Management of metabolic acidosis with sodium bicarbonate therapy over a two-year period in adult kidney transplant patients had no impact on the fall in estimated glomerular filtration rate (GFR), says an article published in The Lancet.
In kidney transplant patients, metabolic acidosis is frequent and is linked to deteriorating graft function. While sodium bicarbonate therapy successfully treats metabolic acidosis, its impact on graft function has not been investigated in any prospective research. In order to determine if sodium bicarbonate medication will retain graft function and decrease the trend of estimated glomerular filtration rate reduction in kidney transplant recipients, Nilufar Mohebbi and colleagues conducted this study.
In a multicenter, single-blind, randomized, placebo-controlled phase 3 experiment at three university hospitals in Switzerland, the Preserve-Transplant Study included adult male & female long-term kidney transplant patients if they had had the transplant more than a year prior. A stable allograft function in the six months prior to research participation, an estimated GFR of 15 mL/min per 173 m2 to 89 mL/min per 173 m2, and a serum bicarbonate of 22 mmol/L or less were important inclusion criteria. Using varying block sizes of two and four, multiple-block randomization was performed. Two years were spent on treatment. At an initial dosage of 500 mg or 1000 mg three times per day, acid-resistant soft gelatine capsules containing 500 mg of sodium bicarbonate or matching 500 mg placebo capsules were administered.
All randomly assigned patients who underwent a baseline visit were included in the modified intention-to-treat population used for the primary efficacy analysis. All individuals who took at least one dosage of the study medicine were considered to be part of the safety population.
The key findings of this study were:
1. 1114 kidney transplant candidates with metabolic acidosis were evaluated for study eligibility between June 12, 2017, and July 10, 2019.
2. 242 patients were randomly allocated to the research groups after 872 individuals were removed.
3. Two patients were secondary excluded, leaving 240 patients for the intention-to-treat analysis.
4. The sodium bicarbonate group’s median annual estimated GFR slope was -1413 mL/min per 173 m2 and the placebo group’s median annual estimated GFR slope was -0722 mL/min per 173 m2 and mean -1862 mL/min per 173 m2 during the course of the 2-year treatment period.
5. The mean difference per 1 73 m2 per year was -032 mL/min.
6. A sensitivity analysis supported the original study, and a subgroup analysis revealed no variations in estimated GFR slopes that were significant.
7. Sodium bicarbonate therapy effectively corrected metabolic acidosis throughout a 2-year treatment period by raising serum bicarbonate from 213 mmol/L (SD 26) to 230 mmol/L (27) and blood pH from 737 (SD 006) to 739 (004), despite the estimated GFR slope not showing a significant difference between the treatment groups.
8. Both groups experienced similar adverse events including major adverse events.
9. Three study subjects passed away. One (1% of the patients in the placebo group) died from acute respiratory distress syndrome brought on by SARS-CoV-2, and another (1% of the patients) went into cardiac arrest due to severe dehydration brought on by diarrhea, hypotension, acute renal damage, and metabolic acidosis.
Reference:
Mohebbi, N., Ritter, A., Wiegand, A., Graf, N., Dahdal, S., Sidler, D., Arampatzis, S., Hadaya, K., Mueller, T. F., Wagner, C. A., & Wüthrich, R. P. (2023). Sodium bicarbonate for kidney transplant recipients with metabolic acidosis in Switzerland: a multicentre, randomised, single-blind, placebo-controlled, phase 3 trial. In The Lancet (Vol. 401, Issue 10376, pp. 557–567). Elsevier BV. https://doi.org/10.1016/s0140-6736(22)02606-x
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