Associations of Proteinuria Trajectories with Kidney Failure and Death in Individuals with CKD

Kidney360. 2025 Jun 26. doi: 10.34067/KID.0000000849. Online ahead of print.

Abstract

Background: Despite repeating proteinuria measurements multiple times during the clinical course of a patient with CKD, clinicians may overlook the significance of temporal patterns of proteinuria. In addition, it is unclear whether proteinuria trajectories identify sub-populations with varying risks of adverse clinical outcomes.

Methods: We used group-based trajectory modeling to identify proteinuria trajectories based on annual urine protein-to-creatinine ratio (UPCR) measurements in 3209 participants of the Chronic Renal Insufficiency Cohort Study who were alive and did not reach end-stage kidney disease (ESKD) within 3 years of study entry. Multivariable-adjusted Cox proportional hazards models tested the associations of UPCR trajectories with ESKD and death in those who survived beyond the 3rd annual visit.

Results: Trajectory analyses identified 4 discrete groups based on annual UPCR measurements: low-slowly rising (n=1528), high-slowly rising (n=1363), regressing (n=114), and rapidly rising (n=204). Compared to the low-slowly rising proteinuria trajectory group, participants in the other proteinuria trajectory groups had lower socioeconomic status, a greater prevalence of comorbid conditions, and lower eGFR. During a median follow-up of 8.6 years, 547 participants progressed to ESKD, and 836 participants died. Compared to the low-slowly rising group, all proteinuria trajectory groups were associated with higher risks of subsequent ESKD, but only the high-slowly rising group was associated with a higher risk of death.

Conclusions: Trajectories of repeated proteinuria measurements identify subgroups of patients with CKD that have increased risks of ESKD and death independent of known risk factors.