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Abstract: TH-PO998

Incremental Reduction of Proteinuria and Kidney Survival in FSGS

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Troost, Jonathan P., University of Michigan, Ann Arbor, Michigan, United States
  • Trachtman, Howard, NYU Langone Health, New York, New York, United States
  • Kaskel, Frederick J., Children’s Hospital at Montefiore, Bronx, New York, United States
  • Friedman, Aaron L., University of Minnesota, Minneapolis, Minnesota, United States
  • Moxey-Mims, Marva M., Children's National Health System, Washington, District of Columbia, United States
  • Gassman, Jennifer J., Cleveland Clinic, Cleveland, Ohio, United States
  • Walsh, Liron, Goldfinch Bio, Boston, Massachusetts, United States
  • Gipson, Debbie S., University of Michigan Mott Children's Hospital, Ann Arbor, Michigan, United States
Background

Proteinuria remission has been shown to predict disease progression in focal segmental glomerulosclerosis (FSGS). This study examines if incremental reductions in proteinuria are associated with improved kidney survival even if a complete or partial remission is not reached.

Methods

Data are from the NIH/NIDDK FSGS clinical trial of 138 steroid resistant patients randomized to cyclosporine or mycophenolate mofetil (no difference in trial endpoint of proteinuria remission). Linear-mixed effects models tested if week 26 proteinuria was associated with subsequent slope of estimated glomerular filtration rate (eGFR). Stratified Cox-proportional hazards models tested if time-varying proteinuria was associated with time to kidney failure. Model interaction terms and sensitivity analyses tested for an incremental impact of proteinuria on outcome for those with urine protein: creatinine ratio >1.5g/g. Analyses were adjusted for age, race, baseline proteinuria and eGFR, and treatment arm.

Results

A 1-log increase in proteinuria was associated with a -5.1 ml/year difference in change in eGFR per year (95% CI=-8.3 to -2.0 p<0.001). There was an analogous relationship between time-varying proteinuria and time to kidney failure: HR per log-proteinuria=3.94 (95% CI=1.79 to 8.68 p<0.001). Findings remained the same when limited to those with proteinuria >1.5g/g at week 26.

Conclusion

These findings agree with previous reports of an important proteinuria threshold at approximately 1.5g/g associated with a large clinical benefit, but also support that a reduction in proteinuria—even if not to below 1.5g/g—is still associated with improved survival. Clinical trials should consider reductions in proteinuria as a marker of future preservation of kidney function.

Funding

  • NIDDK Support