Vitamin D receptor activation with calcitriol for reducing urinary angiotensinogen in patients with type 2 diabetic chronic kidney disease

Background Recently, it has been reported that urinary angiotensinogen levels is a specific index of the intrarenal renin-angiotensin-aldosterone system (RAAS) status and it is significantly correlated with urinary albumin: creatinine (Cr) ratio in hypertensive patients. The aim of the present study was to assess the effect of activation of the Vitamin D receptor with calcitriol on albuminuria and urinary angiotensinogen as a novel biomarker of the intra-renal RAAS status in patients with diabetic nephropathy (DN). Methods Ninety-eight patients with type 2 diabetes and albuminuria who were treated with RAAS inhibitors (angiotensin-converting enzyme inhibitor (ACE-i) or angiotensin receptor blocker (ARB)) have participated in this study. Patients were randomized to receive either placebo (n = 50) or 0.25 mu g/day calcitriol (n = 48). We have examined urinary albumin: Cr ratio and urinary angiotensinogen: Cr ratio before and 24 weeks later after treatment in both group. Results The mean urinary albumin: Cr ratio and urinary angiotensinogen: Cr ratio were significantly higher in patients with DN than in normal controls (p<0.001). Urinary angiotensinogen: Cr ratio was significantly, positively correlated with urinary albumin: Cr ratio in both groups (in the placebo group; p = 0.01, r = 0.4236, in calcitriol group; p = 0.01, r = 0.4564). Conclusion These data indicated that administration of Vitamin D receptor activator in combination with RAAS inhibitors had an additional benefit in lowering albuminuria in patients with DN. More pronounced reduction of urinary albumin: Cr ratio that was positively correlated with angiotensinogen: Cr ratio in calcitriol group suggested that Vitamin D receptor activation might blunt albuminuria by reducing urinary angiotensinogen levels reflecting intra-renal RAAS status.