This study examined the association between cystatin C levels and mortality risk in a cohort of 3075 elderly adults aged 70-79 years over 6 years of follow up. The researchers found:
1) Higher cystatin C levels were strongly associated with higher mortality risk, even after adjusting for demographic and health factors. Each increasing quintile of cystatin C showed higher mortality hazards.
2) Creatinine levels were not significantly associated with mortality after adjusting for other factors.
3) The association between cystatin C and mortality did not differ by gender or race. Cystatin C was associated with cardiovascular and non-cardiovascular mortality but not cancer mortality.
4) Cystatin C
Cystatin C - Early Risk Assessment of Renal Impairment MAY18Randox Reagents
Cystatin C is a small (13 kDa) cysteine proteinase inhibitor, produced by all nucleated cells at a constant rate. Cystatin C travels through the bloodstream to the kidneys where it is freely filtered by the glomerular membrane, resorbed and fully catabolised by the proximal renal tubes. Consequently, Cystatin C is the ideal biomarker of GFR function.
Cystatin-C is a protein produced by all nucleated cells and filtered out of the bloodstream by healthy kidneys. It is a more sensitive marker of kidney function than creatinine, as its levels rise earlier when glomerular filtration rate decreases. Measurement of cystatin-C can help detect chronic kidney disease at an earlier stage than creatinine. The document discusses the history, molecular biology, structure, role in medicine, prevalence, and stages of chronic kidney disease, highlighting how cystatin-C can be a useful marker for detecting and monitoring kidney function and disease.
Cystatin C is a small protein produced by all nucleated cells at a constant rate and freely filtered by the kidneys without reabsorption. It is an accurate marker for glomerular filtration rate and early kidney dysfunction. The document discusses the history, molecular biology, production, and fate of cystatin C in the body. It also covers the use of cystatin C to estimate kidney function and its role as a prognostic marker for cardiovascular disease and mortality.
The EVOLVE trial studied the effect of cinacalcet on cardiovascular disease in patients undergoing dialysis. The randomized controlled trial compared cinacalcet to placebo in 3,883 adults on dialysis to evaluate the primary composite endpoint of time to death or first nonfatal cardiovascular event. Secondary endpoints included time to individual components of the primary endpoint like myocardial infarction or fracture, as well as death from cardiovascular causes. The trial was designed to test the hypothesis that cinacalcet treatment might reduce mortality and cardiovascular risks by decreasing levels of phosphorus, PTH, and calcium phosphorus product known to be associated with higher mortality in dialysis patients.
This document discusses the physiology and clinical management of PTH and mineral metabolism disorders in patients with chronic kidney disease (CKD). It provides an overview of calcium, phosphorus, vitamin D, and PTH regulation and how their homeostasis is disrupted in CKD. Secondary hyperparathyroidism leads to elevated PTH levels and disturbances in calcium and phosphorus. If not properly managed, this can result in renal osteodystrophy, vascular calcification, and increased risk of cardiovascular events and mortality. The document reviews therapeutic options like phosphate binders and vitamin D analogs to control mineral levels and treat secondary hyperparathyroidism in CKD patients.
This document discusses chronic kidney disease-mineral and bone disorder (CKD-MBD). It defines CKD-MBD and renal osteodystrophy. It notes that CKD-MBD is characterized by abnormalities in calcium, phosphorus, PTH, or vitamin D metabolism. It also discusses secondary hyperparathyroidism in CKD and characteristics of major CKD-related bone diseases. The document then presents two patient case studies and questions related to interpreting lab results and determining appropriate treatment steps for managing mineral and bone disorders in the patients.
This case report describes a 75-year-old man with prostate cancer undergoing watchful waiting who was found to have pernicious anemia, a severe vitamin B12 deficiency. Over 10 months, his prostate cancer progressed more rapidly than expected based on Gleason score and PSA levels. After starting vitamin B12 injections for pernicious anemia treatment, the patient's PSA and prostatic acid phosphatase levels initially increased rapidly before stabilizing. The authors propose that the patient's vitamin B12 deficiency may have modulated the growth and progression of his prostate cancer, and that B12 replacement accelerated cancer marker levels initially before stabilization. They recommend screening prostate cancer patients undergoing watchful waiting for vitamin B12 deficiency.
Cystatin C - Early Risk Assessment of Renal Impairment MAY18Randox Reagents
Cystatin C is a small (13 kDa) cysteine proteinase inhibitor, produced by all nucleated cells at a constant rate. Cystatin C travels through the bloodstream to the kidneys where it is freely filtered by the glomerular membrane, resorbed and fully catabolised by the proximal renal tubes. Consequently, Cystatin C is the ideal biomarker of GFR function.
Cystatin-C is a protein produced by all nucleated cells and filtered out of the bloodstream by healthy kidneys. It is a more sensitive marker of kidney function than creatinine, as its levels rise earlier when glomerular filtration rate decreases. Measurement of cystatin-C can help detect chronic kidney disease at an earlier stage than creatinine. The document discusses the history, molecular biology, structure, role in medicine, prevalence, and stages of chronic kidney disease, highlighting how cystatin-C can be a useful marker for detecting and monitoring kidney function and disease.
Cystatin C is a small protein produced by all nucleated cells at a constant rate and freely filtered by the kidneys without reabsorption. It is an accurate marker for glomerular filtration rate and early kidney dysfunction. The document discusses the history, molecular biology, production, and fate of cystatin C in the body. It also covers the use of cystatin C to estimate kidney function and its role as a prognostic marker for cardiovascular disease and mortality.
The EVOLVE trial studied the effect of cinacalcet on cardiovascular disease in patients undergoing dialysis. The randomized controlled trial compared cinacalcet to placebo in 3,883 adults on dialysis to evaluate the primary composite endpoint of time to death or first nonfatal cardiovascular event. Secondary endpoints included time to individual components of the primary endpoint like myocardial infarction or fracture, as well as death from cardiovascular causes. The trial was designed to test the hypothesis that cinacalcet treatment might reduce mortality and cardiovascular risks by decreasing levels of phosphorus, PTH, and calcium phosphorus product known to be associated with higher mortality in dialysis patients.
This document discusses the physiology and clinical management of PTH and mineral metabolism disorders in patients with chronic kidney disease (CKD). It provides an overview of calcium, phosphorus, vitamin D, and PTH regulation and how their homeostasis is disrupted in CKD. Secondary hyperparathyroidism leads to elevated PTH levels and disturbances in calcium and phosphorus. If not properly managed, this can result in renal osteodystrophy, vascular calcification, and increased risk of cardiovascular events and mortality. The document reviews therapeutic options like phosphate binders and vitamin D analogs to control mineral levels and treat secondary hyperparathyroidism in CKD patients.
This document discusses chronic kidney disease-mineral and bone disorder (CKD-MBD). It defines CKD-MBD and renal osteodystrophy. It notes that CKD-MBD is characterized by abnormalities in calcium, phosphorus, PTH, or vitamin D metabolism. It also discusses secondary hyperparathyroidism in CKD and characteristics of major CKD-related bone diseases. The document then presents two patient case studies and questions related to interpreting lab results and determining appropriate treatment steps for managing mineral and bone disorders in the patients.
This case report describes a 75-year-old man with prostate cancer undergoing watchful waiting who was found to have pernicious anemia, a severe vitamin B12 deficiency. Over 10 months, his prostate cancer progressed more rapidly than expected based on Gleason score and PSA levels. After starting vitamin B12 injections for pernicious anemia treatment, the patient's PSA and prostatic acid phosphatase levels initially increased rapidly before stabilizing. The authors propose that the patient's vitamin B12 deficiency may have modulated the growth and progression of his prostate cancer, and that B12 replacement accelerated cancer marker levels initially before stabilization. They recommend screening prostate cancer patients undergoing watchful waiting for vitamin B12 deficiency.
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.
The document describes research using the ZDSD rat model to study diabetic nephropathy. Key findings include:
1) ZDSD rats exhibit nephropathy that closely mimics that observed in obese, insulin resistant patients as shown by elevated biomarkers, albuminuria, oxidative stress, and histological analysis.
2) Terminal kidney weights are highest in ZDSD rats, indicating significant diabetic nephropathy, along with increased urine volume and microalbumin levels.
3) Histological analysis shows glomerular sclerosis, nodular sclerosis, thickened glomerular basement membranes, and podocyte effacement in ZDSD rats, consistent with diabetic nephropathy
Chronic Kidney Disease (CKD) is a major public health problem, with diabetes and hypertension being leading causes. CKD is defined by reduced kidney function (GFR <60 mL/min/1.73m2) and/or markers of kidney damage such as albuminuria. While CKD may cause few symptoms initially, it disrupts homeostasis and hormone production. Estimated GFR (eGFR) and urine albumin-to-creatinine ratio (UACR) are used to screen, diagnose, and monitor CKD. The ACP recommends ACE inhibitors or ARBs to treat hypertension in CKD, and statins to manage lipids. Blood pressure targets in CKD may differ from
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.
Hyperphosphatemia in CKD patients; The Magnitude of The Problem - Prof. Alaa ...MNDU net
Hyperphosphatemia in CKD patients; The Magnitude of The Problem
Prof. Alaa Sabry - Professor of Nephrology
Mansoura Nephrology and Dialysis Unit (MNDU) Course
Malnutrition , inflammation ,and atherosclerosis (MIA syndrome in heamodialy...dr_ekbalabohashem
This document discusses malnutrition, inflammation, and atherosclerosis (MIA) syndrome in hemodialysis patients. It covers several topics:
1. Malnutrition is highly prevalent in hemodialysis patients, affecting up to 75%, and is associated with multiple factors like metabolic acidosis and dialysis-induced catabolism.
2. Inflammation is also common in these patients, with C-reactive protein levels elevated in 30-50%. Inflammation contributes to accelerated atherosclerosis and is a risk factor for cardiovascular mortality.
3. Several markers can assess nutritional status and inflammation in hemodialysis patients, including serum albumin, prealbumin, cholesterol, and C-reactive
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)
1. Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder affecting 7-10% of women of reproductive age, characterized by chronic anovulation, hyperandrogenism, and polycystic ovaries.
2. Insulin resistance, present in 50-70% of women with PCOS independent of obesity, contributes significantly to its pathogenesis by driving hyperinsulinemia and hyperandrogenism.
3. While classical insulin target tissues are resistant, the ovary remains sensitive to insulin's effects on androgen production, resulting in the "central paradox" of PCOS.
Diabetic nephropathy is a chronic kidney disease characterized by gradually increasing urinary albumin excretion, high blood pressure, declining kidney function, and presence of diabetic retinopathy. It develops in 20-40% of people with diabetes and is the leading cause of end-stage renal disease. The pathophysiology involves metabolic and hemodynamic pathways as well as genetic factors. Hyperglycemia causes kidney damage through increased polyol pathway flux, formation of advanced glycation end products, activation of protein kinase C, and other mechanisms. Hemodynamic changes from hypertension increase glomerular pressure and permeability. Genetic factors like ACE polymorphisms also influence risk. Progression is associated with proteinuria, anemia
pathophysiology and therapy of diabetic nephropathyMuhamed Al Rohani
This document discusses diabetic nephropathy, which is the leading cause of end-stage renal disease. It begins with an overview of the epidemiology and risk factors for diabetic nephropathy. It then covers the pathophysiology and pathological stages, explaining the progression from increased glomerular filtration rate to decreased GFR and kidney damage. Treatment focuses on tight blood glucose and blood pressure control using ACE inhibitors, ARBs, or a combination to slow the progression of kidney disease. Clinical trials demonstrate that these drugs can reduce proteinuria and prevent worsening of renal function in patients with diabetes.
Proteinuria as Cardiovascular Risk FactorJAFAR ALSAID
This document discusses proteinuria as a cardiovascular risk factor. It begins with the pathophysiology of proteinuria and the glomerular filtration barrier. It then discusses the relationship between proteinuria and cardiovascular disease, kidney disease, and inflammation. Studies show proteinuria is associated with increased risk of cardiovascular events and mortality. The degree of proteinuria also correlates with hypertension and left ventricular dysfunction. Managing proteinuria through angiotensin receptor blockers and ACE inhibitors can reduce cardiovascular risk. The document concludes proteinuria is a significant risk factor for cardiovascular disease in patients with chronic kidney disease or diabetes.
This document discusses chronic kidney disease-mineral and bone disorder (CKD-MBD). It begins with an overview of the key components involved in CKD-MBD, including calcium, phosphorus, parathyroid hormone, vitamin D, fibroblast growth factor 23, and magnesium. The document then presents two clinical cases involving patients with CKD and discusses treatment options based on their lab results. It also covers the roles of vitamin D and magnesium in vascular pathology and mortality in CKD patients. Guidelines for the treatment of secondary hyperparathyroidism from KDIGO are also summarized.
Diabetic nephropathy is a chronic kidney disease that develops over many years in people with diabetes. It is characterized by increased urinary albumin excretion, hyperglycemia, high blood pressure, declining kidney function, and the absence of other kidney diseases. According to studies, 20-44% of people with diabetes develop kidney failure and require renal replacement therapy like dialysis. The pathophysiology of diabetic nephropathy involves metabolic pathways like increased polyol pathway flux, hexosamine pathway flux, formation of advanced glycation end products, and activation of protein kinase C, as well as hemodynamic changes and genetic factors. Major therapeutic interventions include controlling blood glucose, blood pressure, lipids, restricting protein intake,
This document discusses proteinuria, or increased protein in the urine. It defines proteinuria and outlines its causes, which can include primary kidney diseases, overflow of abnormal proteins, or secondary causes from non-kidney diseases. The document describes different types of proteinuria including glomerular, tubular, and overflow, and explains how to detect, evaluate, and differentiate between the types using urine tests like dipstick, sulfosalicylic acid, protein electrophoresis, and immunoassay. It provides guidance on classifying and further investigating persistent proteinuria to determine its underlying cause and renal pathology.
Disease related mineral and bone disorderOther Mother
1. Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) is a systemic disorder affecting mineral and bone metabolism in patients with CKD.
2. Proper classification and definitions of CKD-MBD and its related conditions like renal osteodystrophy are needed to improve diagnosis and treatment.
3. Abnormalities in mineral metabolism like high phosphorus and PTH levels are linked to increased mortality in patients with CKD, so controlling these factors is important for improving outcomes.
The document discusses biomarkers for detecting acute kidney injury (AKI). It notes that serum creatinine is currently used but is not an early indicator. Newer biomarkers like NGAL can detect AKI earlier, within 2 hours after an event instead of 1-2 days with creatinine. Having early biomarkers could allow for improved understanding, earlier treatment and better outcomes for AKI patients. The document reviews studies on NGAL for detecting AKI in settings like cardiac surgery, contrast-induced nephropathy, sepsis, and kidney transplantation.
This document discusses bone and mineral disease in patients with chronic kidney disease. Key points:
1) Patients with chronic kidney disease often develop metabolic bone disease due to abnormalities in calcium, phosphorus, vitamin D, and parathyroid hormone levels. This can lead to bone abnormalities like osteitis fibrosa or adynamic bone.
2) Secondary hyperparathyroidism is common, driven by phosphorus retention, low vitamin D, and decreased calcium sensing by the parathyroid glands. High PTH then causes high bone turnover.
3) In addition to bone effects, extraskeletal calcification can occur in blood vessels, skin, and other tissues in patients with kidney disease. Care involves monitoring mineral
1) Coronary artery calcification is significant and progressive in a majority of patients with early chronic kidney disease. There is an association between arterial calcification and increased risk of all-cause mortality in chronic kidney disease patients on dialysis.
2) While the data are not entirely consistent, some studies have found relatively less progression of vascular calcification with sevelamer versus calcium-containing phosphate binders among patients with chronic kidney disease.
3) One randomized controlled trial found that among hemodialysis patients treated with either calcium acetate or sevelamer for 1 year, there was similar progression of coronary artery calcification with intensive lowering of LDL-C levels in both groups.
This document discusses diabetic nephropathy, which affects 300 million people worldwide and is a leading cause of end-stage renal disease. It progresses through 5 stages from early diabetes with hyperfiltration to end-stage renal disease requiring renal replacement therapy. Screening involves testing for microalbuminuria and management focuses on strict glycemic and blood pressure control as well as ACE inhibitors or ARBs to preserve kidney function. The goal is to prevent progression of kidney damage through lifestyle modifications and medical treatment.
Guidelines For Assessment Of C Visk In Rsymptomatic AdultsJuan Menendez
The document provides guidelines for cardiovascular risk assessment in asymptomatic adults from the 2010 ACCF/AHA. It recommends using global risk scores that incorporate multiple traditional risk factors. It recommends obtaining family history of CVD but does not recommend genetic testing. It also does not recommend various tests such as natriuretic peptides, lipid assessments beyond standard profiles, or C-reactive protein in certain groups. It provides recommendations for use of other tests in specific intermediate-risk groups such as carotid intima-media thickness or coronary artery calcium scoring.
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.
The document describes research using the ZDSD rat model to study diabetic nephropathy. Key findings include:
1) ZDSD rats exhibit nephropathy that closely mimics that observed in obese, insulin resistant patients as shown by elevated biomarkers, albuminuria, oxidative stress, and histological analysis.
2) Terminal kidney weights are highest in ZDSD rats, indicating significant diabetic nephropathy, along with increased urine volume and microalbumin levels.
3) Histological analysis shows glomerular sclerosis, nodular sclerosis, thickened glomerular basement membranes, and podocyte effacement in ZDSD rats, consistent with diabetic nephropathy
Chronic Kidney Disease (CKD) is a major public health problem, with diabetes and hypertension being leading causes. CKD is defined by reduced kidney function (GFR <60 mL/min/1.73m2) and/or markers of kidney damage such as albuminuria. While CKD may cause few symptoms initially, it disrupts homeostasis and hormone production. Estimated GFR (eGFR) and urine albumin-to-creatinine ratio (UACR) are used to screen, diagnose, and monitor CKD. The ACP recommends ACE inhibitors or ARBs to treat hypertension in CKD, and statins to manage lipids. Blood pressure targets in CKD may differ from
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.
Hyperphosphatemia in CKD patients; The Magnitude of The Problem - Prof. Alaa ...MNDU net
Hyperphosphatemia in CKD patients; The Magnitude of The Problem
Prof. Alaa Sabry - Professor of Nephrology
Mansoura Nephrology and Dialysis Unit (MNDU) Course
Malnutrition , inflammation ,and atherosclerosis (MIA syndrome in heamodialy...dr_ekbalabohashem
This document discusses malnutrition, inflammation, and atherosclerosis (MIA) syndrome in hemodialysis patients. It covers several topics:
1. Malnutrition is highly prevalent in hemodialysis patients, affecting up to 75%, and is associated with multiple factors like metabolic acidosis and dialysis-induced catabolism.
2. Inflammation is also common in these patients, with C-reactive protein levels elevated in 30-50%. Inflammation contributes to accelerated atherosclerosis and is a risk factor for cardiovascular mortality.
3. Several markers can assess nutritional status and inflammation in hemodialysis patients, including serum albumin, prealbumin, cholesterol, and C-reactive
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)
1. Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder affecting 7-10% of women of reproductive age, characterized by chronic anovulation, hyperandrogenism, and polycystic ovaries.
2. Insulin resistance, present in 50-70% of women with PCOS independent of obesity, contributes significantly to its pathogenesis by driving hyperinsulinemia and hyperandrogenism.
3. While classical insulin target tissues are resistant, the ovary remains sensitive to insulin's effects on androgen production, resulting in the "central paradox" of PCOS.
Diabetic nephropathy is a chronic kidney disease characterized by gradually increasing urinary albumin excretion, high blood pressure, declining kidney function, and presence of diabetic retinopathy. It develops in 20-40% of people with diabetes and is the leading cause of end-stage renal disease. The pathophysiology involves metabolic and hemodynamic pathways as well as genetic factors. Hyperglycemia causes kidney damage through increased polyol pathway flux, formation of advanced glycation end products, activation of protein kinase C, and other mechanisms. Hemodynamic changes from hypertension increase glomerular pressure and permeability. Genetic factors like ACE polymorphisms also influence risk. Progression is associated with proteinuria, anemia
pathophysiology and therapy of diabetic nephropathyMuhamed Al Rohani
This document discusses diabetic nephropathy, which is the leading cause of end-stage renal disease. It begins with an overview of the epidemiology and risk factors for diabetic nephropathy. It then covers the pathophysiology and pathological stages, explaining the progression from increased glomerular filtration rate to decreased GFR and kidney damage. Treatment focuses on tight blood glucose and blood pressure control using ACE inhibitors, ARBs, or a combination to slow the progression of kidney disease. Clinical trials demonstrate that these drugs can reduce proteinuria and prevent worsening of renal function in patients with diabetes.
Proteinuria as Cardiovascular Risk FactorJAFAR ALSAID
This document discusses proteinuria as a cardiovascular risk factor. It begins with the pathophysiology of proteinuria and the glomerular filtration barrier. It then discusses the relationship between proteinuria and cardiovascular disease, kidney disease, and inflammation. Studies show proteinuria is associated with increased risk of cardiovascular events and mortality. The degree of proteinuria also correlates with hypertension and left ventricular dysfunction. Managing proteinuria through angiotensin receptor blockers and ACE inhibitors can reduce cardiovascular risk. The document concludes proteinuria is a significant risk factor for cardiovascular disease in patients with chronic kidney disease or diabetes.
This document discusses chronic kidney disease-mineral and bone disorder (CKD-MBD). It begins with an overview of the key components involved in CKD-MBD, including calcium, phosphorus, parathyroid hormone, vitamin D, fibroblast growth factor 23, and magnesium. The document then presents two clinical cases involving patients with CKD and discusses treatment options based on their lab results. It also covers the roles of vitamin D and magnesium in vascular pathology and mortality in CKD patients. Guidelines for the treatment of secondary hyperparathyroidism from KDIGO are also summarized.
Diabetic nephropathy is a chronic kidney disease that develops over many years in people with diabetes. It is characterized by increased urinary albumin excretion, hyperglycemia, high blood pressure, declining kidney function, and the absence of other kidney diseases. According to studies, 20-44% of people with diabetes develop kidney failure and require renal replacement therapy like dialysis. The pathophysiology of diabetic nephropathy involves metabolic pathways like increased polyol pathway flux, hexosamine pathway flux, formation of advanced glycation end products, and activation of protein kinase C, as well as hemodynamic changes and genetic factors. Major therapeutic interventions include controlling blood glucose, blood pressure, lipids, restricting protein intake,
This document discusses proteinuria, or increased protein in the urine. It defines proteinuria and outlines its causes, which can include primary kidney diseases, overflow of abnormal proteins, or secondary causes from non-kidney diseases. The document describes different types of proteinuria including glomerular, tubular, and overflow, and explains how to detect, evaluate, and differentiate between the types using urine tests like dipstick, sulfosalicylic acid, protein electrophoresis, and immunoassay. It provides guidance on classifying and further investigating persistent proteinuria to determine its underlying cause and renal pathology.
Disease related mineral and bone disorderOther Mother
1. Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) is a systemic disorder affecting mineral and bone metabolism in patients with CKD.
2. Proper classification and definitions of CKD-MBD and its related conditions like renal osteodystrophy are needed to improve diagnosis and treatment.
3. Abnormalities in mineral metabolism like high phosphorus and PTH levels are linked to increased mortality in patients with CKD, so controlling these factors is important for improving outcomes.
The document discusses biomarkers for detecting acute kidney injury (AKI). It notes that serum creatinine is currently used but is not an early indicator. Newer biomarkers like NGAL can detect AKI earlier, within 2 hours after an event instead of 1-2 days with creatinine. Having early biomarkers could allow for improved understanding, earlier treatment and better outcomes for AKI patients. The document reviews studies on NGAL for detecting AKI in settings like cardiac surgery, contrast-induced nephropathy, sepsis, and kidney transplantation.
This document discusses bone and mineral disease in patients with chronic kidney disease. Key points:
1) Patients with chronic kidney disease often develop metabolic bone disease due to abnormalities in calcium, phosphorus, vitamin D, and parathyroid hormone levels. This can lead to bone abnormalities like osteitis fibrosa or adynamic bone.
2) Secondary hyperparathyroidism is common, driven by phosphorus retention, low vitamin D, and decreased calcium sensing by the parathyroid glands. High PTH then causes high bone turnover.
3) In addition to bone effects, extraskeletal calcification can occur in blood vessels, skin, and other tissues in patients with kidney disease. Care involves monitoring mineral
1) Coronary artery calcification is significant and progressive in a majority of patients with early chronic kidney disease. There is an association between arterial calcification and increased risk of all-cause mortality in chronic kidney disease patients on dialysis.
2) While the data are not entirely consistent, some studies have found relatively less progression of vascular calcification with sevelamer versus calcium-containing phosphate binders among patients with chronic kidney disease.
3) One randomized controlled trial found that among hemodialysis patients treated with either calcium acetate or sevelamer for 1 year, there was similar progression of coronary artery calcification with intensive lowering of LDL-C levels in both groups.
This document discusses diabetic nephropathy, which affects 300 million people worldwide and is a leading cause of end-stage renal disease. It progresses through 5 stages from early diabetes with hyperfiltration to end-stage renal disease requiring renal replacement therapy. Screening involves testing for microalbuminuria and management focuses on strict glycemic and blood pressure control as well as ACE inhibitors or ARBs to preserve kidney function. The goal is to prevent progression of kidney damage through lifestyle modifications and medical treatment.
Guidelines For Assessment Of C Visk In Rsymptomatic AdultsJuan Menendez
The document provides guidelines for cardiovascular risk assessment in asymptomatic adults from the 2010 ACCF/AHA. It recommends using global risk scores that incorporate multiple traditional risk factors. It recommends obtaining family history of CVD but does not recommend genetic testing. It also does not recommend various tests such as natriuretic peptides, lipid assessments beyond standard profiles, or C-reactive protein in certain groups. It provides recommendations for use of other tests in specific intermediate-risk groups such as carotid intima-media thickness or coronary artery calcium scoring.
Update on genetics and molecular biology.pdfssuser5b0f5e
This document summarizes recent studies on genetics and molecular biology related to cardiovascular disease risk. It discusses:
1) A study that found familial hypercholesterolemia variants in 1.7% of early myocardial infarction cases vs 0.6% of controls, and a high polygenic risk score in 17% of cases vs 5% of controls. Both were associated with a similar 3.7-fold risk of early myocardial infarction.
2) Advances in characterizing genetic variants associated with familial hypercholesterolemia, but limitations in classification.
3) A study suggesting that inhibition of ATP-citrate lyase may lower cardiovascular risk similarly to statins by reducing LDL-cholesterol.
Clinical, laboratory and histological associations in clinical, laboratory an...Dr. sreeremya S
Clinical, laboratory and histological associations in clinical, laboratory and histological associations in adults with nonalcoholic fatty liver disease
Dyslipidemia and CVS by Mohit Soni and Chandan KumarOlgaGoryacheva4
My students Mohit Soni and Chandan Kumar had presented this topic in our 22nd Student Scientific Society Conference in the department of Propaedeutic of Internal Diseases No.2
Uterine fibroids are common tumors in women that can lead to hysterectomy. This study examined the association between uterine fibroids and cardiovascular disease using data from the Coronary Artery Risk Development in Young Adult Women's Study. The study found that cardiovascular risk factors like higher BMI and hypertension were more prevalent in women with fibroids. Initial analyses found higher rates of subclinical disease markers like coronary artery calcium in women with fibroids, but these associations disappeared after adjusting for shared risk factors. The study concludes that fibroids may not directly increase cardiovascular risk, but that fibroids and cardiovascular disease share underlying risk factors like obesity and hypertension. Long-term follow up is still needed to examine the relationship between fibroids and actual cardiovascular events
This study examined genetic variants in DNA repair genes and their association with prostate cancer risk in a population-based case-control study conducted in China. The study genotyped 191 prostate cancer cases and 305 controls for five single nucleotide polymorphisms (SNPs) in DNA repair genes. Statistical analysis found that variants in the XRCC1 and MGMT genes were associated with increased prostate cancer risk, and that these associations were modified by factors like abdominal obesity, insulin resistance, and diet. The study provides evidence that DNA repair capacity may influence prostate cancer risk. Larger confirmation studies in other populations are still needed.
This document discusses prostate cancer epidemiology, etiology, and diagnostic evaluation. It notes that prostate cancer is the second most commonly diagnosed cancer in men worldwide, with incidence varying widely between regions. Family history and genetics play a role in prostate cancer risk. Screening remains controversial, with initial widespread PSA screening in the US associated with decreased mortality, though over-diagnosis is a concern. Guidelines now suggest informing men aged 55-69 of PSA screening benefits and risks.
This study investigated the relationship between age and pulse pressure (PP) in subjects with untreated essential hypertension based on their plasminogen activator inhibitor (PAI)-1 gene polymorphism. The results showed that subjects with the deletion/deletion genotype had a significantly steeper age-related increase in PP compared to those with the insertion/insertion or insertion/deletion genotypes, after adjusting for potential confounding factors. This suggests that the PAI-1 gene polymorphism modulates the effects of aging on PP increases in hypertensive individuals.
Author Profile - http://baligadiagnostics.com/dr-vivek-baliga/
In this presentation, Dr Vivek Baliga discusses some of the common cardiac conditions that are seen in post menopausal women.
Serum interleukin - 6 level among sudanese patients with chronic kidney disease
Authors:Safaa I.A Nasr , Rbab A.M Adam , Hala M.M Ibrahim , Afra S.A Abdelgadir , Ibrahim Alkider , Solomon M. Gamde , Simon P. Abriba
Int J Biol Med Res. 2023; 14(4): 7652-7654 | Abstract | PDF File
We conducted a retrospective study of 178 community dwelling elderly on anemia which was defined as hemoglobin < 13 gm/ dl in males and < 12 gm/dl in females (WHO guidelines).
Methods: This was a retrospective chart review of patients aged ≥ 95 years, who were seen over a two year period at the University of Arkansas for Medical Sciences.
Benefits os Statins in Elderly Subjects Without Established Cardiovascular Di...Rodrigo Vargas Zapana
Statins significantly reduced the risk of myocardial infarction by 39.4% and the risk of stroke by 23.8% in elderly subjects without established cardiovascular disease. However, statins did not significantly reduce the risk of all-cause mortality or cardiovascular mortality. New cancer onset was also not significantly different between the statin-treated and placebo groups. The meta-analysis included 8 randomized controlled trials with a total of 24,674 elderly subjects who were followed for an average of 3.5 years.
Statin Use Cancer Related Mortality M Wilmath Nov2012 Whh Adult MedMario Wilmath
1. Researchers examined the association between statin use and cancer-related mortality using Danish national registries containing data on cancer diagnoses, prescriptions, and deaths from 1995-2007.
2. They found that cancer patients who used statins had a 15% lower risk of death from cancer compared to non-users.
3. The potential benefits were highest for colon, liver, esophageal, and prostate cancers. However, the study had limitations such as lacking treatment data for most patients and being limited to Denmark. Further research is still needed.
This document discusses special considerations for cardiac dysfunction in older adults living with cancer. It begins with objectives to apply a framework for multimorbidity and review cardiovascular physiology of aging and considerations in cardio-oncology for older adults. It then discusses how chronic diseases increase with age, including cancer and heart disease. Older adults are underrepresented in oncology trials despite having high rates of cancer. A comprehensive geriatric assessment is recommended to identify vulnerabilities beyond standard oncology assessments. Certain chemotherapy agents have increased cardiotoxicity risks in older patients. A multimorbidity framework is presented to guide management of multiple chronic conditions. Strategies are discussed to minimize cardiac complications in older cancer patients, including risk stratification, cardioprotective therapies
The document discusses chronic kidney disease in elderly patients. It notes that the elderly population is growing rapidly and will more than double between 2000 and 2030. Chronic kidney disease is also an epidemic among the elderly, as aging leads to a decline in kidney function even without other risk factors. Outcomes of chronic kidney disease and end-stage renal disease are generally worse in elderly patients compared to younger patients due to higher rates of comorbidities. Management of chronic kidney disease in the elderly requires an individualized approach balancing treatment goals with patient preferences and prognosis. Palliative care is also an important part of care for elderly patients with advanced chronic kidney disease or end-stage renal disease.
This document summarizes new concepts in hemostasis, which is the process of blood clotting and wound healing. It discusses three phases of coagulation - initiation, amplification, and propagation. The initiation phase begins when tissue factor is exposed by damaged blood vessels, forming a complex with factor VIIa that activates small amounts of factors IX and X. This generates low levels of thrombin, starting the amplification phase where feedback loops dramatically increase coagulation factor activity through activation of factors V and VIII. High levels of thrombin then propagate fibrin clot formation. The document also reviews platelet activation and interactions with endothelial cells that regulate thrombus formation and coagulation.
Hougie 2004-journal of-thrombosis_and_haemostasisLAB IDEA
The document provides historical context on the development of the cascade/waterfall hypothesis of blood coagulation. It discusses the landmark 1964 papers by Macfarlane and Davie & Ratnoff that independently proposed the cascade model. Macfarlane described coagulation as a "cascade" and "photochemical amplifier", while Davie & Ratnoff termed it the "waterfall" concept. Both proposed coagulation occurs through a series of enzymatic reactions between clotting factors. The collaboration between clinical researcher Ratnoff and biochemist Davie led to the influential "waterfall" paper.
El documento resume el sistema de coagulación, incluyendo la hemostasia secundaria, los componentes como plaquetas y factores de coagulación, y los mecanismos como la cascada de coagulación. También describe la regulación de la hemostasia a través de sistemas anticoagulantes como la antitrombina III y la proteína C, y la evaluación por laboratorio incluyendo pruebas como el tiempo de sangrado, recuento de plaquetas, y tiempos de protrombina y tromboplastina parcial activada.
Este documento resume información sobre parasitosis intestinales. Explica que los parásitos intestinales incluyen protozoos, helmintos y pueden causar cuadros clínicos variables, desde infecciones asintomáticas hasta afectar uno o más órganos. Describe en detalle la amibiasis intestinal causada por Entamoeba histolytica, incluyendo su ciclo de vida, manifestaciones clínicas, diagnóstico y tratamiento. También menciona brevemente la balantidiasis.
CLASE ASCITIS
DR. RAUL CARRILLO ORTIZ
MODULO MEDICINA INTERNA
ROTACIÓN PATOLOGÍA CLÍNICA
DEPARTAMENTO DE MEDICINA Y NUTRICIÓN
UNIVERSIDAD DE GUANAJUATO
Las enfermedades musculares esqueléticas incluyen una variedad de condiciones que causan debilidad muscular. El diagnóstico adecuado requiere historia clínica, marcadores musculares como enzimas y proteínas, electromiografía y biopsia muscular para diferenciar alteraciones musculares de las neurológicas. Existen diferentes mecanismos fisiopatológicos involucrados como fenómenos autoinmunes, y condiciones pueden ser congénitas o adquiridas. El laboratorio juega un papel importante en el
Este documento describe la enfermedad hepática grasa no alcohólica (EHGNA), también conocida como esteatosis hepática. Define la EHGNA como la acumulación de grasa en el hígado en ausencia de consumo excesivo de alcohol. Explica que la EHGNA puede evolucionar a esteatohepatitis no alcohólica, cirrosis y hepatocarcinoma si no se corrigen los factores de riesgo subyacentes. Finalmente, discute las opciones de tratamiento, que incluyen cambios en el estilo de
Historical perspective and future direction of coagulation researchLAB IDEA
This document provides a historical perspective on the advances made in coagulation research over the past 100 years. Remarkable progress has been achieved, starting from early clinical observations of rare bleeding disorders to current understanding involving complex reaction pathways. Key developments include the discovery of coagulation factors and inhibitors through study of patient plasma, development of laboratory tests enabling factor assays, and evolving cascade models incorporating new knowledge. Recent technologies like gene targeting and stem cells promise further insights. Close collaboration between basic scientists and clinicians has been important to research progress and clinical applications. Future areas may include gene and cell-based therapies building on past successes translating basic research into improved patient care.
Lipoprotein (a) [Lp(a)] levels are strongly associated with cardiovascular disease risk. Lp(a) consists of an LDL-like particle bound to apolipoprotein(a) [apo(a)]. Apo(a) is produced in the liver and its production rate is the main determinant of plasma Lp(a) levels. Recent studies show that ligands of the farnesoid X receptor can significantly lower Lp(a) levels by inhibiting apo(a) transcription. While lowering Lp(a) may reduce cardiovascular risk, consensus reports have been cautious about routinely measuring Lp(a) due to lack of intervention studies demonstrating that lowering Lp(a) reduces hard endpoints and lack of effective medications to lower Lp(
This document summarizes the pathophysiology, diagnosis, and management of metabolic acidosis. It describes how metabolic acidosis is characterized by a reduction in serum bicarbonate and secondary decreases in arterial carbon dioxide partial pressure and blood pH. Acute metabolic acidosis lasting minutes to days is more common and often due to organic acid overproduction, while chronic metabolic acidosis lasting weeks to years usually reflects bicarbonate wasting or impaired renal acidification. Diagnosing the cause involves calculating the serum anion gap to classify disorders as normal or elevated. Adverse effects differ between acute and chronic forms. Treatment of acute metabolic acidosis with base administration is controversial due to lack of benefit and potential complications, while chronic metabolic acidosis treatment
El documento describe la alcalosis metabólica. Explica que es un trastorno metabólico frecuente en pacientes hospitalizados que causa un aumento de los niveles de bicarbonato en la sangre. Las causas incluyen la infusión de bicarbonato, pérdidas gástricas o renales de ácidos, y el uso de diuréticos. El tratamiento se enfoca en corregir la causa subyacente, restaurar los niveles de cloro y tratar las complicaciones como la hipopotasemia.
El documento describe los tres sistemas principales que regulan la concentración de iones de hidrógeno (H+) en el cuerpo: 1) los sistemas amortiguadores químicos de los líquidos orgánicos, 2) el centro respiratorio, y 3) los riñones. Los sistemas amortiguadores químicos reaccionan en segundos, el aparato respiratorio actúa en minutos, y los riñones tienen la respuesta más lenta en horas o días. Los riñones juegan un papel clave al secretar iones de hid
El documento resume los conceptos clave de acidosis y alcalosis, incluyendo las definiciones de acidosis y alcalosis, las causas de acidosis metabólica, y formulas y medidas utilizadas para evaluar trastornos del equilibrio ácido-base como el anión gap, gap osmolal urinario y brecha delta.
La lesión renal aguda (LRA) se define como la pérdida rápida de la función renal dentro de las 48 horas, lo que resulta en la retención de desechos en la sangre como la creatinina y la urea. La LRA puede ser prerrenal, causada por una perfusión renal inadecuada; intrínseca, causada por daño al riñón; u obstructiva posrenal, causada por una obstrucción del tracto urinario. El diagnóstico incluye exámenes clínicos y de laboratorio como la medición de creatin
El documento resume varios artículos y libros sobre lesión aguda renal, incluyendo Waikar S.S., Bonventre J.V. (2016) que discute la lesión aguda renal en el libro Harrison. Principios de Medicina Interna, 19e. También se mencionan artículos de Kidney International Supplements (2012) y Lancet (2012) que tratan sobre este tema.
TRASTORNOS DE LA COAGULACION EN HEPATOPATIASLAB IDEA
Este documento describe los trastornos de la coagulación que pueden ocurrir en pacientes con enfermedad hepática, incluyendo alteraciones plaquetarias, disminución en la síntesis de factores de coagulación, disfibrinogenemia e hiperfibrinólisis. Explica que estos trastornos ocurren cuando los niveles plasmáticos de los factores de coagulación están por debajo del 30-40% de los niveles normales. Finalmente, resume los tratamientos utilizados para corregir estos trastornos, como
El documento describe la hepatitis B, un virus que causa inflamación del hígado. El virus de la hepatitis B es un DNA envuelto que puede causar infección aguda o crónica. La transmisión ocurre principalmente a través del contacto con sangre o fluidos corporales. La infección aguda generalmente se resuelve espontáneamente, mientras que la infección crónica puede conducir a cirrosis o cáncer de hígado. El diagnóstico se realiza mediante pruebas serológicas y la carga viral. No existe un tratamiento
Fasting is not routinely required for determination of a lipid profileLAB IDEA
This document provides a joint consensus statement from the European Atherosclerosis Society and European Federation of Clinical Chemistry and Laboratory Medicine regarding fasting vs. non-fasting lipid profiles. It finds that observational data indicate maximal mean changes after meals are small and not clinically significant. It recommends the routine use of non-fasting lipid profiles to improve patient compliance, while fasting may be considered if non-fasting triglycerides are over 5 mmol/L. Abnormal non-fasting concentrations that should be flagged are outlined.
La trombocitopenia idiopática es un trastorno caracterizado por la producción de autoanticuerpos contra las plaquetas. Puede presentarse en niños de 2 a 4 años después de infecciones respiratorias o en adultos, especialmente mujeres entre 15 y 40 años. Los síntomas incluyen petequias, equimosis y sangrado de las encías. El tratamiento incluye corticoesteroides, inmunoglobulina o esplenectomía.
2. J Am Soc Nephrol 17: 254 –261, 2006 Cystatin C and Mortality Risk in the Elderly 255
whether the association of cystatin C with mortality differed by Johnson & Johnson Vitros 950 analyzer (New Brunswick, NJ); the
race. intraindividual coefficient of variation approximately 2%.
The Health, Aging, and Body Composition Study (Health For our primary analyses, we categorized cystatin C into quintiles.
ABC) is a cohort of well-functioning elderly people, aged 70 to We also repeated our analyses with cystatin C concentrations grouped
into low (quintile 1, 0.84 mg/L), medium (quintiles 2 to 4, 0.84 to 1.18
79 yr, that includes a large number of black men and women. In
mg/L), and high (quintile 5, 1.18 mg/L). These categories were
Health ABC, we measured serum cystatin C at baseline to
presented to reflect better the association of cystatin C with mortality
determine whether cystatin C concentrations were associated risk and to facilitate comparisons with other studies (13).
with mortality risk. The specific objectives of these inquiries
were (1) to determine the association of cystatin C concentra-
Secondary Predictors
tions with mortality risk and to contrast this association with
Other characteristics were used in these analyses as adjustment vari-
that of serum creatinine concentrations, (2) to evaluate whether
ables to determine the independence of the association of serum cys-
the association differed by race and gender, and (3) to investi- tatin C with mortality. These included sociodemographic factors (age,
gate whether inflammatory factors were potential mediators for gender, race, clinical site, education level); lifestyle factors (current
the association between cystatin C and mortality. smoking defined by current versus former or never; alcohol use defined
by 1 drink per week, with no use defined as 1 drink per week; body
mass index); comorbid conditions (diabetes defined by use of hypogly-
Materials and Methods
cemic agents, self-report, fasting plasma glucose 126 mg/dl or an oral
Design and Participants
glucose tolerance test 200 mg/dl; hypertension by either self-report
Health ABC is a prospective study that was initiated by investigators
plus use of antihypertensive medications, or measured systolic BP
at the National Institute on Aging to investigate the effect of age-related
140 mmHg or diastolic BP 90 mmHg; chronic heart failure, coronary
changes in body composition and health on subsequent health and
heart disease, myocardial infarction, angina, coronary artery bypass,
incident functional limitation and disability. Each of the two study
chronic obstructive pulmonary disease, and cerebrovascular disease,
sites, Pittsburgh, PA, and Memphis, TN, recruited participants who
which all were by self-report in this study); serum chemistries (glucose,
were aged 70 to 79 yr from a list of Medicare beneficiaries between
total cholesterol, HDL cholesterol, triglycerides, and albumin, all mea-
April 1997 and June 1998. The goal of recruitment was to have a cohort
sured by a colorimetric technique on a Johnson & Johnson Vitros 950
of highly functional older people at baseline that was nearly balanced
analyzer). LDL was calculated using the Friedewald equation (15).
among men and women and white and black individuals. Race status
Baseline blood draws were taken after an 8-h fast. Samples then were
was obtained from the Health Care Financing Administration (now the
aliquotted and stored at 80°C until analysis; all transportation was
Centers for Medicare and Medicaid Services) database; recruitment was
conducted using dry ice. Medications were brought in by the partici-
at random among all age-eligible individuals within each stratum of
pant and recorded. We were particularly interested in use of aspirin,
race (black and white). Inclusion criteria were (1) ability to walk one
blockers, angiotensin-converting enzyme inhibitors, calcium antago-
quarter mile, climb 10 steps, and perform basic activities of daily living
nists, statins, and diuretics as predictors of survival.
without difficulty; (2) absence of life-threatening illness; and (3) plans
Measures of IL-6, TNF- , and C-reactive protein (CRP) were per-
to remain in the geographic area for at least 3 yr. The cohort enrolled
formed using ELISA kits from R&D Systems (Minneapolis, MN). De-
3075 participants who completed baseline evaluations, 42% of whom
tectable limits were 0.10 pg/ml for IL-6, 0.18 pg/ml for TNF- , and
were black. Adequate specimens for analysis of cystatin C were avail-
0.007 mg/L for CRP. Interassay coefficients of variation were deter-
able for 3044 (99%), the sample for this analysis. All participants gave
mined by duplicate analyses of 150 specimens; 10.3, 8.0, and 15.8% for
informed written consent; the protocol was approved by the Institu-
IL-6, CRP, and TNF- , respectively.
tional Review Boards of the clinical sites and the Data Coordinating
Center (University of California, San Francisco, San Francisco, CA).
Outcomes
Follow-up occurred every 6 mo either by telephone or by annual
Kidney Function
visits to clinical centers. Deaths were ascertained by review of local
Cystatin C was measured at the Health ABC core laboratory (Uni-
obituaries, by reports to the clinical centers by family members, or by
versity of Vermont, Burlington, VT) using a BNII nephelometer (Dade
means of the semiannual contacts. Immediate and underlying causes of
Behring Inc., Deerfield, IL) that used a particle-enhanced immunon-
death were determined by a central adjudication committee on the
epholometric assay (N Latex Cystatin C) (14). Among 61 healthy indi-
basis of review of the death certificate, all recent hospital records, and
viduals with three cystatin C measurements over a 6-mo period, the
interview with the next of kin. Causes of death in this analysis were
intraindividual coefficient of variation was 7.7%, reflecting long-term
categorized as cardiovascular, cancer, and infection/other, on the basis
stability of the measurement. The assay range is 0.195 to 7.330 mg/L,
of the underlying cause adjudicated by committee according to specific
with the reference range for young, healthy individuals reported as 0.53
prestated protocols. One death was attributable to unknown causes,
to 0.95 mg/L. The assay remained stable over five cycles of freeze/thaw
and this individual was grouped with infection/other. These analyses
without change in the measurement.
include all deaths that had occurred through August 30, 2004.
Before measuring cystatin C, we compared cystatin C concentrations
in serum and EDTA-citrated plasma specimens from other individuals
and found a linear slope of 0.977 and R2 of 0.958 using linear regression; Statistical Analyses
compared with the serum measures, the plasma measures were slightly We used ANOVA to compare the mean ( SD) serum cystatin C
lower on average (mean difference 0.03 0.02 mg/L; absolute range of concentrations by gender, by race, and across the four race/gender
differences 0.00 to 0.07 mg/L). We chose to use the plasma specimens, subgroups. We compared the distribution of each secondary predictor
which had been stored at 70°C, for the measurement of cystatin C in variable across quintiles of cystatin C, using the 2 test for categorical
the Health ABC cohort. Creatinine was used as a comparative mea- variables and ANOVA for continuous variables. Certain measures were
surement of kidney function, assayed by a colorimetric technique on a log-transformed because of their rightward skew (glucose, triglycer-
3. 256 Journal of the American Society of Nephrology J Am Soc Nephrol 17: 254 –261, 2006
ides, CRP, IL-6, TNF- , and creatinine). Mortality rates (%/yr) were 1.03 0.36 mg/L; P 0.0001). By race and gender subgroups,
determined by quintile of cystatin C cystatin C (mean SD) concentrations were 1.00 0.30 mg/L
Staged multivariable proportional hazards models were used to eval- in black women (referent), 1.02 0.35 mg/L in white women
uate the adjusted association of cystatin C quintiles with subsequent (P 0.19), 1.07 0.43 mg/L in black men (P 0.0001), and
mortality risk. Following an unadjusted model, adjustments for socio-
1.09 0.31 mg/L in white men (P 0.0001).
demographic characteristics, lifestyle factors, comorbid conditions, and
Table 1 displays baseline characteristics by quintile of cysta-
serum chemistry measurements were made with variables that were
selected on the basis of their having an unadjusted association with
tin C. Higher concentrations of cystatin C were associated with
mortality at P 0.05. Once we had defined the optimal adjusted model, older age, male gender, white race, and higher body mass index
we then tested the effects of the three inflammatory biomarkers IL-6, (Table 1). The prevalence of diabetes, hypertension, coronary
CRP, and TNF- . We repeated these analyses modeling cystatin C as a heart disease, cerebrovascular disease, and heart failure in-
continuous variable. creased with ascending quintiles of cystatin C, as did higher
To quantify the potential mediating effect of the inflammatory fac- levels of triglycerides and lower levels of LDL and HDL. Levels
tors, we compared the parameter estimate ( coefficient) from the of the inflammatory factors CRP, IL-6, and TNF- all increased
multivariable model before and after adjustment for each inflammatory with rising quintiles of cystatin C.
factor. We considered the percentage change in the parameter estimate
as a metric for the extent to which each biomarker mediated the
association between cystatin C and mortality.
Race and Gender Subgroups
Mortality risk differed markedly across demographic sub-
We checked the linearity of the relationship between cystatin C and
all-cause mortality by the addition of a quadratic term to an unadjusted groups: 2.0%/yr in white women, 2.8%/yr in black women,
proportional hazards model. A nonlinear relationship was initially 3.3%/yr in white men, and 5.5%/yr in black men. In each
detected, but upon further examination, 12 (0.50%) cystatin C outliers subgroup, however, low, medium, and high cystatin C concen-
were responsible for the significance of the quadratic term. The qua- tration seemed to distinguish three levels of mortality risk
dratic term was not significant in adjusted analyses or when the 12 (Figure 1). We found no significant interaction of cystatin C and
outliers were excluded. These 12 individuals were included in all either gender (P 0.09) or race (P 0.07) for predicting
subsequent analyses. After determining the relation between cystatin C mortality. In addition, there was no significant interaction of
and all-cause mortality, we proceeded with analyses of cause-specific gender and cystatin C within white (P 0.18) or black indi-
mortality. In these analyses, we modeled cystatin C as a continuous
viduals (P 0.11). Conversely, there were no cystatin C and
variable and determined the relative hazard associated with a per-SD
race interactions within men (P 0.19) or women (P 0.45).
increase in cystatin C.
We determined the mortality rates across the four gender/race sub-
groups. We evaluated whether gender and race modified the associa- Cystatin C and Mortality Risk
tion of cystatin C with mortality risk. First we constructed Kaplan After 6 yr of follow-up, 557 participants had died. All-cause
Meier curves plotting the mortality risk of low (quintile 1), medium mortality risk increased substantially from the lowest quintile
(quintiles 2 to 4), and high (quintile 5) cystatin C concentrations among of cystatin C to the highest (Figure 2). Quintiles 2 to 4 had
white women, white men, black women, and black men. We separately similar mortality risks that were 60 to 90% higher than quintile
tested for the presence of an interaction of cystatin C quintiles with race 1, whereas the risk in quintile 5 was three-fold that of quintile
and with gender. In addition, we tested for an interaction of cystatin C 1 (Table 2). The association of the highest quintile of cystatin C
and race within each gender and of cystatin C and gender within each with mortality was attenuated somewhat by adjustment for
race.
sociodemographic factors, prevalent diseases, and laboratory
To compare creatinine as a predictor of mortality, we categorized
measurements (adjusted model); however, risk for death in the
creatinine into gender-specific quintiles, meaning that each quintile had
roughly equal numbers of men and women. We repeated the staged,
highest quintile and in the middle quintiles remained signifi-
multivariate analyses as described above for cystatin C for the entire cantly elevated compared with the lowest quintile.
cohort. We tested for creatinine interactions with gender and race,
separately. Effect of Inflammation
Analyses were conducted using SAS v.8 (SAS Institute, Cary, NC). Adjustment for the three inflammatory biomarkers (CRP,
Testing of the proportional hazards assumption was performed using IL-6, and TNF- ) seemed to attenuate the association of each of
S-Plus V6.1 (Insightful Corp., Seattle, WA). The proportional hazards the upper three quintiles with mortality risk, but all quintiles
assumption was met for all models. Two-sided P 0.05 were consid- remained at significantly greater risk compared with the lowest
ered statistically significant. quintile. We next adjusted for the inflammatory makers indi-
vidually to test for which had the greatest mediating effect.
Results Without adjustment for inflammation, the parameter estimate
Baseline Comparisons ( coefficient) for the high cystatin C quintile was 1.00 0.18.
Among the 3044 participants in Health ABC with serum Adjustment for each of the biomarkers individually had the
cystatin C and 3047 participants with creatinine measurements, following effects on the parameter estimate: TNF- 0.82 0.17,
the mean SD cystatin C was 1.05 0.34 mg/L and the mean IL-6 0.93 0.17, and CRP 0.95 0.16. Adjustment by all three
SD creatinine was 1.06 0.42 mg/dl. Cystatin C concentra- biomarkers attenuated the parameter estimate to 0.79 0.18.
tions were significantly higher in men than in women (1.08 Thus, the modest attenuation of risk related to adjustment for
0.36 versus 1.01 0.33 mg/L; P 0.0001) and in white indi- inflammatory markers was largely attributable to TNF- rather
viduals compared with black individuals (1.06 0.33 versus than IL-6 or CRP.
4. J Am Soc Nephrol 17: 254 –261, 2006 Cystatin C and Mortality Risk in the Elderly 257
Table 1. Comparison of patient characteristics by cystatin C quintilea
Cystatin C Quintile (mg/L)
Characteristic (Baseline)
0.84 0.84 to 0.93 0.94 to 1.03 1.04 to 1.18 1.19 P
(n 578) (n 590) (n 605) (n 654) (n 617)
Age (yr) 73.0 2.8 73.2 2.8 73.6 2.9 74.0 2.9 74.3 2.9 0.001
Men 194 (34) 260 (44) 304 (50) 379 (58) 340 (55) 0.001
Black 283 (49) 262 (44) 266 (44) 231 (35) 223 (36) 0.001
Site
Memphis 317 (55) 309 (52) 289 (48) 311 (48) 304 (49) 0.05
Pittsburgh 261 (45) 281 (48) 316 (52) 343 (53) 313 (51)
Education 12 yr 241 (42) 246 (42) 244 (40) 277 (42) 270 (44) 0.82
Current smoker 49 (9) 60 (10) 69 (11) 66 (10) 70 (11) 0.45
Alcohol use 304 (53) 302 (51) 301 (50) 316 (48) 283 (46) 0.15
Body mass index (kg/m2) 26.3 4.8 27.1 4.8 27.5 4.7 27.7 4.7 28.3 4.9 0.001
Diabetes 82 (14) 74 (13) 75 (12) 100 (15) 132 (21) 0.001
Hypertension 255 (44) 265 (45) 289 (48) 345 (53) 397 (64) 0.001
Chronic obstructive 3 (1) 4 (1) 4 (1) 7 (1) 12 (2) 0.08
pulmonary disease
Cancer 99 (17) 102 (17) 107 (18) 133 (20) 136 (22) 0.11
Coronary heart disease 87 (15) 94 (16) 111 (18) 151 (23) 176 (29) 0.001
Cerebrovascular disease 36 (6) 39 (7) 35 (6) 61 (9) 73 (12) 0.001
Heart failure 7 (1) 11 (2) 13 (2) 19 (3) 44 (7) 0.001
LDL (mg/dl) 124 33 122 34 124 35 120 34 118 37 0.004
HDL (mg/dl) 60 18 56 17 54 17 51 16 50 16 0.001
Triglyceridesb (mg/dl) 120 62 131 78 135 73 148 85 156 103 0.001
Albumin (g/dl) 4.0 0.3 4.0 0.3 4.0 0.3 4.0 0.3 4.0 0.3 0.12
Glucoseb (mg/dl) 103 33 104 40 105 37 105 31 107 36 0.08
CRPb (mg/L) 2.7 4.8 2.6 3.3 2.6 3.2 2.9 4.5 4.2 6.8 0.001
IL-6b (pg/ml) 2.0 1.7 2.2 1.8 2.2 1.7 2.5 2.0 3.0 2.2 0.001
TNF- b (pg/ml) 2.6 1.0 3.0 1.6 3.2 1.1 3.7 1.6 4.8 2.2 0.001
Cystatin C (mg/L) 0.75 0.07 0.88 0.03 0.99 0.03 1.10 0.04 1.48 0.52 NA
Creatinineb (mg/dl) 0.87 0.15 0.94 0.15 1.01 0.08 1.07 0.19 1.39 0.76 0.001
Statin use 70 (12.1) 75 (12.7) 77 (12.7) 83 (12.7) 88 (14.3) 0.84
blocker use 54 (9.3) 73 (12.4) 81 (13.4) 86 (13.2) 119 (19.3) 0.001
Aspirin use 198 (34.3) 214 (36.3) 207 (34.2) 252 (38.5) 272 (44.1) 0.002
ACE inhibitor use 70 (12.1) 63 (10.7) 83 (13.7) 115 (17.6) 130 (21.1) 0.001
Calcium antagonist use 122 (21.1) 127 (21.5) 132 (21.8) 153 (23.4) 166 (26.9) 0.10
a
Data are n (%) or mean SD. Conventional units are displayed; to convert to systeme international units, multiply LDL
and HDL by 0.0259 for mmol/L, triglycerides by 0.0113 for mmol/L, albumin by 10 for g/L, glucose by 0.0555 for mmol/L,
and creatinine by 88.4 for mol/L. CRP, C-reactive protein; ACE, angiotensin-converting enzyme.
b
P values obtained by using the log transformation.
We repeated these analyses with cystatin C modeled as a Stratification by Race
continuous variable per SD (0.34 mg/L). In the unadjusted The associations (HR; 95% CI) of ascending quintiles of cys-
model, each 0.34 m/L of cystatin C was associated with a tatin C with mortality risk in white individuals were 1.0 (ref-
1.24-fold (95% confidence interval [CI], 1.20 to 1.28) risk for erent), 1.74 (1.01 to 3.01), 1.32 (0.75 to 2.32), 1.63 (0.96 to 2.76),
death. This result was unchanged by adjustment for sociode- and 1.93 (1.13 to 3.31) after adjustment for sociodemographic
mographic characteristics, lifestyle factors, comorbid condi- characteristics, lifestyle factors, comorbid conditions, serum
tions, and serum chemistry measurements (hazard ratio [HR], chemistry, and inflammatory markers. These adjusted HR (95%
1.24; 95% CI, 1.19 to 1.30). However, adjustment for the inflam- CI) in black individuals were 1.0 (referent), 1.64 (1.00 to 2.70),
matory markers did moderately attenuate the association of 1.72 (1.06 to 2.81), 1.50 (0.90 to 2.50), and 2.39 (1.47 to 3.88).
cystatin C with all-cause mortality (HR, 1.16; 95% CI, 1.09 to Increasing quintiles of creatinine were not associated with mor-
1.24). tality risk in white or black individuals. The adjusted HR (95%
5. 258 Journal of the American Society of Nephrology J Am Soc Nephrol 17: 254 –261, 2006
risk group had a 57% increase in risk, and the high-risk group
had a 120% increase in risk compared with low-risk partici-
pants (Table 3).
Cause-Specific Mortality
The cause of death was broadly categorized as death caused
by cardiovascular disease (n 177); cancer (n 137); or infec-
tious, other, and unknown (n 242). After multivariable anal-
ysis including adjustment for inflammation, cystatin C concen-
tration (per SD, 0.3 mg/L) was associated with the outcomes of
cardiovascular death (HR, 1.20; 95% CI 1.11 to 1.30) and death
from infectious/other/unknown cause (HR 1.33; 95% CI 1.24 to
1.41) but not with cancer death (HR 1.12; 95% CI 0.96 to 1.31).
Creatinine Quintiles and Mortality
Figure 1. Nelson-Aalen cumulative hazard functions are shown For comparison with cystatin C, we also evaluated gender-
in white women (a), black women (b), white men (c), and black specific quintiles of creatinine as predictors of mortality (Table
men (d). Each curve displays mortality risks among partici- 4). In unadjusted analysis, the fifth quintile had a significantly
pants with low ( 0.84 mg/L), medium (0.84 to 1.18 mg/L), and higher mortality risk compared with the first quintile, but quin-
high ( 1.19 mg/L) cystatin C concentrations, stratified by gen- tiles 2 to 4 had similar risk as quintile 1. After adjustment for
der/race subgroup: White women, white men, black women, sociodemographic factors, prevalent diseases, and laboratory
and black men. Each figure shows significant differences by measurements, the fifth quintile remained associated with a
cystatin C category (P 0.001). 40% higher mortality risk in both black and white participants.
Further adjustment for inflammatory biomarkers substantially
attenuated this association and rendered it nonsignificant. Tests
for interaction in adjusted models were not significant for race
(P 0.37) and only marginally significant for gender (P 0.07).
Discussion
Cystatin C is an alternative measure of kidney function that
is attractive because of its reported independence from the
influence of muscle mass. In the Health ABC cohort of well-
functioning, ambulatory elderly, we found that cystatin C was
a strong and independent predictor of mortality, an association
that did not differ significantly by race or gender. The quintiles
of cystatin C seemed to describe three distinct levels of mortal-
ity risk, low (quintile 1), medium (quintiles 2 to 4), and high
(quintile 5). Although it remained highly significant, the asso-
Figure 2. Cystatin C quintiles and mortality risk. This figure ciation of high cystatin C concentrations (quintile 5) with mor-
displays the annual all-cause mortality risk by quintile of cys- tality was modestly attenuated by adjustment for inflammatory
tatin C. Cutpoints for cystatin C quintiles are 0.84, 0.84 to 0.93, biomarkers, suggesting that inflammation partially mediated
0.94 to 1.03, 1.04 to 1.18, and 1.19 mg/L. P 0.001 for the pathway from chronic kidney disease to mortality risk,
comparison across quintiles. although risk in both the middle and high quintiles remained
statistically significant. In contrast, only the highest gender-
specific quintile of creatinine predicted mortality, and this associ-
CI) in white individuals were 1.0 (referent), 1.13 (0.74 to 1.70), ation became nonsignificant after adjustment for inflammation.
0.86 (0.55 to 1.34), 1.02 (0.64 to 1.64), and 1.10 (0.71 to 1.70). The results of this study confirm the findings from the Car-
These adjusted HR (95% CI) in black individuals were 1.0 diovascular Health Study (CHS) that previously compared the
(referent), 0.78 (0.44 to 1.39), 1.02 (0.61 to 1.71), 1.12 (0.67 to associations of cystatin C and creatinine with mortality risk
1.88), and 1.15 (0.72 to 1.84). (13). The CHS investigators similarly found that quintiles of
cystatin C could define low, medium, and high mortality risk.
Reclassification of Risk Groups Some differences in the cutpoints of cystatin C to define low,
We repeated the analyses after classifying participants as low medium, and high risk were noted between the two studies. In
(quintile 1), medium (quintiles 2 to 4), or high (quintile 5) risk CHS, the low-risk group was defined as the lower two quintiles
on the basis of cystatin C concentrations (Table 3). The absolute ( 1.0 mg/L), whereas in this study, the lowest risk was in
mortality risk ranged three-fold from the low- to high-risk participants in quintile 1 ( 0.84 mg/L). Both CHS and Health
categories. After full adjustment for all covariates, the medium- ABC found the fifth quintile to be at markedly increased mor-
6. J Am Soc Nephrol 17: 254 –261, 2006 Cystatin C and Mortality Risk in the Elderly 259
Table 2. Association of cystatin C quintiles with all-cause mortalitya
Cystatin C Quintile (mg/L)
Model
0.84 0.84 to 0.93 0.94 to 1.03 1.04 to 1.18 1.19
All participants (N) 578 590 605 654 617
Events 58 94 103 119 183
Unadjusted 1.0 1.63 (1.17 to 2.27) 1.78 (1.29 to 2.46) 1.90 (1.38 to 2.60) 3.41 (2.53 to 4.59)
Adjustedb 1.0 1.71 (1.22 to 2.40) 1.64 (1.17 to 2.30) 1.71 (1.23 to 2.39) 2.69 (1.95 to 3.70)
Adjusted inflammationc 1.0 1.74 (1.21 to 2.50) 1.51 (1.05 to 2.18) 1.49 (1.04 to 2.13) 2.18 (1.53 to 3.10)
a
Data are hazard ratio (95% confidence interval).
b
Adjusted for race, age, gender, site, education level, current smoking status, cardiovascular disease, LDL cholesterol, HDL
cholesterol, body mass index, albumin, hypertension, diabetes, coronary heart disease, cerebrovascular disease, and heart
failure.
c
Adjusted for all of the above variables plus IL-6, CRP, and TNF- ; results were similar when inflammation markers were
considered individually as well.
Table 3. Low, medium, and high cystatin C concentrations association with all-cause mortalitya
Cystatin C (mg/L)
Low Medium High
( 0.84) (0.84 to 1.18) ( 1.19)
N 578 1849 617
Events 58 316 183
Absolute risk (%/yr) 1.7 2.9 5.4
Unadjusted 1.00 1.77 (1.34 to 2.35) 3.41 (2.53 to 4.59)
Adjustedb 1.00 1.69 (1.26 to 2.27) 2.69 (1.95 to 3.70)
Adjusted inflammationc 1.00 1.57 (1.14 to 2.17) 2.20 (1.55 to 3.13)
a
Data are hazard ratio (95% confidence interval).
b
Adjusted for race, age, gender, site, education level, current smoking status, cardiovascular disease, LDL cholesterol, HDL
cholesterol, body mass index, albumin, hypertension, diabetes, coronary heart disease, cerebrovascular disease, and heart
failure.
c
Adjusted for all of the above variables plus IL-6, CRP, and TNF- .
Table 4. Creatinine and mortality riska
Creatinine Quintile (mg/dl)
Model
1 2 3 4 5
All participants (N) 463 687 667 517 713
Events 80 96 99 85 198
Unadjusted 1.0 0.80 (0.60 to 1.08) 0.84 (0.63 to 1.13) 0.95 (0.70 to 1.29) 1.71 (1.32 to 2.22)
Adjustedb 1.0 0.95 (0.69 to 1.29) 0.93 (0.68 to 1.27) 1.07 (0.77 to 1.47) 1.40 (1.05 to 1.86)
Adjusted inflammationc 1.0 1.00 (0.72 to 1.39) 0.95 (0.68 to 1.32) 1.11 (0.79 to 1.57) 1.16 (0.86 to 1.58)
a
Data are hazard ratio (95% confidence interval).
b
Adjusted for race, age, gender, site, education, current smoking status, cardiovascular disease, LDL cholesterol, HDL
cholesterol, body mass index, albumin, hypertension, diabetes, coronary heart disease, cerebrovascular disease, and heart
failure.
c
Adjusted for all of the above variables plus IL-6, CRP, and TNF- .
tality risk, although the cutpoint for quintile 5 was 1.19 mg/L population based. As kidney disease is associated with frailty
in Health ABC and 1.28 mg/L in CHS. The lower distribution (16), participants with kidney dysfunction would be less likely
of cystatin C concentrations in this study is probably due to to qualify for the Health ABC study. In addition, Health ABC
Health ABC participants’ having been selected on the basis of has a greater proportion of black participants, who seem to
preserved physical function, whereas CHS recruitment was have lower cystatin C concentrations.
7. 260 Journal of the American Society of Nephrology J Am Soc Nephrol 17: 254 –261, 2006
A somewhat surprising finding from this study was the more accurately predicts mortality risk than serum creatinine in
absence of association across creatinine quintiles and mortality older people. In addition to predicting death, cystatin C was an
risk, as risk was elevated only in the highest quintile. Because independent predictor of congestive heart failure, stroke, and
Health ABC participants were selected for their preserved func- myocardial infarction in the CHS (13,24). Two cohort studies of
tionality, we had hypothesized that elevated creatinine concen- patients with acute coronary syndrome have found that cysta-
trations would be a strong and independent prognostic factor. tin C predicted subsequent cardiovascular events better than
However, unlike the results for cystatin C, creatinine concen- creatinine (25,26). To demonstrate clinical utility, however,
trations in the highest quintile were no longer associated with studies will need to determine whether diagnostic or screening
increased risk for death after adjustment for inflammation. strategies that are based on cystatin C can change clinical
Furthermore, the uniform mortality risk across the lower four practice compared with strategies that are based on creatinine
quintiles contrasts sharply with the three distinct levels of risk or estimated GFR and thus lead to improvement in clinical
defined by cystatin C. These observations suggest that the outcomes.
multiple determinants of creatinine generation in the elderly Four limitations of this study should be considered. Because the
limit its utility as a prognostic marker and perhaps as a diag- Health ABC study was composed solely of ambulatory elderly
nostic test. The reliance on serum creatinine in clinical research people, the described associations of cystatin C with mortality in
up to this time may have obscured the pathophysiologic im- younger populations or among elderly with significant functional
portance of kidney function in the elderly. disability cannot necessarily be extrapolated. Second, we cannot
An important and novel aspect of this study is its ability to be certain that the association of cystatin C with adverse outcomes
compare creatinine and cystatin C as mortality predictors in is solely due to its approximation of kidney function. Although a
black and white individuals. The association of higher cystatin study suggested that cystatin C was influenced by factors other
C concentrations with higher mortality risk was roughly uni- than GFR, the study measured creatinine clearance rather than
form among black and white participants. However, we found GFR, so its conclusions remain speculative (27). However, we are
that cystatin C was a much stronger predictor of mortality than unaware of any direct toxic role of cystatin C or of a mediator
creatinine in black and white participants. The observation that activated by cystatin C or secreted temporally in association with
cystatin C concentrations were lower in black than in white cystatin C that would account for these findings. Third, as with
individuals is puzzling, however, particularly as the same was any observational study, there is likely to be residual confounding.
found in the CHS. A possible explanation is that the black Severity differences in measured factors (e.g., hypertension, dia-
participants had better kidney function than the white partici- betes) and a variety of unmeasured factors, such as homocysteine,
pants, but this seems unlikely as the prevalences of diabetes lipoprotein (a), oxidative stress, and asymmetric dimethyl argi-
and elevated inflammatory markers were higher in black par- nine, might modify the association between higher cystatin C
ticipants overall, and black men had higher levels of systolic BP concentrations and mortality. However, residual confounding is
than white men (17,18). Another explanation could be that unlikely to extinguish the relatively large relative risks associated
cystatin C concentrations approximate GFR differently in black with the highest quintile of cystatin C concentration. Fourth, al-
and white individuals. A comparison of cystatin C and creati- though we believe that the cause of death classification was rig-
nine-based estimated GFR as determinants of directly mea- orous, we cannot exclude the possibility of misclassification. In
sured GFR in elderly black individuals would be an important particular, among deaths that were classified as infection/other,
topic for future study. we cannot exclude the possibility that cardiovascular disease was
Inflammatory biomarkers are known to be elevated in people also a contributor.
with chronic kidney disease (19,20) and to be independent In summary, we found that cystatin C was a strong and inde-
predictors of mortality risk in the elderly (21). This study also pendent risk factor for all-cause and cause-specific mortality in a
suggests that inflammation may modify somewhat the strength cohort of ambulatory elderly. Quintiles of cystatin C effectively
of the association between cystatin C and mortality, as inflam- delineated participants at low, medium, and high risk regardless
matory cytokines were increased in Health ABC patients in the of race or gender, whereas creatinine quintiles were unassociated
highest quintile of cystatin C, and the point estimate for the with mortality after similar adjustment. We hypothesize that the
fifth quintile was attenuated after adjustment for CRP, IL-6, and sensitivity of cystatin C relative to creatinine for small declines in
TNF- . Despite adjustment for CRP, IL-6, and TNF- , however, kidney function is the likely explanation for the difference in risk
the association of cystatin C with mortality risk remained profiles. Future studies that measure both serum cystatin C and
strong and independent. This finding argues against the hy- creatinine concentrations should address the potential clinical role
pothesis that cystatin C is primarily a reflection of systemic for cystatin C in the diagnosis and management of kidney disease
inflammation rather than kidney function, as has been sug- and its associated complications.
gested (22). Furthermore, a recent study by Perkins et al. (23)
found that cystatin C correlated tightly with serial measure-
Acknowledgments
ments of GFR by iothalamate clearance, whereas creatinine- Health ABC was supported through the National Institute on Aging
based Modification of Diet in Renal Disease was a much weaker contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106. The
reflection of GFR. National Institute on Aging had substantial involvement in data col-
The potential role of cystatin C in clinical care warrants lection, analysis, and interpretation and manuscript preparation. Dr.
investigation, now that two studies have shown that cystatin C Shlipak and Ms. Wassel-Fyr at the Coordinating Center had full access
8. J Am Soc Nephrol 17: 254 –261, 2006 Cystatin C and Mortality Risk in the Elderly 261
to all of the data files. Dr. Shlipak is funded by R01 HL073208-01 and plasma, without use of the preparative ultracentrifuge.
RO1 DK066488-01, the American Federation for Aging Research and Clin Chem 18: 499 –502, 1972
National Institute on Aging (Paul Beeson Scholars Program), and the 16. Shlipak MG, Stehman-Breen C, Fried LF, Song X, Siscovick
Robert Wood Johnson Foundation (Generalist Faculty Scholars Pro- D, Fried LP, Psaty BM, Newman AB: The presence of
gram). frailty in elderly persons with chronic renal insufficiency.
Am J Kidney Dis 43: 861– 867, 2004
17. Rooks RN, Simonsick EM, Miles T, Newman A, Kritchev-
References sky SB, Schulz R, Harris T: The association of race and
1. Fried LF, Shlipak MG, Crump C, Bleyer AJ, Gottdiener JS, socioeconomic status with cardiovascular disease indica-
Kronmal RA, Kuller LH, Newman AB: Renal insufficiency tors among older adults in the health, aging, and body
as a predictor of cardiovascular outcomes and mortality in composition study. J Gerontol B Psychol Sci Soc Sci 57:
elderly individuals. J Am Coll Cardiol 41: 1364 –1372, 2003 S247–S256, 2002
2. Fried LP, Kronmal RA, Newman AB, Bild DE, Mittelmark 18. Visser M, Pahor M, Taaffe DR, Goodpaster BH, Simonsick
MB, Polak JF, Robbins JA, Gardin JM: Risk factors for EM, Newman AB, Nevitt M, Harris TB: Relationship of
5-year mortality in older adults: The Cardiovascular interleukin-6 and tumor necrosis factor-alpha with muscle
Health Study. JAMA 279: 585–592, 1998
mass and muscle strength in elderly men and women: The
3. Walter LC, Brand RJ, Counsell SR, Palmer RM, Landefeld
Health ABC Study. J Gerontol A Biol Sci Med Sci 57: M326 –
CS, Fortinsky RH, Covinsky KE: Development and valida-
M332, 2002
tion of a prognostic index for 1-year mortality in older
19. Muntner P, He J, Astor BC, Folsom AR, Coresh J: Tradi-
adults after hospitalization. JAMA 285: 2987–2994, 2001
tional and nontraditional risk factors predict coronary
4. Lindeman RD, Tobin J, Shock NW: Longitudinal studies on
heart disease in chronic kidney disease: Results from the
the rate of decline in renal function with age. J Am Geriatr
atherosclerosis risk in communities study. J Am Soc Nephrol
Soc 33: 278 –285, 1985
16: 529 –538, 2005
5. US Renal Data System: USRDS 1999 Annual Data Report.
20. Shlipak MG, Fried LF, Crump C, Bleyer AJ, Manolio TA,
Bethesda, National Institutes of Health, National Institute
Tracy RP, Furberg CD, Psaty BM: Elevations of inflamma-
of Diabetes and Digestive and Kidney Diseases, 2001
tory and procoagulant biomarkers in elderly persons with
6. Rowe TF, Magee K, Cunningham FG: Pregnancy and renal
renal insufficiency. Circulation 107: 87–92, 2003
tubular acidosis. Am J Perinatol 16: 189 –191, 1999
7. Seliger SL, Davis C, Stehman-Breen C: Gender and the 21. Tice JA, Browner W, Tracy RP, Cummings SR: The relation
progression of renal disease. Curr Opin Nephrol Hypertens of C-reactive protein levels to total and cardiovascular
10: 219 –225, 2001 mortality in older US women. Am J Med 114: 199 –205, 2003
8. Kassirer JP: Clinical evaluation of kidney function—Tubu- 22. Curhan G: Cystatin C: A marker of renal function or some-
lar function. N Engl J Med 285: 499 –502, 1971 thing more? Clin Chem 51: 293–294, 2005
9. Kassirer JP: Clinical evaluation of kidney function—Glo- 23. Perkins BA, Nelson RG, Ostrander BE, Blouch KL,
merular function. N Engl J Med 285: 385–389, 1971 Krolewski AS, Myers BD, Warram JH: Detection of renal
10. Coll E, Botey A, Alvarez L, Poch E, Quinto L, Saurina A, function decline in patients with diabetes and normal or
Vera M, Piera C, Darnell A: Serum cystatin C as a new elevated GFR by serial measurements of serum cystatin C
marker for noninvasive estimation of glomerular filtration concentration: Results of a 4-year follow-up study. J Am
rate and as a marker for early renal impairment. Am J Soc Nephrol 16: 1404 –1412, 2005
Kidney Dis 36: 29 –34, 2000 24. Sarnak MJ, Katz R, Stehman-Breen CO, Fried LF, Jenny NS,
11. Oddoze C, Morange S, Portugal H, Berland Y, Dussol B: Psaty BM, Newman AB, Siscovick D, Shlipak MG: Cysta-
Cystatin C is not more sensitive than creatinine for detect- tin-C as a risk factor for heart failure in older adults. Ann
ing early renal impairment in patients with diabetes. Am J Intern Med 142: 497–505, 2005
Kidney Dis 38: 310 –316, 2001 25. Koenig W, Twardella D, Brenner H, Rothenbacher D:
12. Dharnidharka VR, Kwon C, Stevens G: Serum cystatin C is Plasma concentrations of cystatin C in patients with coro-
superior to serum creatinine as a marker of kidney func- nary heart disease and risk for secondary cardiovascular
tion: A meta-analysis. Am J Kidney Dis 40: 221–226, 2002 events: More than simply a marker of glomerular filtration
13. Shlipak MG, Sarnak M, Katz R, Fried LF, Seliger SL, New- rate. Clin Chem 51: 321–327, 2005
man AB, Siscovick DS, Stehman-Breen CO: Cystatin-C and 26. Jernberg T, Lindahl B, James S, Larsson A, Hansson LO,
risk for mortality and cardiovascular disease in elderly Wallentin L: Cystatin C: A novel predictor of outcome in
adults. N Engl J Med 352: 2049 –2060, 2005 suspected or confirmed non-ST-elevation acute coronary
14. Erlandsen EJ, Randers E, Kristensen JH: Evaluation of the syndrome. Circulation 110: 2342–2348, 2004
Dade Behring N Latex Cystatin C assay on the Dade Be- 27. Knight EL, Verhave JC, Spiegelman D, Hillege HL, de
hring Nephelometer II System. Scand J Clin Lab Invest 59: Zeeuw D, Curhan GC, de Jong PE: Factors influencing
1– 8, 1999 serum cystatin C levels other than renal function and the
15. Friedewald WT, Levy RI, Fredrickson DS: Estimation of the impact on renal function measurement. Kidney Int 65:
concentration of low-density lipoprotein cholesterol in 1416 –1421, 2004
Access to UpToDate on-line is available for additional clinical information
at http://www.jasn.org/