Effects of Dialysate Calcium Concentration on Bone, Mineral Metabolism, and Vascular Outcomes in Maintenance Hemodialysis: A Systematic Review and Meta-Analysis

Background/Objectives: The optimal dialysate calcium concentration in maintenance hemodialysis remains uncertain because reducing calcium exposure may limit calcium loading but can also stimulate parathyroid hormone secretion and impair intradialytic cardiovascular stability. We evaluated randomized evidence across bone, mineral metabolism, vascular, and acute safety outcomes. Methods: PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), and Scopus were searched from database inception through 10 July 2026, with targeted citation and publication-status updating through 1 August 2026. Randomized parallel, crossover, factorial, and multi-period trials comparing dialysate calcium concentrations in adults receiving hemodialysis or hemodiafiltration were eligible. Acute and chronic outcomes were analyzed separately. Pooled estimates used inverse-variance random-effects models with DerSimonian–Laird estimation and modified Hartung–Knapp confidence intervals. Results: Twenty-four randomized parent trials were included. Lower dialysate calcium reduced end-of-dialysis ionized calcium (paired mean difference, −0.193 mmol/L; 95% CI, −0.258 to −0.128), with substantial heterogeneity. Point estimates for chronic parathyroid hormone and total alkaline phosphatase were higher and serum calcium lower, but all confidence intervals crossed the null. No clear effects were demonstrated for phosphate, calcium–phosphate product, lumbar bone mineral density, coronary artery calcification, or carotid intima–media thickness. Acute parathyroid hormone, blood pressure, calcium-balance, and QTc estimates suggested greater parathyroid stimulation, lower hemodynamic measures, less calcium gain, and longer QTc with lower calcium, but were imprecise. Adverse events were unsuitable for pooling. Conclusions: Lower dialysate calcium consistently lowers postdialysis ionized calcium, but its long-term skeletal and vascular effects remain uncertain. No single concentration appears universally optimal; prescription should be individualized according to mineral metabolism phenotype, cardiovascular tolerance, dialysis modality, and concomitant therapy.