Sodium bicarbonate for kidney transplant recipients with metabolic acidosis in Switzerland: a multicentre, randomised, single-blind, placebo-controlled, phase 3 trial

Mohebbi, Nilufar; Ritter, Alexander; Wiegand, Anna; Graf, Nicole; Dahdal, Suzan; Sidler, Daniel; Arampatzis, Spyridon; Hadaya, Karine; Mueller, Thomas; Wagner, Carsten A.; Wüthrich, Rudolf P.

doi:10.1016/s0140-6736(22)02606-x

Cited by 13 publications

(8 citation statements)

References 30 publications

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“…The largest sodium bicarbonate trial, the UBI Study, demonstrated a lower risk of CKD progression, ESKD, and mortality [64]. However, in kidney transplant recipients, a positive effect on kidney outcomes was not observed, potentially because the transplanted kidney is subjected to additional mechanisms of kidney damage that cannot be overcome by alkali therapy alone [66]. In addition, the treatment of metabolic acidosis with the gastrointestinal hydrochloric acid binder veverimer did not have a positive effect on kidney events [62].…”

Section: Discussionmentioning

confidence: 99%

“…It is important to note that other studies have not demonstrated a positive effect of alkali therapy in patients with kidney disease and metabolic acidosis. These include a two-year trial conducted in kidney transplant recipients, called the Preserve-Transplant Study [66], and the BiCARB Trial, in which sodium bicarbonate treatment was associated with higher rates of hospitalization and worse physical performance [67]. The VALOR-CKD trial, which tested the effect of the gastrointestinal binder veverimer on CKD progression in patients with overt metabolic acidosis, also did not demonstrate a positive effect on kidney health [62].…”

Section: Kidney Effectsmentioning

confidence: 99%

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Metabolic Acidosis in CKD: Pathogenesis, Adverse Effects, and Treatment Effects

Raphael

2024

IJMS

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Metabolic acidosis is a frequent complication of chronic kidney disease and is associated with a number of adverse outcomes, including worsening kidney function, poor musculoskeletal health, cardiovascular events, and death. Mechanisms that prevent metabolic acidosis detrimentally promote further kidney damage, creating a cycle between acid accumulation and acid-mediated kidney injury. Disrupting this cycle through the provision of alkali, most commonly using sodium bicarbonate, is hypothesized to preserve kidney function while also mitigating adverse effects of excess acid on bone and muscle. However, results from clinical trials have been conflicting. There is also significant interest to determine whether sodium bicarbonate might improve patient outcomes for those who do not have overt metabolic acidosis. Such individuals are hypothesized to be experiencing acid-mediated organ damage despite having a normal serum bicarbonate concentration, a state often referred to as subclinical metabolic acidosis. Results from small- to medium-sized trials in individuals with subclinical metabolic acidosis have also been inconclusive. Well-powered clinical trials to determine the efficacy and safety of sodium bicarbonate are necessary to determine if this intervention improves patient outcomes.

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Section: Discussionmentioning

confidence: 99%

Section: Kidney Effectsmentioning

confidence: 99%

Metabolic Acidosis in CKD: Pathogenesis, Adverse Effects, and Treatment Effects

Raphael

2024

IJMS

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“…In kidney transplantation, an increasing number of observational studies have seen an association of MA with decreasing allograft function or allograft failure [ 12 , 81 , 94 ]. However, to date, there is only one randomized-controlled trial in the kidney transplant setting (Preserve-Transplant Study) [ 71 ]. Surprisingly, this multicentric placebo-controlled trial over 2 years did not find a beneficial effect of sodium bicarbonate on eGFR slope as surrogate renal endpoint in 240 KTRs with MA underlining the importance of randomized evidence before treatment recommendations are made.…”

Section: Kidney Transplantationmentioning

confidence: 99%

Metabolic acidosis in chronic kidney disease: mere consequence or also culprit?

Kuhn,

Mohebbi,

Ritter

2024

Pflugers Arch - Eur J Physiol

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Metabolic acidosis is a frequent complication in non-transplant chronic kidney disease (CKD) and after kidney transplantation. It occurs when net endogenous acid production exceeds net acid excretion. While nephron loss with reduced ammoniagenesis is the main cause of acid retention in non-transplant CKD patients, additional pathophysiological mechanisms are likely inflicted in kidney transplant recipients. Functional tubular damage by calcineurin inhibitors seems to play a key role causing renal tubular acidosis. Notably, experimental and clinical studies over the past decades have provided evidence that metabolic acidosis may not only be a consequence of CKD but also a driver of disease. In metabolic acidosis, activation of hormonal systems and the complement system resulting in fibrosis have been described. Further studies of changes in renal metabolism will likely contribute to a deeper understanding of the pathophysiology of metabolic acidosis in CKD. While alkali supplementation in case of reduced serum bicarbonate < 22 mmol/l has been endorsed by CKD guidelines for many years to slow renal functional decline, among other considerations, beneficial effects and thresholds for treatment have lately been under intense debate. This review article discusses this topic in light of the most recent results of trials assessing the efficacy of dietary and pharmacological interventions in CKD and kidney transplant patients.

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“…Consequently, patients may be exposed to lower plasma concentrations of mycophenolic acid [ 69 ]. The recent randomized Preserve–Transplant Study failed to show the benefit of correcting metabolic acidosis with sodium bicarbonate in the attempt to slow the decline of estimated GFR [ 70 ].…”

Section: Metabolic Acidosismentioning

confidence: 99%

Non-Traditional Non-Immunological Risk Factors for Kidney Allograft Loss—Opinion

Andrian

Siriteanu

Covic

et al. 2023

JCM

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Rates of late allograft loss have improved slowly in the last decades. Well described traditional risk factors that influence allograft survival include cardiovascular events, rejection, infections and post-transplant neoplasia. Here, we critically evaluate the influence of several non-immunological, non-traditional risk factors and describe their impact on allograft survival and cardiovascular health of kidney transplant recipients. We assessed the following risk factors: arterial stiffness, persistent arteriovenous access, mineral bone disease, immunosuppressive drugs residual levels variability, hypomagnesemia, glomerular pathological alterations not included in Banff criteria, persistent inflammation and metabolic acidosis.

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Sodium bicarbonate for kidney transplant recipients with metabolic acidosis in Switzerland: a multicentre, randomised, single-blind, placebo-controlled, phase 3 trial

Cited by 13 publications

References 30 publications

Metabolic Acidosis in CKD: Pathogenesis, Adverse Effects, and Treatment Effects

Metabolic Acidosis in CKD: Pathogenesis, Adverse Effects, and Treatment Effects

Metabolic acidosis in chronic kidney disease: mere consequence or also culprit?

Non-Traditional Non-Immunological Risk Factors for Kidney Allograft Loss—Opinion

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