Overall and site-specific fracture rates vary by kidney failure cause in patients receiving dialysis, a new study finds. It remains unclear whether disease- or treatment-related factors or both account for these differences.
Among 491,496 patients receiving hemodialysis or peritoneal dialysis in the 1997-2014 US Renal Data System (USRDS) database, 62,954 patients (12.8%) experienced a first fracture over a median follow-up of 2 years.
Investigators examined fracture risk by 7 causes of kidney failure: diabetic nephropathy, autosomal polycystic kidney disease (ADPKD), and 5 types of glomerulonephritis. Immunoglobulin A (IgA) nephropathy served as the reference group.
In an adjusted multivariable analysis, overall fracture risk was a significant 43% and 37% higher among patients with diabetic nephropathy and ADPKD, respectively, and a significant 22%, 16%, and 13% higher among patients with vasculitis, membranous nephropathy, and focal segmental glomerulosclerosis (FSGS), respectively, compared with patients with IgA nephropathy, Susan Ziolkowski, MD, of Stanford University School of Medicine in California, and colleagues reported in Clinical Kidney Journal. Fracture risk was a significant 15% lower among patients with lupus nephritis vs IgA nephropathy.
Investigators found the highest fracture rates (per 1000 person-years) of 50, 46, and 40 in the diabetic nephropathy, vasculitis, and ADPKD groups, respectively, and the lowest fracture rate of 20 in the lupus nephritis group.
By skeletal site, only patients with diabetic nephropathy had a significantly increased risk (by 83%) for lower femur fracture compared with the IgA nephropathy group. Only patients with vasculitis had a significantly higher risk (by 33%) for vertebral fracture. The risks for arm or lower leg fractures were significantly increased by 90%, 87%, 32%, and 27% with diabetic nephropathy, ADPKD, membranous nephropathy, and FSGS, respectively, compared with IgA nephropathy. The investigators found no significant differences between groups in hip fracture rates.
The investigators hypothesized that the high fracture risk in patients with diabetic nephropathy or ADPKD, especially in the arm and lower leg, might be due to long-standing secondary hyperparathyroidism.
Other variable contributors to fracture risk in patients with kidney diseases include systemic inflammation, use of corticosteroids or calcineurin inhibitors, urinary loss of vitamin D due to nephrotic-range proteinuria, and alterations in bone mechano-sensing in ADPKD. There are many other possible contributors, however. The USRDS database lacked information on levels of phosphate, parathyroid hormone, and other parameters of bone and mineral metabolism, current and prior medications, disease activity, kidney disease duration, and muscle function, precluding further analyses.
“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,” Dr Ziolkowski’s team concluded. “Future research is needed to uncover the pathogenic mechanisms underlying disease-specific risks.”
Ziolkowski S, Liu S, Montez-Rath ME, et al. Association between cause of kidney failure and fracture incidence in a national US dialysis population cohort study. Clinical Kidney J. Published online September 12, 2022. doi:10.1093/ckj/sfac193