Proteinuria Reduction and Kidney Survival in Focal Segmental Glomerulosclerosis

Abstract Rationale & Objective Remission of proteinuria has been shown to be associated with lower rates of kidney disease progression among people with focal segmental glomerulosclerosis (FSGS). The goal of this study was to evaluate if reductions in proteinuria following treatment are associated with greater kidney survival. Study Design Cohort analysis of clinical trial participants Setting & Participants Patients with steroid resistant FSGS enrolled in a randomized treatment trial that compared cyclosporine to mycophenolate mofetil plus dexamethasone. Predictors Reduction in proteinuria measured during 26 weeks after initiating treatment Outcomes Repeated measures of estimated glomerular filtration rate (eGFR) and, time to end-stage kidney disease (ESKD) or death assessed between 26 weeks and 54 months after randomization Analytic Approach Multivariable, linear-mixed effects models with subject-specific slope and intercept to estimate the association of change in proteinuria over 26 weeks while receiving treatment with the subsequent slope of change in eGFR. Multivariable, time-varying Cox-proportional hazards models were used to estimate the association of changes in proteinuria with time to ESKD or death. Results 138 of 192 trial participants were included. Changes in proteinuria over 26 weeks were significantly related to eGFR slope. A 1 unit reduction in log-transformed urinary protein:creatinine ratio was associated with a 3.90 ml/year rise in eGFR (95% CI=2.01 to 5.79). This difference remained significant after adjusting for complete remission. There was an analogous relationship between time-varying proteinuria and time to end-stage kidney disease: the HR for ESKD or death per 1 unit reduction in log-transformed urinary protein-creatinine ratio was 0.23 (95% CI=0.12 to 0.44). Limitations Limited to individuals with steroid-resistant FSGS followed for a maximum of five-years. Conclusions These findings provide evidence for the benefit of urinary protein reduction in FSGS. Reductions in proteinuria warrant further evaluation as a potential surrogate for preservation of kidney function that may inform the design of future clinical trials.