Work

Clinical impact of ionized calcium and hidden hypocalcemia on cardiovascular outcomes in dialysis patients

Year: 2026

Type: article

Abstract: BACKGROUND: Calcium homeostasis is critical for cardiovascular health in chronic kidney disease (CKD). Ionized calcium is biologically active, but clinical monitoring typically relies on total or albumin-corrected calcium, which may misclassify calcium status and mask abnormalities such as hidden hypocalcemia. We examined the associations of ionized calcium levels and hidden hypocalcemia with cardiovascular outcomes in dialysis patients. METHODS: We analyzed 637 maintenance dialysis patients from the prospective, multicenter ORCHESTRA cohort with ionized calcium measurements at baseline, 6, and 12 months. To minimize reverse causality, patients experiencing events within the first 12 months were excluded from time-to-event analyses. Total, albumin-corrected, and ionized calcium were categorized as low, normal, or high, and patients were further classified into concordant or discordant groups (both normal, hidden hypocalcemia, true hypocalcemia, hidden hypercalcemia, true hypercalcemia). Cox models assessed associations of baseline and longitudinal calcium categories with major adverse cardiovascular events (MACE; cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) and all-cause mortality. RESULTS: During a median follow-up of 1.1 years after the 12-month assessment, 61 MACE and 52 deaths occurred. When evaluated using 12-month averaged values, total, corrected, and ionized calcium categories were not significantly associated with MACE or mortality. However, patients with ≥2 ionized hypocalcemic measurements had a higher risk of MACE (adjusted hazard ratio (HR) 3.62; 95% confidence intervals 1.25-10.46). Hidden hypocalcemia (normal total or corrected calcium with low ionized calcium) was associated with increased MACE risk both at baseline (total × ionized HR 2.94; corrected × ionized HR 2.81) and in longitudinal analyses (corrected × ionized ≥ 2 episodes HR 4.58). No calcium category was associated with mortality. CONCLUSIONS: Total and albumin-corrected calcium were not associated with cardiovascular outcomes. By contrast, recurrent hidden hypocalcemia was associated with excess MACE risk. These findings suggest that evaluating discordance between total and ionized calcium may provide clinically relevant information beyond conventional calcium measures in dialysis patients.

Source: Nephrology Dialysis Transplantation

DOI: 10.1093/ndt/gfag057