Mortality rates across 25-hydroxyvitamin D (25[OH]D) levels among adults with and without estimated glomerular filtration rate <60 ml/min/1.73 m2: the third national health and nutrition examination survey

Abstract

Background: Previous studies exploring the association between 25[OH]D levels and mortality in adults with and without kidney disease utilized 25[OH]D thresholds that have recently been scrutinized by the Institute of Medicine Committee to Review Dietary References Intakes for Vitamin D and Calcium.

Objective: We explored all-cause mortality rates across the spectrum of 25[OH]D levels over an eighteen-year follow-up among adults with and without an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2).

Design: The study included 1,097 U.S. adults with eGFR <60 ml/min/1.73 m(2) and 14, 002 adults with eGFR ≥60 ml/min/1.73 m(2). Mortality rates and rate ratios (RR) across 25[OH]D groups were calculated with Poisson regression and restricted cubic splines while adjusting for covariates.

Results: Prevalence of 25[OH]D levels <30 and <20 ng/ml among adults with eGFR <60 ml/min/1.73 m(2) was 76.5% (population estimate 6.2 million) and 35.4% (population estimate 2.9 million), respectively. Among adults with eGFR ≥ 60 ml/min/1.73 m(2), 70.5% had 25[OH]D levels <30 ng/ml (population estimate 132.2 million) while 30.3% had 25[OH]D levels <20 ng/ml (population estimate 56.8 million). Significantly higher mortality rates were noted among individuals with 25[OH]D levels <12 ng/ml compared to referent group (24 to <30 ng/ml): RR1.41 (95% CI 1.17, 1.71) among individuals with eGFR <60 ml/min/1.73 m(2) and RR 1.32 (95% CI 1.13, 1.56) among individuals with eGFR ≥ 60 ml/min/1.73 m(2) after adjustment for covariates including co-morbid conditions. Mortality rates were fairly similar across all 25[OH]D groups with levels >20 ng/ml after adjustment for all covariates.

Conclusions: Regardless of presence of eGFR <60 ml/min/1.73 m(2), mortality rates across groups with 25[OH]D levels 20-40 ng/ml are similar.

Figure 1. Flowchart of individuals included in the analysis of the association between 25[OH]D and all-cause mortality.

Figure 2. Age-, sex-, season- and race/ethnicity-adjusted mortality rates per 1,000 person-years by 25(OH)D groups among adults with eGFR <60 ml/min/1.73 m².

Figure 2 includes all participants (with eGFR <60 ml/min/1.73 m²) and under 3 exclusion strategies: 1) Exclusion of participants who died within one year of baseline examination; 2) Exclusion of participants who died within two years of baseline examination; 3) Exclusion of participants who died within three years of baseline examination. Rates were computed using Poisson regression analysis after grouping 25[OH] D values into 7 groups.

Figure 3. Age-, sex-, season- and race/ethnicity-adjusted mortality rates per 1,000 person-years by 25(OH)D groups among adults without eGFR <60 ml/min/1.73 m².

Figure 3 includes all participants (without eGFR <60 ml/min/1.73 m²) and under 3 exclusion strategies: 1) Exclusion of participants who died within one year of baseline examination; 2) Exclusion of participants who died within two years of baseline examination; 3) Exclusion of participants who died within three years of baseline examination. Rates were computed using Poisson regression analysis after grouping 25[OH] D values into 7 groups.

Figure 4. Adjusted mortality rate ratios by 25[OH]D groups for participants with eGFR<60 ml/min/1.73 m².

Rate ratios were computed using Poisson regression analysis with 25[OH]D modeled via restricted cubic splines, and covariates age, sex, season, race/ethnicity, co-morbidities (history of diabetes, congestive heart failure, stroke, and myocardial infarction), education status, smoking, systolic blood pressure, eGFR, body mass index. The median of the fifth 25[OH]D group (24 ng/mL−29.9 ng/mL) was used as the referent value. Error bars represent 95% confidence intervals.

Figure 5. Adjusted mortality rate ratios by 25[OH]D groups for participants with eGFR≥ ml/min/1.73 m².

Rate ratios were computed using Poisson regression analysis with 25[OH]D modeled via restricted cubic splines, and covariates age, sex, season, race/ethnicity, co-morbidities (history of diabetes, congestive heart failure, stroke, and myocardial infarction), education status, smoking, systolic blood pressure, eGFR, body mass index. The median of the fifth 25[OH]D group (24 ng/mL−29.9 ng/mL) was used as the referent value. Error bars represent 95% confidence intervals.