Long-term effects of citric acid-based bicarbonate haemodialysis on patient outcomes: a survival propensity score–matched study in western France
Authors: Potier Jacky , Dolley-Hitze Thibault , Hamel Didier , Landru Isabelle , Cardineau Erick , Queffeulou Guillaume , Zagdoun Elie , Renaudineau Eric , Molinari Nicolas , Gamon Lucie , Morena Marion , Cristol Jean-Paul , Canaud Bernard 
Published: November 2019

Abstract

Background
Citric acid–based bicarbonate haemodialysis (CIT-HD) has gained more clinical acceptance over the last few years in France and is a substitute for other acidifiers [e.g. acetic acid (CH3COOH) and hydrochloric acid (HCl)]. This trend was justified by several clinical benefits compared with CH3COOH as well as the desire to avoid the consequences of the corrosive action of HCl, but a nationwide clinical report raised concerns about the long-term safety of CIT-HD. The aim of this study was to assess the long-term effects of CIT-HD exposure on patient outcomes in western France.

Methods
This is a population-based retrospective multicentre observational study performed in 1132 incident end-stage kidney disease patients in five sanitary territories in western France who started their renal replacement therapy after 1 January 2008 and followed up through 15 October 2018. Relevant data, collected prospectively with the same medical software, were anonymously aggregated for the purposes of the study. The primary goal of this study was to investigate the effects of citrate exposure on all-cause mortality. To provide a control group to CIT-HD one, propensity score matching (PSM) at 2:1 was performed in two steps: the first analysis was intended to be exploratory, comparing patients who received citrate ≤80% of the time (CIT-HD ≤80) versus those who received citrate &gt;80% of the time (CIT-HD &gt;80), while the second analysis was intended to be explanatory in comparing patients with 0% (CIT-HD0) versus 100% citrate time exposure (CIT-HD100).

Results
After PSM, in the exploratory part of the analysis, 432 CIT-HD ≤80 patients were compared with 216 CIT-HD &gt;80 patients and no difference was found for all-cause mortality using the Kaplan–Meier model (log-rank 0.97), univariate Cox regression analysis {hazard ratio [HR] 1.01 [95% confidence interval (CI) 0.71–1.40]} and multivariate Cox regression analysis [HR 1.11 (95% CI 0.76–1.61)] when adjusted for nine variables with clinical pertinence and high statistical relevance in the univariate analysis. In the explanatory part of the analysis, 316 CIT-HD0 patients were then compared with 158 CIT-HD100 patients and no difference was found using the Kaplan–Meier model (log-rank 0.06), univariate Cox regression analysis [HR 0.69 (95% CI 0.47–1.03)] and multivariate Cox regression analysis [HR 0.87 (95% CI 0.57–1.33)] when adjusted for seven variables with clinical pertinence and high statistical relevance in the univariate analysis.

Conclusions
Findings of this study support the notion that CIT-HD exposure ≤6 years has no significant effect on all-cause mortality in HD patients. This finding remains true for patients receiving high-volume online haemodiafiltration, a modality most frequently prescribed in this cohort.