Association of Urine-to-Plasma Urea Ratio with Outcomes in Patients with Chronic Kidney Disease: A Retrospective Cohort Study

Background: Estimated glomerular filtration rate (eGFR) and proteinuria are the gold-standard markers for kidney function used traditionally to assess kidney outcomes. Increased evidence of tubule involvement in nearly all causes of chronic kidney disease (CKD) warrants exploring the association between markers of tubular function with clinical outcomes in patients with CKD. Methods: We conducted a single center retrospective cohort study in 626 patients with eGFR <60 mL/min/1.73m2. We examined the association between spot urine-to-plasma (U/P) urea and the incidence of kidney failure, all-cause death, and their composite outcome using the Kaplan-Meier method and multivariable-adjusted Cox proportional hazards models. Results: Our cohort predominantly consisted of males (96%) with a mean±standard deviation age of 67.4±10.8 years and eGFR of 23.6±10.5 mL/min/1.73m2. There were 448 composite outcome events (event rate: 159/1000 patient-years; 95% confidence interval (CI): 145-175) over a median follow-up of 4.5 years. Lower U/P urea was associated with a higher risk of the composite outcome in unadjusted (hazard ratio and 95%CI for 1 log-unit lower U/P urea: 1.98 [1.73-2.26], p<0.001) and after multivariable adjustment (1.67 [1.37-2.07], p<001). Associations were similar for kidney failure and for all-cause death. Conclusion: Lower U/P urea, a marker of tubular dysfunction, is associated with a higher risk of adverse clinical outcomes in patients with moderate and advanced CKD, independent of eGFR and proteinuria.