Hyperphosphatemia, but Not Hypercalcemia, Predicts Cardiovascular Risk After Kidney Transplantation

Abstract Objective Kidney transplant recipients (KTR) face a heightened risk of cardiovascular disease, but the impact of post-transplant mineral bone disorders on this risk remains unclear. This study investigated the association between serum calcium, phosphate, and calcium-phosphate (Ca×P) product levels and cardiovascular outcomes. Methods In this retrospective cohort study, adult KTR transplanted between 2005 and 2014, at a large center were analyzed. The primary outcome was Major Adverse Cardiovascular Events (MACE). Secondary outcomes included all-cause mortality and a composite of MACE and mortality. Cumulative exposure to abnormal mineral levels was assessed using time-weighted average (TWA) calculations. Cox proportional hazard models were used to evaluate associations adjusting for confounders, including estimated glomerular filtration rate (eGFR). Mineral abnormalities were analyzed both as continuous variables and by quartiles. Results The study included 649 KTR (median follow-up: 2,943 days), with 109 patients (16.8%) experiencing MACE. Over time, calcium exposure decreased, while phosphate and Ca×P product exposure increased. Hypercalcemia was not significantly associated with MACE, all-cause mortality, or the composite outcome. In contrast, hyperphosphatemia remained significantly associated with increased risk of MACE (HR 1.414, 95%CI 1.044 -1.916) and the composite outcome (HR 1.353, 95%CI 1.064 -1.721) even after adjustment for eGFR. Elevated, Ca×P product levels were similarly associated with increased cardiovascular risk (HR 1.055 per mg2/dL2, 95% CI 1.015-1.096; HR 1.043 per mg2/dL2, 95% CI 1.013-1.075, respectively). Conclusions While hypercalcemia does not independently predict cardiovascular outcomes post-transplant, sustained hyperphosphatemia and elevated Ca×P product are significant risk factors for adverse cardiovascular events in KTR.