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25-hydroxyvitamin D levels, race, and the progression of kidney disease.

ABSTRACT: Black individuals have lower 25-hydroxyvitamin D [25(OH)D] levels and experience a disproportionate burden of ESRD compared with white individuals. Animal studies suggest that vitamin D has renoprotective effects. We evaluated the contribution of low 25(OH)D levels on incidence of ESRD using data from the Third National Health and Nutrition Examination Survey-linked Medicare claims files (n = 13,328). We included baseline (1988 through 1994) measurements of 25(OH)D and assessed the incidence of ESRD through July 31, 2001. Overall, 34% of non-Hispanic black individuals had 25(OH)D levels <15 ng/ml compared with 5% of non-Hispanic white individuals (P < 0.001). During a median of 9.1 yr, 65 participants developed ESRD. After adjustment for demographic, socioeconomic, and clinical and laboratory factors (including diabetes, hypertension, estimated GFR, and albuminuria), participants with 25(OH)D levels <15 ng/ml had a 2.6-fold greater incidence of ESRD than those with levels > or =15 ng/ml (incidence rate ratio 2.64; 95% confidence interval [CI] 1.00 to 7.05; P = 0.05). After adjustment for clinical covariates but not 25(OH)D levels, non-Hispanic black individuals had a 2.83-fold (95% CI 1.03 to 7.77) higher risk for developing ESRD compared with non-Hispanic white individuals. Additional adjustment for 25(OH)D levels reduced the risk by 58% (incidence rate ratio 1.77; 95% CI 0.38 to 8.21). In summary, low 25(OH)D levels associate with development of ESRD even after adjustment for multiple risk factors. Low 25(OH)D levels may account for a substantial proportion of the increased risk for ESRD experienced by black individuals.

SUBMITTER: Melamed ML

PROVIDER: S-EPMC2794237 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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25-hydroxyvitamin D levels, race, and the progression of kidney disease.

Melamed Michal L ML Astor Brad B Michos Erin D ED Hostetter Thomas H TH Powe Neil R NR Muntner Paul P

Journal of the American Society of Nephrology : JASN 20091029 12

Black individuals have lower 25-hydroxyvitamin D [25(OH)D] levels and experience a disproportionate burden of ESRD compared with white individuals. Animal studies suggest that vitamin D has renoprotective effects. We evaluated the contribution of low 25(OH)D levels on incidence of ESRD using data from the Third National Health and Nutrition Examination Survey-linked Medicare claims files (n = 13,328). We included baseline (1988 through 1994) measurements of 25(OH)D and assessed the incidence of ...[more]

PMID: 19875805

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Project description:BackgroundConversion of 25-hydroxyvitamin D (25[OH]D) to the active form of vitamin D occurs primarily in the kidney. Observational studies suggest 25(OH)D clearance from the circulation differs by kidney function and race. However, these potential variations have not been tested using gold-standard methods.MethodsWe administered intravenous, deuterated 25(OH)D3 (d-25[OH]D3) in a pharmacokinetic study of 87 adults, including 43 with normal eGFR (≥60 ml/min per 1.73 m2), 24 with nondialysis CKD (eGFR <60 ml/min per 1.73 m2), and 20 with ESKD treated with hemodialysis. We measured concentrations of d-25(OH)D3 and deuterated 24,25-dihydroxyvitamin D3 at 5 minutes and 4 hours after administration, and at 1, 4, 7, 14, 21, 28, 42, and 56 days postadministration. We calculated 25(OH)D clearance using noncompartmental analysis of d-25(OH)D3 concentrations over time. We remeasured 25(OH)D clearance in a subset of 18 participants after extended oral vitamin-D3 supplementation.ResultsThe mean age of the study cohort was 64 years; 41% were female, and 30% were Black. Mean 25(OH)D clearances were 360 ml/d, 313 ml/d, and 263 ml/d in participants with normal eGFR, CKD, and kidney failure, respectively (P=0.02). After adjustment for age, sex, race, and estimated blood volume, lower eGFR was associated with reduced 25(OH)D clearance (β=-17 ml/d per 10 ml/min per 1.73 m2 lower eGFR; 95% CI, -21 to -12). Black race was associated with higher 25(OH)D clearance in participants with normal eGFR, but not in those with CKD or kidney failure (P for interaction=0.05). Clearance of 25(OH)D before versus after vitamin-D3 supplementation did not differ.ConclusionsUsing direct pharmacokinetic measurements, we show that 25(OH)D clearance is reduced in CKD and may differ by race.Clinical trial registry name and registration numberClearance of 25-hydroxyvitamin D in Chronic Kidney Disease (CLEAR), NCT02937350; Clearance of 25-hydroxyvitamin D3 During Vitamin D3 Supplementation (CLEAR-PLUS), NCT03576716.

Project description:BackgroundAmong patients in the United States with chronic kidney disease, black patients are at increased risk for end-stage renal disease, as compared with white patients.MethodsIn two studies, we examined the effects of variants in the gene encoding apolipoprotein L1 (APOL1) on the progression of chronic kidney disease. In the African American Study of Kidney Disease and Hypertension (AASK), we evaluated 693 black patients with chronic kidney disease attributed to hypertension. In the Chronic Renal Insufficiency Cohort (CRIC) study, we evaluated 2955 white patients and black patients with chronic kidney disease (46% of whom had diabetes) according to whether they had 2 copies of high-risk APOL1 variants (APOL1 high-risk group) or 0 or 1 copy (APOL1 low-risk group). In the AASK study, the primary outcome was a composite of end-stage renal disease or a doubling of the serum creatinine level. In the CRIC study, the primary outcomes were the slope in the estimated glomerular filtration rate (eGFR) and the composite of end-stage renal disease or a reduction of 50% in the eGFR from baseline.ResultsIn the AASK study, the primary outcome occurred in 58.1% of the patients in the APOL1 high-risk group and in 36.6% of those in the APOL1 low-risk group (hazard ratio in the high-risk group, 1.88; P<0.001). There was no interaction between APOL1 status and trial interventions or the presence of baseline proteinuria. In the CRIC study, black patients in the APOL1 high-risk group had a more rapid decline in the eGFR and a higher risk of the composite renal outcome than did white patients, among those with diabetes and those without diabetes (P<0.001 for all comparisons).ConclusionsRenal risk variants in APOL1 were associated with the higher rates of end-stage renal disease and progression of chronic kidney disease that were observed in black patients as compared with white patients, regardless of diabetes status. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.).

Project description:Low vitamin D concentrations are prevalent in patients with chronic kidney disease (CKD). We investigated the relationship between plasma 25-hydroxyvitamin D (25[OH]D) or 1,25-dihydroxyvitamin D (1,25[OH](2)D) concentrations with death, cardiovascular events, and dialysis therapy initiation in patients with advanced CKD.The HOST (Homocysteinemia in Kidney and End Stage Renal Disease) Study was a randomized double-blind trial evaluating the effects of high doses of folic acid on death and long-term dialysis therapy initiation in patients with advanced CKD (stages 4 and 5 not yet on dialysis therapy). 25(OH)D and 1,25(OH)(2)D were measured in stored plasma samples obtained 3 months after trial initiation and evaluated at clinically defined cutoffs (<10, 10-30, and >30 ng/mL) and tertiles (<15, 15-22, and >22 pg/mL), respectively. Cox proportional hazard models were used to examine the association between vitamin D concentrations and clinical outcomes.1,099 patients with advanced CKD from 36 Veteran Affairs Medical Centers.25(OH)D and 1,25(OH)(2)D concentrations.Death, cardiovascular events, and time to initiation of long-term dialysis therapy.After a median follow-up of 2.9 years, 41% (n = 453) died, whereas 56% (n = 615) initiated dialysis therapy. Mean 25(OH)D and 1,25(OH)(2)D concentrations were 21 ± 10 ng/mL and 20 ± 11 pg/mL, respectively. After adjustment for potential confounders, the lowest tertile of 1,25(OH)(2)D was associated with death (HR, 1.33; 95% CI, 1.01-1.74) and initiation of long-term dialysis therapy (HR, 1.78; 95% CI, 1.40-2.26) compared with the highest tertile. The association with death and initiation of dialysis therapy was moderately attenuated after adjustment for plasma fibroblast growth factor 23 (FGF-23) concentrations (HRs of lower tertiles of 1.20 [95% CI, 0.91-1.58] and 1.56 [95% CI, 1.23-1.99], respectively, compared with highest tertile). There was no association between 25(OH)D concentrations and outcomes.Participants were mostly men.Low plasma 1,25(OH)(2)D concentrations are associated with death and initiation of long-term dialysis therapy in patients with advanced CKD. FGF-23 level may attentuate this relationship.

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25-hydroxyvitamin D levels, race, and the progression of kidney disease.

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25-hydroxyvitamin D levels, race, and the progression of kidney disease.

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