Vitamin D and proteinuria: a critical review of molecular bases and clinical experience

Proteinuria is the main predictor of chronic kidney disease progression. Drugs that block the renin-angiotensin-aldosterone (RAA) system reduce protein uria and slow down the progression of the disease. However, its effect is suboptimal, and residual proteinuria persists as an important predictor of renal impairment. Vitamin D has pleiotropic effects that could have an impact on these parameters. In this work, we critically review the molecular and experimental bases that suggest the antiproteinuric effect of vitamin D receptor (VDR) activation and the evidence available on its antiproteinuric effect in clinical practice. In animal models, we observed the antiproteinuric effect of VDR activation, which could be due to direct protective action on the podocyte or other pleiotropic effects that slow down RAA system activation, inflammation and fibrosis. Clinical trials are generally conducted in patients with a vitamin D deficiency or insufficiency and the most major trial (VITAL) did not demonstrate that paricalcitol improved the study's primary endpoint (decrease in the urinary albumin creatinine quotient). In this sense, the information available is insufficient to advise the use of native vitamin D or VDR activators such as renoprotective antiproteinuric drugs beyond the experimental level. Two Spanish clinical trials and one Italian attempt to determine the effect of paricalcitol and vitamin D on residual proteinuria in various clinical circumstances (PALIFE, NEFROVID and PROCEED).