Lose the Sodium Bicarb? Fewer Pills Needed for Kidney Transplant

Giving adult kidney transplant recipients sodium bicarbonate to correct metabolic acidosis may not help preserve graft function and instead represents an unnecessary "pill burden," new clinical trial data from Switzerland suggest.

Bicarbonate supplementation has been shown to reduce chronic kidney disease (CKD) progression and is currently recommended for nontransplanted patients with CKD who have serum bicarbonate levels below 22 mmol/L.

However, while metabolic acidosis is even more common and severe in kidney transplant recipients with CKD, there are fewer data to guide practice in those individuals.

Now, in the first randomized, prospective, placebo-controlled study to investigate the question, 2 years of supplementation with sodium bicarbonate among kidney transplant recipients with metabolic acidosis did not affect the decline in estimated glomerular filtration rate (eGFR), suggesting it did not help preserve graft function, Nilufar Mohebbi, MD, and colleagues write in their article published online in The Lancet.

"Thus, treatment with sodium bicarbonate should not be generally recommended to preserve [eGFR]...in kidney transplant recipients with chronic kidney disease who have metabolic acidosis. The reasons for the absence of effect in kidney transplant recipients versus a positive effect in patients with [CKD] who are not transplant recipients might be diverse and requires further study," the authors note.

Editorialists Agree, Say Study Fills Important Information Gap

This new trial "fills an important knowledge gap in the daily treatment of renal allograft recipients," say Klemens Budde, MD, and Fabian Halleck, MD, in an accompanying editorial.

"Although these patients frequently have mild metabolic acidosis, there is now good evidence that correction of acidosis will not have any detectable effect on renal function."

"Thus, sodium bicarbonate can safely be omitted, reducing the pill burden in patients," note the editorialists, from the Department of Nephrology at Charité Universitätsmedizin Berlin, Germany.

No Difference in eGFR Slopes With Bicarbonate Supplementation

The findings are from the Preserve-Transplant Study, a multicenter, randomized, single-blind, placebo-controlled phase 3 trial conducted at three Swiss university hospitals by Mohebbi, of the Division of Nephrology, University Hospital, Zurich, Switzerland, and colleagues.

In the trial, 242 adults who had received kidney transplants more than a year prior to the study and who had an eGFR of 15-89 mL/min/1.73m² and serum bicarbonate of 22 mmol/L or less were randomized 1:1 to oral sodium bicarbonate 1.5-4.5 g/day or matching placebo for 2 years.

Of note, 93% were taking standard calcineurin inhibitor-based immunosuppressive treatment regimens, which partly explains the greater frequency and severity of the metabolic acidosis in kidney transplant recipients with CKD compared to people with CKD who have not received transplants as "the additional effects of calcineurin inhibitors might not be easily antagonized with alkali treatment," the editorialists note.

They stress that the bicarbonate did correct the metabolic acidosis: "Around 3 g sodium bicarbonate treatment (six pills) led to correction of acidosis and serum bicarbonate concentrations, whereas placebo-treated patients had a constant mild acidosis."

However, this didn't translate into a significant difference in eGFR between the two groups.

In the sodium bicarbonate group, eGFR declined from 48.2 mL/min/1.73m² down to 45.5 mL/min/1.73m² at 24 months, while in the placebo group, it decreased from 47.7 mL/min/1.73m² down to 46.2 mL/min/1.73m².

The mean between-group difference in the calculated yearly estimated slopes of eGFR decline over the 2-year period was 0.032 mL/min/1.73m², which was not significant.

The urine albumin-to-creatinine ratio was 5.7% higher at 2 years in the sodium bicarbonate group, but this was also not significant (P = .72). Median office systolic and diastolic blood pressures also didn't differ between the two groups.

Adverse events, including serious events, were similar in the two groups.

"As always in medicine, patients should be treated based on the best evidence and not laboratory values or hypotheses...Until new evidence shows a clear benefit of acidosis correction, the practical and evidence-based treatment decision should be to avoid the additional pill burden and the costs for the health system," conclude Budde and Halleck.

Findings Can't Be Extrapolated Beyond Transplant Patients

Budde and Halleck also point out that the reduced effect of renin–angiotensin system blockade is another example of a different treatment response in transplanted kidneys versus CKD without transplant and why these new findings on sodium bicarbonate can't be extrapolated from one group to the other.

Yet another example, they say, is the sodium-glucose cotransporter-2 (SGLT2) Inhibitors, "where the beneficial effects in patients with CKD should not be extrapolated to renal transplant recipients."

"Rigorously conducted trials are needed to generate the evidence for the benefits and risks of this promising class of drugs in kidney transplant recipients," they conclude.

This study was financed by the investigator-initiated clinical trial program of the Swiss National Science Foundation. Mohebbi has reported receiving lecture fees from Forum für Medizinische Fortbildung and Boehringer Ingelheim. Budde has reported receiving honoraria or travel support from AiCuris, Astellas, Astra, CareDx, Carealytics Digital Health, Chiesi, MSD, Neovii, Natera, Paladin, Stada, Takeda, Veloxis, and Vifor. Halleck has reported receiving honoraria or travel support from MSD, Hansa, Chiesi, and Novartis.

Lancet. Published online January 25, 2023. Abstract, Editorial

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in The Washington Post, NPR's Shots blog, and Diabetes Forecast magazine. She is on Twitter: @MiriamETucker.

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