William M. McClellan

Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis.

BACKGROUND Substantial controversy surrounds the use of estimated glomerular filtration rate (eGFR) and albuminuria to define chronic kidney disease and assign its stages. We undertook a meta-analysis to assess the independent and combined associations of eGFR and albuminuria with mortality. METHODS In this collaborative meta-analysis of general population cohorts, we pooled standardised data for all-cause and cardiovascular mortality from studies containing at least 1000 participants and baseline information about eGFR and urine albumin concentrations. Cox proportional hazards models were used to estimate hazard ratios (HRs) for all-cause and cardiovascular mortality associated with eGFR and albuminuria, adjusted for potential confounders. FINDINGS The analysis included 105,872 participants (730,577 person-years) from 14 studies with urine albumin-to-creatinine ratio (ACR) measurements and 1,128,310 participants (4,732,110 person-years) from seven studies with urine protein dipstick measurements. In studies with ACR measurements, risk of mortality was unrelated to eGFR between 75 mL/min/1.73 m(2) and 105 mL/min/1.73 m(2) and increased at lower eGFRs. Compared with eGFR 95 mL/min/1.73 m(2), adjusted HRs for all-cause mortality were 1.18 (95% CI 1.05-1.32) for eGFR 60 mL/min/1.73 m(2), 1.57 (1.39-1.78) for 45 mL/min/1.73 m(2), and 3.14 (2.39-4.13) for 15 mL/min/1.73 m(2). ACR was associated with risk of mortality linearly on the log-log scale without threshold effects. Compared with ACR 0.6 mg/mmol, adjusted HRs for all-cause mortality were 1.20 (1.15-1.26) for ACR 1.1 mg/mmol, 1.63 (1.50-1.77) for 3.4 mg/mmol, and 2.22 (1.97-2.51) for 33.9 mg/mmol. eGFR and ACR were multiplicatively associated with risk of mortality without evidence of interaction. Similar findings were recorded for cardiovascular mortality and in studies with dipstick measurements. INTERPRETATION eGFR less than 60 mL/min/1.73 m(2) and ACR 1.1 mg/mmol (10 mg/g) or more are independent predictors of mortality risk in the general population. This study provides quantitative data for use of both kidney measures for risk assessment and definition and staging of chronic kidney disease. FUNDING Kidney Disease: Improving Global Outcomes (KDIGO), US National Kidney Foundation, and Dutch Kidney Foundation.Background A comprehensive evaluation of the independent and combined associations of estimated glomerular filtration rate (eGFR) and albuminuria with mortality is required for assessment of the impact of kidney function on risk in the general population, with implications for improving the definition and staging of chronic kidney disease (CKD).

Anemia and Renal Insufficiency Are Independent Risk Factors for Death among Patients with Congestive Heart Failure Admitted to Community Hospitals: A Population-Based Study

The purpose of this retrospective cohort study was to examine the associations among chronic kidney disease, anemia, and risk of death among patients with heart failure. Retrospective cohort study. Patients with a principal diagnosis of heart failure (ICD9 codes 402.01, 402.11, 402.91, 404.01, 404.11, 404.91, and 428.xx) were included. Chronic kidney disease (CKD) was defined as a serum creatinine >1.4 mg/dl for women and >1.5 mg/dl for men. There were 665 eligible patients in the sample with a mean (SD) age of 75.7 (10.9) yr; 60% were women, 71% were white, and 38% had CKD. On admission, a hematocrit > or =40% was found for 30.3% of the patients; 22.9% had a hematocrit between 36% and 40%, 33.2% between 30% and 35%, and 13.6% had a hematocrit of <30%. The 1-yr death rates among individuals with and without CKD were 44.9% and 31.4%, respectively (relative risk [RR], 1.43; 95% confidence interval [CI], 1.17 to 1.75). The mortality at 1 yr was 31.2% for individuals with a hematocrit > or =40%; 33.8% (RR, 1.08; 95% CI. 0.79 to 1.47) for hematocrit 36 to 39%; 36.7% (RR, 1.17; 95% CI, 0.89 to 1.54) for hematocrit between 30 and 35%; and 50.0% (RR, 1.60; 95% CI, 1.19 to 2.16) for those with a hematocrit <30% (chi(2) for trend was 7.37; P = 0.007). Both hematocrit and serum creatinine were independently associated with increased risk of death during follow-up after controlling for other patient risk factors. In conclusion, CKD and anemia are frequent among older patients with heart failure and are independent predictors of subsequent risk of death.

Detection of Chronic Kidney Disease With Creatinine, Cystatin C, and Urine Albumin-to-Creatinine Ratio and Association With Progression to End-Stage Renal Disease and Mortality

CONTEXT A triple-marker approach for chronic kidney disease (CKD) evaluation has not been well studied. OBJECTIVE To evaluate whether combining creatinine, cystatin C, and urine albumin-to-creatinine ratio (ACR) would improve identification of risks associated with CKD compared with creatinine alone. DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study involving 26,643 US adults enrolled in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study from January 2003 to June 2010. Participants were categorized into 8 groups defined by estimated glomerular filtration rate (GFR) determined by creatinine and by cystatin C of either <60 or ≥60 mL/min/1.73 m(2) and ACR of either <30 or ≥30 mg/g. MAIN OUTCOME MEASURES All-cause mortality and incident end-stage renal disease with median follow-up of 4.6 years. RESULTS Participants had a mean age of 65 years, 40% were black, and 54% were women. Of 26,643 participants, 1940 died and 177 developed end-stage renal disease. Among participants without CKD defined by creatinine, 24% did not have CKD by either ACR or cystatin C. Compared with those with CKD defined by creatinine alone, the hazard ratio for death in multivariable-adjusted models was 3.3 (95% confidence interval [CI], 2.0-5.6) for participants with CKD defined by creatinine and ACR; 3.2 (95% CI, 2.2-4.7) for those with CKD defined by creatinine and cystatin C, and 5.6 (95% CI, 3.9-8.2) for those with CKD defined by all biomarkers. Among participants without CKD defined by creatinine, 3863 (16%) had CKD detected by ACR or cystatin C. Compared with participants who did not have CKD by any measure, the HRs for mortality were 1.7 (95% CI, 1.4-1.9) for participants with CKD defined by ACR alone, 2.2 (95% CI, 1.9-2.7) for participants with CKD defined by cystatin C alone, and 3.0 (95% CI, 2.4-3.7) for participants with CKD defined by both measures. Risk of incident end-stage renal disease was higher among those with CKD defined by all markers (34.1 per 1000 person-years; 95% CI, 28.7-40.5 vs 0.33 per 1000 person-years; 95% CI, 0.05-2.3) for those with CKD defined by creatinine alone. The second highest end-stage renal disease rate was among persons missed by the creatinine measure but detected by both ACR and cystatin C (rate per 1000 person-years, 6.4; 95% CI, 3.6-11.3). Net reclassification improvement for death was 13.3% (P < .001) and for end-stage renal disease was 6.4% (P < .001) after adding estimated GFR cystatin C in fully adjusted models with estimated GFR creatinine and ACR. CONCLUSION Adding cystatin C to the combination of creatinine and ACR measures improved the predictive accuracy for all-cause mortality and end-stage renal disease.

The prevalence of anemia in patients with chronic kidney disease

SUMMARY Objective: Anemia is a complication of chronic kidney disease and may contribute to adverse clinical outcomes. Early identification and treatment of anemia may improve cardiovascular morbidity and mortality. No large-scale population data are available specifically for patients with chronic kidney disease regarding prevalence of anemia, subpopulations at risk, and relationships between anemia and kidney function. This study was undertaken to address these questions in patients with chronic kidney disease, and investigate the relationship between anemia and glomerular filtration rate. Research design and methods: Large-scale, cross-sectional, US multicenter survey; 5222 patients (mean age, 68.2 years; 46.6% male); 237 physician practices. Eligible patients: ≥ 18 years of age; serum creatinine: 1.5 mg/dL–6.0 mg/dL (females), 2.0 mg/dL–6.0 mg/dL (males). Main outcome measures: Primary study end point: prevalence and severity of anemia (hemoglobin ≤ 12 g/dL). Data further stratified by hemoglobin (≤ 12 g/dL, ≤ 10 g/dL). Results: Primary etiologies of chronic kidney disease (5222 evaluable patients): diabetes (49.5%); hypertension (33.0%). Glomerular filtration rate: < 60 mL/min/1.73 m2 for 97.7% of evaluable patients. Mean ± SD serum creatinine level: 2.2 mg/dL ± 0.9 mg/dL; 2.5 mg/dL ± 1.0 mg/dL for males, 2.0 mg/dL ± 0.8 mg/dL for females. Mean ± SD hemoglobin: 12.2 g/dL ± 1.6 g/dL (47.7% had hemoglobin ≤ 12 g/dL; 8.9% had hemoglobin ≤ 10 g/dL). Prevalence of anemia was strongly associated with declining glomerular filtration rate. Percentage of patients with hemoglobin ≤ 12 g/dL increased from 26.7% to 75.5% when glomerular filtration rate decreased from ≥ 60 mL/min/1.73 m2 to < 15 mL/min/1.73 m2. Prevalence of hemoglobin ≤ 10 g/dL increased substantially from 5.2% to 27.2% when glomerular filtration rate diminished from ≥ 60 mL/min/1.73 m2 to < 15 mL/min/1.73 m2. After controlling for other patient characteristics associated with increased prevalence of anemia, the prevalence odds ratio for hemoglobin ≤ 10 g/dL was 0.54 (0.49–0.60) and for hemoglobin ≤ 12 g/dL was 0.68 (0.65–0.72), with each 10-mL/min/1.73 m2 increase in glomerular filtration rate. Predictors of anemia: diabetes, female sex, and race/ethnicity. Conclusions: Anemia was present in 47.7% of 5222 predialysis patients with chronic kidney disease. Prevalence of anemia increased as kidney function decreased. Certain subgroups are at increased risk for anemia.

Long-term risk of mortality and end-stage renal disease among the elderly after small increases in serum creatinine level during hospitalization for acute myocardial infarction.

BACKGROUND Although small changes in creatinine level during hospitalization have been associated with risk of short-term mortality, associations with posthospitalization end-stage renal disease (ESRD) and long-term mortality are unknown. We assessed the relationship between change in serum creatinine levels up to 3.0 mg/dL and death and ESRD among elderly survivors of hospitalization for acute myocardial infarction. METHODS Retrospective cohort study of a nationally representative sample of Medicare beneficiaries admitted with acute myocardial infarction to nonfederal US hospitals between February 1994 and July 1995. Outcomes were mortality and ESRD through June 2004. RESULTS The 87 094 eligible patients admitted to 4473 hospitals had a mean age of 77.1 years; for the 43.2% with some creatinine increase, quartiles of increase were 0.1, 0.2, 0.3 to 0.5, and 0.6 to 3.0 mg/dL. Incidence of ESRD and mortality ranged from 2.3 and 139.1 cases per 1000 person-years, respectively, among patients with no increase to 20.0 and 274.9 cases per 1000 person-years in the highest quartile of creatinine increase. Compared with patients without creatinine increase, adjusted hazard ratios by quartile of increase were 1.45, 1.97, 2.36, and 3.26 for ESRD and 1.14, 1.16, 1.26, and 1.39 for mortality, with no 95% confidence intervals overlapping 1.0 for either end point. CONCLUSION In a nationally representative sample of elderly patients discharged after hospitalization for acute myocardial infarction, small changes in serum creatinine level during hospitalization were associated with an independent higher risk of ESRD and death.

Kidney Function and Cognitive Impairment in US Adults: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study

BACKGROUND The association between kidney function and cognitive impairment has not been assessed in a national sample with a wide spectrum of kidney disease severity. STUDY DESIGN Cross-sectional. SETTING & PARTICIPANTS 23,405 participants (mean age, 64.9 +/- 9.6 years) with baseline measurements of creatinine and cognitive function participating in the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study, a study of stroke risk factors in a large national sample. PREDICTOR Estimated glomerular filtration rate (eGFR). OUTCOME Cognitive impairment. MEASUREMENTS Chronic kidney disease (CKD) was defined as eGFR less than 60 mL/min/1.73 m(2). Kidney function was analyzed in 10-mL/min/1.73 m(2) increments in those with CKD, and in exploratory analyses, across the range of kidney function. Cognitive function was assessed using the 6-Item Screener, and participants with a score of 4 or less were considered to have cognitive impairment. RESULTS CKD was associated with an increased prevalence of cognitive impairment independent of confounding factors (odds ratio, 1.23; 95% confidence interval, 1.06 to 1.43). In patients with CKD, each 10-mL/min/1.73 m(2) decrease in eGFR less than 60 mL/min/1.73 m(2) was associated with an 11% increased prevalence of impairment (odds ratio, 1.11; 95% confidence interval, 1.04 to 1.19). Exploratory analyses showed a nonlinear association between eGFR and prevalence of cognitive impairment, with a significant increased prevalence of impairment in those with eGFR less than 50 and 100 mL/min/1.73 m(2) or greater. LIMITATIONS Longitudinal measures of cognitive function were not available. CONCLUSIONS In US adults, lower levels of kidney function are associated with an increased prevalence of cognitive impairment. The prevalence of impairment appears to increase early in the course of kidney disease; therefore, screening for impairment should be considered in all adults with CKD.

Functional status and quality of life: Predictors of early mortality among patients entering treatment for end stage renal disease

We investigated the association between functional status and quality of life in newly-entered dialysis patients and the subsequent risk of mortality. We enrolled the patients from 37 dialysis facilities in two southeastern states (n = 294). Functional status was assessed by the Karnofsky Performance Scale (KPS) and quality of life by the Spitzer Quality of Life Index (SQLI). During a mean (SE) follow-up of 479.6 (109.4) days 49 patients (16.4%) of the cohort died. The mean KPS score (SE) for survivors was 7.31 (0.11) and for non-survivors was 5.89 (0.26), P less than 0.0001. The mean SQLI score (SE) for survivors was 6.74 (0.15) and non-survivors was 4.95 (0.28), P less than 0.0001. Strong gradients of the risk of mortality were found for both measurements. After controlling for other covariates including age, race, sex, primary cause of renal failure and the presence of comorbidity, both the KPS and SQLI scores were independently correlated with risk of mortality. We conclude that functional status and quality of life are strong independent risk factors for subsequent mortality in new dialysis patients. These are easily measured indicators which may serve to predict subsequent risk of mortality or adjust case-mix estimates for comparisons between dialysis populations.

Association of High Serum Creatinine and Anemia Increases the Risk of Coronary Events: Results from the Prospective Community-Based Atherosclerosis Risk in Communities (ARIC) Study

Coronary heart disease (CHD) is a major cause of morbidity and mortality in patients with chronic kidney disease or anemia. The purpose of this study was to examine whether the association between renal function and risk of CHD is modified by hemoglobin (Hgb) status. Analyses were based on data from the Atherosclerosis Risk in Communities study, a community-based study of risk factors for CHD in middle-aged people. People with known CHD at baseline were excluded from the analysis. Participants were followed for 9 yr for the occurrence of CHD. Anemia was defined as Hgb <13 g/dl in men and <12 g/dl in women. Cox proportional hazards models were used to assess the relative risk (RR) of CHD occurrence according to Hgb status, after adjusting for other risk factors (demographics, lipids, diabetes, hypertension, smoking, body mass index, and carotid intima-media thickness). A total of 13,329 participants were included. The interaction between Hgb concentration and serum creatinine (Scr) was significant (P = 0.02). Among people with anemia, a Scr >/=1.2 mg/dl in women or >/=1.5 mg/dl in men was associated with a higher risk of CHD (RR, 2.74; 95% confidence interval, 1.42 to 5.28) than those with normal Scr. In contrast, among those without anemia, this association was not noted (RR, 1.20; 95% confidence interval, 0.86 to 1.67). In conclusion, this study indicates that high Scr is associated with almost a threefold risk of CHD among middle-aged people with anemia, whereas no increased risk is found in people with high Scr in the absence of anemia.

Early detection and treatment of renal disease in hospitalized diabetic and hypertensive patients: Important differences between practice and published guidelines☆☆☆

This study was performed to ascertain the degree to which the care of hospitalized diabetic and hypertensive patients conforms to published guidelines for the detection and management of early renal disease. It was designed as a retrospective chart audit. Six hospitals, four nonurban referral centers, and two urban teaching institutions provided the data. Patients were a random sample of Medicare beneficiaries, with a mean age (SD) of 65.6 (9.1) years, admitted during 1994 with a primary or secondary diagnosis of either diabetes (n = 260) or hypertension (n = 327). A urinalysis was obtained for 163 (62.7%) of the diabetic patients. Among diabetics who had their urine tested, 31.3% had 1+ or greater dipstick proteinuria. A serum creatinine was obtained for 298 (91%) of the hypertensive patients, and 11.8% had a value of 1.5 mg/dL or greater. Abnormal renal function tests were recorded in the discharge summaries of 7.8% of the diabetic and 11.4% of the hypertensive patients. Patients with abnormal renal function were no more likely to be treated with angiotensin-converting enzyme inhibitors (ACEIs). Nonsteroidal antiinflammatory drugs (NSAIDs) were prescribed for 6% of diabetic and 8.8% of hypertensive patients with abnormal renal function at discharge. Despite the high prevalence of renal functional abnormalities detected by routine laboratory tests administered to elderly hospitalized diabetic and hypertensive patients, the medical records of these patients did not document awareness or appropriate management of the potential underlying kidney disease.

Racial Differences in the Incidence of Hypertensive End-Stage Renal Disease (ESRD) Are Not Entirely Explained by Differences in the Prevalence of Hypertension

Blacks experience a disproportionate risk of end-stage renal disease (ESRD) compared with whites. The increased prevalence of hypertension in blacks has been suggested as an explanation for this increased risk. We were able to examine this possibility using hypertensive ESRD incidence rates in a population with well-characterized prevalence of hypertension and rate of its control. After adjusting rates of hypertensive ESRD for age, sex, and differences in the prevalence of hypertension by race, we found black:white (B:W) relative risk still to be increased. Prevalence estimates for moderate-severe hypertension and differences in the control of hypertension between the two race groups are of insufficient magnitude to explain the increase in adjusted relative risk. This observation provides further support for the possibility that there are racial differences in the susceptibility to renal damage from elevated BP, which may explain increased risk for hypertensive ESRD in blacks, or that hypertension is being erroneously diagnosed as the cause of ESRD in blacks when another cause is present.