Hypocalcemia in Dialysis Is Not Associated with Increased Mortality: Evidence from a Population-Based Cohort

Introduction: Recent research underscores the risks of maintaining a positive calcium balance in hemodialysis (HD) patients. This study aims to evaluate outcomes based on the calcium levels of HD patients, specifically those with hypocalcemia. Methods: In this retrospective cohort study, data from 71,101 HD patients were analyzed and classified into six groups based on calcium levels: severe hypocalcemia (<7.5 mg/dL, n = 1078), moderate hypocalcemia (7.5-7.99 mg/dL, n = 4000), mild hypocalcemia (8.0-8.39 mg/dL, n = 9846), lower-normal calcium (8.4-9.29 mg/dL, n = 38,697), upper-normal calcium (9.3-10.19 mg/dL, n = 14,505), and hypercalcemia (≥10.2 mg/dL, n = 1975). Results: The numbers of deaths, CVE, and fracture at the end point of the follow-up were recorded: 401 (37.2%), 189 (23.2%), and 224 (20.8%) in the severe hypocalcemia group, respectively; 1523 (38.1%), 663 (22.8%), and 802 (20.1%) in the moderate hypocalcemia group, respectively; 3985 (40.5%), 1618 (22.9%), and 2054 (20.9%) in the mild hypocalcemia group, respectively; 17,067 (44.1%), 6948 (24.9%), and 8676 (22.4%) in the lower-normal calcium group, respectively; 6904 (47.6%), 2967 (27.3%), and 3471 (23.9%) in the upper-normal calcium group, respectively; and 1074 (54.4%), 457 (30.0%), and 473 (23.9%) in the hypercalcemia group, respectively. The 5-year patient survival rates for the severe hypocalcemia, moderate hypocalcemia, mild hypocalcemia, lower-normal calcium, upper-normal calcium, and hypercalcemia groups were 73.9%, 70.0%, 68.8%, 66.4%, 66.1%, and 62.8%, respectively. The 5-year cardiovascular event-free survival rates for the severe hypocalcemia, moderate hypocalcemia, mild hypocalcemia, lower-normal calcium, upper-normal calcium, and hypercalcemia groups were 78.2%, 79.0%, 78.2%, 76.2%, 75.3%, and 72.6%, respectively. The hazard ratios (HRs) for the all-cause mortality (HR: 0.94, 95% CI: 0.84-1.05) and cardiovascular events (HR: 0.98, 95% CI: 0.84-1.15) of the severe hypocalcemia group were consistently not higher than those of the lower-normal calcium group even after thorough adjustments were made for various clinical variables. Multivariable Cox regression analyses revealed that the HRs for all-cause mortality and cardiovascular events of the mild hypocalcemia groups were lower than those of the lower-normal calcium group. Serum calcium levels were not associated with increased risk of fracture. Conclusions: Patients with various degrees of hypocalcemia, including severe hypocalcemia, were not associated with increased mortality and cardiovascular event rates. We suggest that symptoms and clinical presentation should be prioritized rather than simply targeting the normalization of calcium levels in hypocalcemia correction.