Effect of oral sodium bicarbonate supplementation on urine TGF-�� in normal serum bicarbonate CKD, a randomized...

The consequences of chronic subclinical metabolic acidosis, characterized by an increase in single nephron ammonium generation, contribute to the progression of chronic kidney disease (CKD). Therefore, sodium bicarbonate (NaHCO₃) supplementation in CKD with normal serum bicarbonate patients may reduce kidney fibrosis and slow CKD progression. This study aimed to evaluate the impact of high-dose NaHCO₃ supplementation on urinary transforming growth factor-beta (TGF-β), a biomarker of kidney fibrosis, in non-diabetic CKD patients with normal serum bicarbonate levels. We conducted a single-center, randomized, open-label controlled trial in patients with non-diabetic CKD stage 3-4 and normal serum bicarbonate (22-26 mEq/L). Participants were randomized to receive high-dose NaHCO₃ (0.8 mEq/kg/day) or standard care for 12 weeks. The primary outcome was the change in urinary TGF-β-to-creatinine ratio from baseline. Secondary outcomes included changes in urinary albumin-to-creatinine ratio (UACR), urine pH, serum electrolytes, blood pressure, and adverse events. A total of 64 participants were randomized (NaHCO₃ group: n = 32; control group: n = 32). There was no significant difference in the percentage change of urinary TGF-β (NaHCO₃: -1.86% vs. control: 5.75%; p = 0.477). However, the NaHCO₃ group demonstrated a significant increase in urine pH mean difference (0.56; 95% CI: 0.3,0.82 vs. 0,95% CI -0.24,0.24; p = 0.002) compared to the control group. Similarly, no significant differences were observed in UACR, serum electrolytes, blood pressure, or body weight between groups. No serious adverse events were reported. High-dose NaHCO₃ supplementation in non-diabetic CKD patients with normal serum bicarbonate levels did not significantly reduce urinary TGF-β over 12 weeks but effectively increased urine pH without adverse effects. These findings suggest that NaHCO₃ is safe; however, its role in modulating profibrotic biomarkers in CKD requires further investigation. Longer-term studies and alternative alkali therapies should be explored to determine the optimal strategies for preserving kidney function in this population.Clinical trial registration: TCTR20240817007 (17/08/2024).