Higher bicarbonate targets fail to slow kidney decline in advanced chronic kidney disease trial

For decades, nephrologists have prescribed sodium bicarbonate to patients whose failing kidneys can no longer keep the blood’s acid load in check, operating on the plausible assumption that neutralizing this acidity protects the remaining filters of the kidney from further damage. That long-standing practice has now been put to one of its most direct tests. In a randomized trial conducted at the Medical University of Vienna and published in Scientific Reports, researchers led by Martina Gaggl and Gere Sunder-Plassmann compared two different treatment strategies in patients with advanced chronic kidney disease and overt metabolic acidosis, asking a deceptively simple question: does pushing serum bicarbonate to a higher target actually slow the loss of kidney function? The answer, after two years of follow-up, was no. Patients steered toward higher bicarbonate concentrations fared no better than those kept at a more conservative level, a finding that challenges the intensity, though not necessarily the principle, of alkaline supplementation in kidney care.

The SoBic study, as the trial is known, enrolled patients with stage 3 to 4 chronic kidney disease whose serum bicarbonate concentrations were 21 mmol/L or below, a threshold that defines clinically relevant metabolic acidosis in this population. Participants were randomly assigned to one of two open-label treatment arms: one targeting a serum bicarbonate of approximately 24 ± 1 mmol/L, near the lower bound of the normal laboratory range, and the other targeting approximately 20 ± 1 mmol/L, a level that corrects the most dangerous acidity while avoiding aggressive alkalinization. Sodium bicarbonate doses were titrated individually against repeated blood measurements, and the investigators tracked the estimated glomerular filtration rate, the standard measure of kidney filtering capacity, over 104 weeks. In total, 58 subjects were randomized, of whom 49 completed the full follow-up; two participants died and four began dialysis during the study period, reflecting the serious trajectory of advanced kidney disease even under close specialist care.

The treatment separation achieved by the protocol was substantial and well documented. The median sodium bicarbonate dose in the higher-target intervention group reached 6.7 grams per day, with an interquartile range of 4.2 to 8.4 grams, doses that are meaningful in daily clinical terms and comparable to those used in prior observational and interventional work. Roughly 70 percent of participants in each arm successfully reached their assigned bicarbonate target, and the resulting between-group difference in serum bicarbonate averaged 3.57 mmol/L at week 47 and 3.64 mmol/L at week 104, with confidence intervals comfortably excluding zero. In other words, this was not a trial that failed because the intervention failed to change the biology being measured. The acid-base chemistry of the blood was genuinely and durably shifted between the two groups, giving the comparison real biological teeth.

What that shift did not produce was a difference in kidney trajectory. Across the two years of follow-up, the estimated glomerular filtration rate declined by a mean of 5.8 ml/min per 1.73 m², a figure consistent with the expected progression of stage 3 to 4 disease. The difference in eGFR change between the high-target and low-target groups was −0.98 ml/min per 1.73 m², with a 95 percent confidence interval spanning −3.08 to 1.12 and a p-value of 0.648. That interval includes both a modest benefit and a modest harm, but its center sits essentially at zero, and the authors concluded that targeting higher serum bicarbonate concentrations was not associated with a clinically meaningful benefit in patients with advanced chronic kidney disease and overt metabolic acidosis. For a field accustomed to thinking of acid retention as an active driver of scarring, the result is a sobering recalibration.

The biological rationale for the original hypothesis was never frivolous. Metabolic acidosis in chronic kidney disease arises because damaged nephrons lose the ability to excrete the daily acid generated by protein metabolism, and the resulting low bicarbonate, low pH environment has been linked in laboratory and animal models to increased ammoniagenesis, activation of the complement cascade, stimulation of endothelin production, and promotion of interstitial fibrosis. Observational cohorts repeatedly showed that patients with lower bicarbonate levels progress faster to kidney failure, and smaller interventional studies, including trials of oral sodium bicarbonate in earlier-stage disease, suggested possible slowing of decline. Those converging lines of evidence were strong enough to earn alkaline therapy a firm place in international guidelines, which recommend correcting bicarbonate below roughly 22 mmol/L. What the observational data could never settle, however, was whether low bicarbonate was a cause of progression or simply a marker of more severe underlying disease.

That distinction is precisely where randomized trials earn their authority, and the SoBic result illustrates why. By randomly assigning the target rather than letting disease severity dictate it, the Vienna team severed the confounding that has plagued the field. The outcome suggests that, at least in patients who already have advanced disease and established acidosis, the residual acidity that remains at a 20 mmol/L target does not measurably accelerate scarring compared with near-normal levels. It remains possible that earlier correction, before substantial nephron mass is lost, could still matter; the trial was designed and powered for stage 3 to 4 patients, not for the large population of stage 1 to 2 individuals with mild acid-base abnormalities. It is also possible that the two-year window, while respectable, is too short to reveal a divergence that accumulates over a decade of progression.

The study’s limitations deserve honest framing alongside its strengths. With 58 randomized participants and 49 completers, SoBic is a small trial, and its confidence intervals, while centered on zero, cannot exclude effects of up to roughly 3 ml/min per 1.73 m² in either direction. The open-label design, unavoidable given the nature of the intervention, means that neither participants nor clinicians were blinded, although the primary endpoint of eGFR decline is a laboratory measurement far less susceptible to expectation effects than symptom-based outcomes. The mortality and dialysis initiation that occurred during follow-up, while consistent with the natural history of the enrolled population, further reduced the analytical sample. The authors and the funding structure, which came from a Vienna municipal medical-science fund with study medication provided free of charge by the manufacturer and no role for the manufacturer in the study’s conduct or reporting, present the work transparently as a targeted hypothesis test rather than a definitive practice-changing mega-trial.

Even so, the clinical implications are immediate and practical. Guidelines currently recommend correcting serum bicarbonate in chronic kidney disease, but they have been notably silent on how high to push it. SoBic provides the first direct randomized evidence that a target near 20 mmol/L achieves the recognized goals of acidosis correction without sacrificing any measurable kidney protection relative to a more aggressive 24 mmol/L target. For patients, that could mean fewer grams of sodium bicarbonate per day, and with that a reduced sodium load, a real consideration in a population where volume overload and hypertension are constant management challenges. Large bicarbonate doses bring sodium into the circulation, and the trial’s higher-target arm was effectively also a higher-sodium arm, a trade-off that clinicians weighing the result will want to keep in view.

The broader lesson resonates well beyond nephrology. Metabolic acidosis joins a growing list of biomarkers, from uric acid to homocysteine to C-reactive protein in other contexts, whose strong observational associations with disease progression have evaporated or diminished under randomized scrutiny. Association, the trial reminds us, is a hypothesis, not a mechanism. The Vienna team’s careful dose titration, their verification that the bicarbonate gap was genuinely achieved and sustained, and their null result on the hard endpoint of filtration decline together form a model of how to interrogate a guideline-supported practice that has never been properly stress-tested. For the millions of people living with chronic kidney disease worldwide, the message is not that bicarbonate therapy is useless; correction of overt acidosis remains standard care with documented symptomatic and nutritional rationale. The message is narrower and sharper: once acidosis is corrected to a reasonable degree, chasing a higher number on the chemistry panel does not buy additional kidney years. In a specialty where every pill and every millimole of sodium counts, that is a finding worth taking seriously.

Subject of Research: Sodium bicarbonate treatment targets for metabolic acidosis in stage 3–4 chronic kidney disease

Article Title: A randomized trial of high versus low serum bicarbonate targets and glomerular filtration rate decline in stage 3–4 chronic kidney disease

Article References: Gaggl, M., Aigner, C., Repitz, A., Riesenhuber, S., Sliber, C., Madern, M., Gleiss, A., Fraunschiel, M., Schmidt, A., & Sunder-Plassmann, G. (2026). A randomized trial of high versus low serum bicarbonate targets and glomerular filtration rate decline in stage 3–4 chronic kidney disease. Scientific Reports. https://doi.org/10.1038/s41598-026-68492-9

Image Credits: AI Generated

DOI: 10.1038/s41598-026-68492-9

Keywords: chronic kidney disease, metabolic acidosis, sodium bicarbonate, serum bicarbonate, glomerular filtration rate, eGFR decline, randomized trial, SoBic study, nephrology, alkaline supplementation, kidney function, clinical guidelines