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Andrew S Levey

Publications and source records attributed to Andrew S Levey.

At least 19 recordsLinked to original sources
PubMed2006

Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate.

BACKGROUND: Glomerular filtration rate (GFR) estimates facilitate detection of chronic kidney disease but require calibration of the serum creatinine assay to the laboratory that developed the equation. The 4-variable equation from the Modification of Diet in Renal Disease (MDRD) Study has been reexpressed for use with a standardized assay. OBJECTIVE: To describe the performance of the revised 4-variable MDRD Study equation and compare it with the performance of the 6-variable MDRD Study and Cockcroft-Gault equations. DESIGN: Comparison of estimated and measured GFR. SETTING: 15 clinical centers participating in a randomized, controlled trial. PATIENTS: 1628 patients with chronic kidney disease participating in the MDRD Study. MEASUREMENTS: Serum creatinine levels were calibrated to an assay traceable to isotope-dilution mass spectrometry. Glomerular filtration rate was measured as urinary clearance of 125I-iothalamate. RESULTS: Mean measured GFR was 39.8 mL/min per 1.73 m2 (SD, 21.2). Accuracy and precision of the revised 4-variable equation were similar to those of the original 6-variable equation and better than in the Cockcroft-Gault equation, even when the latter was corrected for bias, with 90%, 91%, 60%, and 83% of estimates within 30% of measured GFR, respectively. Differences between measured and estimated GFR were greater for all equations when the estimated GFR was 60 mL/min per 1.73 m2 or greater. LIMITATIONS: The MDRD Study included few patients with a GFR greater than 90 mL/min per 1.73 m2. Equations were not compared in a separate study sample. CONCLUSIONS: The 4-variable MDRD Study equation provides reasonably accurate GFR estimates in patients with chronic kidney disease and a measured GFR of less than 90 mL/min per 1.73 m2. By using the reexpressed MDRD Study equation with the standardized serum creatinine assay, clinical laboratories can report more accurate GFR estimates.

Adult↗
PubMed2006

Adiponectin and mortality in patients with chronic kidney disease.

Adiponectin is presumed to possess antiatherogenic and cardioprotective properties. Limited data exist on the relationship between adiponectin and mortality in the earlier stages of chronic kidney disease. The Modification of Diet in Renal Disease study was a randomized, controlled trial that was conducted between 1989 and 1993. Adiponectin was measured in frozen samples that were obtained at baseline (N = 820). Survival status and cause of death, up to December 31, 2000, were obtained from the National Death Index. Multivariable Cox models were used to examine the relationship of adiponectin with all-cause and cardiovascular mortality. Mean +/- SD age was 52 +/- 12 yr, and mean +/- SD glomerular filtration rate (GFR) rate was 33 +/- 12 ml/min per 1.73 m2. Eighty-five percent of participants were white, and 60% were male. Mean +/- SD adiponectin was 12.8 +/- 8.0 mug/ml. Triglycerides, insulin resistance, glucose, body mass index, GFR, C-reactive protein, and albumin were inversely related and proteinuria and HDL cholesterol were directly related to adiponectin. During the 10-year follow-up period, 201 (25%) participants died of any cause, and 122 (15%) from cardiovascular disease. In multivariable adjusted Cox models, a 1-mug/ml increase in adiponectin was associated with a 3% (hazard ratio 1.03; 95% confidence interval 1.01 to 1.05; P = 0.02) increased risk for all-cause and 6% (hazard ratio 1.06; 95% confidence interval 1.03 to 1.09; P < 0.001) increased risk for cardiovascular mortality. High, rather than low, adiponectin is associated with increased mortality in this cohort of patients with chronic kidney disease stages 3 to 4. Further studies are necessary to confirm this association and to elucidate the underlying mechanisms.

Adiponectin↗
PubMed2006

Relationship between homocysteine and mortality in chronic kidney disease.

BACKGROUND: The relationship between total homocysteine (tHcy) and outcomes has not been investigated in patients with chronic kidney disease stages 3 to 4. METHODS AND RESULTS: The Modification of Diet in Renal Disease Study was a randomized, controlled trial of 840 patients. Serum tHcy was measured in frozen samples collected at baseline (n=804). Survival status and cause of death were obtained from the National Death Index. To evaluate its association with all-cause and cardiovascular disease (CVD) mortality, tHcy was evaluated both as tertiles (<14.7, 14.7 to 19.5, > or =19.6 micromol/L) and as a continuous variable (per 10/micromol/L). Participants had a mean age of 52+/-12 years and glomerular filtration rate (GFR) of 33+/-12 mL/min per 1.73 m2; 60% were male, and 85% were white. During a median follow-up of 10 years, 195 (24%) died from any cause, and 118 (15%) from CVD. The level of GFR was lower and proteinuria higher in the highest tHcy tertile. There was no association between the highest tertile of tHcy and all-cause (hazard ratio [HR]; 95% confidence interval [CI[, 1.32, 0.94 to 1.85) or CVD (HR; 95% CI, 1.50, 0.96 to 2.34) mortality in univariate analyses; this association was further attenuated by adjustment for GFR (HR; 95% CI all-cause, 1.04, 0.72 to 1.51; CVD, 1.20, 0.73 to 1.95). There was no association between tHcy as a continuous variable and all-cause (0.98, 0.83 to 1.16) or CVD (1.04, 0.85 to 1.27) mortality. CONCLUSIONS: Hyperhomocystinemia does not appear to be a risk factor for all-cause or CVD mortality in the Modification of Diet in Renal Disease Study. Prior studies demonstrating an association between tHcy and CVD risk may have inadequately adjusted for the confounding effects of kidney function.

Adult↗
PubMed2006

Rationale and design of the Folic Acid for Vascular Outcome Reduction In Transplantation (FAVORIT) trial.

BACKGROUND: Patients with chronic kidney disease, including kidney transplant recipients, are at high risk for cardiovascular disease (CVD). In addition to the constellation of traditional CVD risk factors in chronic kidney disease, elevated total homocysteine (tHcy) is notably more prevalent among the general population. The Folic Acid for Vascular Outcome Reduction In Transplantation (FAVORIT) trial is designed to evaluate whether lowering tHcy using vitamin supplementation reduces CVD events in renal transplant recipients. METHODS: FAVORIT is a multicenter double-blind randomized controlled clinical trial. Participants are clinically stable renal transplant recipients who are 6 months or longer posttransplant with elevated tHcy. Patients are randomized to a multivitamin that includes either a high-dose or low-dose of folic acid (5 or 0 mg), vitamin B6 (50 or 1.4 mg), and vitamin B12 (1000 or 2 microg). The primary end point is a composite of incident or recurrent CVD outcomes, that is, coronary heart, cerebrovascular, or abdominal aortic/lower extremity arterial events. A sample size of 4000 is estimated to provide 87% power to detect a 20% treatment effect. Recruitment is expected to continue until July 2006, with follow-up through June 2010. RESULTS: From August 2002 through December 2004, 2234 of the target 4000 patients were enrolled. In accordance with trial design, mean (SD) screening tHcy was elevated (17.4 +/- 6.2 micromol/L), and mean (SD) estimated creatinine clearance was consistent with stable renal function (58.0 +/- 18.6 mL/min). Evaluating baseline results to date, 42% of the randomized participants had a history of diabetes mellitus, and 21% had prevalent CVD. CONCLUSIONS: The FAVORIT trial is designed with sufficient power and follow-up time to detect a clinically relevant change in CVD risk between renal transplant recipients receiving a high or low tHcy-lowering folic acid multivitamin. Preliminary screening and baseline data support the trial's objectives.

Adult↗
PubMed2006

Chronic kidney disease after nephrectomy in patients with renal cortical tumours: a retrospective cohort study.

BACKGROUND: Chronic kidney disease is a graded and independent risk factor for substantial comorbidity and death. We aimed to examine new onset of chronic kidney disease in patients with small, renal cortical tumours undergoing radical or partial nephrectomy. METHODS: We did a retrospective cohort study of 662 patients with a normal concentration of serum creatinine and two healthy kidneys undergoing elective partial or radical nephrectomy for a solitary, renal cortical tumour (</=4 cm) between 1989 and 2005 at a referral cancer centre. Glomerular filtration rate (GFR) was estimated with the abbreviated Modification in Diet and Renal Disease Study equation. Separate analysis was undertaken, with chronic kidney disease defined as GFR lower than 60 mL/min per 1.73 m(2) and GFR lower than 45 mL/min per 1.73 m(2). FINDINGS: 171 (26%) patients had pre-existing chronic kidney disease before surgery. After surgery, the 3-year probability of freedom from new onset of GFR lower than 60 mL/min per 1.73 m(2) was 80% (95% CI 73-85) after partial nephrectomy and 35% (28-43; p<0.0001) after radical nephrectomy; corresponding values for GFRs lower than 45 mL/min per 1.73 m(2) were 95% (91-98) and 64% (56-70; p<0.0001), respectively. Multivariable analysis showed that radical nephrectomy remained an independent risk factor for patients developing new onset of GFR lower than 60 mL/min per 1.73 m(2) (hazard ratio 3.82 [95% CI 2.75-5.32]) and 45 mL/min per 1.73 m(2) (11.8 [6.24-22.4]; both p<0.0001). INTERPRETATION: Because the baseline kidney function of patients with renal cortical tumours is lower than previously thought, accurate assessment of kidney function is essential before surgery. Radical nephrectomy is a significant risk factor for the development of chronic kidney disease and might no longer be regarded as the gold standard treatment for small, renal cortical tumours.

Adult↗
PubMed2006

Cerebrovascular disease in maintenance hemodialysis patients: results of the HEMO Study.

BACKGROUND: Cerebrovascular disease (CBVD) in hemodialysis patients is associated with significant morbidity and mortality. A secondary analysis of CBVD in the Hemodialysis (HEMO) Study was performed. Specific objectives were to: (1) determine risk factors for the presence of CBVD at baseline, (2) assess risk factors for the subsequent occurrence of cerebrovascular deaths, and (3) analyze the effects of dose and flux on cerebrovascular mortality. METHODS: The HEMO Study was a randomized multicenter study evaluating the effects of high-dose versus standard-dose and high-flux versus low-flux hemodialysis. There were 1,846 patients enrolled, with a mean follow-up of 2.84 years. RESULTS: Factors associated with the baseline presence of CBVD included age (P < 0.0001), presence of any cardiac disease (P < 0.0001), and diabetes mellitus (P < 0.0001). There were 65 deaths caused by CBVD (event rate, 1.2/100 patient-years). Multivariate Cox regression using a backward-variables selection procedure showed that diabetes, lower albumin level, greater hematocrit, and lower body mass index at baseline were associated significantly with subsequent CBVD death. There was no effect of flux or dose on overall rate of CBVD deaths. However, an interaction was found between baseline CBVD status and flux intervention on CBVD death (P = 0.016). In the subgroup of patients without the baseline presence of CBVD, high-flux dialysis was associated with a lower risk for death caused by CBVD (P = 0.016). A borderline interaction between years of dialysis therapy and flux on subsequent CBVD death was detected (P = 0.05). The beneficial effect of high flux was evident in those on hemodialysis therapy for longer than 3.7 years (P = 0.012). CONCLUSION: High flux was associated with decreased CBVD mortality in those without known CBVD at baseline and those on hemodialysis therapy for longer than 3.7 years. This secondary analysis strengthens, but does not prove, the hypothesis that high-flux treatment may attenuate the death rate from vascular disease.

Aged↗
PubMed2006

Cardiovascular outcomes and all-cause mortality: exploring the interaction between CKD and cardiovascular disease.

BACKGROUND: Chronic kidney disease (CKD) is a risk factor for cardiovascular disease (CVD). Concurrently, CVD may promote CKD, resulting in a vicious cycle. We evaluated this hypothesis by exploring whether CKD and CVD have an additive or synergistic effect on future cardiovascular and mortality outcomes. METHODS: Patients were pooled from 4 community-based studies: Atherosclerosis Risk in Communities, Framingham Heart, Framingham Offspring, and Cardiovascular Health Study. CKD is defined by an estimated glomerular filtration rate less than 60 mL/min/1.73 m(2) (<1 mL/s/1.73 m(2)). Baseline CVD included myocardial infarction, angina, stroke, transient ischemic attack, claudication, heart failure, and coronary revascularization. The primary outcome is a composite of cardiac events, stroke, and death. Secondary outcomes included individual components. Multivariable analyses using Cox regression examined differences in study outcomes. The interaction of CKD and CVD was tested. RESULTS: The study population included 26,147 individuals. During 10 years, 4% (n = 2,927) of individuals with no CKD or CVD developed the primary outcome, 33% (n = 518) with only CKD, 37% (n = 1,260) with only CVD, and 66% (n = 459) with both. Both CKD (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.16 to 1.35; P < 0.0001) and CVD (HR, 1.83; 95% CI, 1.72 to 1.95; P < 0.0001) were independent risk factors for the primary outcome. The interaction term CKD x CVD was not statistically significant (HR, 0.98; 95% CI, 0.85 to 1.13; P = 0.74). Similar results were obtained for secondary outcomes. CONCLUSION: CKD and CVD are both strong independent risk factors for adverse cardiovascular and mortality outcomes in the general population. Although individuals with both risk factors are at extremely high risk, there does not appear to be a synergistic effect of CKD and CVD on outcomes.

Aged↗
PubMed2006

Effect of dietary protein restriction on the progression of kidney disease: long-term follow-up of the Modification of Diet in Renal Disease (MDRD) Study.

BACKGROUND: The long-term effect of a low-protein diet on the progression of chronic kidney disease is unknown. We evaluated effects of protein restriction on kidney failure and all-cause mortality during extended follow-up of the Modification of Diet in Renal Disease Study. METHODS: Study A was a randomized controlled trial from 1989 to 1993 of 585 patients with predominantly nondiabetic kidney disease and a moderate decrease in glomerular filtration rate (25 to 55 mL/min/1.73 m(2) [0.42 to 0.92 mL/s/1.73 m(2)]) assigned to a low- versus usual-protein diet (0.58 versus 1.3 g/kg/d). We used registries to ascertain the development of kidney failure (initiation of dialysis therapy or transplantation) or a composite of kidney failure and all-cause mortality through December 31, 2000. We used Cox regression models and intention-to-treat principles to compute hazard ratios for the low- versus usual-protein diet, adjusted for baseline glomerular filtration rate and other factors previously associated with the rate of decrease in glomerular filtration rate. We estimated hazard ratios for the entire follow-up period and then, in time-dependent analyses, separately for 2 consecutive 6-year periods of follow-up. RESULTS: Kidney failure and the composite outcome occurred in 327 (56%) and 380 patients (65%), respectively. After adjustment for baseline factors, hazard ratios were 0.89 (95% confidence interval [CI], 0.71 to 1.12) and 0.88 (95% CI, 0.71 to 1.08), respectively. Adjusted hazard ratios for both outcomes were lower during the first 6 years (0.68; 95% CI, 0.51 to 0.93 and 0.66; 95% CI, 0.50 to 0.87, respectively) than afterward (1.27; 95% CI, 0.90 to 1.80 and 1.29; 95% CI, 0.94 to 1.78; interaction P = 0.008 and 0.002, respectively). Limitations include lack of data for dietary intake and clinical conditions after conclusion of the trial. CONCLUSION: The efficacy of a 2- to 3-year intervention of dietary protein restriction on progression of nondiabetic kidney disease remains inconclusive. Future studies should include a longer duration of intervention and follow-up.

Blood Pressure↗
PubMed2005

Serum beta-2 microglobulin levels predict mortality in dialysis patients: results of the HEMO study.

In the randomized Hemodialysis (HEMO) Study, chronic high-flux dialysis, as defined by higher beta-2 microglobulin (beta(2)M) clearance, compared with low-flux dialysis did not significantly alter all-cause mortality in the entire cohort but was associated with lower mortality in long-term dialysis patients. This analysis examined the determinants of serum beta(2)M levels and the associations of serum beta(2)M levels or dialyzer beta(2)M clearance with mortality. In a multivariable regression model that examined 1704 patients, baseline residual kidney urea clearance and dialyzer beta(2)M clearance were strong predictors of predialysis serum beta(2)M levels at 1 mo of follow-up, with regression coefficients of -7.21 (+/-0.69 SE) mg/L per ml/min per 35 L urea volume (P < 0.0001) and -1.94 (+/-0.30) mg/L per ml/min (P < 0.0001),respectively. In addition, black race and baseline years on dialysis correlated positively whereas age, diabetes, serum albumin, and body mass index correlated negatively with serum beta(2)M levels (P < 0.05). In time-dependent Cox regression models, mean cumulative predialysis serum beta(2)M levels but not dialyzer beta(2)M clearance were associated with all-cause mortality (relative risk = 1.11 per 10-mg/L increase in beta(2)M level; 95% confidence interval 1.05 to 1.19; P = 0.001), after adjustment for residual kidney urea clearance and number of prestudy years on dialysis. This association is supportive of the potential value of beta(2)M as a marker to guide chronic hemodialysis therapy.

Adult↗
PubMed2005

Recommendations for improving serum creatinine measurement: a report from the Laboratory Working Group of the National Kidney Disease Education Program.

BACKGROUND: Reliable serum creatinine measurements in glomerular filtration rate (GFR) estimation are critical to ongoing global public health efforts to increase the diagnosis and treatment of chronic kidney disease (CKD). We present an overview of the commonly used methods for the determination of serum creatinine, method limitations, and method performance in conjunction with the development of analytical performance criteria. Available resources for standardization of serum creatinine measurement are discussed, and recommendations for measurement improvement are given. METHODS: The National Kidney Disease Education Program (NKDEP) Laboratory Working Group reviewed problems related to serum creatinine measurement for estimating GFR and prepared recommendations to standardize and improve creatinine measurement. RESULTS: The NKDEP Laboratory Working Group, in collaboration with international professional organizations, has developed a plan that enables standardization and improved accuracy (trueness) of serum creatinine measurements in clinical laboratories worldwide that includes the use of the estimating equation for GFR based on serum creatinine concentration that was developed from the Modification of Diet in Renal Disease (MDRD) study. CONCLUSIONS: The current variability in serum creatinine measurements renders all estimating equations for GFR, including the MDRD Study equation, less accurate in the normal and slightly increased range of serum creatinine concentrations [<133 micromol/L (1.5 mg/dL)], which is the relevant range for detecting CKD [<60 mL.min(-1).(1.73 m2)(-1)]. Many automated routine methods for serum creatinine measurement meet or exceed the required precision; therefore, reduction of analytical bias in creatinine assays is needed. Standardization of calibration does not correct for analytical interferences (nonspecificity bias). The bias and nonspecificity problems associated with some of the routine methods must be addressed.

Calibration↗
PubMed2005

Glycosylated hemoglobin and mortality in patients with nondiabetic chronic kidney disease.

In the general population, hyperglycemia in the absence of diabetes may be associated with increased risk for mortality. Hyperglycemia is prevalent in chronic kidney disease; however, the relationship between glycosylated hemoglobin (HbA(1c)) as a marker of chronic hyperglycemia and outcomes has not been studied in nondiabetic chronic kidney disease. HbA(1c) was measured at baseline in the randomized cohort of the Modification of Diet in Renal Disease Study (n = 840). Participants with diabetes (n = 43), fasting glucose levels >126 mg/dl (n = 20), or missing HbA(1c) levels (n = 9) were excluded. Survival status until December 2000 was obtained from the National Death Index. Death was classified as cardiovascular (CVD) when the primary cause was International Classification of Disease, Ninth Revision codes 390 to 459. Cox models were performed to assess the relationship of HbA(1c) with all-cause and CVD mortality. Mean (SD) age was 52 (12) years, and mean (SD) GFR was 32 (12) ml/min per 1.73 m(2). Eighty-six percent of participants were white, and 61% were male. Mean (SD) HbA(1c) was 5.6% (0.5). A total of 169 (22%) patients died, 96 (13%) from CVD. After adjustment for randomization assignments and demographic, CVD, and kidney disease factors, HbA(1c) was a predictor of all-cause mortality (hazard ratio per 1% increase 1.73; 95% confidence interval 1.24 to 2.41; P = 0.001). There was a trend toward statistical significance in the relationship between HbA(1c) and CVD mortality (hazard ratio per 1% increase 1.53; 95% confidence interval 0.96 to 2.43; P = 0.07). HbA(1c) is associated with increased mortality in nondiabetic kidney disease. Hyperglycemia may be a potential therapeutic target and HbA(1c) may be important as a risk stratification tool in this high-risk population.

Adult↗
PubMed2005

Anemia as a risk factor for cardiovascular disease and all-cause mortality in diabetes: the impact of chronic kidney disease.

Anemia is a potential nontraditional risk factor for cardiovascular disease (CVD). This study evaluated whether anemia is a risk factor for adverse outcomes in people with diabetes and whether the risk is modified by the presence of chronic kidney disease (CKD). Persons with diabetes from four community-based studies were pooled: Atherosclerosis Risk in Communities, Cardiovascular Health Study, Framingham Heart Study, and Framingham Offspring Study. Anemia was defined as a hematocrit <36% in women and <39% in men. CKD was defined as an estimated GFR of 15 to 60 ml/min per 1.73 m(2). Study outcomes included a composite of myocardial infarction (MI)/fatal coronary heart disease (CHD)/stroke/death and each outcome separately. Cox regression analysis was used to study the effect of anemia on the risk for outcomes after adjustment for potential confounders. The study population included 3015 individuals: 30.4% were black, 51.6% were women, 8.1% had anemia, and 13.8% had CKD. Median follow-up was 8.6 yr. There were 1215 composite events, 600 MI/fatal CHD outcomes, 300 strokes, and 857 deaths. In a model with a CKD-anemia interaction term, anemia was associated with the following hazard ratios (95% confidence intervals) in patients with CKD: 1.70 (1.24 to 2.34) for the composite outcome, 1.64 (1.03 to 2.61) for MI/fatal CHD, 1.81 (0.99 to 3.29) for stroke, and 1.88 (1.33 to 2.66) for all-cause mortality. Anemia was not a risk factor for any outcome in those without CKD (P > 0.2 for all outcomes). In persons with diabetes, anemia is primarily a risk factor for adverse outcomes in those who also have CKD.

Anemia↗