Association between cause of kidney failure and fracture incidence in a national US dialysis population cohort study

Background Whether fracture rates, overall and by fracture site, vary by cause of kidney failure in patients receiving dialysis is unknown. Methods Using the US Renal Data System, we compared fracture rates across seven causes of kidney failure in patients who started dialysis between 1997 and 2014. We computed unadjusted and multivariable adjusted proportional sub-distribution hazard models, with fracture events (overall, and by site) as the outcome and immunoglobulin A nephropathy as the reference group. Kidney transplantation and death were competing events. Results Among 491 496 individuals, with a median follow-up of 2.0 (25%, 75% range 0.9-3.9) years, 62 954 (12.8%) experienced at least one fracture. Patients with diabetic nephropathy, vasculitis or autosomal polycystic kidney disease (ADPKD) had the highest (50, 46 and 40 per 1000 person-years, respectively), and patient with lupus nephritis had the lowest (20 per 1000 person-years) fracture rates. After multivariable adjustment, diabetic nephropathy [hazard ratio (HR) 1.43, 95% confidence interval 1.33-1.53], ADPKD (HR 1.37, 1.26-1.48), vasculitis (HR 1.22, 1.09-1.34), membranous nephropathy (HR 1.16, 1.02-1.30) and focal segmental glomerulosclerosis (FSGS) (HR 1.13, 1.02-1.24) were associated with a significantly higher, and lupus nephritis with a significantly lower (HR 0.85, 0.71-0.98) fracture hazard. The hazards for upper extremity and lower leg fractures were significantly higher in diabetic nephropathy, ADPKD, FSGS and membranous nephropathy, while the hazard for vertebral fracture was significantly higher in vasculitis. Our findings were limited by the lack of data on medication use and whether fractures were traumatic or non-traumatic, among other factors. Conclusions Fracture risk, overall and by fracture site, varies by cause of end-stage kidney disease. Future work to determine underlying pathogenic mechanisms contributing to differential risks might inform more tailored treatment strategies. Our study was limited by lack of data regarding numerous potential confounders or mediators including medications and measures or bone biomarkers. Lay Summary Whether cause of kidney failure determines fracture risk in patients receiving dialysis had not been the focus of any prior study. This study of patients who initiated dialysis in the USA between 1997 and 2014 determined that those with diabetic nephropathy had the highest, and those with lupus nephritis the lowest, overall fracture rates. After multivariable adjustment, comparing with immunoglobulin A nephropathy, the hazards for upper extremity and lower leg fractures were higher in diabetic nephropathy, autosomal dominant polycystic kidney disease, focal segmental glomerular sclerosis and membranous nephropathy; the hazard for vertebral fracture was higher in vasculitis; and the hazard for hip fracture did not differ significantly by cause of kidney failure. These findings can support clinical care, by informing more accurate counseling regarding fracture risk and identifying higher-risk patient groups to target for preventative care. Future research is needed to uncover the pathogenic mechanisms underlying disease-specific risks.