Dialysate Calcium Concentration below 3.0 mEq/L Is Not Associated with Improved Outcomes in the Japanese Dialysis Outcomes and Practice Patterns Study

Abstract

Background: Abnormal chronic kidney disease-mineral and bone disorder (CKD-MBD) markers have been associated with adverse outcomes in hemodialysis (HD) patients. Dialysate calcium concentration (D-Ca) likely influences serum calcium and phosphorus levels. Optimal D-Ca level remains unclear. We hypothesized that higher D-Ca is associated with cardiovascular events and mortality among Japanese HD patients. Methods: Enrollment data of chronic HD patients in the prospective observational study JDOPPS, phases 1–5 (1999–2015), provided exposures and covariates. All-cause mortality, non-arrhythmic cardiovascular events (NonAR-CVE), or their composites were analyzed by D-Ca, and divided into 2.5, 2.75, and 3.0 mEq/L. To minimize confounding by indication, analyses were restricted to facilities in which at least 90% of patients received the same D-Ca prescription. Association of D-Ca level with outcomes was evaluated in Cox models stratified by phase and accounting for facility clustering. Covariates describing patient demographics, comorbidities, laboratory values, CKD-MBD therapy, and facility attributes provided adjustment. Results: Of 9,201 patients included, 25.0% had D-Ca of 2.5 mEq/L; 6.8% D-Ca 2.75; and 68.2% D-Ca 3.0. Median follow-up time was 2.03 years. D-Ca was not associated with all-cause mortality, with hazards ratios for 2.5 vs. 3.0 mEq/L of 0.90 and 95% CI (0.73–1.11), nor with other outcomes. One effect modification occurred, protective for lower D-Ca on NonAR-CVE in the absence of cardiovascular comorbidities (p = 0.032), although corresponding D-Ca effects were not significant after multiple comparisons adjustment (p = 0.261 [D-Ca 2.5] and 0.125 [D-Ca 2.75]). Conclusion: Lowering D-Ca level below 3.0 mEq/L seems not to have a meaningful effect on patient outcomes.

Dialysate calcium, alfacalcidol, and clinical outcomes: A post-hoc analysis of the J-DAVID trial

“…However, the association of D-Ca and the combined outcome was again not significant. Similar to our results, another observational study derived from the Japanese Dialysis Outcomes and Practice Patterns Study reported that the difference in D-Ca was not related to the survival based on the results of 9,201 patients with a median follow-up of 2.03 years [ 16 ]. Thus, the low statistical power does not fully explain the neutral results on the D-Ca in this range and clinical outcomes in this study.…”

<p>Efficacy and Safety of Evocalcet Evaluated by Dialysate Calcium Concentration in Patients with Secondary Hyperparathyroidism Undergoing Hemodialysis</p>

“…18 Although one dialysate calcium concentration of 2.75 mEq/L became available in 1993 in Japan, 19 any dialysate calcium concentrations below 3.0 mEq/L were unlikely to have a clinically significant effect on patient prognosis. 20 Unlike in other countries, where singlepatient dialysis fluid delivery systems have been used based on each patient's condition, a central dialysis fluid delivery system has been adopted for the past 45 years in Japan with the dialysate calcium concentration determined based on the policy of the medical facility. 21 Because evocalcet and cinacalcet both lower the serum calcium concentration, their efficacy and safety may be affected by the concentration of dialysate calcium.…”