Journal of Family Medicine and Primary Care · 5 authors, 4 centres
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This double-blind RCT found that daily 0.25 mg active vitamin D (calcitriol) for 12 weeks significantly reduced proteinuria in patients with type 2 diabetic nephropathy. Proteinuria dropped from a baseline mean of 931.60 mg/24h to 502.95 mg/24h in the intervention group, while the control group showed minimal change. The anti-proteinuric effect became statistically significant after two months of treatment, with no significant changes in GFR, FBS, or blood pressure over time.
**Background:** Diabetic nephropathy (DN) is a common and severe complication of type 2 diabetes (T2D), with proteinuria serving as both a clinical indicator and independent risk predictor for DN progression. Preclinical evidence suggests that active vitamin D (calcitriol) may protect renal function by suppressing the renin-angiotensin-aldosterone system (RAAS), reducing podocyte apoptosis, and increasing hepatocyte growth factor. However, human studies evaluating the anti-proteinuric effect of vitamin D in DN have yielded conflicting results, and most evidence comes from laboratory models rather than clinical trials. This study aimed to determine the anti-proteinuria effects of active vitamin D in patients with type 2 DN.
**Methods:** This was a double-blind randomized clinical trial conducted in 2021 at Golestan and Imam Hospitals in Ahvaz, Iran. Forty patients with type 2 DN and proteinuria >500 mg/24h were enrolled via convenience sampling and randomly assigned to intervention (n=20) and control (n=20) groups using block randomization. Inclusion criteria included age 30–70 years, T2D diagnosis for at least 3 months, proteinuria >500 mg/24h, and plasma hydroxyvitamin D level >20 ng/mL. Exclusion criteria included hypercalcemia (>10 mg/dL), serum phosphorus >5.5 mg/dL, uncontrolled hypertension (>140/90 mmHg), hyperparathyroidism, kidney stones, CKD, heart failure, calcium/phosphorus metabolic disorders, pregnancy, and lactation. The intervention group received 0.25 mg active vitamin D (calcitriol) daily for 12 weeks. Both groups continued standard therapy including oral glucose-lowering agents or insulin and valsartan (at stable doses for at least 3 months prior). Measurements of FBS, calcium, phosphorus, creatinine, GFR, systolic/diastolic blood pressure, and 24-hour urinary proteinuria were taken at baseline and at the end of months 1, 2, and 3. HbA1c was measured at baseline and study end. Statistical analysis used repeated measures analysis, t-tests, and analysis of covariance.
**Key Results:** The study included 21 males (52.5%) and 19 females (47.5%), with a mean age of 55.52±6.58 years. Baseline characteristics were comparable between groups. The primary finding was a significant reduction in proteinuria in the intervention group. Mean proteinuria in the intervention group decreased from 931.60±231.76 mg/24h at baseline to 814.40±185.30 at month 1, 697.55±171.98 at month 2, and 502.95±118.40 at month 3. In the control group, proteinuria changed from 907.55±220.52 at baseline to 896.40±198.70, 902.35±176.41, and 868.75±180.68 at months 1, 2, and 3 respectively. Between-group differences became significant at month 2 (P=0.001) and month 3 (P=0.000). Repeated measures analysis confirmed a significant decrease in proteinuria over time in the intervention group (P=0.000) but not in controls (P=0.319). No significant between-group differences were observed for FBS (P=0.235), calcium (P=0.393), phosphorus (P=0.694), creatinine (P=0.232), GFR (P=0.347), systolic blood pressure (P=0.615), or diastolic blood pressure (P=0.115) over the study period. However, at individual time points, calcium was significantly higher in the intervention group at month 2 (P=0.015) and month 3 (P=0.033), and creatinine was significantly lower in the intervention group at month 2 (P=0.011) and month 3 (P=0.009). Systolic and diastolic blood pressure were significantly lower in the intervention group at months 2 and 3, though overall trends over time were not significant. HbA1c did not differ between groups at baseline (P=0.204) or at month 3 (P=0.130).
**Clinical Implications:** This study provides evidence that daily administration of 0.25 mg active vitamin D (calcitriol) for at least 8–12 weeks significantly reduces proteinuria in patients with type 2 diabetic nephropathy, without causing hypercalcemia, hyperphosphatemia, or significant changes in renal function as measured by GFR. The anti-proteinuric effect appears to require a minimum of two months of treatment to become statistically significant. Active vitamin D may serve as a useful adjunctive therapy to RAAS blockade in managing proteinuria in DN. The lack of effect on GFR, FBS, and HbA1c suggests the anti-proteinuric mechanism is independent of glycemic control. Limitations include the small sample size (n=40), short duration (12 weeks), single-center design, and exclusion of patients with vitamin D deficiency (<20 ng/mL), which limits generalizability to vitamin D-deficient populations. Larger, longer-term studies are needed to confirm these findings and assess effects on hard renal outcomes.