Fractures after kidney transplantation: Incidence, predictors, and association with mortality

Background Major fractures (MF) are associated with increased mortality in the general population and represent an even higher risk in patients with chronic kidney disease. We investigated incidence, predictors and clinical outcomes associated with first MF (MFfirst) following kidney transplantation (KT). Methods We used the Swedish National Renal Registry of 3992 first KT recipients (2005–2016) (median age 53 years, 65% men) and identified all MFfirst in hip, spine, humerus and forearm following KT. We estimated incidence rates and predictors of MFfirst using flexible parametric hazard models and Fine-Gray analysis accounting for competing risk of death, and risk of all-cause mortality following MFfirst using Cox proportional hazards models with fracture as time-varying exposure. Results During median follow-up of 4.8 years (IQR 2.2–7.9 years), there were 279 fractures of which 139 were forearm fractures. The crude incidence rate of MFfirst (n = 279) was 13.5/1000 patient-years and that of hip fractures (n = 69) 3.4/1000 patient-years. The multivariate-adjusted fracture incidence rates were highest during the first 6 months following KT, and 86% higher in women than in men. High age, female sex, previous history of MF, diabetes nephropathy, pretransplant dialysis therapy and acute rejection were associated with increased risk for MFfirst, whereas pre-emptive KT was associated with lower risk of MFfirst. Spline curves showed markedly higher impact of higher age on risk of MFfirst in women than in men. MFfirst (n = 279) independently predicted increased all-cause mortality risk (hazard ratio, HR, 1.78(95%CI 1.35–2.36)). Among MFfirst, with humerus fracture as reference, hip fracture (HR, 4.68(95%CI 1.56–14.06)) and spine fracture (HR, 4.02(95%CI 1.19–13.54)), but not forearm fracture (HR, 1.17 (95%CI 0.38–3.53)), were associated with increased all-cause mortality risk. Conclusions The initial 6 months following kidney transplantation is a high-risk period for MF. Among MF, hip fracture and spine fracture associate with substantially increased all-cause mortality risk.