Vitamin D therapy on diabetic nephropathy

Abstract

Diabetic nephropathy (DN) is the leading cause of end stage renal disease and despite optimum therapy including ACEI/ARBs, a sizable proportion of patients with proteinuria progress to renal failure. It is likely that high renin level induced by RAS (Renin Angiotensin System) blockade may contribute to this and vitamin D is found to have an inhibitory effect over RAS as it reduces renin synthesis. This study was conducted to examine the effects of vitamin D therapy on renal functions of patients with DN. The aims of the study were to determine the prevalence and associated factors of DN among adult diabetics attending medical clinics in Teaching Hospital, Galle (THG) and to determine the effect of vitamin D therapy on DN, cardiovascular morbidity and bone mineral density (BMD). Phase 1: Crosssectional study involving patients with diabetes attending medical clinics in the THG. Their serum creatinine and urinary albumin (UA) levels were checked. Phase 2: A double-blind, randomized, placebo controlled study to determine the therapeutic efficacy of vitamin D. Patients with DN (UA >30 mg/g of creatinine) whose estimated glomerular filtration rate (eGFR) was more than 30 mL/min were selected and their plasma renin, Parathyroid hormone (PTH), serum vitamin D, serum calcium, serum creatinine, fasting blood sugar (FBS), lipid profile, ECG and bone mineral density (BMD) were done as baseline measurements. Subjects were randomized into two groups and treatment group was given vitamin D3,50000IU (0.25ml) intramuscularly (IM) monthly for 6 months. The control group received same volume of distilled water IM. The investigations were repeated after 6 months of therapy. BMD was measured at 12months in a randomly selected subgroup of patients. The mean (SD) age was 61 (11) years and 75 % of them were females. Among them 66% had albuminuria (microalbuminuria-60.9%; macroalbuminuria- 5.1 %). The risk factors for albuminuria were poor glycaemic control and duration of the disease. Prevalence of low eGFR was 42.9% (n=174); and it was associated with age and smoking. Retinopathy and neuropathy were associated with albuminuria but not with low eGFR. Of 155 patients invited, 85 were randomly assigned to two groups after exclusions and 82 completed the study. After six months, mean reduction of urinary albumin to creatinine ratio in the treatment and control group were 51.8 mg/g (P=0.06) and 22.4 mg/g (P<0.001), respectively (between group difference P=0.001). Significant increase in the eGFR was observed in the treatment group while eGFR remained unchanged in the control group (P=0.006 for the between-groups difference). Mean reduction in plasma renin in the treatment group and control group were 5.85 pg/mL (P < 0.001) and 0.95 pg/mL (not sigficant), respectively. After vitamin D treatment, total body BMD, total body BMC (bone mineral content) and BMDs of total spine, femoral neck and total hip regions increased by 2.0%, 2.2%, and 1.8%, 2.1% and 2.6% (P<0.05 for all), respectively in the treatment group. In the same group after 6 months of stopping treatment, marginal but a statistically significant reduction of total BMD and BMC was observed (P=0.009) while all regional BMDs remained unchanged. In the control group, none of the BMD/BMC measurements changed significantly during trial and post-trial period. No significant effect was observed in cardiovascular risk scores. In conclusion, vitamin D3 has beneficial effects on patients with diabetic nephropathy. This study was performed at the University o f Ruhuna, Sri Lanka and the results were included in a thesis with two published papers for a PhD degree with the University o f Ruhuna, Sri Lanka and defended the thesis on 19lh o f February 2015.