Proteinuria screening and risk of bone fracture: a retrospective cohort study using a nationwide population-based database

Abstract

ABSTRACT Background and hypothesis Proteinuria is associated with an increased risk of kidney function deterioration, cardiovascular disease, or cancer. Previous reports suggesting an association between kidney dysfunction and bone fracture may be confounded by concomitant proteinuria and were inconsistent regarding the association between proteinuria and bone fracture. Therefore, we aimed to evaluate the association using a large administrative claims database in Japan. Methods Using the DeSC database, we retrospectively identified individuals with laboratory data including urine dipstick test between August 2014 and February 2021. We evaluated the association between proteinuria and vertebral or hip fracture using multivariable Cox regression analyses adjusted for various background factors including kidney function. We also performed subgroup analyses stratified by sex and kidney function and sensitivity analyses with Fine & Gray models considering death as a competing risk. Results We identified 603 766 individuals and observed 21 195 fractures. With reference to the negative proteinuria group, the hazard ratio for hip or vertebral fracture was 1.10 [95% confidence interval (CI), 1.05–1.14] and 1.16 (95%CI, 1.11–1.22) in the trace and positive proteinuria group, respectively, in the Cox regression analysis. The subgroup analyses showed similar trends. The Fine & Gray model showed a subdistribution hazard ratio of 1.09 (95%CI, 1.05–1.14) in the trace proteinuria group and 1.15 (95% CI, 1.10–1.20) in the positive proteinuria group. Conclusions Proteinuria was associated with an increased risk of developing hip or vertebral fractures after adjustment for kidney function. Our results highlight the clinical importance of checking proteinuria for predicting bone fractures.