#NephMadness 2024: Metabolic Acidosis – Show Me the Money!

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Navdeep Tangri
Former AJKD Blog Contributor

Navdeep Tangri, MD, PhD, FRCPC, is an Assistant Professor in the Division of Nephrology at the University of Manitoba and an Adjunct Assistant Professor at Tufts University. He received his medical training at University of Manitoba, and completed an internal medicine residency at McGill University. He subsequently enrolled as a clinical research fellow at Tufts Medical Center in Boston and completed a PhD in clinical and translational research.

He manages a broad based research lab with projects aimed at studying 1) predictive modeling as it applies to the epidemiology of chronic kidney disease and kidney failure; 2) physical and cognitive function in advanced CKD; and 3) health disparities and CKD and ESRD care.

Read Dr. Tangri’s posts.

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Navdeep Tangri, MD, PhD, FRCPC

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Navdeep Tangri @NavTangri

Dr. Navdeep Tangri is Professor in the Department of Medicine at the University of Manitoba. He is interested in developing and implementing prediction models that help physicians recognize high risk CKD early, and act to prevent progression well before kidney failure. He loves all things Arsenal FC.

Competitors for the Metabolic Acidosis Region

Team 1: CKD/Outpatient vs Team 2: AKI/ICU

Those of you of similar vintage to me will remember Cuba Gooding Jr shouting at Tom Cruise, “Show me the money!”

Metabolic Acidosis in CKD is very much a story of, “Show me the evidence.” Like a lot of good stories in nephrology or renal physiology, it starts with something intuitive – acid is bad, dissolves bones, follows up with studies in dogs conducted in the 50s and 60s, and leads to conviction in early 2000s from a single center RCT (unblinded) by Dr. De Brito-Ashurst and Yaqoob. The story then ages in Italy, similar to good wine, and we are sold completely by the time Dr. Iorio and others from the UBI study tell us in yet another unblinded study that we must treat and the benefits are larger than we could ever imagine.

So, there is clearly a feel-good vibe about metabolic acidosis in CKD. And in this state of mind, we begin to ignore the well-done trials that are convincingly negative. There is a well-done single center (blinded) study from New York that is negative for change in kidney function or muscle strength. Another one from Colorado, also blinded, negative for changes in kidney or vascular function. And finally, one from the UK, the Bicarb study, a randomized double blind multi center trial that is completely negative on every outcome and shows that, similar to real world data, adherence to sodium bicarbonate is poor.

Nonetheless, the optimism in clinical practice continues. All of us find flaws in the negative studies, and ignore the obvious flaws in the positive studies. After all, sodium bicarbonate is cheap, and fruits and vegetables have other pleotropic effects that likely go beyond metabolic acidosis. That was, until 2023, when we have a multicenter trial in transplant and the largest trial of a treatment for metabolic acidosis in CKD (Veverimer -VALOR-CKD) publish their findings. First, in patients with a kidney transplant, oral sodium bicarbonate does not change the slope of eGFR. And then veverimer, in a study of 1,480 participants across more than 300 sites, does not affect the decline in kidney function or any of the secondary endpoints.

Critics of the VALOR study will point out that there was a lack of separation in serum bicarbonate levels in the treatment groups. However, the separation seen in VALOR was not different from any of the well done (randomized, double blind) studies of sodium bicarbonate, and not a single randomized double blind study of treatment of metabolic acidosis in CKD has shown an improvement in kidney function. This is finally acknowledged in the 2024 KDIGO clinical practice guidelines, where there is no longer a graded recommendation for the treatment of metabolic acidosis or a target recommended serum bicarbonate level, but rather a practice point that suggests treating to keep serum bicarbonate levels > 18 mEq/l.

So, why do I think you should choose Metabolic Acidosis in CKD? Well first, there is much more drama here than Metabolic Acidosis is AKI/ICU. Second – this is truly a change in practice for many/most of us – and if we don’t elevate this up the bracket practice wont change and patients will continue treatment with oral sodium bicarbonate with a polypharmacy burden that’s completely unjustified. Third – from a researcher’s perspective, a false belief in sodium bicarbonate has held back important clinical trials for randomizing patients with moderate to severe metabolic acidosis. This should now be wide open. Future iterations of trials (like the BASE trial) which were previously done in patients with bicarbonate levels > 22 or 24, should now be enrolling patients with serum bicarbonate levels between 16-22 mEq/l.

As a community, we should wait for a positive finding from a well performed randomized double blind placebo controlled trial of treatment of metabolic acidosis before prescribing oral sodium bicarbonate. Its time for baking soda to show me the money!

– Guest Post written by Navdeep Tangri @NavTangri

As with all content on the AJKD Blog, the opinions expressed are those of the author of each post and are not necessarily shared or endorsed by the AJKD Blog, AJKD, the National Kidney Foundation, Elsevier, or any other entity unless explicitly stated.

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