Dataset Information

Serum Calcitriol Concentrations and Kidney Function Decline, Heart Failure, and Mortality in Elderly Community-Living Adults: The Health, Aging, and Body Composition Study.

ABSTRACT: RATIONALE & OBJECTIVES:Lower 25-hydroxyvitamin D concentrations have been associated with risk for kidney function decline, heart failure, and mortality. However, 25-hydroxyvitamin D requires conversion to its active metabolite, calcitriol, for most biological effects. The associations of calcitriol concentrations with clinical events have not been well explored. STUDY DESIGN:Case-cohort study. SETTING & PARTICIPANTS:Well-functioning community-living older adults aged 70 to 79 years at inception who participated in the Health, Aging, and Body Composition (Health ABC) Study. PREDICTOR:Serum calcitriol measured using positive ion electrospray ionization-tandem mass spectrometry. OUTCOMES:Major kidney function decline (?30% decline in estimated glomerular filtration rate from baseline), incident heart failure (HF), and all-cause mortality during 10 years of follow-up. ANALYTIC APPROACH:Baseline calcitriol concentrations were measured in a random subcohort of 479 participants and also in cases with major kidney function decline [n=397]) and incident HF (n=207) during 10 years of follow-up. Associations of serum calcitriol concentrations with these end points were evaluated using weighted Cox regression to account for the case-cohort design, while associations with mortality were assessed in the subcohort alone using unweighted Cox regression. RESULTS:During 8.6 years of mean follow-up, 212 (44%) subcohort participants died. In fully adjusted models, each 1-standard deviation lower calcitriol concentration was associated with 30% higher risk for major kidney function decline (95% CI, 1.03-1.65; P=0.03). Calcitriol was not significantly associated with incident HF (HR, 1.16; 95% CI, 0.94-1.47) or mortality (HR, 1.01; 95% CI, 0.81-1.26). We observed no significant interactions between calcitriol concentrations and chronic kidney disease status, baseline intact parathyroid or fibroblast factor 23 concentrations. LIMITATIONS:Observational study design, calcitriol measurements at a single time point, selective study population of older adults only of white or black race. CONCLUSIONS:Lower calcitriol concentrations are independently associated with kidney function decline in community-living older adults. Future studies will be needed to clarify whether these associations reflect lower calcitriol concentrations resulting from abnormal kidney tubule dysfunction or direct mechanisms relating lower calcitriol concentrations to more rapid loss of kidney function.

SUBMITTER: Selamet U

PROVIDER: S-EPMC6245577 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Serum Calcitriol Concentrations and Kidney Function Decline, Heart Failure, and Mortality in Elderly Community-Living Adults: The Health, Aging, and Body Composition Study.

Selamet Umut U Katz Ronit R Ginsberg Charles C Rifkin Dena E DE Fried Linda F LF Kritchevsky Stephen B SB Hoofnagle Andrew N AN Bibbins-Domingo Kirsten K Drew David D Harris Tamara T Newman Anne A Gutiérrez Orlando M OM Sarnak Mark J MJ Shlipak Michael G MG Ix Joachim H JH

American journal of kidney diseases : the official journal of the National Kidney Foundation 20180606 3

<h4>Rationale & objectives</h4>Lower 25-hydroxyvitamin D concentrations have been associated with risk for kidney function decline, heart failure, and mortality. However, 25-hydroxyvitamin D requires conversion to its active metabolite, calcitriol, for most biological effects. The associations of calcitriol concentrations with clinical events have not been well explored.<h4>Study design</h4>Case-cohort study.<h4>Setting & participants</h4>Well-functioning community-living older adults aged 70 to ...[more]

PMID: 29885925

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Project description:BackgroundIn 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 m(2) and CKD progression among community-living persons with predominantly preserved kidney function is unknown.Study designLongitudinal observational cohort study.Setting & participantsWell-functioning community-living elders aged 70-79 years at inception.PredictorSerum bicarbonate level measured at the time of collection by arterialized venous blood sample using an arterial blood gas analyzer.OutcomesChange in eGFR over 7 years, and new eGFR < 60 mL/min/1.73 m(2) with a rate of loss of at least 1 mL/min/1.73 m(2) per year.MeasurementsLinear 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 m(2).ResultsAt baseline, mean eGFR was 84 ± 16 (SD)mL/min/1.73 m(2), 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 eGFR0.55 (95% CI, 0.13-0.97) mL/min/1.73 m(2) 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 m(2), 252 (25%) developed incident eGFRs < 60 mL/min/1.73 m(2) 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 m(2) (OR, 1.72; 95% CI, 0.97-3.07) compared with those with higher bicarbonate concentrations.LimitationsOnly 2 measurements of kidney function separated by 7 years and loss to follow-up due to intervening mortality in this elderly population.ConclusionsLower serum bicarbonate concentrations are associated independently with decline in eGFR and incident eGFR < 60 mL/min/1.73 m(2) 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.

Dataset Information

Serum Calcitriol Concentrations and Kidney Function Decline, Heart Failure, and Mortality in Elderly Community-Living Adults: The Health, Aging, and Body Composition Study.

Publications

Serum Calcitriol Concentrations and Kidney Function Decline, Heart Failure, and Mortality in Elderly Community-Living Adults: The Health, Aging, and Body Composition Study.

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