Metabolic Acidosis in Chronic Kidney Disease

Table of Contents

1. Why Failing Kidneys Cannot Clear Acid
2. How Often It Happens, and at What Stage
3. Bicarbonate as a Blood Test: What the Numbers Mean
4. Low Bicarbonate and Kidney Decline in Observational Studies
5. What Has Been Measured in Muscle
6. What Has Been Measured in Bone
7. Sodium Bicarbonate Trials: Positive and Null
8. Fruit and Vegetable Trials
9. Veverimer: An Acid Binder and Its Regulatory Outcome
10. What the Guidelines State
11. What Is Not Known
12. Key Research Papers
13. Connections
14. Featured Videos

Why Failing Kidneys Cannot Clear Acid

Metabolism and food leave a steady load of acid in the body. Researchers describe the typical diet of industrialized countries as acid-producing. Blood buffers such as bicarbonate soak up that acid at once, and the kidneys then get rid of it and make new bicarbonate to replace what was used.

The kidney's main route is ammonium, a form of acid carried out in the urine. The 2024 Kidney Disease: Improving Global Outcomes (KDIGO) guideline describes the problem directly: as filtration falls, the kidney's ability to excrete hydrogen ions and generate bicarbonate falls too, and chronic metabolic acidosis develops. A 2016 review by Kraut and Madias describes the same sequence, with less ammonium leaving in the urine, acid building up, and, often, serum bicarbonate dropping.

A small feeding study shows how the body adapts before the blood test changes. In 8 people with chronic kidney disease and 6 without, all eating the same fixed-acid diet, those with kidney disease had lower urine ammonium, and also lower urine citrate, a base the body can hold on to. The authors read the citrate result as a possible way the body compensates, and suggested urine citrate as an early marker.

Two explanations for why retained acid might do harm come mainly from laboratory work:

• Ammonia in the remaining kidney tissue. In rats with most of their kidney tissue removed, adding sodium bicarbonate to the diet led to less tubular damage, less deposited complement (an inflammatory protein system) and lower ammonia in the kidney's vein blood. The authors proposed that surviving kidney units making extra ammonia injure themselves. This was shown in rats, not in people.
• Bone as a buffer. A 2022 review by Bushinsky and Krieger describes bone releasing carbonate and phosphate to buffer acid, at the expense of its mineral content, a process drawn largely from short-term and long-term laboratory models.

This kind of acidosis is different from renal tubular acidosis, where the tubules fail while overall filtration is often relatively preserved, and from sudden acid crises such as lactic acidosis.

How Often It Happens, and at What Stage

Metabolic acidosis usually arrives late in kidney disease, though not always. Studies report:

• Rising with lost filtration. In 1,038 French adults whose filtration was measured directly, acidosis was present in 2% at 60–90 ml/min and in 39% below 20 ml/min. A measured filtration rate of 40 ml/min was the level at which a threshold would catch 90% of those with acidosis.
• Large pooled data. The 2024 guideline reports that serum bicarbonate starts to fall progressively once estimated glomerular filtration rate (eGFR) drops below 60 ml/min. It gives an adjusted prevalence of bicarbonate below 22 mmol/L of 7.7% with diabetes and 6.7% without at stage 3 with little urine protein, rising to 38.3% and 35.9% at stage 5 with heavy urine protein.
• Across a United States cohort. In the Chronic Renal Insufficiency Cohort, 17.3% had bicarbonate below 22 mM at the start. The authors point out that most people at stage 4 had normal bicarbonate and some at stage 3 had low bicarbonate, so filtration is not the whole story. Urine albumin, smoking, anemia and high potassium were among the other factors linked to low levels.
• By stage in one center. In a Polish center's 964 patients, 56.0% of those at stage 5 without dialysis had acidosis, against 38.5% on hemodialysis and 2.5% on peritoneal dialysis. The cause of the kidney disease made no significant difference.
• In stage 3 and 4 patients. Of 41,749 patients in a United States health system, 13.9% had bicarbonate below 23 mmol/L.

Children differ. The 2024 guideline reports that 38–60% of children with kidney disease in two cohorts had bicarbonate below 22 mmol/L, and that acidosis in children is also likely to slow growth.

Bicarbonate as a Blood Test: What the Numbers Mean

Serum bicarbonate appears on the routine basic metabolic panel. Many labs and papers report it as total carbon dioxide. Results are given in mEq/L or mmol/L, which for bicarbonate are the same number. These are the values that come up most in the research:

• 22 to 29: the normal range used in the veverimer trials. Another large study used 22–30.
• Below 22: the usual research definition of metabolic acidosis in chronic kidney disease.
• Below 18: the example the 2024 guideline gives of acidosis with potential clinical implications in adults.
• 24 to 26: the range the 2020 Kidney Disease Outcomes Quality Initiative (KDOQI) nutrition guideline is reported to suggest maintaining, and the target used in one Indian trial described below.
• Above 24: in the Chronic Renal Insufficiency Cohort, each extra 1 mEq/L above 24 went with a 14% higher risk of heart failure (hazard ratio 1.14).
• Above 32: in the study of 41,749 patients, this high level went with higher mortality (hazard ratio 1.74), and the overall curve was J-shaped, with risk at both ends.

The test has limits. A 2021 review by Kim notes that results can shift when a sample is exposed to air or testing is delayed, and that values differ between laboratory methods. The same review notes that a low bicarbonate shows up only once acidosis has advanced, that blood pH adds information, and that a slow fall in filtration can happen even with bicarbonate in the normal range. This is why urine citrate and ammonium are being studied as earlier markers.

Low Bicarbonate and Kidney Decline in Observational Studies

These studies follow people over time. They can show that low bicarbonate and faster decline travel together, but not that one causes the other. Sicker kidneys both clear less acid and fail faster, which makes the two hard to separate.

• Bronx clinic cohort. Among 5,422 adults, bicarbonate of 22 mEq/L or less carried a 1.54 times hazard of kidney disease progression compared with 25–26 mEq/L, after adjustment. The middle band of 23–24 showed no difference (0.97), and neither did 27 or more (1.14).
• Chronic Renal Insufficiency Cohort. Among 3,939 participants at stages 2–4, each 1 mEq/L rise in bicarbonate went with a 3% lower risk of a kidney outcome (hazard ratio 0.97). The link was stronger above 45 ml/min. Bicarbonate was not independently linked to atherosclerotic events or to death from any cause.
• Modification of Diet in Renal Disease participants. In this study the lowest bicarbonate quarter had 2.22 times the hazard of kidney failure compared with the highest. Once baseline filtration was added to the analysis, the association disappeared (hazard ratio 1.05, not significant), and the authors concluded the risk was not independent of baseline filtration.
• Large records study. Among 51,558 people at stages 3–5, the two-year rate of a combined outcome (a 40% or greater fall in estimated glomerular filtration rate, dialysis or transplant, or death) was 48% with acidosis and 17% with normal bicarbonate before adjustment. After adjustment, each 1 mEq/L rise went with a hazard ratio of 0.926.
• Mortality. In the study of 41,749 patients, low bicarbonate went with a hazard ratio for death of 1.23. The link was not significant among people with stage 4 disease and diabetes.

The 2024 guideline sums up this kind of evidence by saying that the causality of such associations remains to be demonstrated.

What Has Been Measured in Muscle

In rats and in short human studies. In rats with kidney failure, muscle broke down faster through the ubiquitin-proteasome system, a cell machine that digests proteins, and feeding the rats sodium bicarbonate prevented the increase. In a small human study, nine patients with chronic kidney failure had four weeks of sodium bicarbonate and four weeks of sodium chloride. A tracer measure of body protein breakdown fell from 122.4 to 88.3 on bicarbonate, and stayed near the starting level on sodium chloride (116.2).

In older adults followed over time. Among 1,544 well-functioning older adults, bicarbonate below 23 mEq/L went with a 1.58 times hazard of new lasting difficulty walking or climbing stairs, compared with 26 mEq/L or more. This held with and without kidney disease. Bicarbonate was not significantly linked to change in walking speed.

In trials, the results split.

• An Indian open-label trial in 188 people at stages 3–4 with bicarbonate below 22 mEq/L aimed for 24–26 mEq/L. After 6 months, lean body mass was 36.8 kg against 36 kg with standard care, and mid-arm muscle circumference 22.9 cm against 22.6 cm.
• A small Thai trial (42 people finishing) compared a higher bicarbonate target with a standard one over 4 months. Muscle mass by electrical scan rose from 26.0 to 26.7 kg in the higher group, while grip strength did not differ.
• A 149-person United States placebo-controlled trial, in people whose average bicarbonate was already normal at 24.0 mEq/L, found no significant difference in sit-to-stand time over 2 years.
• The BiCARB trial, which the 2024 Kidney Disease: Improving Global Outcomes guideline calls the largest placebo-controlled trial of oral sodium bicarbonate, enrolled 300 people aged 60 or older with bicarbonate below 22 mmol/L. At 12 months, physical performance scores were 8.3 on bicarbonate and 8.8 on placebo, with no significant effect (adjusted difference −0.4). Quality-of-life scores were lower on bicarbonate.

A 2023 meta-analysis of 12 studies and 1,995 patients pooled these results and found improved mid-arm muscle circumference (standardized difference 0.35) and sit-to-stand performance (P = 0.003), with no significant effect on grip strength, protein intake or serum albumin. The pooled result sits alongside BiCARB's null finding, and how much it matters in daily life is unsettled.

What Has Been Measured in Bone

The laboratory case is firm in models: the Bushinsky and Krieger review describes acid dissolving bone mineral, slowing bone-building cells, stimulating bone-resorbing cells and raising calcium loss in urine, with a net calcium loss almost certainly drawn from bone.

Evidence in people with kidney disease is much thinner, and the trials so far are mostly null:

• General population. Among 9,724 United States adults, not selected for kidney disease, women with bicarbonate of 27 mEq/L or more had 0.018 g/cm² higher total bone density than women below 24 mEq/L, and 31% lower odds of low bone mass. This was a single measurement at one point in time.
• Fractures on dialysis. Among 890 Japanese hemodialysis patients with overactive parathyroid glands, bicarbonate below 20 mmol/L went with 1.93 times the risk of any fracture compared with 20.0–21.9 mmol/L. Higher levels (22 mmol/L or more) also went with more fractures, and risk was lowest near 21.0 mmol/L.
• Bone density trial. The 149-person placebo-controlled trial found no significant difference in bone mineral density over 2 years. Its participants mostly did not have low bicarbonate at the start, which its authors list as a limitation.
• Bone markers. In a later analysis of the BASE pilot trial, 28 weeks of sodium bicarbonate raised soluble klotho, a protein tied to mineral handling, in a dose-dependent way. It had no significant effect on any other bone marker measured, including parathyroid hormone and bone-specific alkaline phosphatase.

No trial read for this page tested fracture as an outcome.

Sodium Bicarbonate Trials: Positive and Null

Trials reporting benefit

• London, 2009. 134 adults with creatinine clearance of 15–30 ml/min and bicarbonate of 16–20 mmol/L received oral sodium bicarbonate or standard care for 2 years, with no placebo. Kidney function fell by 1.88 ml/min with bicarbonate and 5.93 ml/min without. Rapid decline occurred in 9% against 45%, and kidney failure in 6.5% against 33%. Nutrition measures also improved.
• Hypertensive kidney disease, 2010. A blinded 5-year trial in people with relatively preserved function (mean estimated glomerular filtration rate 75 ml/min) compared bicarbonate with placebo or sodium chloride. Kidney function fell more slowly on bicarbonate.
• UBI study, Italy, 2019. An open-label trial of 740 people at stages 3–5, mean bicarbonate 21.5 mmol/L, followed for up to 36 months. Doubling of creatinine occurred in 6.6% on bicarbonate and 17.0% on standard care, dialysis started in 6.9% and 12.3%, and death occurred in 3.1% and 6.8%. There was no significant effect on blood pressure, weight or hospital stays. People with advanced heart failure were not included.
• India, 2020. The 188-person open-label trial above reported higher kidney function at 6 months (32.74 against 28.2) and rapid decline in 20.2% against 41.5%.

Trials reporting no benefit

• BiCARB, United Kingdom, 2020. 300 older adults, double-blind, up to 3 g a day against placebo. There was no significant effect on physical function or on kidney function (difference 0.6 ml/min, P = 0.39). The 2024 guideline reports kidney failure in 33 of 152 on bicarbonate and 33 of 148 on placebo (hazard ratio 0.97). Adverse events were more frequent on bicarbonate (457 against 400), and the authors judged it unlikely to be cost-effective.
• United States, 2020. In the 149-person trial, bicarbonate was given at 0.4 mEq per kg a day. Kidney function, blood pressure and weight did not differ significantly from placebo.
• Vascular function, 2023. In 109 people at stages 3b–4 with normal bicarbonate, 12 months of treatment did not improve arterial stiffness. A short-lived artery improvement at 1 month disappeared by 6 and 12 months, and estimated glomerular filtration rate did not change significantly.
• Preserve-Transplant, Switzerland, 2023. In 240 kidney transplant recipients with bicarbonate of 22 mmol/L or less, 2 years of treatment corrected the acid (21.3 to 23.0 mmol/L), but the yearly fall in function was almost the same: a mean of −1.830 on bicarbonate and −1.862 on placebo.

Trials of dose and form

• BASE pilot, 2020. 194 people took 0.5 or 0.8 mEq per kg of lean body weight, or placebo, for 28 weeks. Both doses were well tolerated with no significant change in blood pressure, weight or potassium, and the higher dose lowered urine ammonium more. Urine albumin rose by 12% on the lower dose and 30% on the higher dose. This was a safety and dosing study, not an outcome trial.
• Sodium citrate against sodium bicarbonate, 2024. In 124 people at stages 3b and 4, both raised bicarbonate by about 6 mmol/L with no significant difference in kidney function change. People stopped the study drug because of side effects in 17.7% on bicarbonate and 4.8% on citrate.

Pooled results

Meta-analyses mix the open trials with the blinded ones, and their conclusions move with the choice of trials:

• 2021, 15 trials, 2,445 people. Slower kidney decline (standardized difference 0.26) and a lower risk of kidney failure (risk ratio 0.53), both graded low certainty. The effect on death was uncertain.
• The 2024 guideline's reading of that review. Restricting to placebo-controlled trials, it reports no confirmed effect on kidney failure (hazard ratio 0.81, confidence interval 0.54–1.22).
• 2024, 14 trials, 2,037 people. Better estimated glomerular filtration rate (standardized difference 0.33), fewer hospital stays (odds ratio 0.37), more mid-arm muscle, no difference in death, and slightly higher systolic blood pressure. The authors point to a risk of bias from missing double-blinding.
• 2025, 22 studies, 2,932 people. Bicarbonate rose by 2.59, and the rise in estimated glomerular filtration rate was not significant (0.93).
• Blood pressure, 2023, 14 trials, 2,110 people. No effect on systolic pressure or need for blood-pressure medicine. This differs from the 2024 pooled result above, which reported a small rise.

Sodium bicarbonate delivers sodium. Researchers have raised this as a concern for people with reduced kidney function, and the trial data on fluid and blood pressure above are mixed. Baking soda as a household product has its own hazards, covered on the Baking Soda page. Decisions about these medicines belong with a clinician, who can see potassium, fluid and bicarbonate results.

Fruit and Vegetable Trials

Most fruits and vegetables leave base behind after digestion, so a research group in Texas tested food as the buffer. Their trials gave fruit and vegetables in amounts calculated to cut dietary acid by half, and compared them with sodium bicarbonate. The published abstracts do not list individual foods. The Kidney-Friendly Diet page introduces the stage 4 and stage 3 trials. Their details and the later follow-up are below:

• 30 days, stages 1 and 2. Urine markers of kidney injury did not change in stage 1. In stage 2, both food and bicarbonate lowered them to a similar extent compared with controls.
• 1 year, stage 4. 71 people with plasma total carbon dioxide below 22 mM. Readings rose from 19.5 to 21.2 mM on bicarbonate, 1.0 mEq per kg a day, and from 19.3 to 19.9 mM on fruit and vegetables. Bicarbonate moved the number more. estimated glomerular filtration rate did not differ between the groups, and plasma potassium did not rise in either.
• 3 years, stage 3. 108 people with milder readings of 22–24 mmol/L. Readings fell on usual care and rose in the other two groups. Kidney function fell in everyone, but less on food or bicarbonate than on usual care.
• 5 years, non-diabetic with heavy urine protein. 108 people, 36 per group. The net fall in estimated glomerular filtration rate was 18.8 on usual care, 12.3 on bicarbonate at 0.3 mEq per kg a day, and 10.0 on fruit and vegetables, with the last two not differing. Systolic pressure was lower on fruit and vegetables than on either other arm, and that group also had lower low-density lipoprotein cholesterol and lipoprotein(a), and higher vitamin K1.
• The same 5-year trial, later analysis. People with a heart attack or stroke numbered 0 on fruit and vegetables, 2 on bicarbonate and 6 on usual care. The analysis was post hoc, with small numbers.

The 2024 guideline describes this body of work as four small trials showing a comparable benefit to sodium bicarbonate in controlling acidosis. Most of the trials come from one group, and no large independent trial with kidney failure as its outcome was found for this page.

Potassium is the obvious question for advanced disease, since fruit and vegetables carry a lot of it and failing kidneys struggle to clear it. The stage 4 trial found no rise, but the abstract does not state who was kept out on potassium grounds, so the finding cannot be stretched to everyone with advanced disease. The Kidney-Friendly Diet page covers how potassium limits vary by stage and blood results.

None of the acid-load trials read for this page tested fermented foods such as natto, tempeh or miso, so nothing can be reported about their effect on acidosis. Natto and tempeh are named among plant proteins on the Kidney-Friendly Diet page, which also records that miso is very salty.

Veverimer: An Acid Binder and Its Regulatory Outcome

Veverimer takes a different approach from baking soda. It is a polymer, taken as a suspension in water, that is not absorbed, binds hydrochloric acid and removes it from the gut, with no added sodium. The earlier trials and later meta-analyses of bicarbonate level were positive, and the kidney outcome trial was null. The two 2019 trials below were funded by the drug's developer.

• 14 days, 135 patients, 2018. Tested under a code name, it raised bicarbonate by 3.2–3.9 mEq/L compared with no change on placebo. Levels fell nearly back to baseline within 2 weeks of stopping.
• 12 weeks, 217 patients, 2019. At 6 g a day, 59% reached the bicarbonate goal against 22% on placebo. Gut side effects were the most common treatment-related events (13% against 5%), with diarrhea in 9% against 3%.
• 40-week extension, 196 patients, 2019. 63% against 38% met the goal at week 52. Patient-reported physical function improved by 12.1 points more than on placebo, and the repeat chair-stand test time improved by 4.3 seconds against 1.4 seconds.
• Meta-analyses. A 2021 review of 3 trials reported a bicarbonate gain of 3.08 and a physical function gain of 5.25 points. A 2026 review of 4 studies reported a gain of 2.90 mmol/L with adverse events in the abstract not differing significantly; its full text also reports a higher risk of high potassium with veverimer.

The Food and Drug Administration decision and the outcome trial

The drug's application went through the Food and Drug Administration's Accelerated Approval Program, which relies on a surrogate marker, here serum bicarbonate. In August 2020 the agency issued a complete response letter, meaning the application was not approved as submitted. According to that report, the letter asked for more data on the size and durability of the effect on bicarbonate and on whether it applied to the United States population, and raised whether the effect was reasonably likely to predict clinical benefit. The letter is reported as identifying no safety issues.

The outcome trial, VALOR-CKD, followed. It enrolled 1,480 people from 35 countries with estimated glomerular filtration rate 20–40 ml/min and bicarbonate of 12–20 mEq/L. All first took the drug, which raised bicarbonate from 17.5 to 23.4 mEq/L, and then they were randomized to continue or switch to placebo. Progression (kidney failure, a sustained 40% fall in estimated glomerular filtration rate, or death from kidney failure) occurred in 149 of 741 on veverimer and 148 of 739 on placebo (hazard ratio 0.99, confidence interval 0.8–1.2). Serious and overall adverse events did not differ.

The result does not settle the larger question. The two groups ended up only about 1 mEq/L apart (22.0 against 20.9 at month 3), a smaller gap than the authors expected. They say this may have hindered their ability to test the idea that treating acidosis slows decline. A search of the agency's approved-drug data on 5 November 2026 returned no product under the generic name veverimer.

What the Guidelines State

Guideline positions have moved as the trials came in. These are statements by the panels, reported as such.

• Kidney Disease Outcomes Quality Initiative, 2003. As described in the 2021 review by Kim, this guideline recommended keeping total carbon dioxide at 22 mEq/L or above, with alkali salts if necessary.
• Kidney Disease: Improving Global Outcomes, 2012. As the 2024 update recounts, it gave a graded (2B) recommendation for alkali, justified as a possibly low-cost, high-benefit treatment, based on one trial reporting kidney and nutrition benefits.
• Kidney Disease Outcomes Quality Initiative nutrition guideline, 2020. A commentary by an Australian and New Zealand guideline group reports that it recommends a Mediterranean and high fruit and vegetable diet to improve lipids, lower body weight and blood pressure and reduce net acid production, with individual advice to fit potassium and protein needs. A 2023 meta-analysis reports that it suggests keeping bicarbonate at 24–26 mmol/L.
• Kidney Disease: Improving Global Outcomes, 2024. The panel no longer gives a graded recommendation, stating this is because of a lack of large trials supporting treatment. Practice Point 3.10.1 reads: "consider use of pharmacological treatment with or without dietary intervention to prevent development of acidosis with potential clinical implications (e.g., serum bicarbonate <18 mmol/l in adults)." Practice Point 3.10.2 speaks of monitoring so that treatment does not push bicarbonate above the upper limit of normal or harm blood pressure control, serum potassium or fluid status.

The 2024 panel's reasoning is plain: placebo-controlled trials have found no good evidence that correcting bicarbonate has important effects on clinical outcomes, yet sodium bicarbonate clearly raises the number and is a suitable way to prevent more severe acidosis. The panel adds that large trials are required to find a precise threshold. A 2016 review also notes that the target level is unclear, and that raising bicarbonate above 24 mEq/L might be linked to worsening cardiovascular disease.

So the two current guidelines use quite different numbers, 18 and 24–26. The 2024 document came after more of the null trials, and the 2020 document is a nutrition guideline, which gives it a different scope.

What Is Not Known

• Whether correcting acidosis slows kidney failure. Open trials say yes, blinded trials mostly say no, and the one large outcome trial separated its groups by only about 1 mEq/L. A properly sized trial with a clear bicarbonate gap has not been reported for this page.
• The right level. Treating below 22 mEq/L, below 18 mmol/L, or to 24–26 mmol/L have all been proposed. The 2024 guideline lists this question in its research agenda.
• Whether the harm comes from acid or from the disease. One large analysis lost its link to kidney failure once baseline filtration was counted.
• Whether treating before bicarbonate falls helps. Placebo-controlled trials in people with normal average bicarbonate were null for muscle, bone and blood vessels, while the 5-year blinded trial in hypertensive kidney disease and the stage 3 food trial reported slower decline.
• Fractures and daily function. Bone trials measure density and markers rather than fractures, and the muscle findings conflict.
• Food at scale. The fruit and vegetable trials are small and mostly from one group. Their results need independent testing, including in people with potassium problems.
• Children. The 2024 guideline states that no trials have examined bicarbonate supplementation on kidney disease progression or growth in children.

Further context on slowing decline is on the Slowing Chronic Kidney Disease Progression page.

Key Research Papers

1. de Brito-Ashurst I, Varagunam M, Raftery MJ, Yaqoob MM. Bicarbonate supplementation slows progression of CKD and improves nutritional status. J Am Soc Nephrol. 2009;20(9):2075-84. PubMed PMID: 19608703
2. BiCARB study group. Clinical and cost-effectiveness of oral sodium bicarbonate therapy for older patients with chronic kidney disease and low-grade acidosis (BiCARB): a pragmatic randomised, double-blind, placebo-controlled trial. BMC Med. 2020;18(1):91. PubMed PMID: 32268897
3. Di Iorio BR, Bellasi A, Raphael KL, Santoro D, Aucella F, Garofano L, Ceccarelli M, Di Lullo L, Capolongo G, Di Iorio M, Guastaferro P, Capasso G; UBI Study Group. Treatment of metabolic acidosis with sodium bicarbonate delays progression of chronic kidney disease: the UBI Study. J Nephrol. 2019;32(6):989-1001. PubMed PMID: 31598912
4. Melamed ML, Horwitz EJ, Dobre MA, Abramowitz MK, Zhang L, Lo Y, Mitch WE, Hostetter TH. Effects of Sodium Bicarbonate in CKD Stages 3 and 4: A Randomized, Placebo-Controlled, Multicenter Clinical Trial. Am J Kidney Dis. 2020;75(2):225-234. PubMed PMID: 31699517
5. Raphael KL, Isakova T, Ix JH, Raj DS, Wolf M, Fried LF, Gassman JJ, Kendrick C, Larive B, Flessner MF, Mendley SR, Hostetter TH, Block GA, Li P, Middleton JP, Sprague SM, Wesson DE, Cheung AK. A Randomized Trial Comparing the Safety, Adherence, and Pharmacodynamics Profiles of Two Doses of Sodium Bicarbonate in CKD: the BASE Pilot Trial. J Am Soc Nephrol. 2020;31(1):161-174. PubMed PMID: 31848294
6. Raphael KL, Katz R, Larive B, Kendrick C, Isakova T, Sprague S, Wolf M, Raj DS, Fried LF, Gassman J, Hoofnagle A, Cheung AK, Ix JH. Oral Sodium Bicarbonate and Bone Turnover in CKD: A Secondary Analysis of the BASE Pilot Trial. J Am Soc Nephrol. 2024;35(1):57-65. PubMed PMID: 38170601
7. Yang TY, Lin HM, Wang HY, Chuang MH, Hsieh CC, Tsai KT, Chen JY. Sodium Bicarbonate Treatment and Clinical Outcomes in Chronic Kidney Disease with Metabolic Acidosis: A Meta-Analysis. Clin J Am Soc Nephrol. 2024;19(8):959-969. PubMed PMID: 38980732
8. Hultin S, Hood C, Campbell KL, Toussaint ND, Johnson DW, Badve SV. A Systematic Review and Meta-Analysis on Effects of Bicarbonate Therapy on Kidney Outcomes. Kidney Int Rep. 2021;6(3):695-705. PubMed PMID: 33732984
9. Visser WJ, van de Braak EEM, de Mik-van Egmond AME, van der Burgh AC, de Roos NM, Jans I, van der Hoef I, Olieman JF, Hoorn EJ, Severs D. Effects of correcting metabolic acidosis on muscle mass and functionality in chronic kidney disease: a systematic review and meta-analysis. J Cachexia Sarcopenia Muscle. 2023;14(6):2498-2508. PubMed PMID: 37728018
10. Goraya N, Simoni J, Jo CH, Wesson DE. A comparison of treating metabolic acidosis in CKD stage 4 hypertensive kidney disease with fruits and vegetables or sodium bicarbonate. Clin J Am Soc Nephrol. 2013;8(3):371-81. PubMed PMID: 23393104
11. Goraya N, Simoni J, Jo CH, Wesson DE. Treatment of metabolic acidosis in patients with stage 3 chronic kidney disease with fruits and vegetables or oral bicarbonate reduces urine angiotensinogen and preserves glomerular filtration rate. Kidney Int. 2014;86(5):1031-8. PubMed PMID: 24694986
12. Goraya N, Simoni J, Jo C, Wesson DE. Dietary acid reduction with fruits and vegetables or bicarbonate attenuates kidney injury in patients with a moderately reduced glomerular filtration rate due to hypertensive nephropathy. Kidney Int. 2012;81(1):86-93. PubMed PMID: 21881553
13. Goraya N, Munoz-Maldonado Y, Simoni J, Wesson DE. Fruit and Vegetable Treatment of Chronic Kidney Disease-Related Metabolic Acidosis Reduces Cardiovascular Risk Better than Sodium Bicarbonate. Am J Nephrol. 2019;49(6):438-448. PubMed PMID: 30995657
14. Goraya N, Munoz-Maldonado Y, Simoni J, Wesson DE. Treatment of Chronic Kidney Disease-Related Metabolic Acidosis With Fruits and Vegetables Compared to NaHCO(3) Yields More and Better Overall Health Outcomes and at Comparable Five-Year Cost. J Ren Nutr. 2021;31(3):239-247. PubMed PMID: 32952009
15. Bushinsky DA, Hostetter T, Klaerner G, Stasiv Y, Lockey C, McNulty S, Lee A, Parsell D, Mathur V, Li E, Buysse J, Alpern R. Randomized, Controlled Trial of TRC101 to Increase Serum Bicarbonate in Patients with CKD. Clin J Am Soc Nephrol. 2018;13(1):26-35. PubMed PMID: 29102959
16. Wesson DE, Mathur V, Tangri N, Stasiv Y, Parsell D, Li E, Klaerner G, Bushinsky DA. Veverimer versus placebo in patients with metabolic acidosis associated with chronic kidney disease: a multicentre, randomised, double-blind, controlled, phase 3 trial. Lancet. 2019;393(10179):1417-1427. PubMed PMID: 30857647
17. Wesson DE, Mathur V, Tangri N, Stasiv Y, Parsell D, Li E, Klaerner G, Bushinsky DA. Long-term safety and efficacy of veverimer in patients with metabolic acidosis in chronic kidney disease: a multicentre, randomised, blinded, placebo-controlled, 40-week extension. Lancet. 2019;394(10196):396-406. PubMed PMID: 31248662
18. Tangri N, Mathur VS, Bushinsky DA, Klaerner G, Li E, Parsell D, Stasiv Y, Walker M, Wesson DE, Wheeler DC, Perkovic V, Inker LA. VALOR-CKD: A Multicenter, Randomized, Double-Blind Placebo-Controlled Trial Evaluating Veverimer in Slowing Progression of CKD in Patients with Metabolic Acidosis. J Am Soc Nephrol. 2024;35(3):311-320. PubMed PMID: 38261535
19. Liu W, Li L, Zhang X, Dong H, Lu M. Efficacy and Safety of Veverimer in the Treatment of Metabolic Acidosis Caused by Chronic Kidney Disease: A Meta-analysis. Front Pharmacol. 2021;12:643128. PubMed PMID: 33995050
20. Islampanah M, Karami S, Salehi S, Akbari A, Noradini A, Tafazolimoghadam A, Yousefi S, Pirzad S. Veverimer in treating metabolic acidosis in chronic kidney disease patients: a systematic review and meta-analysis of randomized clinical trials. BMC Nephrol. 2026;27(1):144. PubMed PMID: 41723402
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