Low Daily Protein Intake and Risk of Kidney Failure and Mortality in Chronic Kidney Disease

Importance While protein restriction is a cornerstone of chronic kidney disease (CKD) management, its long-term benefits on clinical outcomes in Asian populations, who often have lower body mass and muscle reserves, remain unclear. Objective To investigate the association between daily protein intake (DPI) and the risk of kidney failure requiring replacement therapy (KFRT) and all-cause mortality in patients with non–dialysis-dependent CKD. Design, Setting, and Participants This prospective cohort study used data from the Korean Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD). Participants with CKD at stages ranging from 1 to predialysis 5 were enrolled between 2011 and 2016 from 9 tertiary hospitals in South Korea. The study observation period ended on January 31, 2024. Data analysis was performed from February 2024 to May 2026. Exposures DPI was objectively estimated using 24-hour urinary nitrogen excretion at baseline. The participants were categorized by DPI: less than 0.6, 0.6 to less than 0.8, 0.8 to less than 1.0, 1.0 to less than 1.2, and 1.2 or greater. Main Outcomes and Measures The primary outcome was the onset of KFRT. Secondary outcomes included all-cause mortality and major adverse cardiovascular events (MACEs). Fine-Gray subdistribution hazard models were used to account for the competing risk of death. Results A total of 1861 participants (mean [SD] age, 53.7 [12.0] years; 1304 [61.1%] male) were analyzed, with a median (range) follow-up of 9.3 (0.01-12.37) years. The lowest DPI group (<0.6 g/kg/d) was associated with increased risk of KFRT (subdistribution hazard ratio [sHR], 1.42; 95% CI, 1.09-1.85) as well as all-cause mortality (sHR, 2.17; 95% CI, 1.17-4.03), but not MACEs, compared with the highest DPI group (>1.2 g/kg/d). Furthermore, a nonlinear association was observed, where excessively low protein intake was associated with an increased risk of KFRT. Conclusions and Relevance In this cohort study of 1861 patients with nondialysis CKD, low protein intake was not associated with significant nephroprotection and was associated with a higher risk of KFRT and all-cause mortality. These findings suggest that rigid protein restriction should be balanced with nutritional monitoring to prevent protein-energy wasting, particularly in populations with lower muscle mass, and a more individualized approach to dietary protein management in CKD may be warranted.