Albuminuria and the risk of incident stroke and stroke types in older adults.

BACKGROUND: The kidney biomarker that best reflects risk of stroke is unknown. We sought to evaluate the association of stroke with 3 kidney biomarkers: albuminuria, cystatin C, and glomerular filtration rate. METHODS: These 3 biomarkers were determined in 3,287 participants without history of stroke from the Cardiovascular Health Study, a longitudinal cohort study of men and women age 65 years and older from 4 US communities. The biomarkers were albuminuria ascertained using urinary albumin-to-creatinine ratio (UACR) from morning spot urine, creatinine-based estimated glomerular filtration rate (eGFR), and cystatin C. Outcomes were incident stroke (any, ischemic, or hemorrhagic) during follow-up between 1996 and 2006. RESULTS: A total of 390 participants had an incident stroke: 81% ischemic, 12% hemorrhagic, and 7% unclassified. In adjusted Cox regression models, UACR was more strongly related to any stroke, ischemic stroke, and hemorrhagic stroke than eGFR and cystatin C. The hazard ratio (HR) of any stroke comparing the top to bottom quintile of UACR was 2.10 (95% confidence interval [CI] 1.47-3.00), while HR for eGFR was 1.29 (95% CI 0.91-1.84) and for cystatin C was 1.22 (95% CI 0.85-1.74). When considering clinically relevant categories, elevated UACR was associated with increased hazard of any stroke and ischemic stroke regardless of eGFR or cystatin C categories. CONCLUSIONS: UACR was the kidney biomarker most strongly associated with risk of incident stroke. Results in this elderly cohort may not be applicable to younger populations. These findings suggest that measures of glomerular filtration and permeability have differential effects on stroke risk.

Glycosylated hemoglobin and the risk of death and cardiovascular mortality in the elderly.

BACKGROUND AND AIMS: Glycosylated hemoglobin (HbA(1c)) has been associated with incident cardiovascular disease (CVD), but the findings are inconsistent. We tested the hypothesis that HbA(1c) may be associated with an increased risk of death and cardiovascular mortality in older adults. METHODS AND RESULTS: We evaluated the association between HbA(1c) with all-cause and cardiovascular mortality in 810 participants without a history of diabetes in a sub-study of the Cardiovascular Health Study (CHS), a community cohort study of individuals > or =65 years of age. Glycosylated hemoglobin was measured at baseline and all-cause and cardiovascular mortality was assessed during the follow-up period. The relation between baseline HbA(1c) and death was evaluated with multivariate Cox proportional hazards regression models. After a median follow-up of 14.2 years, 416 deaths were observed. The crude incidence rates of all-cause mortality across HbA(1c) groups were: 4.4% per year, 4.3% per year and 4.6% per year for tertile 1 (< or =5.6%), tertile 2 (5.61-6.20%) and tertile 3 (> or =6.21%), respectively. In unadjusted and fully adjusted analyses, baseline HbA(1c) was not associated with all-cause mortality and cardiovascular mortality (hazard ratio: 1.16 [95% confidence interval 0.91-1.47] and hazard ratio: 1.31 [95% confidence interval 0.90-1.93], respectively for the highest HbA(1c) tertile compared with the lowest). CONCLUSION: These results suggest that HbA(1c) does not significantly predict all-cause and cardiovascular mortality in non-diabetic community-dwelling older adults.

Inflammation and cardiovascular events in individuals with and without chronic kidney disease.

Inflammation and chronic kidney disease predict cardiovascular events. Here we evaluated markers of inflammation including fibrinogen, albumin and white blood cell count in individuals with and without stages 3-4 chronic kidney disease to assess inflammation as a risk factor for adverse events, the synergy between inflammation and chronic kidney disease, and the prognostic ability of these inflammatory markers relative to that of C-reactive protein. Using Atherosclerosis Risk in Communities and Cardiovascular Health Study data, inflammation was defined by worst quartile of at least 2 of these 3 markers. In Cox regression models, inflammation was assessed as a risk factor for a composite of cardiac events, stroke and mortality as well as components of this composite. Among 20 413 patients, inflammation was identified in 3594 and chronic kidney disease in 1649. In multivariable analyses, both inflammation and chronic kidney disease predicted all outcomes, but their interaction was non-significant. In 5597 patients with C-reactive protein levels, inflammation and elevated C-reactive protein had similar hazard ratios. When focusing only on individuals with the worst quartile of white cell count and albumin, results remained consistent.

Long-term outcomes in nondiabetic chronic kidney disease.

The Modification of Diet in Renal Disease (MDRD) Study examined the effects of strict blood pressure control and dietary protein restriction on the progression of kidney disease. Here, we retrospectively evaluated outcomes of nondiabetic participants with stages 2-4 chronic kidney disease (CKD) from randomized and nonrandomized cohorts of the MDRD Study. Kidney failure and survival status through December of 2000, were obtained from the US Renal Data System and the National Death Index. Event rates were calculated for kidney failure, death, and a composite outcome of death and kidney failure. In the 1666 patients, rates for kidney failure were four times higher than that for death. Kidney failure was a more likely event than death in subgroups based on baseline glomerular filtration rate, proteinuria, kidney disease etiology, gender, and race. It was only among those older than 65 that the rate for death approximated that for kidney failure. In contrast to other populations with CKD, our study of relatively young subjects with nondiabetic disease has found that the majority of the participants advanced to kidney failure with a low competing risk of death. In such patients, the primary emphasis should be on delaying progression of kidney disease.

Fetuin-A is not associated with mortality in chronic kidney disease.

Fetuin-A is a serum protein that inhibits vascular calcification such that lower levels are associated with a higher prevalence of vascular calcification and mortality risk among end-stage renal disease populations. We analyzed data of 822 persons in the Modification of Diet in Renal Disease study, a randomized, controlled trial of persons with predominantly non-diabetic stage 3-4 chronic kidney disease (CKD). Serum fetuin-A levels were measured in baseline serum. Survival status and cause of death were determined by the National Death Index. Cox proportional hazard models evaluated the association of fetuin-A levels with all-cause and cardiovascular mortality. Glomerular filtration ranged from 13 to 55 ml per min per 1.73 m(2). During a median follow-up of 9.5 years, 25% of persons died from any cause and 12% died from a cardiovascular cause. Compared to the lowest tertile, no association was found between the highest fetuin-A tertile and all-cause or cardiovascular mortality. Similarly, no association was found between fetuin-A as a continuous variable and all-cause or cardiovascular mortality. Our study shows that serum fetuin-A levels are not related to all-cause or cardiovascular mortality among persons with predominantly non-diabetic stage 3 or 4 CKD.

Factors associated with serum leptin in patients with chronic kidney disease.

BACKGROUND AND AIMS: Serum leptin levels are elevated in patients with kidney failure. Data on the associations of serum leptin and on the relationship of leptin with both kidney function and inflammation, are limited in patients with reduced glomerular filtration rate (GFR). We evaluated the independent associations of serum leptin in patients with reduced GFR. MATERIAL AND METHODS: Serum leptin and C-reactive protein (CRP) were measured in samples from 798 participants of the Modification of Diet in Renal Disease Study. Multivariable analysis was used to evaluate the independent effects of kidney function and CRP on leptin levels. RESULTS: Median (interquartile range) of serum leptin was 9.1 ng/ml (14.0). Female gender, higher percent body fat, higher insulin levels, older age, lower GFR and higher CRP were associated with higher serum leptin levels and explained 51% of the variability in the logarithm of serum leptin levels. After adjusting for the other variables, a 10 ml/min/1.73 m2 lower GFR was associated with 6% higher mean serum leptin levels. Percent body fat and gender, explained 45% of the variability in serum leptin levels. CONCLUSIONS: Level of kidney function and CRP are associated with serum leptin in patients with reduced GFR. However, there is a stronger association between serum leptin and indices of body fat and gender in patients in the earlier stages of chronic kidney disease. 50% of the variability remains unexplained in patients with reduced GFR.

Epsilon-aminocaproic acid and renal complications: case report and review of the literature.

Epsilon-aminocaproic acid (EACA) is a potent anti-fibrinolytic agent that is used in the treatment of excessive bleeding resulting from a systemic fibrinolytic state. It can also be used to treat hematuria through its action on decreasing urinary fibrinolysis. A broad range of renal complications has been ascribed to EACA. Although they are rare, they may be life-threatening and should therefore be immediately recognized.

Cardiovascular disease risk factors in chronic renal insufficiency.

BACKGROUND: Coronary heart disease (CHD) is an important cause of morbidity and mortality in end-stage renal disease (ESRD). Prevention of CHD in ESRD requires identification and treatment of coronary risk factors in chronic renal insufficiency (CRI). METHODS: We evaluated the prevalence of "traditional coronary risk factors" in CRI in 1,795 patients enrolled in the baseline period of Modification of Diet in Renal Disease (MDRD) Study. Using a cross-sectional design, we determined the relationship of these risk factors to the level of glomerular filtration rate (GFR) and proteinuria. We also predicted the CHD risk in the MDRD Study baseline cohort using the coronary point score. RESULTS: 64.0% had blood pressure > or = 130/85 mmHg despite antihypertensive therapy. 64.2% had LDL cholesterol > or = 130 mg/dl, while 38.3% had HDL cholesterol < 35 mg/dl. After adjustment for age, gender and the presence of diabetes, GFR was inversely associated with systolic blood pressure and positively associated with HDL cholesterol, but not associated with total or LDL cholesterol. After adjustment for age. gender and the presence of diabetes, proteinuria was positively associated with systolic and diastolic blood pressure, total serum cholesterol and LDL cholesterol, and inversely associated with HDL cholesterol. Nonetheless, the predicted CHD risk, even at a very low GFR, was similar to the risk in the general population and lower than the observed rate of de novo CHD in incident dialysis patients. CONCLUSIONS: "Traditional coronary risk factors" are highly prevalent in CRI and vary with the level of renal function. However, the coronary point score does not appear to explain the extent of increased CHD risk in ESRD. Non-traditional risk factors may also contribute to CHD in ESRD.

Pulmonary infectious mortality among patients with end-stage renal disease.

BACKGROUND: Infection is the second-leading cause of death among patients with end-stage renal disease (ESRD). This is due in part to advanced age, comorbid conditions, and immune dysfunction observed in uremic states. Although one may hypothesize that pulmonary infectious mortality is higher among patients with ESRD compared with the general population (GP), no such data are currently available. METHODS: We compared annual pulmonary infectious mortality rates among patients with ESRD to those in the GP. The data were abstracted from the United States Renal Data System and the National Center for Health Statistics, respectively, and were stratified by age, gender, race, and presence or absence of diabetes mellitus (DM). In the GP, primary and multiple cause-of-death analyses were performed to account for potential limitations of the data sources. RESULTS: Overall, pulmonary infectious mortality rate was 14-fold to 16-fold higher in dialysis patients and approximately twofold higher in renal transplant recipients compared with the GP. After stratification for age, differences between groups decreased but retained their magnitude. CONCLUSION: Patients with ESRD treated with dialysis have higher pulmonary infectious mortality rates compared with the GP, even after stratification for age, race, and DM. Consequently, this patient population must be considered at high risk for the development of lethal pulmonary infections.

Prediction equations to estimate glomerular filtration rate: an update.

The level of glomerular filtration rate can be estimated from the serum creatinine concentration and other easily measured patient variables from prediction equations developed using multivariable regression techniques. Recently, a new equation has been developed from the Modification of Diet in Renal Disease study, which is more accurate than other equations and more accurate than measurement of creatinine clearance. The authors recommend using prediction equations in clinical practice to estimate the level of glomerular filtration rate.

New approaches to the treatment of calcium and phosphorus abnormalities in patients on hemodialysis.

Disturbances in calcium and phosphorus are common in patients who are on chronic hemodialysis. Current therapy consists mainly of administration of calcium-containing phosphate binders and calcitriol. However, the use of these therapies has been limited by both iatrogenic hypercalcemia and hyperphosphatemia. Indeed, hyperphosphatemia and elevations in the calcium x phosphorus product have recently been linked to increased mortality and a high burden of cardiac calcifications on electron-beam computed tomography. Novel therapeutic agents such as sevelamer and vitamin D analogs have thus been developed with the goal of decreasing oral calcium loading and hypercalcemia. We provide an algorithm for the management of calcium and phosphorus abnormalities, based on newer recommendations for tighter calcium and phosphorus control with a lower target for the calcium x phosphorus product.

Reduced kidney function and anemia as risk factors for mortality in patients with left ventricular dysfunction.

OBJECTIVES: We sought to evaluate the relationship between the level of kidney function, level of hematocrit and their interaction on all-cause mortality in patients with left ventricular (LV) dysfunction. BACKGROUND: Anemia and reduced kidney function occur frequently in patients with heart failure. The level of hematocrit and its relationship with renal function have not been evaluated as risk factors for mortality in patients with LV dysfunction. METHODS: We retrospectively examined the Studies Of LV Dysfunction (SOLVD) database. Glomerular filtration rate (GFR) was predicted using a recently validated formula. Kaplan-Meier survival analyses were used to compare survival times between groups stratified by level of kidney function (predicted GFR) and hematocrit. Cox proportional-hazards regression was used to explore the relationship of survival time to level of kidney function, hematocrit and their interaction. RESULTS: Lower GFR and hematocrit were associated with a higher prevalence of traditional cardiovascular risk factors. In univariate analysis, reduced kidney function and lower hematocrit, in men and in women, were risk factors for all-cause mortality (p < 0.001 for both). After adjustment for other factors significant in univariate analysis, a 10 ml/min/1.73 m(2) lower GFR and a 1% lower hematocrit were associated with a 1.064 (95% CI: 1.033, 1.096) and 1.027 (95% CI: 1.015, 1.038) higher risk for mortality, respectively. At lower GFR and lower hematocrit, the risk was higher (p = 0.022 for the interaction) than that predicted by both factors independently. CONCLUSIONS: Decreased kidney function and anemia are risk factors for all-cause mortality in patients with LV dysfunction, especially when both are present. These relationships need to be confirmed in additional studies.

Cause and management of heart failure in patients with chronic renal disease.

Heart failure occurs in 40% of patients with end-stage renal disease and is a major determinant of mortality. Heart failure occurs in patients with left ventricular systolic dysfunction (dilated left ventricle) as well as those with a normal resting ejection fraction (nondilated left ventricle). This report describes the cause of heart failure among patients with end-stage renal disease and the effect of heart failure on survival. We also discuss the impact of renal failure on the medical management of these patients.

Estimating the glomerular filtration rate. Dos and don'ts for assessing kidney function.

The National Kidney Foundation's guidelines for CKD make the following recommendations about assessment of kidney function. Estimates of GFR are the best overall indices of the level of kidney function. The level of GFR should be estimated from prediction equations that take into account the serum creatinine concentration and some or all of the following variables: age, gender, race, and body size. In adults, the MDRD study and Cockcroft-Gault equations provide useful estimates of GFR. In children, the Schwartz and Counahan-Barratt equations are useful. The serum creatinine concentration should not be used alone to assess the level of kidney function. Clinical laboratories should report an estimate of GFR using a prediction equation, in addition to reporting the creatinine measurements. Autoanalyzer manufacturers and clinical laboratories should calibrate serum creatinine assays using an international standard. Measurement of creatinine clearance using timed (e.g., 24-hour) urine collections does not improve the estimate of GFR over that provided by prediction equations. A 24-hour urine sample provides useful information for estimation of GFR in individuals with exceptional dietary intake (vegetarian diet, use of creatine supplements) or muscle mass (amputation, malnutrition, muscle wasting). It is also useful for assessment of diet and nutritional status and need to start dialysis.

Epidemiology, diagnosis, and management of cardiac disease in chronic renal disease.

There is an extremely high burden of cardiovascular disease (CVD) in patients with renal disease. Both traditional as well as uremia-related factors are contributory. Diagnosis of CVD has limitations in patients with renal disease, and suspicion for the presence of CVD needs to be high even in the absence of classic symptoms. Prevention and management of CVD is similar to the general population but important differences need to be noted.

Mortality caused by sepsis in patients with end-stage renal disease compared with the general population.

BACKGROUND: In the United States, infection is second to cardiovascular disease as the leading cause of death in patients with end-stage renal disease (ESRD), and septicemia accounts for more than 75% of this category. This increased susceptibility to infections is partly due to uremia, old age, and comorbid conditions. Although it is intuitive to believe that mortality caused by sepsis may be higher in patients with ESRD compared with the general population (GP), no such data are currently available. METHODS: We compared annual mortality rates caused by sepsis in patients with ESRD (U.S. Health Care Financing Administration 2746 death notification form) with those in the GP (death certificate). Data were abstracted from the U.S. Renal Data System (1994 through 1996 Special Data request) and the National Center for Health Statistics. Data were stratified by age, gender, race, and diabetes mellitus (DM). Sensitivity analyses were performed to account for potential limitations of the data sources. RESULTS: Overall, the annual percentage mortality secondary to sepsis was approximately 100- to 300-fold higher in dialysis patients and 20-fold higher in renal transplant recipients (RTRs) compared with the GP. Mortality caused by sepsis was higher among diabetic patients across all populations. After stratification for age, differences between groups decreased but retained their magnitude. These findings remained robust despite a wide range of sensitivity analyses. Indeed, mortality secondary to sepsis remained approximately 50-fold higher in dialysis patients compared with the GP, using multiple cause-of-death analyses; was approximately 50-fold higher in diabetic patients with ESRD compared with diabetic patients in the GP, when accounting for underreporting of DM on death certificates in the GP; and was approximately 30-fold higher in RTRs compared with the GP, when accounting for the incomplete ascertainment of cause of death among RTRs. Furthermore, despite assignment of primary cause-of-death to major organ infections in the GP, annual mortality secondary to sepsis remained 30- to 45-fold higher in the dialysis population. CONCLUSIONS: Patients with ESRD treated by dialysis have higher annual mortality rates caused by sepsis compared with the GP, even after stratification for age, race, and DM. Consequently, this patient population should be considered at high-risk for the development of lethal sepsis.

Atherosclerotic cardiovascular disease risks in chronic hemodialysis patients.

BACKGROUND: Cardiovascular diseases are the most common causes of death among chronic hemodialysis patients, yet the risk factors for these events have not been well established. METHODS: In this cross-sectional study, we examined the relationship between several traditional cardiovascular disease risk factors and the presence or history of cardiovascular events in 936 hemodialysis patients enrolled in the baseline phase of the Hemodialysis Study sponsored by the U.S. National Institutes of Health. The adjusted odds ratios for each of the selected risk factors were estimated using a multivariable logistic regression model, controlling for the remaining risk factors, clinical center, and years on dialysis. RESULTS: Forty percent of the patients had coronary heart disease. Nineteen percent had cerebrovascular disease, and 23% had peripheral vascular disease. As expected, diabetes and smoking were strongly associated with cardiovascular diseases. Increasing age was also an important contributor, especially in the group less than 55 years and in nondiabetic patients. Black race was associated with a lower risk of cardiovascular diseases than non-blacks. Interestingly, neither serum total cholesterol nor predialysis systolic blood pressure was associated with coronary heart disease, cerebrovascular disease, or peripheral vascular disease. Further estimation of the coronary risks in our cohort using the Framingham coronary point score suggests that traditional risk factors are inadequate predictors of coronary heart disease in hemodialysis patients. CONCLUSIONS: Some of the traditional coronary risk factors in the general population appear to be also applicable to the hemodialysis population, while other factors did not correlate with atherosclerotic cardiovascular diseases in this cross-sectional study. Nontraditional risk factors, including the uremic milieu and perhaps the hemodialysis procedure itself, are likely to be contributory. Further studies are necessary to define the cardiovascular risk factors in order to devise preventive and interventional strategies for the chronic hemodialysis population.

Cardiovascular disease and chronic renal disease: a new paradigm.

Cardiovascular disease (CVD) is a major cause of morbidity and mortality among patients with chronic renal disease (CRD). Despite Improvement in treatment for CVD over the past 30 years, CVD mortality is approximately 15 times higher in dialysis patients than in the general population. The high prevalence of CVD among Incident dialysis patients suggests that CVD begins in earlier stages of CRD, and that implementation of risk factor reduction strategies earlier in the course of CRD may provide an opportunity to prevent CVD in CRD. Based on parallels between CVD and renal disease progression, we have proposed a paradigm that CVD and CRD are outcomes of the same underlying disorders. We propose that risk factor reduction strategies used to prevent CVD in the general population also be applied to patients with CRD, with the hope of preventing progression of renal disease, as well as preventing CVD.

Severe access recirculation secondary to free flow between the lumens of a dual-lumen dialysis catheter.

Over the last decade, it has been increasingly recognized that recirculation is present to some extent in all dual-lumen dialysis catheters. In addition, despite the recognition that dual-lumen dialysis catheters are not ideal as long-term hemodialysis access, their use for this purpose has increased secondary to both poor vascular access in an older and sicker dialysis population as well as their convenience. Although infection and thrombosis remain the most common complications of dialysis catheters, we report a case of severe access recirculation secondary to free flow between the two lumens of a tunneled, cuffed silicone dual-lumen dialysis catheter. We take this opportunity to discuss recirculation in dialysis catheters and to review potential causes of catheter breakdown.