Vitamin D, Proteinuria, Diabetic Nephropathy, and Progression of CKD

Although the endocrine effects of vitamin D are widely recognized, somewhat less appreciated is that vitamin D may serve paracrine functions through local activation by 1-alpha-hydroxylase and thus maintain immunity, vascular function, cardiomyocyte health, and abrogate inflammation and insulin resistance. In the kidney, vitamin D may be important for maintaining podocyte health, preventing epithelial-to-mesenchymal transformation, and suppressing renin gene expression and inflammation. Replacement with pharmacologic dosages of vitamin D receptor agonists (VDRA) in animal models of kidney disease consistently show reduction in albuminuria, abrogation of glomerulosclerosis, glomerulomegaly, and glomerular inflammation, effects that may be independent of BP and parathyroid hormone, but the effects of VDRA in preventing tubulointerstitial fibrosis and preventing the progression of kidney failure in these animal models are less clear. Emerging evidence in patients with chronic kidney disease (CKD) show that vitamin D can reduce proteinuria or albuminuria even in the presence of angiotensin-converting enzyme inhibition. In addition to reducing proteinuria, VDRA may reduce insulin resistance, BP, and inflammation and preserve podocyte loss providing biologic plausibility to the notion that the use of VDRA may be associated with salubrious outcomes in patients with diabetic nephropathy. Patients with CKD have a very high prevalence of deficiency of 25-hydroxyvitamin D. Whether pharmacologic dosages of vitamin D instead of VDRA in patients with CKD can overcome the paracrine and endocrine functions of this vitamin remains unknown. To demonstrate the putative benefits of native vitamin D and VDRA among patients with CKD, randomized, controlled trials are needed.