Vitamin D & its analogues in type 2 diabetic nephropathy: a systematic review

Abstract

Nephropathy is one of the major complications of diabetes often leading to chronic kidney disease (CKD). Inflammation and oxidative stress are associated with pathogenesis of diabetic nephropathy (DN) and found to be regulated by nuclear receptors such as vitamin D receptors (VDR). Vitamin D and its analogues have been effectively used in patients with CKD. The review attempts to summarize the available evidence on the role of vitamin D in DN. Electronic databases (MEDLINE, EMBASE, and Cochrane Library) were searched for studies assessing the role of vitamin D or its analogues on kidney function in type 2 diabetic patients. Studies evaluating kidney functions (urinary albumin/protein creatinine ratio, albuminuria and eGFR) were included and quality and risk of bias assessment performed. Additionally effect on 25 (OH) vitamin D, calcium and HbA1c were evaluated. The mean or its % change along with their standard deviation (SD) was used for reporting our results. RevMan (V5.2) was used for data analysis. Six studies included in this review evaluated the role of cholecalciferol, calcitriol and paricalcitol in patients with DN. Study designs differed (three randomized, one non-randomized and two uncontrolled trials) with varying degree of quality and risk of biases. Vitamin D analogues showed significant improvement in kidney function in two randomized studies. None of the studies reported significant incidences of hypercalcemia. Vitamin D analogues show significant improvement of kidney function in DN. Randomized controlled trials with longer duration, comparing the efficacy of vitamin D and its analogues are needed.Electronic supplementary materialThe online version of this article (doi:10.1186/s40200-015-0186-6) contains supplementary material, which is available to authorized users.

Vitamin D and Renal Disease

“…As already mentioned, VD is linked to renin-angiotensin aldosterone system suppression, renal protection, antiproteinuric effects, improved diabetes control, and reduced cancer risk. Pleiotropic effects were detected in CKD patients too-treatment with VD and vitamin D analogs in patients with renal disease led to reduced proteinuria; similar findings were reported in patients with diabetic nephropathy with a relatively low risk for hypercalcemia [51,52]. However, the studies dealing with CKD patients are relatively few, compared to those reporting VD pleiotropy in the general population.…”

VDR Activation Reduces Proteinuria and High-Glucose-Induced Injury of Kidneys and Podocytes by Regulating Wnt Signaling Pathway

“…It has been well documented that 1, 25(OH) 2 D 3 mediates the VDR’s biological effects by binding to it and then recruiting cofactors to form a transcriptional complex that binds to vitamin D response elements (VDRE) in the promoter region of target genes to alter transcriptional events within the target cells [8, 9]. Recent studies have shown that VDR-mediated signal transduction pathways play a critical role in the development of DN, such as inflammatory response [10], immune regulation, reduction of proteinuria, inhibition of the Ras system [9, 11], and prevention of fibrosis [12]. VDR can prevent the progression of diabetes by promoting islet cell repair and reducing insulin resistance and glucose tolerance(13).…”

“…Paricalcitol (19-nor-1, 25-hydroxy-vitamin D2), a synthetic vitamin D analog, can reduce urinary albumin in type 2 DM patients [9, 13-15]. As a vitamin D receptor agonist, it has been used for the treatment of hyperparathyroidism.…”

Vitamin D3 Partly Antagonizes Advanced-Glycation Endproducts-Induced NFκB Activation in Mouse Podocytes

“…In addition, it has been shown that AGE-BSA activates proinflammatory pathways in other cell systems [22,23,24]. Although clinical studies have suggested that paricalcitol may have advantages over ‘classical' vitamin D3 [25,26], in our in vitro study, vitamin D3 and paricalcitol were equally effective in suppressing the NFκB activation (albeit in some experiments, e.g. retention of the p65 subunit in the cytoplasm, vitamin D3 was even more effective, whereas in other experiments, paricalcitol appears to work better than vitamin D3).…”