Rapid decline of kidney function increases cardiovascular risk in the elderly.
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ABSTRACT:
SUBMITTER: Shlipak MG
PROVIDER: S-EPMC2794238 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background and objectivesElevations in N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T are associated with poor cardiovascular outcomes. Whether elevations in these cardiac biomarkers are associated with decline in kidney function was evaluated.Design, setting, participants, & measurementsN-terminal pro-B-type natriuretic peptide and troponin T were measured at baseline in 3752 participants free of heart failure in the Cardiovascular Health Study. eGFR was determined from the Chronic Kidney Disease Epidemiology Collaboration equation using serum cystatin C. Rapid decline in kidney function was defined as decline in serum cystatin C eGFR?30%, and incident CKD was defined as the onset of serum cystatin C eGFR<60 among those without CKD at baseline (n=2786). Cox regression models were used to examine the associations of each biomarker with kidney function decline adjusting for demographics, baseline serum cystatin C eGFR, diabetes, and other CKD risk factors.ResultsIn total, 503 participants had rapid decline in serum cystatin C eGFR over a mean follow-up time of 6.41 (1.81) years, and 685 participants developed incident CKD over a mean follow-up time of 6.41 (1.74) years. Participants in the highest quartile of N-terminal pro-B-type natriuretic peptide (>237 pg/ml) had an 67% higher risk of rapid decline and 38% higher adjusted risk of incident CKD compared with participants in the lowest quartile (adjusted hazard ratio for serum cystatin C eGFR rapid decline, 1.67; 95% confidence interval, 1.25 to 2.23; hazard ratio for incident CKD, 1.38; 95% confidence interval, 1.08 to 1.76). Participants in the highest category of troponin T (>10.58 pg/ml) had 80% greater risk of rapid decline compared with participants in the lowest category (adjusted hazard ratio, 1.80; 95% confidence interval, 1.35 to 2.40). The association of troponin T with incident CKD was not statistically significant (hazard ratio, 1.17; 95% confidence interval, 0.92 to 1.50).ConclusionsElevated N-terminal pro-B-type natriuretic peptide and troponin T are associated with rapid decline of kidney function and incident CKD. Additional studies are needed to evaluate the mechanisms that may explain this association.
| S-EPMC4317737 | biostudies-literature
Project description:ObjectiveWe aimed to investigate the rate of progression of nonalbuminuric chronic kidney disease (CKD) to end-stage kidney disease (ESKD) or death or major cardiovascular events (MACE) compared with albuminuric and nonalbuminuric phenotypes.Research design and methodsWe included 10,185 participants with type 2 diabetes enrolled in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study. Based on baseline albuminuria and estimated glomerular filtration rate (eGFR), participants were classified as having no kidney disease (no CKD), albuminuria only (albuminuric non-CKD), reduced eGFR only (nonalbuminuric CKD), or both albuminuria and reduced eGFR (albuminuric CKD). The rate of eGFR decline and hazard ratios (HRs) for ESKD or death or MACE were calculated.ResultsFor individuals with no CKD and those with nonalbuminuric CKD, the rates of eGFR decline were -1.31 and -0.60 mL/min/year, respectively (P < 0.001). In competing-risks analysis (no CKD as the reference), HRs for ESKD indicated no increased risk for nonalbuminuric CKD (0.76 [95% CI 0.34, 1.70]) and greatest risk for albuminuric CKD (4.52 [2.91, 7.01]). In adjusted Cox models, HRs for death and MACE were highest for albumuniuric CKD (2.38 [1.92, 2.90] and 2.37 [1.89, 2.97], respectively) and were higher for albuminuric non-CKD (1.82 [1.59, 2.08] and 1.88 [1.63, 2.16], respectively) than for those with nonalbuminuric CKD (1.42 [1.14, 1.78] and 1.44 [1.13, 1.84], respectively).ConclusionsThose with nonalbuminuric CKD showed a slower rate of decline in eGFR than did any other group; however, these individuals still carry a greater risk for death and MACE than do those with no CKD.
| S-EPMC7411281 | biostudies-literature
Project description:Purpose:In prior analyses, blood pressure (BP) was related to rapid kidney function decline (RKFD). However, studies of this relationship in populations of advanced age are lacking. In the present study, we therefore examined the relationship between BP and RKFD in a population of 284 hypertensive Chinese individuals over the age of 80. Patients and Methods:All study participants were diagnosed with hypertension (systolic BP [SBP] 160-200 mmHg; diastolic BP [DBP] <110 mmHg). RKFD was defined based upon a decline in estimated glomerular filtration rate (eGFR) >5mL/min per 1.73 m2 per year during follow-up. The Cox regression models (competing risk models) were used for calculating hazard ratios (HRs) to examine the relationship between SBP, DBP, pulse pressure (PP) and RKFD. Results:Over a 3.3-year median follow-up period, 68 study participants (23.9%) were diagnosed with RKFD, while 35 (12.3%) died. After adjusting for confounding variables, we determined that each 10 mmHg rise in SBP and PP was associated with a 34% and 110% increase, respectively, in RKFD risk (adjusted HR: 1.34, 95% confidence interval [CI]: 1.05-1.71 for SBP, p=0.02; HR: 2.10, 95% CI: 0.87-5.08 for PP, p=0.10). In addition, we determined that each 10 mmHg increase in DBP was linked to a 10% reduction in RKFD risk (adjusted HR: 0.90, 95% CI: 0.70-1.14, p=0.37). Conclusion:Our results indicate that SBP, but not DBP or PP, is positively correlated with RKFD risk in a very elderly hypertensive Chinese population.
| S-EPMC7428315 | biostudies-literature
Project description:RATIONALE & OBJECTIVE:Uromodulin is released by tubular epithelial cells into the serum and lower levels are associated with more severe interstitial fibrosis and tubular atrophy. Low serum uromodulin (sUMOD) levels are associated with mortality and cardiovascular disease. However, little is known about the association of sUMOD levels with long-term kidney outcomes in older adults, a population with a high prevalence of interstitial fibrosis and tubular atrophy. STUDY DESIGN:Case-cohort study and case-control study. SETTING & PARTICIPANTS:Random subcohort (n=933) and additional cases of end-stage kidney disease (ESKD) and kidney function decline (?30% decline in estimated glomerular filtration rate [eGFR]) during follow-up of the Cardiovascular Health Study (CHS). PREDICTOR:sUMOD level. OUTCOMES:ESKD (n=14) from the random subcohort and all additional ESKD cases from outside the random subcohort (n=39) during follow-up (10 years, case-cohort study); kidney function decline of?30% eGFR at 9 years of follow-up in individuals with repeated eGFR assessments from the random subcohort (n=56) and additional cases (n=123). 224 participants from the random subcohort served as controls (case-control study). ANALYTICAL APPROACH:Modified multivariable Cox regression for ESKD and multivariable logistic regression for kidney function decline. Both analyses adjusted for demographics, eGFR, urinary albumin-creatinine ratio, and other kidney disease progression risk factors. RESULTS:Mean age of the random subcohort was 78 years, 40% were men, 15% were black. Mean sUMOD level was 127±64ng/mL and eGFR was 63±19mL/min/1.73m2. In multivariable analysis, each 1-SD higher sUMOD level was associated with 63% lower risk for ESKD (HR, 0.37; 95% CI, 0.14-0.95). In demographic-adjusted analyses of kidney function decline, each 1-SD higher sUMOD level was associated with 25% lower odds of kidney function decline (OR, 0.75; 95% CI, 0.60-0.95); after multivariable adjustment, the association was attenuated and no longer significant (OR, 0.88; 95% CI, 0.68-1.14). LIMITATIONS:Possibility of survival bias in the kidney function decline analysis. CONCLUSIONS:Higher sUMOD levels may identify elderly persons at reduced risk for ESKD.
| S-EPMC7188359 | biostudies-literature
Project description:BackgroundCross-sectional studies show a strong association between chronic kidney disease and apparent treatment-resistant hypertension, but the longitudinal association of the rate of kidney function decline with the risk of resistant hypertension is unknown.MethodsThe population-based Three-City included 8,695 participants older than 65 years, 4265 of them treated for hypertension. We estimated the odds ratios (OR) of new-onset apparent treatment-resistant hypertension, defined as blood pressure ? 140/90 mmHg despite use of 3 antihypertensive drug classes or ? 4 classes regardless of blood pressure, associated with the mean estimated glomerular filtration rate (eGFR) level and its rate of decline over 4 years, compared with both controlled hypertension and uncontrolled nonresistant hypertension with ? 2 drugs. GFR was estimated with three different equations.ResultsBaseline prevalence of apparent treatment-resistant hypertension and of controlled and uncontrolled nonresistant hypertension, were 6.5%, 62.3% and 31.2%, respectively. During follow-up, 162 participants developed apparent treatment-resistant hypertension. Mean eGFR decline with the MDRD equation was 1.5±2.9 mL/min/1.73 m² per year: 27.7% of the participants had an eGFR ?3 and 10.1% ? 5 mL/min/1.73 m² per year. After adjusting for age, sex, obesity, diabetes, and cardiovascular history, the ORs for new-onset apparent treatment-resistant hypertension associated with a mean eGFR level, per 15 mL/min/1.73 m² drop, were 1.23 [95% confidence interval 0.91-1.64] compared to controlled hypertension and 1.10 [0.83-1.45] compared to uncontrolled nonresistant hypertension; ORs associated with a decline rate ? 3 mL/min/1.73 m² per year were 1.89 [1.09-3.29] and 1.99 [1.19-3.35], respectively. Similar results were obtained when we estimated GFR with the CKDEPI and the BIS1 equations. ORs tended to be higher for an eGFR decline rate ? 5 mL/min/1.73 m² per year.ConclusionThe speed of kidney function decline is associated more strongly than kidney function itself with the risk of apparent treatment-resistant hypertension in the elderly.
| S-EPMC4726557 | biostudies-literature
Project description:BackgroundRacial differences in rapid kidney function decline exist, but less is known regarding factors associated with rapid decline among African Americans. Greater understanding of potentially modifiable risk factors for early kidney function loss may help reduce the burden of kidney failure in this high-risk population.Study designProspective cohort study.Setting & participants3,653 African American participants enrolled in the Jackson Heart Study (JHS) with kidney function data from 2 of 3 examinations (2000-2004 and 2009-2013). Estimated glomerular filtration rate (eGFR) was calculated from serum creatinine using the CKD-EPI creatinine equation.PredictorsDemographics, socioeconomic status, lifestyle, and clinical risk factors for kidney failure.OutcomesRapid decline was defined as a ≥30% decline in eGFR during follow-up. We quantified the association of risk factors with rapid decline in multivariable models.MeasurementsClinical (systolic blood pressure and albuminuria [albumin-creatinine ratio]) and modifiable risk factors.ResultsMean age was 54±12 (SD) years, 37% were men, average body mass index was 31.8±7.1kg/m(2), 19% had diabetes mellitus (DM), and mean eGFR was 96.0±20mL/min/1.73m(2) with an annual rate of decline of 1.27mL/min/1.73m(2). Those with rapid decline (11.5%) were older, were more likely to be of low/middle income, and had higher systolic blood pressures and greater DM than those with nonrapid decline. Factors associated with ≥30% decline were older age (adjusted OR per 10 years older, 1.51; 95% CI, 1.34-1.71), cardiovascular disease (adjusted OR, 1.53; 95% CI, 1.12-2.10), higher systolic blood pressure (adjusted OR per 17mmHg greater, 1.22; 95% CI, 1.06-1.41), DM (adjusted OR, 2.63; 95% CI, 2.02-3.41), smoking (adjusted OR, 1.60; 95% CI, 1.10-2.31), and albumin-creatinine ratio > 30mg/g (adjusted OR, 1.55; 95% CI, 1.08-1.21). Conversely, results did not support associations of waist circumference, C-reactive protein level, and physical activity with rapid decline.LimitationsNo midstudy creatinine measurement at examination 2 (2005-2008).ConclusionsRapid decline heterogeneity exists among African Americans in JHS. Interventions targeting potentially modifiable factors may help reduce the incidence of kidney failure.
| S-EPMC5445065 | biostudies-literature
Project description:While anemia is associated with poor functional and mortality outcomes in the elderly, the impact of hemoglobin decline is less studied. We evaluated the determinants and consequences of hemoglobin decline in 3,758 non-anemic participants from the Cardiovascular Health Study, a prospective cohort of community-dwelling elderly ?65 years old at baseline and followed for up to 16 years. Hemoglobin was measured at baseline and 3 years later and anemia defined by World Health Organization (WHO) criteria. We modeled hemoglobin decline in two ways: (1) per each 1 g/dL decrease in hemoglobin and (2) development of anemia by the WHO criteria. Among participants without baseline anemia, hemoglobin decreased by 0.4 g/dL and 9% developed anemia over 3 years. Baseline increasing age, female sex, diabetes, and kidney disease predicted hemoglobin decline over 3 years. Baseline increasing age, being African-American, and kidney disease predicted anemia development over 3 years. Hemoglobin decline was associated with subsequent worse cognitive function in men and anemia development with subsequent worse cognitive function in women. Both anemia development (HR 1.39, 95% CI 1.15, 1.69) and hemoglobin decline (HR 1.11, 95% CI 1.04, 1.18 per 1 g/dL decrease) predicted subsequent mortality in men and women. Hemoglobin decreases identified a large group of elderly individuals at risk for subsequent adverse outcomes who would not be identified using the WHO anemia criteria. These data may allow clinicians to identify at-risk elderly individuals for early intervention to improve the quality and quantity of life.
| S-EPMC3860593 | biostudies-literature
Project description:Urinary uromodulin (uUMOD) is the most common secreted tubular protein in healthy adults. However, the relationship between uUMOD and clinical outcomes is still unclear. Here we measured uUMOD in 192 participants of the Cardiovascular Health Study with over a 30% decline in estimated glomerular filtration rate (eGFR) over 9 years, 54 with incident end-stage renal disease (ESRD), and in a random subcohort of 958 participants. The association of uUMOD with eGFR decline was evaluated using logistic regression and with incident ESRD, cardiovascular disease, heart failure, and mortality using Cox proportional regression. Mean age was 78 years and median uUMOD was 25.8??g/ml. In a case-control study evaluating eGFR decline (192 cases and 231 controls), each 1-s.d. higher uUMOD was associated with a 23% lower odds of eGFR decline (odds ratio 0.77 (95% CI 0.62-0.96)) and a 10% lower risk of mortality (hazard ratio 0.90 (95% CI 0.83-0.98)) after adjusting for demographics, eGFR, albumin/creatinine ratio, and other risk factors. There was no risk association of uUMOD with ESRD, cardiovascular disease, or heart failure after multivariable adjustment. Thus, low uUMOD levels may identify persons at risk of progressive kidney disease and mortality above and beyond established markers of kidney disease, namely eGFR and the albumin/creatinine ratio. Future studies need to confirm these results and evaluate whether uUMOD is a marker of tubular health and/or whether it plays a causal role in preserving kidney function.
| S-EPMC4653069 | biostudies-literature
Project description:BACKGROUND:While elevated serum uric acid level (SUA) is a recognized risk factor for chronic kidney disease, it remains unclear whether change in SUA is independently associated with change in estimated glomerular filtration rate (eGFR) over time. Accordingly, we examined the longitudinal associations between change in SUA and change in eGFR over 5 years in a general Japanese population. METHODS:This was a large, single-center, retrospective 5-year cohort study at St. Luke's International Hospital, Tokyo, Japan, between 2004 and 2009. We included 13,070 subjects (30-85 years) in our analyses whose data were available between 2004 and 2009. Of those, we excluded 492 subjects with eGFR <60 mL/min/1.73 m2 at baseline. In addition to examining the entire cohort (n = 12,578), we stratified our analyses by baseline eGFR groups: 60-90, 90-120, and ?120 mL/min/1.73 m2. Linear and logistic regressions models were applied to examine the relationships between baseline and change in SUA, change in eGFR, and rapid eGFR decline (defined as the highest quartile of change in eGFR), adjusted for age, gender, body mass index, abdominal circumference, hypertension, dyslipidemia, and diabetes mellitus. RESULTS:After multivariable adjustments including baseline eGFR, 1 mg/dL increase in baseline SUA was associated with greater odds of developing rapid eGFR decline (OR 1.27, 95% CI 1.17-1.38), and 1 mg/dL increase in SUA over 5 years was associated with 3.77-fold greater odds of rapid eGFR decline (OR 3.77, 95% CI 3.35-4.26). CONCLUSIONS:Elevated baseline SUA and increasing SUA over time were independent risk factors for rapid eGFR decline over 5 years.
| S-EPMC5894505 | biostudies-literature
Project description:Introduction:Impaired kidney function is a robust risk factor for cardiovascular mortality. Age-related annual kidney function decline of 1.0 ml/min per 1.73 m2 after age 40 years is doubled in post-myocardial infarction (MI) patients. Methods:We investigated the impact of the number of cardiovascular risk factors (including unhealthy lifestyle) on annual kidney function decline, in 2426 post-MI patients (60-80 years) of the prospective Alpha Omega Cohort study. Glomerular filtration rate was estimated by serum cystatin C (eGFRcysC) and combined creatinine-cystatin C (eGFRcr-cysC), using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations from 2012. Data were analyzed by multivariable linear and logistic regression. Results:At baseline, mean (SD) eGFRcysC and eGFRcr-cysC were 81.5 (19.6) and 78.5 (18.7) ml/min per 1.73 m2, respectively. Of all patients, 79% were men, 19% had diabetes, 56% had high blood pressure (?140/90 mm Hg), 16% were current smokers, 56% had high serum low-density lipoprotein (LDL of ?2.5 mmol/l), and 23% were obese (body mass index of ?30.0 kg/m2). After multivariable adjustment, the additional annual eGFRcysC decline (95% confidence interval) was as follows: in patients with versus without diabetes, -0.90 (-1.23 to -0.57) ml/min per 1.73 m2; in patients with high versus normal blood pressure, -0.50 (-0.76 to -0.24) ml/min per 1.73 m2; in obese versus nonobese patients, -0.31 (-0.61 to 0.01) ml/min per 1.73 m2; and in current smokers versus nonsmokers, -0.19 (-0.54 to 0.16) ml/min per 1.73 m2. High LDL was not associated with accelerated eGFRcysC decline. Similar results were obtained with eGFRcr-cysC. Conclusion:In older, stable post-MI patients without cardiovascular risk factors, the annual kidney function decline was -0.90 (-1.16 to -0.65) ml/min per 1.73 m2. In contrast, in post-MI patients with ?3 cardiovascular risk factors, the annual kidney function decline was 2.5-fold faster, at -2.37 (-2.85 to -1.89) ml/min per 1.73 m2.
| S-EPMC6035162 | biostudies-literature