U.; Westhoff, T.H.; Fichtner, A. Urinary Tissue
Inhibitor of Metalloproteinase-2 (TIMP-2) • Insulin-Like Growth Factor-Binding Protein 7 (IGFBP7) Predicts
Adverse Outcome in Pediatric Acute Kidney Injury. PLoS ONE 2015, 10, e0143628. [CrossRef]
28. Lima, C.; Macedo, E. Urinary Biochemistry in the Diagnosis of Acute Kidney Injury. Dis. Markers
2018, 2018, 4907024. [CrossRef]
29. Han, W.K.; Bailly, V.; Abichandani, R.; Thadhani, R.; Bonventre, J.V. Kidney Injury Molecule-1 (KIM-1):
A novel biomarker for human renal proximal tubule injury. Kidney Int. 2002, 62, 237–244. [CrossRef]
30. Ostermann, M.; Philips, B.J.; Forni, L.G. Clinical review: Biomarkers of acute kidney injury: Where are we
now? Crit. Care 2012, 16, 233. [CrossRef]
31. Kashani, K.; Cheungpasitporn, W.; Ronco, C. Biomarkers of acute kidney injury: The pathway from discovery
to clinical adoption. Clin. Chem. Lab. Med. 2017, 55, 1074–1089. [CrossRef] [PubMed]
32. Klein, S.J.; Brandtner, A.K.; Lehner, G.F.; Ulmer, H.; Bagshaw, S.M.; Wiedermann, C.J.; Joannidis, M.
Biomarkers for prediction of renal replacement therapy in acute kidney injury: A systematic review and
meta-analysis. Intensive Care Med. 2018, 44, 323–336. [CrossRef] [PubMed]
33. Vanmassenhove, J.; Vanholder, R.; Nagler, E.; Van Biesen, W. Urinary and serum biomarkers for the diagnosis
of acute kidney injury: An in-depth review of the literature*. Nephrol. Dial. Transplant. 2012, 28, 254–273.
[CrossRef]
34. Alge, J.L.; Arthur, J.M. Biomarkers of AKI: A Review of Mechanistic Relevance and Potential Therapeutic
Implications. Clin. J. Am. Soc. Nephrol. 2014, 10, 147–155. [CrossRef]
35. Thongprayoon,C.; Hansrivijit,P.; Kovvuru,K.; Kanduri,S.R.; Torres-Ortiz,A.; Acharya,P.; Gonzalez-Suarez,M.L.;
Kaewput, W.; Bathini, T.; Cheungpasitporn, W. Diagnostics, Risk Factors, Treatment and Outcomes of Acute
Kidney Injury in a New Paradigm. J. Clin. Med. 2020, 9, 1104. [CrossRef]
36. Ali, T.; Khan, I.; Simpson, W.; Prescott, G.; Townend, J.; Smith, W.; Macleod, A. Incidence and Outcomes in
Acute Kidney Injury: A Comprehensive Population-Based Study. J. Am. Soc. Nephrol. 2007, 18, 1292–1298.
[CrossRef]
37. Lameire, N.H.; Bagga, A.; Cruz, D.; De Maeseneer, J.; Endre, Z.; Kellum, J.A.; Liu, K.D.; Mehta, R.L.;
Pannu, N.; Van Biesen, W.; et al. Acute kidney injury: An increasing global concern. Lancet 2013, 382, 170–179.
[CrossRef]
38. Grams, M.E.; Sang, Y.; Ballew, S.H.; Gansevoort, R.T.; Kimm, H.; Kovesdy, C.P.; Naimark, D.; Oien, C.;
Smith, D.H.; Coresh, J.; et al. A Meta-analysis of the Association of Estimated GFR, Albuminuria, Age, Race,
and Sex With Acute Kidney Injury. Am. J. Kidney Dis. 2015, 66, 591–601. [CrossRef]
39. De Zan, F.; Amigoni, A.; Pozzato, R.; Pettenazzo, A.; Murer, L.; Vidal, E. Acute Kidney Injury in Critically Ill
Children: A Retrospective Analysis of Risk Factors. Blood Purif. 2020, 49, 1–7. [CrossRef]
40. Nie, S.; Tang, L.; Zhang, W.; Feng, Z.; Chen, X. Are There Modifiable Risk Factors to Improve AKI?
BioMed Res. Int. 2017, 2017, 5605634. [CrossRef]
41. Anderson, S.; Eldadah, B.; Halter, J.B.; Hazzard, W.R.; Himmelfarb, J.; Horne, F.M.; Kimmel, P.L.; Molitoris, B.A.;
Murthy, M.; O’Hare, A.M.; et al. Acute Kidney Injury in Older Adults. J. Am. Soc. Nephrol. 2011, 22, 28–38.
[CrossRef]
42. Chawla, L.S.; Eggers, P.W.; Star, R.A.; Kimmel, P.L. Acute Kidney Injury and Chronic Kidney Disease as
Interconnected Syndromes. N. Engl. J. Med. 2014, 371, 58–66. [CrossRef]
14. J. Clin. Med. 2020, 9, 1704 14 of 21
43. Yang, L. How Acute Kidney Injury Contributes to Renal Fibrosis. In Renal Fibrosis: Mechanisms and Therapies;
Springer: Singapore, 2019; pp. 117–142. [CrossRef]
44. Zhou, Q.; Zhao, C.; Xie, D.; Xu, D.; Bin, J.; Chen, P.; Liang, M.; Zhang, X.; Hou, F. Acute and acute-on-chronic
kidney injury of patients with decompensated heart failure: Impact on outcomes. BMC Nephrol. 2012, 13, 51.
[CrossRef]
45. Nie, S.; Feng, Z.; Xia, L.; Bai, J.; Xiao, F.; Liu, J.; Tang, L.; Chen, X. Risk factors of prognosis after acute kidney
injury in hospitalized patients. Front. Med. 2017, 11, 393–402. [CrossRef]
46. Kane-Gill, S.L.; Sileanu, F.E.; Murugan, R.; Trietley, G.S.; Handler, S.M.; Kellum, J.A. Risk Factors for Acute
Kidney Injury in Older Adults With Critical Illness: A Retrospective Cohort Study. Am. J. Kidney Dis.
2015, 65, 860–869. [CrossRef]
47. Gameiro, J.; Agapito Fonseca, J.; Jorge, S.; Lopes, J.A. Acute kidney injury in HIV-infected patients: A critical
review. HIV Med. 2019, 20. [CrossRef]
48. Wyatt, C.M.; Arons, R.R.; Klotman, P.E.; Klotman, M.E. Acute renal failure in hospitalized patients with HIV:
Risk factors and impact on in-hospital mortality. AIDS 2006, 20, 561–565. [CrossRef]
49. Hoste, E.A.; Bagshaw, S.M.; Bellomo, R.; Cely, C.M.; Colman, R.; Cruz, D.N.; Edipidis, K.; Forni, L.G.;
Gomersall, C.D.; Govil, D.; et al. Epidemiology of acute kidney injury in critically ill patients:
The multinational AKI-EPI study. Intensive Care Med. 2015, 41, 1411–1423. [CrossRef]
50. Ejaz, A.A.; Beaver, T.M.; Shimada, M.; Sood, P.; Lingegowda, V.; Schold, J.D.; Kim, T.; Johnson, R.J. Uric Acid:
A Novel Risk Factor for Acute Kidney Injury in High-Risk Cardiac Surgery Patients? Am. J. Nephrol. 2009, 30,
425–429. [CrossRef]
51. Ejaz, A.A.; Kambhampati, G.; Ejaz, N.I.; Dass, B.; Lapsia, V.; Arif, A.A.; Asmar, A.; Shimada, M.; Alsabbagh, M.M.;
Aiyer, R.; et al. Post-operative serum uric acid and acute kidney injury. J. Nephrol. 2012, 25, 497–505. [CrossRef]
52. Lapsia, V.; Johnson, R.J.; Dass, B.; Shimada, M.; Kambhampati, G.; Ejaz, N.I.; Arif, A.A.; Ejaz, A.A. Elevated
Uric Acid Increases the Risk for Acute Kidney Injury. Am. J. Med. 2012, 125, 302.e9–302.e17. [CrossRef]
53. Guo, W.; Liu, Y.; Chen, J.-Y.; Chen, S.Q.; Li, H.L.; Duan, C.Y.; Liu, H.Y.; Tan, N. Hyperuricemia Is an
Independent Predictor of Contrast-Induced Acute Kidney Injury and Mortality in Patients Undergoing
Percutaneous Coronary Intervention. Angiology 2015, 66, 721–726. [CrossRef]
54. Kellum, J.A.; Lameire, N. Diagnosis, evaluation, and management of acute kidney injury: A KDIGO summary
(Part 1). Crit. Care 2013, 17, 204. [CrossRef]
55. Ostermann, M.; Liu, K. Pathophysiology of AKI. Best Pract. Res. Clin. Anaesthesiol. 2017, 31, 305–314.
[CrossRef]
56. Case, J.; Khan, S.; Khalid, R.; Khan, A. Epidemiology of Acute Kidney Injury in the Intensive Care Unit.
Crit. Care Res. Pract. 2013, 2013, 479730. [CrossRef]
57. Uchino, S.; Kellum, J.A.; Bellomo, R.; Doig, G.S.; Morimatsu, H.; Morgera, S.; Schetz, M.; Tan, I.; Bouman, C.;
Macedo, E.; et al. Acute Renal Failure in Critically Ill Patients: A Multinational, Multicenter Study. JAMA
2005, 294, 813. [CrossRef]
58. Akcay, A.; Nguyen, Q.; Edelstein, C.L. Mediators of Inflammation in Acute Kidney Injury. Mediat. Inflamm.
2009, 2019, 137072. [CrossRef]
59. Basile, D.P.; Anderson, M.D.; Sutton, T.A. Pathophysiology of Acute Kidney Injury. In Comprehensive Physiology;
John Wiley Sons, Inc.: Hoboken, NJ, USA, 2012. [CrossRef]
60. Devarajan, P. Update on Mechanisms of Ischemic Acute Kidney Injury. J. Am. Soc. Nephrol. 2006, 17, 1503–1520.
[CrossRef]
61. Harty, J. Prevention and management of acute kidney injury. Ulster Med. J. 2014, 83, 149–157.
62. Moore, P.K.; Hsu, R.K.; Liu, K.D. Management of Acute Kidney Injury: Core Curriculum 2018. Am. J.
Kidney Dis. 2018, 72, 136–148. [CrossRef]
63. Ostermann, M.; Liu, K.; Kashani, K. Fluid Management in Acute Kidney Injury. Chest 2019, 156, 594–603.
[CrossRef]
64. Meersch, M.; Schmidt, C.; Hoffmeier, A.; Van Aken, H.; Wempe, C.; Gerss, J.; Zarbock, A. Prevention of
cardiac surgery-associated AKI by implementing the KDIGO guidelines in high risk patients identified by
biomarkers: The PrevAKI randomized controlled trial. Intensive Care Med. 2017, 43, 1551–1561. [CrossRef]
65. Bagshaw, S.M.; Lapinsky, S.; Dial, S.; Arabi, Y.; Dodek, P.; Wood, G.; Ellis, P.; Guzman, J.; Marshall, J.;
Parrillo, J.E.; et al. Acute kidney injury in septic shock: Clinical outcomes and impact of duration of
hypotension prior to initiation of antimicrobial therapy. Intensive Care Med. 2009, 35, 871–881. [CrossRef]
15. J. Clin. Med. 2020, 9, 1704 15 of 21
66. Bouchard, J.; Soroko, S.B.; Chertow, G.M.; Himmelfarb, J.; Ikizler, T.A.; Paganini, E.P.; Mehta, R.L. Program to
Improve Care in Acute Renal Disease (PICARD) Study Group. Fluid accumulation, survival and recovery of
kidney function in critically ill patients with acute kidney injury. Kidney Int. 2009, 76, 422–427. [CrossRef]
67. Wang, N.; Jiang, L.; Zhu, B.; Wen, Y.; Xi, X.-M. Fluid balance and mortality in critically ill patients with acute
kidney injury: A multicenter prospective epidemiological study. Crit. Care 2015, 19, 371. [CrossRef]
68. Vaara, S.T.; Korhonen, A.M.; Kaukonen, K.M.; Nisula, S.; Inkinen, O.; Hoppu, S.; Laurila, J.J.; Mildh, L.;
Reinikainen, M.; Lund, V.; et al. Fluid overload is associated with an increased risk for 90-day mortality in
critically ill patients with renal replacement therapy: Data from the prospective FINNAKI study. Crit. Care
2012, 16, R197. [CrossRef]
69. Bednarczyk, J.M.; Fridfinnson, J.A.; Kumar, A.; Blanchard, L.; Rabbani, R.; Bell, D.; Funk, D.; Turgeon, A.F.;
Abou-Setta, A.M.; Zarychanski, R. Incorporating Dynamic Assessment of Fluid Responsiveness Into
Goal-Directed Therapy. Crit. Care Med. 2017, 45, 1538–1545. [CrossRef]
70. Saugel, B.; Vincent, J.-L.; Wagner, J.Y. Personalized hemodynamic management. Curr. Opin. Crit. Care
2017, 23, 334–341. [CrossRef]
71. Varrier, M.; Ostermann, M. Fluid Composition and Clinical Effects. Crit. Care Clin. 2015, 31, 823–837.
[CrossRef]
72. Finfer, S.; Bellomo, R.; Boyce, N.; French, J.; Myburgh, J.; Norton, R. A Comparison of Albumin and Saline
for Fluid Resuscitation in the Intensive Care Unit. N. Engl. J. Med. 2004, 350, 2247–2256. [CrossRef]
73. Caironi, P.; Tognoni, G.; Masson, S.; Fumagalli, R.; Pesenti, A.; Romero, M.; Fanizza, C.; Caspani, L.; Faenza, S.;
Grasselli, G.; et al. Albumin Replacement in Patients with Severe Sepsis or Septic Shock. N. Engl. J. Med.
2014, 370, 1412–1421. [CrossRef]
74. The SAFE Study Investigators. Saline or Albumin for Fluid Resuscitation in Patients with Traumatic Brain
Injury. N. Engl. J. Med. 2007, 357, 874–884. [CrossRef]
75. Annane, D. Effects of Fluid Resuscitation With Colloids vs Crystalloids on Mortality in Critically Ill Patients
Presenting With Hypovolemic Shock. JAMA 2013, 310, 1809. [CrossRef]
76. Rhodes, A.; Evans, L.E.; Alhazzani, W.; Levy, M.M.; Antonelli, M.; Ferrer, R.; Kumar, A.; Sevransky, J.E.;
Sprung, C.L.; Nunnally, M.E.; et al. Surviving Sepsis Campaign: International Guidelines for Management
of Sepsis and Septic Shock: 2016. Intensive Care Med. 2017, 43, 304–377. [CrossRef]
77. Bayer, O.; Reinhart, K.; Kohl, M.; Kabisch, B.; Marshall, J.; Sakr, Y.; Bauer, M.; Hartog, C.; Schwarzkopf, D.;
Riedemann, N. Effects of fluid resuscitation with synthetic colloids or crystalloids alone on shock reversal,
fluid balance, and patient outcomes in patients with severe sepsis. Crit. Care Med. 2012, 40, 2543–2551.
[CrossRef]
78. Boyer, T.D.; Sanyal, A.J.; Wong, F.; Frederick, R.T.; Lake, J.R.; O’Leary, J.G.; Ganger, D.; Jamil, K.; Pappas, S.C.;
REVERSE Study Investigators. Terlipressin Plus Albumin Is More Effective Than Albumin Alone in
Improving Renal Function in Patients With Cirrhosis and Hepatorenal Syndrome Type 1. Gastroenterology
2016, 150, 1579–1589.e2. [CrossRef]
79. Lee, E.H.; Kim, W.J.; Kim, J.Y.; Chin, J.H.; Choi, D.K.; Sim, J.Y.; Choo, S.J.; Chung, C.H.; Lee, J.W.; Choi, I.C.
Effect of Exogenous Albumin on the Incidence of Postoperative Acute Kidney Injury in Patients Undergoing
Off-pump Coronary Artery Bypass Surgery with a Preoperative Albumin Level of Less Than 4.0 g/dl.
Anesthesiology 2016, 124, 1001–1011. [CrossRef]
80. Udeh, C.I.; You, J.; Wanek, M.R.; Dalton, J.; Udeh, B.L.; Demirjian, S.; Rahman, N.; Hata, J.S. Acute kidney
injury in postoperative shock: Is hyperoncotic albumin administration an unrecognized resuscitation risk
factor? Perioper Med. 2018, 7, 29. [CrossRef]
81. Schortgen, F.; Girou, E.; Deye, N.; Brochard, L. The risk associated with hyperoncotic colloids in patients
with shock. Intensive Care Med. 2008, 34, 2157–2168. [CrossRef]
82. Myburgh, J.A.; Finfer, S.; Bellomo, R.; Billot, L.; Cass, A.; Gattas, D.; Glass, P.; Lipman, J.; Liu, B.;
McArthur, C.; et al. Hydroxyethyl Starch or Saline for Fluid Resuscitation in Intensive Care. N. Engl. J. Med.
2012, 367, 1901–1911. [CrossRef]
83. Perner, A.; Haase, N.; Guttormsen, A.B.; Tenhunen, J.; Klemenzson, G.; Åneman, A.; Madsen, K.R.; Møller, M.H.;
Elkjær, J.M.; Poulsen, L.M.; et al. Hydroxyethyl Starch 130/0.42 versus Ringer’s Acetate in Severe Sepsis. N. Engl.
J. Med. 2012, 367, 124–134. [CrossRef]
16. J. Clin. Med. 2020, 9, 1704 16 of 21
84. Moeller, C.; Fleischmann, C.; Thomas-Rueddel, D.; Vlasakov, V.; Rochwerg, B.; Theurer, P.; Gattinoni, L.;
Reinhart, K.; Hartog, C.S. How safe is gelatin? A systematic review and meta-analysis of gelatin-containing
plasma expanders vs crystalloids and albumin. J. Crit. Care 2016, 35, 75–83. [CrossRef]
85. Semler, M.W.; Self, W.H.; Wanderer, J.P.; Ehrenfeld, J.M.; Wang, L.; Byrne, D.W.; Stollings, J.L.; Kumar, A.B.;
Hughes, C.G.; Hernandez, A.; et al. Balanced Crystalloids versus Saline in Critically Ill Adults. N. Engl.
J. Med. 2018, 378, 829–839. [CrossRef]
86. McCluskey, S.A.; Karkouti, K.; Wijeysundera, D.; Minkovich, L.; Tait, G.; Beattie, W.S. Hyperchloremia After
Noncardiac Surgery Is Independently Associated with Increased Morbidity and Mortality. Anesth Analg.
2013, 117, 412–421. [CrossRef]
87. Chowdhury, A.H.; Cox, E.F.; Francis, S.T.; Lobo, D.N. A Randomized, Controlled, Double-Blind Crossover
Study on the Effects of 2-L Infusions of 0.9% Saline and Plasma-Lyte® 148 on Renal Blood Flow Velocity and
Renal Cortical Tissue Perfusion in Healthy Volunteers. Ann. Surg. 2012, 256, 18–24. [CrossRef]
88. Yunos, N.M.; Bellomo, R.; Hegarty, C.; Story, D.; Ho, L.; Bailey, M. Association Between a Chloride-Liberal vs
Chloride-Restrictive Intravenous Fluid Administration Strategy and Kidney Injury in Critically Ill Adults.
JAMA 2012, 308, 1566. [CrossRef]
89. Raghunathan, K.; Shaw, A.; Nathanson, B.; Stürmer, T.; Brookhart, A.; Stefan, M.S.; Setoguchi, S.; Beadles, C.;
Lindenauer, P.K. Association Between the Choice of IV Crystalloid and In-Hospital Mortality Among
Critically Ill Adults With Sepsis*. Crit. Care Med. 2014, 42, 1585–1591. [CrossRef]
90. Reddy, S.K.; Bailey, M.J.; Beasley, R.W.; Bellomo, R.; Mackle, D.M.; Psirides, A.J.; Young, P.J. Effect of 0.9%
Saline or Plasma-Lyte 148 as Crystalloid Fluid Therapy in the Intensive Care Unit on Blood Product Use and
Postoperative Bleeding After Cardiac Surgery. J. Cardiothorac. Vasc. Anesth. 2017, 31, 1630–1638. [CrossRef]
91. Young, P.; Bailey, M.; Beasley, R.; Henderson, S.; Mackle, D.; McArthur, C.; McGuinness, S.; Mehrtens, J.;
Myburgh, J.; Psirides, A.; et al. Effect of a Buffered Crystalloid Solution vs Saline on Acute Kidney Injury
Among Patients in the Intensive Care Unit. JAMA 2015, 314, 1701. [CrossRef]
92. Self, W.H.; Semler, M.W.; Wanderer, J.P.; Wang, L.; Byrne, D.W.; Collins, S.P.; Slovis, C.M.; Lindsell, C.J.;
Ehrenfeld, J.M.; Siew, E.D.; et al. Balanced Crystalloids versus Saline in Noncritically Ill Adults. N. Engl.
J. Med. 2018, 378, 819–828. [CrossRef]
93. Sen, A.; Keener, C.M.; Sileanu, F.E.; Foldes, E.; Clermont, G.; Murugan, R.; Kellum, J.A. Chloride Content of
Fluids Used for Large-Volume Resuscitation Is Associated With Reduced Survival. Crit. Care Med. 2017, 45,
e146–e153. [CrossRef] [PubMed]
94. Asfar, P.; Meziani, F.; Hamel, J.F.; Grelon, F.; Megarbane, B.; Anguel, N.; Mira, J.P.; Dequin, P.F.; Gergaud, S.;
Weiss, N.; et al. High versus Low Blood-Pressure Target in Patients with Septic Shock. N. Engl. J. Med.
2014, 370, 1583–1593. [CrossRef] [PubMed]
95. Kato, R.; Pinsky, M.R. Personalizing blood pressure management in septic shock. Ann. Intensive Care 2015, 5, 41.
[CrossRef] [PubMed]
96. Futier, E.; Lefrant, J.Y.; Guinot, P.G.; Godet, T.; Lorne, E.; Cuvillon, P.; Bertran, S.; Leone, M.; Pastene, B.;
Piriou, V.; et al. Effect of Individualized vs Standard Blood Pressure Management Strategies on Postoperative
Organ Dysfunction Among High-Risk Patients Undergoing Major Surgery. JAMA 2017, 318, 1346. [CrossRef]
97. De Backer, D.; Biston, P.; Devriendt, J.; Madl, C.; Chochrad, D.; Aldecoa, C.; Brasseur, A.; Defrance, P.;
Gottignies, P.; Vincent, J.L.; et al. Comparison of Dopamine and Norepinephrine in the Treatment of Shock.
N. Engl. J. Med. 2010, 362, 779–789. [CrossRef]
98. Hernández, G.; Teboul, J.-L.; Bakker, J. Norepinephrine in septic shock. Intensive Care Med. 2019, 45, 687–689.
[CrossRef]
99. Leone, M.; Albanèse, J.; Delmas, A.; Chaabane, W.; Garnier, F.; Martin, C. TERLIPRESSIN IN
CATECHOLAMINE-RESISTANT SEPTIC SHOCK PATIENTS. Shock 2004, 22, 314–319. [CrossRef]
100. Albanèse, J.; Leone, M.; Delmas, A.; Martin, C. Terlipressin or norepinephrine in hyperdynamic septic shock:
A prospective, randomized study*. Crit. Care Med. 2005, 33, 1897–1902. [CrossRef]
101. Gordon, A.C.; Mason, A.J.; Thirunavukkarasu, N.; Perkins, G.D.; Cecconi, M.; Cepkova, M.; Pogson, D.G.;
Aya, H.D.; Anjum, A.; Frazier, G.J.; et al. Effect of Early Vasopressin vs Norepinephrine on Kidney Failure in
Patients With Septic Shock. JAMA 2016, 316, 509. [CrossRef]
17. J. Clin. Med. 2020, 9, 1704 17 of 21
102. Russell, J.A.; Walley, K.R.; Singer, J.; Gordon, A.C.; Hébert, P.C.; Cooper, D.J.; Holmes, C.L.; Mehta, S.;
Granton, J.T.; Storms, M.M.; et al. Vasopressin versus Norepinephrine Infusion in Patients with Septic Shock.
N. Engl. J. Med. 2008, 358, 877–887. [CrossRef]
103. Tumlin, J.A.; Murugan, R.; Deane, A.M.; Ostermann, M.; Busse, L.W.; Ham, K.R.; Kashani, K.; Szerlip, H.M.;
Prowle, J.R.; Bihorac, A.; et al. Outcomes in Patients with Vasodilatory Shock and Renal Replacement
Therapy Treated with Intravenous Angiotensin II. Crit. Care Med. 2018, 46, 949–957. [CrossRef] [PubMed]
104. Denton, M.D.; Chertow, G.M.; Brady, H.R. “Renal-dose” dopamine for the treatment of acute renal failure:
Scientific rationale, experimental studies and clinical trials. Kidney Int. 1996, 50, 4–14. [CrossRef] [PubMed]
105. Friedrich, J.O.; Adhikari, N.; Herridge, M.S.; Beyene, J. Meta-Analysis: Low-Dose Dopamine Increases Urine
Output but Does Not Prevent Renal Dysfunction or Death. Ann. Intern Med. 2005, 142, 510. [CrossRef]
[PubMed]
106. Lauschke, A.; Teichgräber, U.K.M.; Frei, U.; Eckardt, K.-U. ‘Low-dose’ dopamine worsens renal perfusion in
patients with acute renal failure. Kidney Int. 2006, 69, 1669–1674. [CrossRef] [PubMed]
107. Schenarts, P.J.; Sagraves, S.G.; Bard, M.R.; Toschlog, E.; Coettler, C.; Newell, M.; Rotondo, M. Low-Dose
Dopamine: A Physiologically Based Review. Curr. Surg. 2006, 63, 219–225. [CrossRef]
108. Mathur, V.S.; Swan, S.K.; Lambrecht, L.J.; Anjum, S.; Fellmann, J.; McGuire, D.; Epstein, M.; Luther, R.R.
The effects of fenoldopam, a selective dopamine receptor agonist, on systemic and renal hemodynamics in
normotensive subjects. Crit. Care Med. 1999, 27, 1832–1837. [CrossRef]
109. Landoni, G.; Biondi-Zoccai, G.G.L.; Tumlin, J.A.; Bov, T.; Luca, M.; Calabro, M.G.; Ranucci, M.; Zangrillo, A.
Beneficial Impact of Fenoldopam in Critically Ill Patients with or at Risk for Acute Renal Failure:
A Meta-Analysis of Randomized Clinical Trials. Am. J. Kidney Dis. 2007, 49, 56–68. [CrossRef]
110. Stone, G.W.; McCullough, P.A.; Tumlin, J.A.; Lepor, N.E.; Madyoon, H.; Murray, P.; Wang, A.; Chu, A.A.;
Schaer, G.L.; Stevens, M.; et al. Fenoldopam Mesylate for the Prevention of Contrast-Induced Nephropathy.
JAMA 2003, 290, 2284. [CrossRef]
111. Allaqaband, S.; Tumuluri, R.; Malik, A.M.; Gupta, A.; Volkert, P.; Shalev, Y.; Bajwa, T. Prospective randomized
study of N-acetylcysteine, fenoldopam, and saline for prevention of radiocontrast-induced nephropathy.
Catheter. Cardiovasc. Interv. 2002, 57, 279–283. [CrossRef]
112. Nigwekar, S.U.; Waikar, S.S. Diuretics in Acute Kidney Injury. Semin. Nephrol. 2011, 31, 523–534. [CrossRef]
113. Ho, K.M. Meta-analysis of frusemide to prevent or treat acute renal failure. BMJ 2006, 333, 420. [CrossRef]
[PubMed]
114. Ho, K.M.; Power, B.M. Benefits and risks of furosemide in acute kidney injury. Anaesthesia 2010, 65, 283–293.
[CrossRef]
115. Uchino, S.; Doig, G.; Bellomo, R.; Morimatsu, H.; Morgera, S.; Schetz, M.; Tan, I.; Bouman, C.; Macedo, E.;
Gibney, N.; et al. Diuretics and mortality in acute renal failure*. Crit. Care Med. 2004, 32, 1669–1677.
[CrossRef]
116. Mehta, R.L. Diuretics, Mortality, and Nonrecovery of Renal Function in Acute Renal Failure. JAMA
2002, 288, 2547. [CrossRef] [PubMed]
117. Perazella, M.A. Drug use and nephrotoxicity in the intensive care unit. Kidney Int. 2012, 81, 1172–1178.
[CrossRef] [PubMed]
118. Morales-Alvarez, M.C. Nephrotoxicity of Antimicrobials and Antibiotics. Adv. Chronic. Kidney Dis. 2020, 27,
31–37. [CrossRef]
119. Pannu, N.; Nadim, M.K. An overview of drug-induced acute kidney injury. Crit. Care Med. 2008, 36,
S216–S223. [CrossRef]
120. Perazella, M.A. Renal Vulnerability to Drug Toxicity. Clin. J. Am. Soc. Nephrol. 2009, 4, 1275–1283. [CrossRef]
121. Nolin, T.D.; Himmelfarb, J. Mechanisms of Drug-Induced Nephrotoxicity. In Adverse Drug Reactions; Springer:
Berlin/Heidelberg, Germany, 2010; pp. 111–130. [CrossRef]
122. Perazella, M.A.; Markowitz, G.S. Drug-induced acute interstitial nephritis. Nat. Rev. Nephrol. 2010, 6, 461–470.
[CrossRef]
123. Hausenloy, D.J.; Yellon, D.M. Remote ischaemic preconditioning: Underlying mechanisms and clinical
application. Cardiovasc. Res. 2008, 79, 377–386. [CrossRef]
18. J. Clin. Med. 2020, 9, 1704 18 of 21
124. Menting, T.P.; Wever, K.E.; Hendriks, E.J.; Van der Vliet, D.J.; Rovers, M.M.; Warle, M.C.
Ischaemic preconditioning for the reduction of renal ischaemia reperfusion injury. In Cochrane Database of
Systematic Reviews; Menting, T.P., Ed.; John Wiley Sons, Ltd.: Chichester, UK, 2013. [CrossRef]
125. Ghaemian, A.; Yazdani, J.; Azizi, S.; Farsavian, A.A.; Nabati, M.; Malekrah, A.; Dabirian, M.; Espahbodi, F.;
Mirjani, B.; Mohsenipouya, H.; et al. Remote Ischemic Preconditioning To Reduce Contrast-Induced
Nephropathy: A Randomized Controlled Trial. Eur. J. Vasc. Endovasc. Surg. 2015, 50, 527–532. [CrossRef]
126. Zarbock, A.; Schmidt, C.; Van Aken, H.; Wempe, C.; Martens, S.; Zahn, P.K.; Wolf, B.; Goebel, U.; Schwer, C.I.;
Rosenberger, P.; et al. Effect of Remote Ischemic Preconditioning on Kidney Injury Among High-Risk Patients
Undergoing Cardiac Surgery. JAMA 2015, 313, 2133. [CrossRef] [PubMed]
127. Huang, J.; Chen, Y.; Dong, B.; Kong, W.; Zhang, J.; Xue, W.; Liu, D.; Huang, Y. Effect of remote ischaemic
preconditioning on renal protection in patients undergoing laparoscopic partial nephrectomy: A ‘blinded’
randomised controlled trial. BJU Int. 2013, 112, 74–80. [CrossRef] [PubMed]
128. Hu, J.; Liu, S.; Jia, P.; Xu, X.; Song, N.; Zhang, T.; Chen, R.; Ding, X. Protection of remote ischemic
preconditioning against acute kidney injury: A systematic review and meta-analysis. Crit. Care 2016, 20, 111.
[CrossRef] [PubMed]
129. Nieminen, M.S.; Pollesello, P.; Vajda, G.; Papp, Z. Effects of Levosimendan on the Energy Balance:
Preclinical and Clinical Evidence. J. Cardiovasc. Pharmacol. 2009, 53, 302–310. [CrossRef]
130. Faisal, S.A.; Apatov, D.A.; Ramakrishna, H.; Weiner, M.M. Levosimendan in Cardiac Surgery: Evaluating the
Evidence. J. Cardiothorac. Vasc. Anesth. 2019, 33, 1146–1158. [CrossRef]
131. Zhou, C.; Gong, J.; Chen, D.; Wang, W.; Liu, M.; Liu, B. Levosimendan for Prevention of Acute Kidney
Injury after Cardiac Surgery: A Meta-analysis of Randomized Controlled Trials. Am. J. Kidney Dis. 2016, 67,
408–416. [CrossRef] [PubMed]
132. Ramachandran, G.; Tulapurkar, M.E.; Harris, K.M.; Arad, G.; Shirvan, A.; Shemesh, R.; Detolla, L.J.;
Benazzi, C.; Opal, S.M.; Kaempfer, R.; et al. A Peptide Antagonist of CD28 Signaling Attenuates Toxic Shock
and Necrotizing Soft-Tissue Infection Induced by Streptococcus pyogenes. J. Infect. Dis. 2013, 207, 1869–1877.
[CrossRef] [PubMed]
133. Bulger, E.M.; Maier, R.V.; Sperry, J.; Joshi, M.; Henry, S.; Moore, F.A.; Moldawer, L.L.; Demetriades, D.;
Talving, P.; Schreiber, M.; et al. A Novel Drug for Treatment of Necrotizing Soft-Tissue Infections. JAMA
Surg. 2014, 149, 528. [CrossRef] [PubMed]
134. Holick, M.F. Vitamin D Deficiency. N. Engl. J. Med. 2007, 357, 266–281. [CrossRef] [PubMed]
135. Amrein, K.; Christopher, K.B.; McNally, J.D. Understanding vitamin D deficiency in intensive care patients.
Intensive Care Med. 2015, 41, 1961–1964. [CrossRef] [PubMed]
136. De Haan, K.; Groeneveld, A.J.; de Geus, H.R.; Egal, M.; Struijs, A. Vitamin D deficiency as a risk factor for
infection, sepsis and mortality in the critically ill: Systematic review and meta-analysis. Crit. Care 2014, 18, 660.
[CrossRef]
137. Ala-Kokko, T.I.; Mutt, S.J.; Nisula, S.; Koskenkari, J.; Liisanantti, J.; Ohtonen, P.; Poukkanen, M.; Laurila, J.J.;
Pettilä, V.; Herzig, K.H.; et al. Vitamin D deficiency at admission is not associated with 90-day mortality in
patients with severe sepsis or septic shock: Observational FINNAKI cohort study. Ann. Med. 2016, 48, 67–75.
[CrossRef]
138. Wolf, M.; Betancourt, J.; Chang, Y.; Shah, A.; Teng, M.; Tamez, H.; Gutierrez, O.; Camargo, C.A., Jr.;
Melamed, M.; Norris, K.; et al. Impact of Activated Vitamin D and Race on Survival among Hemodialysis
Patients. J. Am. Soc. Nephrol. 2008, 19, 1379–1388. [CrossRef]
139. Lai, L.; Qian, J.; Yang, Y.; Xie, Q.; You, H.; Zhou, Y.; Ma, S.; Hao, C.; Gu, Y.; Ding, F. Is the Serum Vitamin D
Level at the Time of Hospital-Acquired Acute Kidney Injury Diagnosis Associated with Prognosis? PLoS ONE
2013, 8, e64964. [CrossRef] [PubMed]
140. Cameron, L.K.; Lei, K.; Smith, S.; Doyle, N.L.; Doyle, J.F.; Flynn, K.; Purchase, N.; Smith, J.; Chan, K.;
Kamara, F.; et al. Vitamin D levels in critically ill patients with acute kidney injury: A protocol for a prospective
cohort study (VID-AKI). BMJ Open 2017, 7, e016486. [CrossRef]
141. Peters, E.; Masereeuw, R.; Pickkers, P. The Potential of Alkaline Phosphatase as a Treatment for
Sepsis-Associated Acute Kidney Injury. Nephron Clin. Pract. 2014, 127, 144–148. [CrossRef]
142. Peters, E.; Geraci, S.; Heemskerk, S.; Wilmer, M.J.; Bilos, A.; Kraenzlin, B.; Gretz, N.; Pickkers, P.; Masereeuw, R.
Alkaline phosphatase protects against renal inflammation through dephosphorylation of lipopolysaccharide
and adenosine triphosphate. Br. J. Pharmacol. 2015, 172, 4932–4945. [CrossRef]
19. J. Clin. Med. 2020, 9, 1704 19 of 21
143. Peters, E.; Heemskerk, S.; Masereeuw, R.; Pickkers, P. Alkaline Phosphatase: A Possible Treatment for
Sepsis-Associated Acute Kidney Injury in Critically Ill Patients. Am. J. Kidney Dis. 2014, 63, 1038–1048.
[CrossRef]
144. Pickkers, P.; Heemskerk, S.; Schouten, J.; Laterre, P.F.; Vincent, J.L.; Beishuizen, A.; Jorens, P.G.; Spapen, H.;
Bulitta, M.; Peters, W.H.; et al. Alkaline phosphatase for treatment of sepsis-induced acute kidney injury:
A prospective randomized double-blind placebo-controlled trial. Crit. Care 2012, 16, R14. [CrossRef]
145. Molitoris, B.A.; Dagher, P.C.; Sandoval, R.M.; Campos, S.B.; Ashush, H.; Fridman, E.; Brafman, A.; Faerman, A.;
Atkinson, S.J.; Thompson, J.D.; et al. siRNA Targeted to p53 Attenuates Ischemic and Cisplatin-Induced
Acute Kidney Injury. J. Am. Soc. Nephrol. 2009, 20, 1754–1764. [CrossRef] [PubMed]
146. Demirjian, S.; Ailawadi, G.; Polinsky, M.; Bitran, D.; Silberman, S.; Shernan, S.K.; Burnier, M.; Hamilton, M.;
Squiers, E.; Erlich, S.; et al. Safety and Tolerability Study of an Intravenously Administered Small Interfering
Ribonucleic Acid (siRNA) Post On-Pump Cardiothoracic Surgery in Patients at Risk of Acute Kidney Injury.
Kidney Int. Rep. 2017, 2, 836–843. [CrossRef] [PubMed]
147. Bagshaw, S.M.; Wald, R. Strategies for the optimal timing to start renal replacement therapy in critically ill
patients with acute kidney injury. Kidney Int. 2017, 91, 1022–1032. [CrossRef] [PubMed]
148. Ostermann, M.; Joannidis, M.; Pani, A.; Floris, M.; De Rosa, S.; Kellum, J.A.; Ronco, C. 17th Acute Disease
Quality Initiative (ADQI) Consensus Group. Patient Selection and Timing of Continuous Renal Replacement
Therapy. Blood Purif. 2016, 42, 224–237. [CrossRef] [PubMed]
149. Wang, A.Y.; Bellomo, R. Renal replacement therapy in the ICU. Curr. Opin. Crit. Care 2018, 24, 437–442.
[CrossRef] [PubMed]
150. Wald, R.; Shariff, S.Z.; Adhikari, N.K.; Bagshaw, S.M.; Burns, K.E.; Friedrich, J.O.; Garg, A.X.; Harel, Z.;
Kitchlu, A.; Ray, J.G. The Association Between Renal Replacement Therapy Modality and Long-Term
Outcomes Among Critically Ill Adults With Acute Kidney Injury. Crit. Care Med. 2014, 42, 868–877.
[CrossRef] [PubMed]
151. Liang, K.V.; Sileanu, F.E.; Clermont, G.; Murugan, R.; Pike, F.; Palevsky, P.M.; Kellum, J.A. Modality of
RRT and Recovery of Kidney Function after AKI in Patients Surviving to Hospital Discharge. Clin. J. Am.
Soc. Nephrol. 2016, 11, 30–38. [CrossRef]
152. Bagshaw, S.M.; Wald, R. Indications and Timing of Continuous Renal Replacement Therapy Application.
In 40 Years of Continuous Renal Replacement Therapy; Karger Publishers: Basel, Switzerland, 2018; pp. 25–37.
[CrossRef]
153. Clark, E.; Wald, R.; Levin, A.; Bouchard, J.; Adhikari, N.K.; Hladunewich, M.; Richardson, R.M.; James, M.T.;
Walsh, M.W.; House, A.A.; et al. Timing the initiation of renal replacement therapy for acute kidney injury in
Canadian intensive care units: A multicentre observational study. Can. J. Anesth./J. Can. d’anesthésie 2012, 59,
861–870. [CrossRef]
154. Karvellas, C.J.; Farhat, M.R.; Sajjad, I.; Mogensen, S.S.; Leung, A.A.; Wald, R.; Bagshaw, S.M. A comparison
of early versus late initiation of renal replacement therapy in critically ill patients with acute kidney injury:
A systematic review and meta-analysis. Crit. Care 2011, 15, R72. [CrossRef]
155. Clec’h,C.; Darmon,M.; Lautrette,A.; Chemouni,F.; Azoulay,E.; Schwebel,C.; Dumenil,A.S.; Garrouste-Orgeas,M.;
Goldgran-Toledano, D.; Cohen, Y.; et al. Efficacy of renal replacement therapy in critically ill patients: A propensity
analysis. Crit. Care 2012, 16, R236. [CrossRef]
156. Elseviers, M.M.; Lins, R.L.; Van der Niepen, P.; Hoste, E.; Malbrain, M.L.; Damas, P.; Devriendt, J.
SHARF investigators. Renal replacement therapy is an independent risk factor for mortality in critically ill
patients with acute kidney injury. Crit. Care 2010, 14, R221. [CrossRef] [PubMed]
157. Zarbock, A.; Kellum, J.A.; Schmidt, C.; Van Aken, H.; Wempe, C.; Pavenstädt, H.; Boanta, A.; Gerß, J.;
Meersch, M. Effect of Early vs Delayed Initiation of Renal Replacement Therapy on Mortality in Critically Ill
Patients With Acute Kidney Injury. JAMA 2016, 315, 2190. [CrossRef]
158. Gaudry, S.; Hajage, D.; Schortgen, F.; Martin-Lefevre, L.; Pons, B.; Boulet, E.; Boyer, A.; Chevrel, G.; Lerolle, N.;
Carpentier, D.; et al. Initiation Strategies for Renal-Replacement Therapy in the Intensive Care Unit. N. Engl.
J. Med. 2016, 375, 122–133. [CrossRef]
159. Barbar, S.D.; Clere-Jehl, R.; Bourredjem, A.; Hernu, R.; Montini, F.; Bruyère, R.; Lebert, C.; Bohé, J.; Badie, J.;
Eraldi, J.P.; et al. Timing of Renal-Replacement Therapy in Patients with Acute Kidney Injury and Sepsis.
N. Engl. J. Med. 2018, 379, 1431–1442. [CrossRef] [PubMed]
20. J. Clin. Med. 2020, 9, 1704 20 of 21
160. STARRT-AKI Investigators. STandard versus Accelerated initiation of Renal Replacement Therapy in Acute
Kidney Injury: Study Protocol for a Multi-National, Multi-Center, Randomized Controlled Trial. Can. J.
Kidney Health Dis. 2019, 6, 205435811985293. [CrossRef] [PubMed]
161. Gaudry, S.; Hajage, D.; Martin-Lefevre, L.; Louis, G.; Moschietto, S.; Titeca-Beauport, D.; La Combe, B.;
Pons, B.; de Prost, N.; Besset, S.; et al. The Artificial Kidney Initiation in Kidney Injury 2 (AKIKI2):
Study protocol for a randomized controlled trial. Trials 2019, 20, 726. [CrossRef]
162. Combes, A.; Bréchot, N.; Amour, J.; Cozic, N.; Lebreton, G.; Guidon, C.; Zogheib, E.; Thiranos, J.C.; Rigal, J.C.;
Bastien, O.; et al. Early High-Volume Hemofiltration versus Standard Care for Post–Cardiac Surgery
Shock. The HEROICS Study. Am. J. Respir. Crit. Care Med. 2015, 192, 1179–1190. [CrossRef]
163. Karakala, N.; Tolwani, A.J. Timing of Renal Replacement Therapy for Acute Kidney Injury. J. Intensive
Care Med. 2019, 34, 94–103. [CrossRef]
164. Srisawat, N.; Sileanu, F.E.; Murugan, R.; Bellomod, R.; Calzavacca, P.; Cartin-Ceba, R.; Cruz, D.; Finn, J.;
Hoste, E.E.; Kashani, K.; et al. Variation in Risk and Mortality of Acute Kidney Injury in Critically Ill Patients:
A Multicenter Study. Am. J. Nephrol. 2015, 41, 81–88. [CrossRef]
165. Park, S.; Cho, H.; Park, S.; Lee, S.; Kim, K.; Yoon, H.J.; Park, J.; Choi, Y.; Lee, S.; Kim, J.H.; et al.
Simple Postoperative AKI Risk (SPARK) Classification before Noncardiac Surgery: A Prediction Index
Development Study with External Validation. J. Am. Soc. Nephrol. 2019, 30, 170–181. [CrossRef]
166. Bedford, M.; Stevens, P.; Coulton, S.; Billings, J.; Farr, M.; Wheeler, T.; Kalli, M.; Mottishaw, T.; Farmer, C.
Development of risk models for the prediction of new or worsening acute kidney injury on or during hospital
admission: A cohort and nested study. Health Serv. Deliv. Res. 2016, 4, 1–160. [CrossRef]
167. Kashani, K.; Rosner, M.H.; Haase, M.; Lewington, A.J.P.; O’Donoghue, D.J.; Wilson, F.P.; Nadim, M.K.;
Silver, S.A.; Zarbock, A.; Ostermann, M.; et al. Quality Improvement Goals for Acute Kidney Injury. Clin. J.
Am. Soc. Nephrol. 2019, 14, 941–953. [CrossRef] [PubMed]
168. Jha, V.; Parameswaran, S. Community-acquired acute kidney injury in tropical countries. Nat. Rev. Nephrol.
2013, 9, 278–290. [CrossRef] [PubMed]
169. Sawhney, S.; Fluck, N.; Fraser, S.D.; Marks, A.; Prescott, G.J.; Roderick, P.J.; Black, C. KDIGO-based acute
kidney injury criteria operate differently in hospitals and the community—Findings from a large population
cohort. Nephrol. Dial. Transplant. 2016, 31, 922–929. [CrossRef] [PubMed]
170. Wang, Y.; Wang, J.; Su, T.; Qu, Z.; Zhao, M.; Yang, L. ISN AKF 0by25 China Consortium. Community-Acquired
Acute Kidney Injury: A Nationwide Survey in China. Am. J. Kidney Dis. 2017, 69, 647–657. [CrossRef]
171. Emmett, L.; Tollitt, J.; McCorkindale, S.; Sinha, S.; Poulikakos, D. The Evidence of Acute Kidney Injury in the
Community and for Primary Care Interventions. Nephron 2017, 136, 202–210. [CrossRef]
172. Malhotra, R.; Kashani, K.B.; Macedo, E.; Kim, J.; Bouchard, J.; Wynn, S.; Li, G.; Ohno-Machado, L.; Mehta, R.
A risk prediction score for acute kidney injury in the intensive care unit. Nephrol. Dial. Transplant. 2017, 32,
814–822. [CrossRef]
173. Göcze, I.; Jauch, D.; Götz, M.; Kennedy, P.; Jung, B.; Zeman, F.; Gnewuch, C.; Graf, B.M.; Gnann, W.;
Banas, B.; et al. Biomarker-guided Intervention to Prevent Acute Kidney Injury After Major Surgery.
Ann. Surg. 2018, 267, 1013–1020. [CrossRef]
174. Joannidis, M.; Druml, W.; Forni, L.G.; Groeneveld, A.B.J.; Honore, P.M.; Hoste, E.; Ostermann, M.;
Oudemans-van Straaten, H.M.; Schetz, M. Prevention of acute kidney injury and protection of renal
function in the intensive care unit: Update 2017. Intensive Care Med. 2017, 43, 730–749. [CrossRef]
175. Hodgson, L.E.; Selby, N.; Huang, T.-M.; Forni, L.G. The Role of Risk Prediction Models in Prevention and
Management of AKI. Semin. Nephrol. 2019, 39, 421–430. [CrossRef]
176. Karsanji, D.J.; Pannu, N.; Manns, B.J.; Hemmelgarn, B.R.; Tan, Z.; Jindal, K.; Scott-Douglas, N.; James, M.T.
Disparity between Nephrologists’ Opinions and Contemporary Practices for Community Follow-Up after
AKI Hospitalization. Clin. J. Am. Soc. Nephrol. 2017, 12, 1753–1761. [CrossRef] [PubMed]
177. Silver, S.A.; Siew, E.D. Follow-up Care in Acute Kidney Injury: Lost in Transition. Adv. Chronic Kidney Dis.
2017, 24, 246–252. [CrossRef] [PubMed]
178. Saran, R.; Li, Y.; Robinson, B.; Abbott, K.C.; Agodoa, L.Y.; Ayanian, J.; Bragg-Gresham, J.; Balkrishnan, R.;
Chen, J.L.; Cope, E.; et al. US Renal Data System 2015 Annual Data Report: Epidemiology of Kidney Disease
in the United States. Am. J. Kidney Dis. 2016, 67, A7–A8. [CrossRef] [PubMed]