DOI: 10.6084/m9.figshare.30461638.v1
title: Modulation of renal inflammation and tubular injury by calcitriol in patients with early diabetic kidney disease: a randomized controlled trial

description: Diabetic kidney disease (DKD) is marked by inflammation, fibrosis and oxidative stress. Calcitriol may offer renoprotective effects by modulating these processes. This double-blind, randomized controlled trial investigated the effects of calcitriol supplementation on kidney injury biomarkers in patients with early DKD. This study randomized 120 patients with controlled type 2 diabetes, albuminuria, and estimated glomerular filtration rate above 45 mL/min/1.73 m<sup>2</sup> to receive either 0.25 mcg/d calcitriol or a placebo for six months. The primary outcomes were changes in urinary nephrin, podocin, kidney injury molecule-1 (KIM-1), interleukin-6 (IL-6), and urinary albumin-to-creatinine ratio (UACR). After 6 months, the calcitriol group showed lower increases in IL-6 levels (baseline 0.72 pg/mL to 0.87 pg/mL) compared to placebo (1.03 pg/mL to 2.94 pg/mL, <i>p</i> = 0.006), and lower KIM-1 levels (0.36 to 0.51 ng/mL vs. 0.55 to 0.99 ng/mL, <i>p</i> = 0.020). Full baseline and post-treatment values are provided in Tables 2. Urinary nephrin levels decreased in the calcitriol group, while change in the placebo group varied. Although UACR decreased more in the calcitriol group, the difference was not statistically significant (<i>p</i> = 0.099). Positive correlations were observed between KIM-1 and IL-6 in both groups, and a moderate correlation between IL-6 and urinary nephrin was observed in in the calcitriol group. No significant adverse events or changes in serum calcium or phosphate levels were reported. These findings suggest that Calcitriol supplementation may provide renoprotection in patients with early DKD by reducing inflammation and tubular injury, with potential effects on podocyte injury. Further research is required to validate these effects and determine the optimal dosing regimens. ClinicalTrials.gov (NCT05298163). The administration of 0.25 mcg/d calcitriol for 6 months was safe and well tolerated, supporting its potential clinical applicability.The protective effects of calcitriol in patients with early-stage DKD was primarily mediated through its anti-inflammatory properties, as evidenced by the significant reduction in urinary IL-6 and KIM-1 levels. The strong correlation between changes in IL-6 and KIM-1 further supports the anti-inflammatory property of calcitriol as a key mechanism underlying its renoprotective action.However, the effects of calcitriol on podocyte injury and albuminuria are limited. This suggests that the benefits of 0.25 mcg/d calcitriol for 6 months benefits in patients with early DKD do not extend to direct podocyte protection. The administration of 0.25 mcg/d calcitriol for 6 months was safe and well tolerated, supporting its potential clinical applicability. The protective effects of calcitriol in patients with early-stage DKD was primarily mediated through its anti-inflammatory properties, as evidenced by the significant reduction in urinary IL-6 and KIM-1 levels. The strong correlation between changes in IL-6 and KIM-1 further supports the anti-inflammatory property of calcitriol as a key mechanism underlying its renoprotective action. However, the effects of calcitriol on podocyte injury and albuminuria are limited. This suggests that the benefits of 0.25 mcg/d calcitriol for 6 months benefits in patients with early DKD do not extend to direct podocyte protection.