Vitamin D: roles in renal and cardiovascular protection

Purpose of this review

Great progress has been made in recent years in understanding the expanding roles of the vitamin D endocrine system beyond calcemic regulation, including pathophysiological actions in the kidney and the cardiovascular system. The purpose of this review is to update the recent advance regarding the effects of vitamin D and its analogs on the renal and cardiovascular system.

Recent findings

Vitamin D deficiency is not only widely associated with chronic kidney disease and cardiovascular disease in humans, but may also accelerate the disease progression. Dysregulation of vitamin D metabolism caused by renal insufficiency contributes to the low vitamin D status. Preclinical and clinical studies have demonstrated impressive therapeutic outcome with low-calcemic vitamin D analogs in renal and cardiovascular disease. The mechanism underlying the renal and cardiovascular protection involves regulation of multiple signaling pathways by vitamin D including nuclear factor κB, Wnt/β-catenin and the renin-angiotensin system.

Summary

The renal and cardiovascular protective activity of vitamin D revealed in recent studies has profound clinical implications. Nutritional correction of vitamin D deficiency and treatment with vitamin D analogs could be therapeutic options for renal and cardiovascular problems. New vitamin D analogs with better renal and cardiovascular therapeutic efficacy are highly desired. More randomized trials are needed to address these issues.

Background

The burden of vitamin D deficiency is growing, affecting approximately more than 1 billion people worldwide [1]. As vitamin D has many pleiotropic effects, vitamin D deficiency has many adverse outcomes, of which a negative impact on the cardiovascular and renal system is of great importance.

As renal and cardiovascular diseases are an important cause of mortality worldwide, understanding the (protective) effects of vitamin D are very important.

Summary
Dysregulation of vitamin D metabolism in kidney disease partly causes vitamin D deficiency.

Vitamin D has many renoprotective actions, shown in experimental models of kidney disease.
Those include:
(1) suppression of the renin–angiotensin system [2],
(2) reduced NF-kB activation and inflammation [3,4],
(3) inhibition of the Wnt/b-catenin pathway [5] and
(4) direct effects on the expression of slit diaphragm proteins [6].

From epidemiological studies, the cardiovascular protective effect of vitamin D has become clear. Animal studies showed the antihypertrophic and antiatherosclerotic activities of vitamin D and its analogs .

The mechanism by which vitamin D is protective for both the cardiovascular and the renal system is multifactorial, involving multiple regulatory pathways.

Conclusion

The renal and cardiovascular effects of vitamin D have become more clear during the last years. It is evident that vitamin D has protective multifactorial effects on both the renal and the cardiovascular system.
Better understanding of the actions of vitamin D could stimulate the development of new vitamin D analog drugs for renal and cardiovascular diseases. Those drugs should have less calcemic effect and a better therapeutic efficacy than the current vitamin D analog drugs.

References

1. Holick MF. Vitamin D deficiency. N Engl J Med 2007; 357:266–281.
2. Zhang Y, Kong J, Deb DK, et al. Vitamin D receptor attenuates renal fibrosis by suppressing the renin-angiotensin system. J Am Soc Nephrol 2010; 21:966–973.
3. Guijarro C, Egido J. Transcription factor-kappa B (NF-kappa B) and renal disease. Kidney Int 2001; 59:415–424.
4. Sun J, Kong J, Duan Y, et al. Increased NF-{kappa}B activity in fibroblasts lacking the vitamin D receptor. Am J Physiol Endocrinol Metab 2006;291:E315–E322
5. He W, Kang YS, Dai C, Liu Y. Blockade of Wnt/beta-catenin signaling by paricalcitol ameliorates proteinuria and kidney injury. J Am Soc Nephrol 2011;22:90–103.
6. Deb DK, Wang Y, Zhang Z, et al. Molecular mechanism underlying 1,25-dihydroxyvitamin D regulation of nephrin gene expression. J Biol Chem 2011;286:32011–32017.