Possible renoprotection by vitamin D in chronic renal disease: beyond mineral metabolism

Abstract

Vitamin D is typically viewed as a key player in the regulation of calcium and phosphate levels and the control of bone metabolism; however, growing evidence suggests that vitamin D deficiency may also have an important role in the progressive loss of renal function. Vitamin D deficiency is particularly frequent in patients with chronic kidney disease, in whom it is associated with increased mortality. Studies indicate that treatment with vitamin D analogues reduces proteinuria, suppresses the renin–angiotensin–aldosterone system (RAAS), and exerts anti-inflammatory and immunomodulatory effects. These pleiotropic effects render vitamin D a potentially interesting treatment modality for renoprotection in patients with chronic kidney disease. Whether vitamin D has clinically relevant renoprotective effects in addition to RAAS blockade is currently under investigation.

Key Points

  • Inadequate vitamin D levels are present in the majority of Western populations, but vitamin D deficiency is more prevalent and severe in patients with chronic kidney disease (CKD)

  • Decreased circulating levels of active vitamin D in patients with CKD may be explained by suppression of renal 1α-hydroxylase activity

  • Vitamin D deficiency has been associated with increased mortality, increased cardiovascular disease and increased risk of fracture

  • Vitamin D analogues might ameliorate the reactive rise in renin observed in patients with CKD treated with suppression of the renin–angiotensin–aldosterone system

  • The antiproteinuric effect of active vitamin D has been confirmed in preclinical studies of CKD and clinical trials to investigate this effect are ongoing

  • Vitamin D has anti-inflammatory and immunomodulatory effects, suggesting that treatment with vitamin D analogues may be particularly beneficial in patients with glomerulonephritis, autoimmune diseases, and renal transplant recipients

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Figure 1: Vitamin D physiology.
Figure 2: Prevalence of vitamin D deficiency in the general population and in patients with chronic kidney disease.
Figure 3: Possible mechanisms of vitamin D deficiency in proteinuric renal disease.
Figure 4: Overview of the potential renoprotective effects of active vitamin D in the damaged kidney.

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Acknowledgements

M. H. de Borst is supported by research grants from the Dutch Kidney Foundation (KJPB.08.07) and the University Medical Center Groningen (Mandema stipend).

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Correspondence to Martin H. de Borst.

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Doorenbos, C., van den Born, J., Navis, G. et al. Possible renoprotection by vitamin D in chronic renal disease: beyond mineral metabolism. Nat Rev Nephrol 5, 691–700 (2009). https://doi.org/10.1038/nrneph.2009.185

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