Vitamin D Status and Risk of ESRD, More to the Puzzle…

Disordered mineral metabolism is known to occur in kidney disease. It is belived that lower 1 alfa hydroxylase reduces conversion of vitamin D [25(OH)D] to [1,25(OH)2D], leading to high PTH levels.  However, vitamin D measurements and supplementation is not routinely performed in CKD patients.  In a recent study published in AJKD, Rebholz et al evaluated the association between vitamin D–related biomarkers and ESRD in a large community-based population.  Vitamin D binding protein, free and bio-available 25(OH)D, total 25(OH)D, and total 1,25(OH)2D levels were measured. The major finding of the study was that higher levels of vitamin D binding protein were independently associated with an increased risk of ESRD, and higher levels of free 25(OH)D and bioavailable 25(OH)D were associated with a lower risk for ESRD. Total levels 25(OH)D and 1,25(OH)2D levels were not associated with ESRD.  In addition, vitamin D binding protein isoforms were highly related with black race, vitamin D binding protein, and free and bioavailable levels of 25(OH)D.

This study is a wonderful addition to the nephrology literature. Mineral metabolism guidelines are a “gray area” without a strong evidence base to support current recommendations. The discovery of FGF-23 and its relationship with kidney outcomes has been a major contribution of the past decade. However, we lack diagnostic tools in the bone mineral disease arena that can predict CKD outcomes, and more importantly, suggest an effective therapy.  In this study, we learned that overall levels of 25(OH)D do not impact kidney disease prognosis. This seems logical since it is the free and bioavailable vitamin D that represent the active forms of vitamin D. Second, this study generates new questions. Should we be directly measuring or indirectly estimating free and bioavailable 25(OH)D, in addition to vitamin D binding levels? Could we then perform a vitamin D randomized controlled trial assessing different vitamin D biomarkers with outcomes? Only further research will resolve these questions.

Magdalena Madero, MD
AJKD Blog contributor

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