Abstract

Abstract Background and Aims The appropriate prescription of dialysate calcium (DCa) concentration for hemodialysis (HD) patients is debated and guidelines are inconsistent. We investigated the association between DCa and all-cause, cardiovascular mortality and sudden cardiac death (SCD). Moreover, we examined the association between serum dialysate calcium gradient (SCa-DCa) and the study outcomes. Method In this historical cohort study, we included adult incident HD patients registered in the clinical database EuCliD® with dialysis initiation between January 1, 2010, and June 30, 2017 (recruitment period) who survived for at least 6 months after starting dialysis (grace period). We observed patients’ outcomes for up to 2 years after the end of the grace period (Figure 1). We categorized patients into 2 groups according to the prescribed DCa in the last 3 months of the grace period (ascertainment period): 1.25 (DCa 1.25) or 1.50 mmol/l (DCa 1.50). We calculated hazard ratio (HR) with 95% confidence intervals (CI) for all study outcomes with Cox Regression. The fully adjusted model included age, sex, ethnicity, diabetes mellitus, cardiovascular disease, liver disease, cancer, vascular access, treatment time, Kt/V, total ultrafiltered volume per session, serum hemoglobin, serum albumin, calcium containing phosphate binders, active vitamin D, Cinacalcet. We added country indicators as random effects. The SCa-DCa (in mEq/l) was calculated as (albumin-correct serum calcium (in mg⁄dl) × 0.5) – (DCa (in mmol/l) × 2) (1). Results We included 12,897 patients with DCa 1.25 and 26,989 patients with DCa 1.50 from 22 countries. The median age was 65 years and the percentage of men was 61% in both groups. In the unadjusted model, patients treated with DCa 1.50 had higher risk of all-cause mortality compared to those treated with DCa 1.25 (HR 1.07 [95% CI 1.01-1.12]. However, this association was not robust when adjusting for potential confounding (HR 1.04 [95% CI 0.97-1.10]). Similarly, we found no evidence of significant adjusted association between DCa and cardiovascular mortality (HR 1.01 [95% CI 0.92-1.11]). We observed a significant adjusted lower association between DCa 1.50 and SCD (HR 0.78 [95% CI 0.65-0.94]). We found significant associations between larger SCa-DCa gradient and all outcomes: all-cause (HR 1.16 per 1 mEq/L increase [95% CI 1.09-1.24]), cardiovascular mortality (HR 1.23 [95% CI 1.12-1.35]) and SCD (HR 1.69 [95% CI 1.41-2.03]). To explore the contribution of gradient components to patients’ risk, we included both DCa and serum calcium level (SCa) in the models. We observed significant associations with all outcomes and SCa, but not with DCa and the interaction between them. In a subgroup analysis of patients with iPTH levels below 130 pg/ml (n = 7,438), we did not find any significant association between DCa and the outcomes. Conclusion In this observational study, no differences in all-cause or cardiovascular mortality were observed with the prescription of DCa 1.50 as compared to 1.25 after adjustment for confounders, whereas the risk of SCD appeared to be lower in the group of DCa 1.50. The association between the SCa-DCa gradient and outcomes appears to be predominantly related to the effect of SCa.

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