Background Uric acid levels are increased in patients with kidney dysfunction. We tested the hypothesis that uric acid may be associated with kidney disease progression. Study Design Cohort study. ...Setting & Participants 5,808 participants of the Cardiovascular Health Study. Predictor Uric acid levels. Outcomes & Measurements Kidney disease progression was defined as a decrease in estimated glomerular filtration rate (GFR) of 3 mL/min/1.73 m2 per year or greater (≥0.05 mL/s) and as incident chronic kidney disease (CKD). Measures of kidney function were estimated GFR using the Modification of Diet in Renal Disease Study equation. Results Higher quintiles of uric acid levels were associated with greater prevalences of estimated GFR less than 60 mL/min/1.73 m2 (<1.00 mL/s) of 7%, 14%, 12%, 25%, and 42% for quintiles 1 (≤4.41 mg/dL ≤262 μmol/L), 2 (4.41 to 5.20 mg/dL 262 to 309 μmol/L), 3 (5.21 to 5.90 mg/dL 310 to 351 μmol/L), 4 (5.91 to 6.90 mg/dL 352 to 410 μmol/L), and 5 (>6.90 mg/dL >410 μmol/L), respectively. In comparison, there was only a modest, but significant, association between quintiles of uric acid levels and progression of kidney function decrease, with adjusted odds ratios of 1.0, 0.88 (95% confidence interval CI, 0.64 to 1.21), 1.23 (95% CI, 0.87 to 1.75), 1.47 (95% CI, 1.04 to 2.07), and 1.49 (95% CI, 1.00 to 2.22) for quintiles 1 through 5, respectively. No significant association was found between uric acid level and incident CKD (adjusted odds ratio, 1.00; 95% CI, 0.89 to 1.14). Limitations Measurements of albuminuria were not available. Conclusions Uric acid levels are associated strongly with prevalent CKD. In comparison, greater uric acid levels had a significant, but much weaker, association with progression of kidney disease.
Abstract Background Often, patients with chronic kidney disease are reported to be unaware of it. We prospectively evaluated the association between awareness of kidney disease to end-stage renal ...disease and mortality. Methods We utilized 2000-2009 data from the National Kidney Foundation's Kidney Early Evaluation Program. Mortality was determined by cross reference to the Social Security Administration Death Master File and development of end stage by cross reference with the United States Renal Data System. Results Of 109,285 participants, 28,244 (26%) had chronic kidney disease defined by albuminuria or estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 . Only 9% (n = 2660) reported being aware of kidney disease. Compared with those who were not aware, participants aware of chronic kidney disease had lower eGFR (49 vs 62 mL/min/1.73 m2 ) and a higher prevalence of albuminuria (52% vs. 46%), diabetes (47% vs 42%), cardiovascular disease (43% vs 28%), and cancer (23% vs 14%). Over 8.5 years of follow-up, aware participants compared with those unaware had a lower rate of survival for end stage (83% and 96%) and mortality (78% vs 81%), P <.001. After adjustment for demographics, socioeconomic factors, comorbidity, and severity of kidney disease, aware participants continued to demonstrate an increased risk for end-stage renal disease (hazard ratio 1.37; 95% confidence interval, 1.07-1.75; P <.0123) and mortality (hazard ratio 1.27; 95% confidence interval, 1.07-1.52; P <.0077) relative to unaware participants with chronic kidney disease. Conclusions Among patients identified as having chronic kidney disease at a health screening, only a small proportion had been made aware of their diagnosis previously by clinicians. This subgroup was at a disproportionately high risk for mortality and end-stage renal disease.
Background The prevalence of chronic kidney disease is growing most rapidly among older adults; however, determinants of impaired kidney function in this population are not well understood. Obesity ...assessed in midlife has been associated with chronic kidney disease. Study Design Cohort study. Setting & Participants 4,295 participants in the community-based Cardiovascular Health Study, aged ≥ 65 years. Predictors Body mass index, waist circumference, and fat mass measured using bioelectrical impedance. Outcome Change in glomerular filtration rate (GFR) during 7 years of follow-up. Measurements Longitudinal estimates of GFR calculated using the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation. Results Estimated GFR decreased by an average of 0.4 ± 3.6 mL/min/1.73 m2 /y, and rapid GFR loss (>3 mL/min/1.73 m2 /y) occurred in 693 participants (16%). Baseline body mass index, waist circumference, and fat mass were each associated with increased risk of rapid GFR loss: ORs, 1.19 (95% CI, 1.09-1.30) per 5 kg/m2 , 1.25 (95% CI, 1.16-1.36) per 12 cm, and 1.14 (95% CI, 1.05-1.24) per 10 kg after adjustment for age, sex, race, and smoking. The magnitude of increased risk was larger for participants with estimated GFR < 60 mL/min/1.73 m2 at baseline ( P for interaction < 0.05). Associations were substantially attenuated by further adjustment for diabetes, hypertension, and C-reactive protein level. Obesity measurements were not associated with change in GFR estimated using serum cystatin C level. Limitations Few participants with advanced chronic kidney disease at baseline, no direct GFR measurements. Conclusion Obesity may be a modifiable risk factor for the development and progression of kidney disease in older adults.
Background The strength and direction of the associations between inflammation and coagulation biomarkers with kidney disease onset and progression remain unclear, especially in a population-based ...setting. Study Design Prospective observational study. Setting & Participants 4,966 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with a cystatin C–based estimate of glomerular filtration rate (eGFRcys ) >60 mL/min/1.73 m2 and at least one follow-up measurement of kidney function. All participants were free of cardiovascular disease at entry. Predictor We evaluated the associations of C-reactive protein (CRP), interleukin 6 (IL-6), fibrinogen, factor VIII, and d -dimer levels with kidney function decrease. Outcomes & Measurements Kidney function decrease was assessed primarily by repeated measurements of eGFRcys over 5 years. Rapid decrease in kidney function was defined as eGFR decrease >3 mL/min/1.73 m2 per year. Incident low eGFR was defined as the onset of eGFRcys <60 mL/min/1.73 m2 at any follow-up examination and eGFRcys decrease ≥1 mL/min/1.73 m2 per year. Results Mean age was 60 years, 39% were white, 52% were women, and 11% had diabetes. Mean eGFRcys was 96 mL/min/1.73 m2 and 7% had albuminuria. Median follow-up was 4.77 years. Higher factor VIII levels (per 1 standard deviation SD of biomarker) had the strongest association with kidney function decrease (β = −0.25; 95% CI, −0.38 to −0.12; P < 0.001), followed by IL-6 (β = −0.16; 95% CI, −0.29 to −0.03; P = 0.01), CRP (β = −0.09; 95% CI, −0.22 to 0.03; P = 0.1), and fibrinogen levels (β = −0.09; 95% CI, −0.22 to 0.04; P = 0.2). Each 1-SD higher concentration of IL-6 (OR, 1.15; 95% CI, 1.07-1.23), factor VIII (OR, 1.11; 95% CI, 1.03-1.18), and CRP (OR, 1.09; 95% CI, 1.02-1.16) at baseline was associated significantly with rapid kidney function decrease. Only IL-6 level was associated significantly with incident low eGFR (OR, 1.09; 95% CI, 1.00-1.19). Limitations Observational study design and absence of measured GFR. Conclusions Inflammation and coagulation biomarkers are associated with decreasing kidney function in ambulatory adults without established cardiovascular disease or chronic kidney disease.
Background In populations with prevalent chronic kidney disease (CKD), lower serum bicarbonate levels are associated with more rapid CKD progression, but whether lower bicarbonate levels also are ...associated with risk of incident estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 and CKD progression among community-living persons with predominantly preserved kidney function is unknown. Study Design Longitudinal observational cohort study. Setting & Participants Well-functioning community-living elders aged 70-79 years at inception. Predictor Serum bicarbonate level measured at the time of collection by arterialized venous blood sample using an arterial blood gas analyzer. Outcomes Change in eGFR over 7 years, and new eGFR < 60 mL/min/1.73 m2 with a rate of loss of at least 1 mL/min/1.73 m2 per year. Measurements Linear and logistic regressions were used to evaluate associations of baseline serum bicarbonate level with change in eGFR and incident eGFR < 60 mL/min/1.73 m2. Results At baseline, mean eGFR was 84 ± 16 (SD) mL/min/1.73 m2 , and serum bicarbonate level was 25.2 ± 1.9 mmol/L. Compared with participants with higher bicarbonate concentrations (23.0-28.0 mmol/L), those with bicarbonate concentrations < 23 mmol/L (n = 85 8%) lost eGFR 0.55 (95% CI, 0.13-0.97) mL/min/1.73 m2 per year faster in models adjusted for demographics, CKD risk factors, baseline eGFR, and urine albumin-creatinine ratio. Among the 989 (92%) participants with baseline eGFRs > 60 mL/min/1.73 m2 , 252 (25%) developed incident eGFRs < 60 mL/min/1.73 m2 at follow-up. Adjusting for the same covariates, participants with bicarbonate concentrations < 23 mmol/L had nearly 2-fold greater odds of incident eGFRs < 60 mL/min/1.73 m2 (OR, 1.72; 95% CI, 0.97-3.07) compared with those with higher bicarbonate concentrations. Limitations Only 2 measurements of kidney function separated by 7 years and loss to follow-up due to intervening mortality in this elderly population. Conclusions Lower serum bicarbonate concentrations are associated independently with decline in eGFR and incident eGFR < 60 mL/min/1.73 m2 in community-living older persons. If confirmed, serum bicarbonate levels may give insight into kidney tubule health in persons with preserved eGFRs and suggest a possible new target for intervention to prevent CKD development.
Background Higher urine albumin-creatinine ratio (ACR) is associated with cardiovascular disease (CVD) events, an association that is stronger than that between spot urine albumin on its own and CVD. ...Urine creatinine excretion is correlated with muscle mass, and low muscle mass also is associated with CVD. Whether low urine creatinine concentration in the denominator of the ACR contributes to the association of ACR with CVD is uncertain. Study Design Prospective cohort study. Setting & Participants 6,770 community-living individuals without CVD. Predictors Spot urine albumin concentration, the reciprocal of the urine creatinine concentration (1/UCr), and ACR. Outcome Incident CVD events. Results During a mean of 7.1 years of follow-up, 281 CVD events occurred. Geometric mean values for spot urine creatinine concentration, urine albumin concentration, and ACR were 95 ± 2 (SD) mg/dL, 0.7 ± 3.7 mg/dL, and 7.0 ± 3.1 mg/g. Urine creatinine concentration was lower in older, female, and low-weight individuals. Adjusted HRs per 2-fold higher increment in each urinary measure with CVD events were similar (1/UCr: 1.07 95% CI, 0.94-1.22; urine albumin concentration: 1.08 95% CI, 1.01-1.14; and ACR: 1.11 95% CI, 1.04-1.18). ACR ≥10 mg/g was associated more strongly with CVD events in individuals with low weight (HR for lowest vs highest tertile: 4.34 vs 1.97; P for interaction = 0.006). Low weight also modified the association of urine albumin concentration with CVD ( P for interaction = 0.06), but 1/UCr did not ( P for interaction = 0.9). Limitations We lacked 24-hour urine data. Conclusions Although ACR is associated more strongly with CVD events in persons with low body weight, this association is not driven by differences in spot urine creatinine concentration. Overall, the associations of ACR with CVD events appear to be driven primarily by urine albumin concentration and less by urine creatinine concentration.
Background Given the increasing costs and poor outcomes of end-stage renal disease (ESRD), we sought to identify risk factors for ESRD in people with preserved estimated glomerular filtration rate ...(eGFR), with or without albuminuria, who were at high risk of ESRD. Methods This cohort study included participants in the National Kidney Foundation's Kidney Early Evaluation Program (KEEP) with eGFR ≥60 mL/min/1.73 m2 at baseline stratified by the presence or absence of albuminuria. The Chronic Kidney Disease Epidemiology Collaboration equation was used to calculate eGFR. Urine was tested for albuminuria by semiquantitative dipstick. The outcome was the development of treated chronic kidney failure, defined as initiation of maintenance dialysis therapy or kidney transplantation, determined by linkage to the US Renal Data System. We used a Cox model with the Fine-Gray method to assess risk factors for treated chronic kidney failure while accounting for the competing risk of death. Results During a median follow-up of 4.8 years, 126 of 13,923 participants with albuminuria (16/10,000 patient-years) and 56 of 109,135 participants without albuminuria (1.1/10,000 patient-years) developed treated chronic kidney failure. Diabetes was a strong risk factor for developing treated chronic kidney failure in participants with and without albuminuria (adjusted HRs of 9.3 95% CI, 5.7-15.3 and 7.8 95% CI, 4.1-14.8, respectively). Black race, lower eGFR, and higher systolic blood pressure also were associated with higher adjusted risks of developing treated chronic kidney failure. Conclusions In a diverse high-risk cohort of KEEP participants with preserved eGFR, we showed that diabetes, higher systolic blood pressure, lower eGFR, and black race were risk factors for developing treated chronic kidney failure irrespective of albuminuria status, although the absolute risk of kidney failure in participants without albuminuria was very low. Our findings support testing for kidney disease in high-risk populations, which often have otherwise unrecognized kidney disease.
Objectives The aim of this study was to evaluate associations of 25-hydroxyvitamin D (25-OHD) and parathyroid hormone (PTH) concentrations separately and in combination with incident cardiovascular ...events and mortality during 14 years of follow-up in the CHS (Cardiovascular Health Study). Background Vitamin D deficiency and PTH excess are common in older adults and may adversely affect cardiovascular health. Methods A total of 2,312 participants who were free of cardiovascular disease at baseline were studied. Vitamin D and intact PTH were measured from previously frozen serum using mass spectrometry and a 2-site immunoassay. Outcomes were adjudicated cases of myocardial infarction, heart failure, cardiovascular death, and all-cause mortality. Results There were 384 participants (17%) with serum 25-OHD concentrations <15 ng/ml and 570 (25%) with serum PTH concentrations ≥65 pg/ml. After adjustment, each 10 ng/ml lower 25-OHD concentration was associated with a 9% greater (95% confidence interval CI: 2% to 17% greater) relative hazard of mortality and a 25% greater (95% CI: 8% to 44% greater) relative hazard of myocardial infarction. Serum 25-OHD concentrations <15 ng/ml were associated with a 29% greater (95% CI: 5% to 55% greater) risk for mortality. Serum PTH concentrations ≥65 pg/ml were associated with a 30% greater risk for heart failure (95% CI: 6% to 61% greater) but not other outcomes. There was no evidence of an interaction between serum 25-OHD and PTH concentrations and cardiovascular events. Conclusions Among older adults, 25-OHD deficiency is associated with myocardial infarction and mortality; PTH excess is associated with heart failure. Vitamin D and PTH might influence cardiovascular risk through divergent pathways.
Background Moderate kidney disease may predispose to infection. We sought to determine whether decreased kidney function, estimated by serum cystatin C level, was associated with the risk of ...infection-related hospitalization in older individuals. Study Design Cohort study. Setting & Participants 5,142 Cardiovascular Health Study (CHS) participants with measured serum creatinine and cystatin C and without estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m2 at enrollment. Predictor The primary exposure of interest was eGFR using serum cystatin C level (eGFRSCysC ). Outcome Infection-related hospitalizations during a median follow-up of 11.5 years. Results In adjusted analyses, eGFRSCysC categories of 60-89, 45-59, and 15-44 mL/min/1.73 m2 were associated with 16%, 37%, and 64% greater risk of all-cause infection-related hospitalization, respectively, compared with eGFRSCysC ≥90 mL/min/1.73 m2 . When cause-specific infection was examined, eGFRSCysC of 15-44 mL/min/1.73 m2 was associated with an 80% greater risk of pulmonary and 160% greater risk of genitourinary infection compared with eGFRSCysC ≥90 mL/min/1.73 m2. Limitations No measures of urinary protein, study limited to principal discharge diagnosis. Conclusions Lower kidney function, estimated using cystatin C level, was associated with a linear and graded risk of infection-related hospitalization. These findings highlight that even moderate degrees of decreased kidney function are associated with clinically significant higher risks of serious infection in older individuals.
Background Laboratory studies suggest that urinary uromodulin, the most common protein in the urine of healthy adults, may protect against urinary tract infection (UTI). Epidemiologic studies ...evaluating this relationship in humans are lacking. Study Design Prospective longitudinal cohort study. Setting & Participants 953 participants enrolled in the Cardiovascular Health Study. Predictor Uromodulin assayed using enzyme-linked immunosorbent assay in spot urine samples. Outcomes Composite of outpatient UTI events or UTI-related hospitalizations and each of them individually identified using International Classification of Diseases, Ninth Revision ( ICD-9 ) codes using negative binomial regression with robust standard errors adjusted for age, race, sex, body mass index, diabetes, estimated glomerular filtration rate, and urinary albumin and urinary creatinine excretion. Results Median uromodulin level was 25.9 (IQR, 17.3-38.9) μg/mL, mean age of participants was 78 years, 61% were women, and 15% were black. There were 331 outpatient UTI events and 87 UTI-related hospitalizations among 186 participants during a median 9.9 years of follow-up. Persons in the highest quartile (>38.93 μg/mL) of uromodulin concentration had a significantly lower risk for the composite outcome (incidence rate ratio IRR, 0.47; 95% CI, 0.29-0.79) compared with those in the lowest quartile (≤17.26 μg/mL). This association remained significant for outpatient UTI events (highest vs lowest quartile even after excluding those with prior UTI: IRR, 0.42; 95% CI, 0.23-0.77). The direction of association with UTI hospitalization was similar, but not statistically significant (IRR, 0.78; 95% CI, 0.39-1.58). Limitations Use of ICD-9 codes to identify outcomes and lack of generalizability to younger populations. Conclusions High urinary uromodulin levels are associated with lower risk for UTI in older community-dwelling adults independent of traditional UTI risk factors. This finding supports prior laboratory data indicating a protective role of uromodulin against UTI. Further research is needed to understand if this may lead to new treatments to prevent or treat UTI.
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