Treatment of metabolic acidosis with sodium bicarbonate delays progression of chronic kidney disease: the UBI Study

Abstract

BackgroundMetabolic acidosis is associated with accelerated progression of chronic kidney disease (CKD). Whether treatment of metabolic acidosis with sodium bicarbonate improves kidney and patient survival in CKD is unclear.MethodsWe conducted a randomized (ratio 1:1). open-label, controlled trial (NCT number: NCT01640119. www.clinicaltrials.gov) to determine the effect in patients with CKD stage 3–5 of treatment of metabolic acidosis with sodium bicarbonate (SB) on creatinine doubling (primary endpoint), all-cause mortality and time to renal replacement therapy compared to standard care (SC) over 36-months. Parametric, non-parametric tests and survival analyses were used to assess the effect of SB on these outcomes.ResultsA total of 376 and 364 individuals with mean (SD) age 67.8 (14.9) years, creatinine clearance 30 (12) ml/min, and serum bicarbonate 21.5 (2.4) mmol/l were enrolled in SB and SC, respectively. Mean (SD) follow-up was 29.6 (9.8) vs 30.3 (10.7) months in SC and SB. respectively. The mean (SD) daily doses of SB was 1.13 (0.10). 1.12 (0.11). and 1.09 (0.12) mmol/kg*bw/day in the first, second and third year of follow-up, respectively. A total of 87 participants reached the primary endpoint [62 (17.0%) in SC vs 25 (6.6%) in SB, p < 0.001). Similarly, 71 participants [45 (12.3%) in SC and 26 (6.9%) in SB, p = 0.016] started dialysis while 37 participants [25 (6.8%) in SC and 12 (3.1%) in SB, p = 0.004] died. There were no significant effect of SB on blood pressure, total body weight or hospitalizations.ConclusionIn persons with CKD 3–5 without advanced stages of chronic heart failure, treatment of metabolic acidosis with sodium bicarbonate is safe and improves kidney and patient survival.Electronic supplementary materialThe online version of this article (10.1007/s40620-019-00656-5) contains supplementary material, which is available to authorized users.

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

“…The mean dose required to reach this serum bicarbonate concentration (some 3-4 mmol/L higher than in the usual care arm) was 6 g/day of sodium bicarbonate-much higher than used in the BiCARB trial. The UBI trial showed a significant reduction in the rate of progression of CKD, death and dialysis commencement in the bicarbonate arm compared to usual care [34]. Patients in this trial were slightly younger (mean age 67 years) and had considerably better renal function (mean eGFR of 36 mL/min/1.73 m 2 ), but the trial was not placebo-controlled or blinded.…”

Mechanism of Action of Veverimer: A Novel, Orally Administered, Nonabsorbed, Counterion-Free, Hydrochloric Acid Binder under Development for the Treatment of Metabolic Acidosis in Chronic Kidney Disease

“…Dietary interventions in patients with CKD and metabolic acidosis, comprising increased intake of fruits and vegetables or reduced animal protein intake, have been shown to be effective in raising serum bicarbonate and slowing kidney disease progression (Goraya et al, 2014;Garneata et al, 2016). Additionally, oral alkali supplementation (sodium bicarbonate, sodium citrate) in patients with CKD and metabolic acidosis has also been shown to increase serum bicarbonate and slow kidney disease progression (de Brito-Ashurst et al, 2009;Phisitkul et al, 2010;Di This article has not been copyedited and formatted. The final version may differ from this version.…”

“…JPET Fast Forward. Published on October 8, 2020 as DOI: 10.1124/jpet.120.000190 at ASPET Journals on October 31, 2020 jpet.aspetjournals.org Iorio et al, 2019;Dubey et al, 2020). These approaches reduce dietary acid intake or neutralize endogenous acid with oral bicarbonate but have the disadvantage of potentially increasing serum potassium (dietary approaches) or introducing significant sodium (oral alkali) in patients with CKD who are prone to hyperkalemia and sodium-sensitive comorbidities .…”

Assessing Acid-Base Status in Patients With CKD: Does Measurement of Blood pH Matter?

“…However, these studies did not include or exclude participants based on blood pH. 7,8 Thus, blood pH may Related article, p. *** not ultimately influence decision making with regard to treatment. The utility of blood pH may be in its prognostic value, wherein hypobicarbonatemia accompanied by acidemia may signal a poorer prognosis than if blood pH were not low, presumably reflecting more substantial acid accumulation (Fig 1).…”