Oral Bicarbonate Therapy in Non-Haemodialysis Dependent Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

Abstract

Metabolic acidosis is a common complication in chronic kidney disease (CKD) patients, and is associated with an accelerated decline in renal function. Oral bicarbonate therapy has been used to counteract metabolic acidosis in CKD for decades. However, until recently, there have been very few intervention studies testing the effectiveness of bicarbonate therapy at improving metabolic acidosis or its consequences in patients with CKD. In this systematic review and meta-analysis, we aimed to examine the outcomes of all published randomised controlled trials (RCTs) that investigated the effect of oral bicarbonate therapy in adults with CKD. Ovid MEDLINE®, EMBASE® and Cochrane Library were searched in mid-October 2018 for English literature, with no restrictions applied to the publication status or date. Seven RCTs that recruited 815 participants met our inclusion criteria after full text review. Oral bicarbonate supplementation resulted in a slightly higher estimated glomerular filtration rate (eGFR) (mean difference 3.1 mL/min per 1.73 m2; 95% CI 1.3–4.9) and serum bicarbonate levels (mean difference 3.4 mmol/L; 95% CI 1.9–4.9) at the end of follow-up (three months to five years) compared to those given placebo or conventional CKD treatment. When limited to studies reporting outcomes at one year, the positive effect of oral bicarbonate therapy on eGFR was attenuated. There were no significant treatment effects in other parameters such as systolic blood pressure (BP) and weight. These findings should be interpreted with caution and further trial evidence is needed to establish the net overall benefit or harm of oral bicarbonate therapy in CKD.

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

“…If bicarbonate was ≥ 22 mmol/L, we asked participants to continue taking one tablet three times a day for the remainder of the trial. Although higher doses of bicarbonate have been used in some previous trials [9], we selected this dose to reflect current UK clinical practice in the treatment of acidosis; we judged that higher doses would be poorly tolerated by older people on multiple medications. No trial-specific dietary advice beyond usual care was given, and no specific recommendations on management of low serum bicarbonate concentrations were given to study physicians.…”

“…In particular, the current trial enrolled an overwhelmingly white European population. CKD of different aetiologies may respond differently and may explain some of the heterogeneity seen in one recent systematic review [9,27].…”

“…increasing serum bicarbonate) could improve physical function, lessen deterioration in renal function and improve measures of cardiovascular health and bone and mineral metabolism in patients with CKD. A recent systematic review [9] found no randomised controlled trial evidence around the effect of bicarbonate on physical function or quality of life; the current trial therefore provides an important test of the effect of bicarbonate on these important patient-centred Generalised linear model with Gaussian distribution and power 0.5 link function to estimate incremental costs and ordinary least squares regression to estimate incremental QALYs (114 complete cases + 47 participants starting renal replacement therapy during the trial with baseline EQ-5D). For incomplete cases, missing cost data were assumed to be zero and missing EQ-5D data were imputed by carrying forward the last observation Two participants from the bicarbonate group without any ICECAP data were excluded from the analysis, n = 159 j Applied average of lower quartile unit cost for haemodialysis (£134/visit) and peritoneal dialysis (£66/visit) k Applied average of upper quartile unit cost for haemodialysis (£180/visit) and peritoneal dialysis (£77/visit) l Two participants (1 from each group) without any life satisfaction data were excluded from the analysis, n = 159 Abbreviations: QALYs quality-adjusted life years, ICER incremental cost-effectiveness ratio, SA sensitivity analysis, ICECAP Investigating Choice Experiments for the preferences of older people CAPability tool, CKD chronic kidney disease outcomes.…”

“…Few trials have tested whether sodium bicarbonate is effective at preventing adverse outcomes from advanced CKD, and is safe in the context of increased sodium load, as opposed to merely increasing the concentration of circulating bicarbonate. Two recent systematic reviews and metaanalyses of small trials of moderate quality suggested a modest beneficial effect on estimated GFR and serum bicarbonate, an uncertain effect on progression to endstage kidney disease and contrasting effects on blood pressure (no effect in one review, and a small increase in the risk of hypertension in the other), and found no data on the effect of bicarbonate on physical function or quality of life [9,10]. The mean age of participants in included trials was young, ranging from 41 to 65 years.…”

Clinical Pharmacists in Chronic Care

“…Kidney disease is a global public health problem, affecting over 750 million persons worldwide [326]. Over 30 million American adults may have CKD [327] and 1.8 million in UK [328]. The global estimated prevalence of CKD is 13.4% (11.7-15.1%), and patients with ESRD needing renal replacement therapy is estimated between 4.902 and 7.083 million [329].…”