Essam F. Elsayed

Uric Acid and Incident Kidney Disease in the Community

Uric acid may mediate aspects of the relationship between hypertension and kidney disease via renal vasoconstriction and systemic hypertension. To investigate the relationship between uric acid and subsequent reduced kidney function, limited-access data of 13,338 participants with intact kidney function in two community-based cohorts, the Atherosclerosis Risks in Communities and the Cardiovascular Health Study, were pooled. Mean baseline serum uric acid was 5.9 +/- 1.5 mg/dl, mean baseline serum creatinine was 0.9 +/- 0.2 mg/dl, and mean baseline estimated GFR was 90.4 +/- 19.4 ml/min/1.73 m(2). During 8.5 +/- 0.9 yr of follow-up, 712 (5.6%) had incident kidney disease defined by GFR decrease (>or=15 ml/min/1.73 m(2) with final GFR <60 ml/min/1.73 m(2)), while 302 (2.3%) individuals had incident kidney disease defined by creatinine increase (>or=0.4 mg/dl with final serum creatinine >1.4 mg/dl in men and 1.2 mg/dl in women). In GFR- and creatinine-based logistic regression models, baseline uric acid level was associated with increased risk for incident kidney disease (odds ratio 1.07 [95% confidence interval 1.01 to 1.14] and 1.11 [95% confidence interval 1.02 to 1.21] per 1-mg/dl increase in uric acid, respectively), after adjustment for age, gender, race, diabetes, systolic BP, hypertension, cardiovascular disease, left ventricular hypertrophy, smoking, alcohol use, education, lipids, albumin, hematocrit, baseline kidney function and cohort; therefore, elevated serum uric acid level is a modest, independent risk factor for incident kidney disease in the general population.

Waist to Hip Ratio, Body Mass Index and Subsequent Kidney Disease and Death

BACKGROUND Chronic kidney disease (CKD) and obesity are important public health concerns. We examined the association between anthropomorphic measures and incident CKD and mortality. STUDY DESIGN Cohort study. SETTING & PARTICIPANTS Individual patient data pooled from the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study. PREDICTORS Waist-to-hip ratio (WHR), body mass index (BMI). OUTCOMES & MEASUREMENTS Incident CKD defined as serum creatinine level increase greater than 0.4 mg/dL with baseline creatinine level of 1.4 mg/dL or less in men and 1.2 mg/dL or less in women and final creatinine level greater than these levels, and, in separate analyses, estimated glomerular filtration rate (eGFR) decrease of 15 mL/min/1.73 m(2) or greater with baseline eGFR of 60 mL/min/1.73 m(2) or greater and final eGFR less than 60 mL/min/1.73 m(2). Multivariable logistic regression to determine the association between WHR, BMI, and outcomes. Cox models to evaluate a secondary composite outcome of all-cause mortality and incident CKD. RESULTS Of 13,324 individuals, mean WHR was 0.96 in men and 0.89 in women and mean BMI was 27.2 kg/m(2) in both men and women. During 9.3 years, 300 patients (2.3%) in creatinine-based models and 710 patients (5.5%) in eGFR-based models developed CKD. In creatinine-based models, each SD increase in WHR was associated with increased risk of incident CKD (odds ratio, 1.22; 95% confidence interval [CI], 1.05 to 1.43) and the composite outcome (hazard ratio, 1.12; 95% CI, 1.06 to 1.18), whereas each SD increase in BMI was not associated with CKD (odds ratio, 1.05; 95% CI, 0.93 to 1.20) and appeared protective for the composite outcome (hazard ratio, 0.94; 95% CI, 0.90 to 0.99). Results of eGFR-based models were similar. LIMITATIONS Single measures of creatinine, no albuminuria data. CONCLUSIONS WHR, but not BMI, is associated with incident CKD and mortality. Assessment of CKD risk should use WHR rather than BMI as an anthropomorphic measure of obesity.

The Relationship Between Nontraditional Risk Factors and Outcomes in Individuals With Stage 3 to 4 CKD

BACKGROUND Chronic kidney disease is associated with increased risk for cardiovascular disease and mortality. Both traditional and nontraditional cardiovascular disease risk factors may contribute. STUDY DESIGN Cohort. SETTINGS & PARTICIPANTS Community-based adult population of the Atherosclerosis Risk in Communities and Cardiovascular Health Studies with estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m(2). PREDICTORS Nontraditional cardiovascular disease risk factors, including body mass index, diastolic blood pressure, and triglyceride, albumin, uric acid, fibrinogen, C-reactive protein, and hemoglobin levels. OUTCOMES Composite of myocardial infarction, stroke, and all-cause mortality. Secondary outcomes included individual components of the composite. RESULTS Of 1,678 individuals with decreased eGFR (mean, 51.1 +/- 8.5 mL/min/1.73 m(2)), 891 (53%) reached the composite end point during a median follow-up of 108 months; 23% had a cardiac event, 45% died, and 14% experienced a stroke. Serum albumin level less than 3.9 g/dL (hazard ratio, 0.68 for every 0.3-g/dL decrease; 95% confidence interval, 0.60 to 0.77), increased serum triglyceride level (hazard ratio, 1.07 for every 50-mg/dL increase; 95% confidence interval, 1.02 to 1.12), C-reactive protein level (hazard ratio, 1.15 per log-unit increase; 95% confidence interval, 1.07 to 1.24), and fibrinogen level (hazard ratio, 1.12 per 50-mg/dL increase; 95% confidence interval, 1.07 to 1.18) independently predicted composite events. Both decreased (<14.5 g/dL) and increased (>14.5 g/dL) hemoglobin levels predicted composite events. Serum albumin level less than 3.9 g/dL and increased serum fibrinogen level independently predicted cardiac events. For serum albumin and hemoglobin levels, the relationship with composite and mortality outcomes was nonlinear (P < 0.001). LIMITATIONS Single assessment of eGFR. No albuminuria data. CONCLUSIONS Several nontraditional cardiovascular disease risk factors predict adverse outcomes in individuals with stage 3 to 4 chronic kidney disease. The relationship between risk factors and outcomes is often nonlinear.

Waist-to-hip ratio and body mass index as risk factors for cardiovascular events in CKD.

BACKGROUND The role of obesity as a risk factor for cardiovascular disease in patients with chronic kidney disease (CKD) is poorly understood. Waist-to-hip ratio (WHR) is less influenced by muscle and bone mass than body mass index (BMI). We compared WHR and BMI as risk factors for cardiac events (myocardial infarction and fatal coronary disease) in persons with CKD. STUDY DESIGN Cohort study. SETTING & PARTICIPANTS Persons with CKD, defined as baseline estimated glomerular filtration rate of 15 to 60 mL/min/1.73 m(2), drawn from 2 community studies: the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study. PREDICTOR WHR, waist circumference, and BMI. OUTCOMES & MEASUREMENTS Myocardial infarction and fatal coronary heart disease. RESULTS Of 1,669 participants with CKD, mean age was 70.3 years and 56% were women. Mean (SD) WHRs were 0.97 +/- 0.08 in men and 0.90 +/- 0.07 in women; mean (SD) BMI was 27.2 +/- 4.6 kg/m(2). During a mean of 9.3 years of follow-up, there were 334 cardiac events. In multivariable-adjusted Cox models, the highest WHR group (n = 386) was associated with an increased risk of cardiac events compared with the lowest WHR group (hazard ratio, 1.36; 95% confidence interval, 1.01 to 1.83). Obesity, defined as BMI greater than 30 kg/m(2) (n = 381), was not associated with cardiac events (hazard ratio, 0.86; 95% confidence interval, 0.62 to 1.20) in comparison to participants with normal BMI (<25 kg/m(2)). Results with waist circumference were similar to those with BMI. LIMITATIONS Absence of a gold standard for measurement of visceral fat. CONCLUSIONS WHR, but not BMI, is associated with cardiac events in persons with CKD. Relying exclusively on BMI may underestimate the importance of obesity as a cardiovascular disease risk factor in persons with CKD.

Lowest Systolic Blood Pressure Is Associated with Stroke in Stages 3 to 4 Chronic Kidney Disease

Hypertension is a risk factor for stroke in the general population, whereas in hemodialysis patients, higher systolic BP (SBP) may be protective. Therefore, this study evaluated the relationship between SBP and stroke in individuals with and without chronic kidney disease (CKD) to assess whether this altered relationship exists in earlier stages of CKD. A secondary evaluation of two community-based, longitudinal, limited-access data sets was performed: Atherosclerosis Risk in Communities and Cardiovascular Health Study. CKD was defined as estimated GFR <60 ml/min per 1.73 m(2). The primary study outcome was definite or probable incident stroke. We used Cox proportional hazards models to assess the relationship between CKD and stroke, focusing on the role of SBP. Among 20,358 individuals studied, 1549 (7.6%) had CKD. During a median duration of 111 mo, 1029 (5.1%) individuals had a stroke. CKD and elevated SBP both independently predicted incident stroke (hazard ratio [HR] 1.22 [95% confidence interval [CI]1.02 to 1.44] and HR 1.18 [95% CI 1.14 to 1.21] per 10-mmHg rise, respectively). Individuals with CKD had a J-shaped relationship with stroke outcomes such that those with SBP <120 mmHg were at significantly increased risk compared with individuals with CKD and SBP 120 to 129 mmHg (HR 2.51; 95% CI 1.30 to 4.87); risk increased for BP >130 mmHg in CKD. This J shape was not seen in individuals without CKD. CKD and elevated SBP are independent risk factors for incident stroke. In CKD, individuals with the lowest BP are at increased risk for stroke. This pattern is not seen in the general population.

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.