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ABSTRACT: BACKGROUND: Atrial fibrillation (AF) frequently occurs in patients with chronic kidney disease (CKD). However, the long-term impact of development of AF on the risk of adverse renal outcomes in patients with CKD is unknown. In this study, we determined the association between incident AF and risk of end-stage renal disease (ESRD) among adults with CKD. METHODS AND RESULTS: We studied adults with CKD (defined as persistent glomerular filtration rate [eGFR] <60 ml/min/1.73 m(2) by the CKD-EPI equation) enrolled in Kaiser Permanente Northern California who were identified between 2002-2010 and who did not have prior ESRD or previously documented AF. Incident AF was identified using primary hospital discharge diagnoses and/or two or more outpatient visits for AF. Incident ESRD was ascertained from a comprehensive health plan registry for dialysis and renal transplant. Among 206,229 adults with CKD, 16,463 developed incident AF. During a mean follow-up of 5.1±2.5 years, there were 345 cases of ESRD that occurred after development of incident AF (74 per 1000 person-years) compared with 6505 cases of ESRD during periods without AF (64 per 1000 person-years, P<0.001). After adjustment for potential confounders, incident AF was associated with a 67% increase in rate of ESRD (hazard ratio 1.67, 95% confidence interval: 1.46-1.91). CONCLUSIONS: Incident AF is independently associated with increased risk of developing ESRD in adults with CKD. Further study is needed to identify potentially modifiable pathways through which AF leads to a higher risk of progression to ESRD.
Circulation 12/2012; · 14.74 Impact Factor
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ABSTRACT: Background: Telomere attrition is a novel risk factor for cardiovascular disease. Studies of telomere length in relation to kidney function are limited. We explored the association of kidney function with telomere length and telomere shortening. Methods: The Heart and Soul Study is a longitudinal study of patients with stable coronary heart disease. Measures of baseline kidney function included: serum creatinine, creatinine-derived estimated glomerular filtration rate (eGFR(CKD-EPI)), 24-hour urine measured creatinine clearance, cystatin C, cystatin C-derived estimated glomerular filtration rate (eGFRcys) and urine albumin to creatinine ratio. Telomere length was measured from peripheral blood leukocytes at baseline (n = 954) and 5 years later (n = 608). Linear regression models were used to test the association of kidney function with (i) baseline telomere length and (ii) change in telomere length over 5 years. Results: At baseline, mean eGFR(CKD-EPI) was 72.6 (±21.5) ml/min/1.73 m(2), eGFRcys was 71.0 (±23.1) ml/min/1.73 m(2) and ACR was 8.6 (±12.3) mg/g. Only lower baseline eGFR(CKD-EPI) was associated with shorter baseline telomere length (9.1 (95% CI 1.2-16.9) fewer base pairs for every 5 ml/min/1.73 m(2) lower eGFR(CKD-EPI)). Lower baseline eGFR(CKD-EPI) (and all other measures of kidney function) predicted more rapid telomere shortening (10.8 (95% CI 4.3-17.3) decrease in base pairs over 5 years for every 5 ml/min/1.73 m(2) lower eGFR(CKD-EPI)). After adjustment for age, these associations were no longer statistically significant. Conclusions: In patients with coronary heart disease, reduced kidney function is associated with (i) shorter baseline telomere length and (ii) more rapid telomere shortening over 5 years; however, these associations are entirely explained by older age.
American Journal of Nephrology 10/2012; 36(5):405-411. · 2.54 Impact Factor
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Nisha Bansal
Nephrology Dialysis Transplantation 06/2012; 27(9):3387-91. · 3.40 Impact Factor
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ABSTRACT: Urine dopamine (DA) is produced in the proximal tubule and has been found to increase in response to dietary phosphorus intake, and to contribute to greater urinary phosphorus excretion in animal models. Whether urine DA is associated with phosphorus homeostasis in humans is uncertain.
This was a cross-sectional study of 884 outpatients. DA was measured from 24-hour urine collections. We examined cross-sectional associations between urine DA and serum phosphorus, 24-hour urine phosphorus (as an indicator of dietary phosphorus absorption), fractional excretion of phosphorus (FEphos), fibroblast growth factor (FGF)-23, and parathyroid hormone (PTH). Models were adjusted for age, sex, race, eGFR, albuminuria, hypertension, heart failure, tobacco use, body mass index, and diuretic use.
Mean age was 66.6 ± 11 years and mean eGFR was 71 ± 21.3 ml/min/1.73 m(2). The mean urine DA was 193 ± 86 µg/day, mean serum phosphorus was 3.6 ± 0.6 mg/dl, mean daily urine phosphorus excretion was 671 ± 312 mg/day, and mean FEphos was 17 ± 9%. In adjusted models, each standard deviation higher DA was associated with 78.4 mg/day higher urine phosphorus and 0.9% lower FEphos (p < 0.05 for both). There was no statistically significant association between urine DA, serum phosphorus, FGF-23 or PTH in adjusted models.
Higher dietary phosphorus absorption is associated with higher urine DA in humans, consistent with animal models. However, higher urine DA is not associated with FGF-23 or PTH, suggesting that known mechanisms of renal tubular handling of phosphorus may not be involved in the renal dopamine-phosphorus regulatory pathway in humans.
American Journal of Nephrology 05/2012; 35(6):483-90. · 2.54 Impact Factor
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ABSTRACT: The aim of this study was to examine whether kidney dysfunction is associated with the type of clinical presentation of coronary heart disease (CHD).
Reduced kidney function increases the risk for developing CHD, but it is not known whether it also influences the acuity of clinical presentation, which has important prognostic implications.
A case-control study was conducted of subjects whose first clinical presentation of CHD was either acute myocardial infarction or stable exertional angina between October 2001 and December 2003. Estimated glomerular filtration rate (eGFR) before the incident event was calculated using calibrated serum creatinine and the abbreviated MDRD (Modification of Diet in Renal Disease) equation. Patient characteristics and use of medications were ascertained from self-report and health plan databases. Multivariable logistic regression was used to examine the association of reduced eGFR and CHD presentation.
A total of 803 adults with incident acute myocardial infarctions and 419 adults with incident stable exertional angina who had baseline eGFRs ≤130 ml/min/1.73 m(2) were studied. Mean eGFR was lower in subjects with acute myocardial infarctions compared with those with stable angina. Compared with eGFR of 90 to 130 ml/min/1.73 m(2), a strong, graded, independent association was found between reduced eGFR and presenting with acute myocardial infarction, with adjusted odds ratios of 1.36 (95% confidence interval: 0.99 to 1.86) for eGFR 60 to 89 ml/min/1.73 m(2), 1.55 (95% confidence interval: 0.92 to 2.62) for eGFR 45 to 59 ml/min/1.73 m(2), and 3.82 (95% confidence interval: 1.55 to 9.46) for eGFR <45 ml/min/1.73 m(2) (p < 0.001 for trend).
An eGFR <45 ml/min/1.73 m(2) is a strong, independent predictor of presenting with acute myocardial infarction versus stable angina as the initial manifestation of CHD.
Journal of the American College of Cardiology 10/2011; 58(15):1600-7. · 14.16 Impact Factor
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ABSTRACT: Patients with chronic kidney disease (CKD) are less likely to receive cardiovascular medications. It is unclear whether differential cardiovascular drug use explains, in part, the excess risk of cardiovascular events and death in patients with CKD and coronary heart disease (CHD).
The ADVANCE Study enrolled patients with new onset CHD (2001-2003) who did (N = 159) or did not have (N = 1088) CKD at entry. The MDRD equation was used to estimate glomerular filtration rate (eGFR) using calibrated serum creatinine measurements. Patient characteristics, medication use, cardiovascular events and death were ascertained from self-report and health plan electronic databases through December 2008.
Post-CHD event ACE inhibitor use was lower (medication possession ratio 0.50 vs. 0.58, P = 0.03) and calcium channel blocker use higher (0.47 vs. 0.38, P = 0.06) in CKD vs. non-CKD patients, respectively. Incidence of cardiovascular events and death was higher in CKD vs. non-CKD patients (13.9 vs. 11.5 per 100 person-years, P < 0.001, respectively). After adjustment for patient characteristics, the rate of cardiovascular events and death was increased for eGFR 45-59 ml/min/1.73 m2 (hazard ratio [HR] 1.47, 95% CI: 1.10 to 2.02) and eGFR < 45 ml/min/1.73 m2 (HR 1.58, 95% CI: 1.00 to 2.50). After further adjustment for statins, β-blocker, calcium channel blocker, ACE inhibitor/ARB use, the association was no longer significant for eGFR 45-59 ml/min/1.73 m2 (HR 0.82, 95% CI: 0.25 to 2.66) or for eGFR < 45 ml/min/1.73 m2 (HR 1.19, 95% CI: 0.25 to 5.58).
In adults with CHD, differential use of cardiovascular medications may contribute to the higher risk of cardiovascular events and death in patients with CKD.
BMC Nephrology 09/2011; 12:44. · 2.18 Impact Factor
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Clinical Journal of the American Society of Nephrology 08/2011; 6(8):1813-4. · 5.23 Impact Factor
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ABSTRACT: Excess weight is paradoxically associated with better cardiovascular disease (CVD) outcomes and mortality in end-stage renal disease (ESRD) patients treated with hemodialysis. This association has been observed in chronic kidney disease (CKD) as well. One potential explanation for this inverse relationship is that the usual positive correlation between severity of CVD risk factors and higher body mass index (BMI) is reversed in CKD. To test this hypothesis, we determined the relationship between BMI and CVD risk factors in patients with and without CKD.
This was a cross-sectional study of the nationally representative US National Health and Nutrition Examination Survey (NHANES) 1999-2006. CKD was defined as glomerular filtration rate <60 ml/min per 1.73 m2. Covariates were age, race/ethnicity, sex and use of relevant prescription medications. Outcome variables were total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, systolic blood pressure (SBP), diastolic blood pressure (DBP), C-reactive protein (CRP) and fasting glucose (FG).
There were 1,895 and 32,431 patients with and without CKD, respectively. Those with CKD were older and had higher BMI. The shapes of the association between BMI and total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, SBP, CRP and FG were similar in those with or without CKD. In a sensitivity analysis excluding patients taking relevant prescription medications, our results did not differ substantially.
CKD did not alter the shapes of the association between higher BMI and CVD risk factors. Inverse associations between BMI and CVD risk factors are unlikely to explain why CKD patients with higher BMI may have better outcomes.
Journal of nephrology 06/2011; 25(3):317-24. · 1.65 Impact Factor
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ABSTRACT: In patients with prevalent coronary heart disease (CHD), studies have found a paradoxical relation in that patients with higher body mass indexes (BMIs) have lower mortality. One possibility is that patients with higher BMIs have greater muscle mass, and higher BMI may be a marker of better overall health status. The aim of this study was to evaluate whether the paradoxical association of BMI with mortality in patients with CHD is attenuated when accounting for urinary creatinine excretion, a marker of muscle mass. The Heart and Soul Study is an observational study of outpatients with stable CHD. Outpatient 24-hour timed urine collections were obtained. Participants were followed up for death for 5.9 ± 1.9 years. Cox proportional-hazards models were used to evaluate the association between gender-specific BMI quintiles and mortality. There were 886 participants in the study population. Participants in higher quintiles of BMI were younger, were more likely to have diabetes mellitus and hypertension, and had higher urinary creatinine excretion rate. Compared to the lowest BMI quintile, subjects in higher BMI quintiles were less likely to die during follow-up. Adjustment for major demographic variables, traditional cardiovascular risk factors, and kidney function did not attenuate the relation. Additional adjustment for urinary creatinine excretion rate did not materially change the association between BMI and all-cause mortality. In conclusion, low muscle mass and low BMI are each associated with greater all-cause mortality, but low muscle mass does not appear to explain why CHD patients with low BMIs have worse prognosis.
The American journal of cardiology 04/2011; 108(2):179-84. · 3.58 Impact Factor
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ABSTRACT: This Practice Point commentary discusses a recent paper by Menon et al. that described the natural history of a cohort of nondiabetic patients with stage 2-4 chronic kidney disease (CKD) who had been recruited from nephrology practices and screened for entry into the Modification of Diet in Renal Disease (MDRD) trial. Kidney failure was the most common outcome during long-term follow-up among these patients and there was a low competing risk of death, findings in contrast to observations in other cohorts of patients with CKD. Patients with lower glomerular filtration rate and greater proteinuria at baseline were at increased risk for both kidney failure and death, but kidney failure remained more likely than death in all glomerular filtration rate subgroups. These results emphasize the heterogeneity of the CKD population. Nephrologists should not rely on CKD staging alone to direct management of or risk-stratify patients with CKD, but should also consider the etiology and rate of progression of kidney disease, patient age and cardiovascular disease risk factors.
Nature Clinical Practice Nephrology 09/2008; 4(10):532-3. · 6.08 Impact Factor
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ABSTRACT: Chronic kidney disease (CKD), anemia, and declining kidney function are recognized as risk factors for adverse outcomes in patients with heart failure. This analysis was conducted to evaluate whether anemia is a risk factor for kidney function decrease in patients with heart failure. Data from the Studies of Left Ventricular Dysfunction (SOLVD), a randomized trial of enalapril versus placebo in patients with ejection fractions <or=35%, were analyzed. After randomization, creatinine measurements were taken at 2 weeks, 6 weeks, 4 months, and every 4 months thereafter. The glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease Study (MDRD) equation, and GFR slope was calculated. "Rapid decrease" was defined as a decrease in the GFR of >or=6 ml/min/1.73 m(2)/year. Anemia was defined as baseline hematocrit <36%. Multivariate logistic regression weighted by the number of GFR assessments was used to test the relation between anemia and rapid decrease. We also evaluated whether CKD (baseline GFR </=60 ml/min/1.73 m(2)) modified the relation between anemia and rapid decrease. In the 6,360 subjects, the mean age was 59 years, 31% had CKD, and 6% had anemia. Median follow-up was 2 years. In multivariate analysis, anemia was associated with a 1.30 increased odds (95% confidence interval 1.18 to 1.45) of rapid decrease in GFR. In subjects with CKD, anemia was associated with a 1.71 increased odds (95% confidence interval 1.43 to 2.05) of rapid decrease, while in subjects without CKD, anemia was associated with a 1.16 increased odds (95% confidence interval 1.03 to 1.31) of rapid decrease (p for interaction <0.001). In conclusion, anemia is associated with a rapid decrease in kidney function in patients with heart failure, particularly in those with underlying CKD.
The American Journal of Cardiology 04/2007; 99(8):1137-42. · 3.37 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
American Journal of Kidney Diseases 10/2006; 48(3):392-401. · 5.43 Impact Factor
