A Pilot Study of the Safety and Efficacy of Alkali Therapy on Vascular Function in Kidney Transplant Recipients

Abstract

Introduction Metabolic acidosis is associated with cardiovascular events, graft function, and mortality in kidney transplant recipients (KTRs). We examined the effect of alkali therapy on vascular endothelial function in KTRs. Methods We performed an 18-week, randomized, double-blind, placebo-controlled crossover pilot study examining the effect of sodium bicarbonate therapy versus placebo on vascular function in 20 adult KTRs at least 1 year from transplant with an estimated glomerular filtration rate (eGFR) ≥45 ml/min per 1.73 m2 and a serum bicarbonate level of 20 to 26 mEq/L. Each treatment period was 8 weeks in duration with a 2-week washout period between treatments. The primary outcome was change in brachial artery flow-mediated dilation (FMD) between sodium bicarbonate treatment and placebo. Results Twenty patients completed the study and were included in the primary analysis. The mean (SD) baseline eGFR of participants was 75 (22) ml/min per 1.73 m2, respectively. Serum bicarbonate levels did not increase significantly with treatment (0.3 [1.5] mEq/L, P = 0.37). Sodium bicarbonate therapy was not associated with worsening blood pressure, weight gain, or hypokalemia. There was no significant increase in FMD after 8 weeks of sodium bicarbonate therapy compared to placebo (mean change in FMD 2.2%, 95% CI –0.1 to 4.6, P = 0.06). There were no significant changes in high-sensitivity C-reactive protein, interleukin-6, eGFR, or urinary albumin-to-creatinine ratio during treatment. Urinary ammonium excretion decreased by 9 mmol/d (P=0.003), with sodium bicarbonate. Conclusions Sodium bicarbonate therapy is safe and feasible in KTRs, and our results strengthen the need for a larger randomized controlled trial.