Effect of oral sodium bicarbonate supplementation on urine TGF-𝜷 in normal serum bicarbonate CKD, a randomized controlled trial

Abstract 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...

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Main Authors: Nipon Ngupis, Bancha Satirapoj, Theerasak Tangwonglert, Ouppatham Supasyndh, Paramat Thimachai, Narongrit Siriwattanasit
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-03733-x
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author Nipon Ngupis
Bancha Satirapoj
Theerasak Tangwonglert
Ouppatham Supasyndh
Paramat Thimachai
Narongrit Siriwattanasit
author_facet Nipon Ngupis
Bancha Satirapoj
Theerasak Tangwonglert
Ouppatham Supasyndh
Paramat Thimachai
Narongrit Siriwattanasit
author_sort Nipon Ngupis
collection DOAJ
description Abstract 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).
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spelling doaj-art-2f7e348ee3b84479905241daa660563d2025-08-20T03:45:24ZengNature PortfolioScientific Reports2045-23222025-07-011511910.1038/s41598-025-03733-xEffect of oral sodium bicarbonate supplementation on urine TGF-𝜷 in normal serum bicarbonate CKD, a randomized controlled trialNipon Ngupis0Bancha Satirapoj1Theerasak Tangwonglert2Ouppatham Supasyndh3Paramat Thimachai4Narongrit Siriwattanasit5Division of Nephrology, Department of Medicine, Phramongkutklao Hospital, College of MedicineDivision of Nephrology, Department of Medicine, Phramongkutklao Hospital, College of MedicineDivision of Nephrology, Department of Medicine, Phramongkutklao Hospital, College of MedicineDivision of Nephrology, Department of Medicine, Phramongkutklao Hospital, College of MedicineDivision of Nephrology, Department of Medicine, Phramongkutklao Hospital, College of MedicineDivision of Nephrology, Department of Medicine, Phramongkutklao Hospital, College of MedicineAbstract 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).https://doi.org/10.1038/s41598-025-03733-xSubclinical metabolic acidosisChronic kidney diseaseUrinary TGF-β
spellingShingle Nipon Ngupis
Bancha Satirapoj
Theerasak Tangwonglert
Ouppatham Supasyndh
Paramat Thimachai
Narongrit Siriwattanasit
Effect of oral sodium bicarbonate supplementation on urine TGF-𝜷 in normal serum bicarbonate CKD, a randomized controlled trial
Scientific Reports
Subclinical metabolic acidosis
Chronic kidney disease
Urinary TGF-β
title Effect of oral sodium bicarbonate supplementation on urine TGF-𝜷 in normal serum bicarbonate CKD, a randomized controlled trial
title_full Effect of oral sodium bicarbonate supplementation on urine TGF-𝜷 in normal serum bicarbonate CKD, a randomized controlled trial
title_fullStr Effect of oral sodium bicarbonate supplementation on urine TGF-𝜷 in normal serum bicarbonate CKD, a randomized controlled trial
title_full_unstemmed Effect of oral sodium bicarbonate supplementation on urine TGF-𝜷 in normal serum bicarbonate CKD, a randomized controlled trial
title_short Effect of oral sodium bicarbonate supplementation on urine TGF-𝜷 in normal serum bicarbonate CKD, a randomized controlled trial
title_sort effect of oral sodium bicarbonate supplementation on urine tgf 𝜷 in normal serum bicarbonate ckd a randomized controlled trial
topic Subclinical metabolic acidosis
Chronic kidney disease
Urinary TGF-β
url https://doi.org/10.1038/s41598-025-03733-x
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