An Outcomes-Based Definition of Proteinuria Remission in Focal Segmental Glomerulosclerosis

Clin J Am Soc Nephrol. 2018 Mar 7;13(3):414-421. doi: 10.2215/CJN.04780517. Epub 2017 Nov 22.


Background and objectives: Proteinuria is used as an indicator of FSGS disease activity, but its use as a clinical trial end point is not universally accepted. The goal of this study was to refine proteinuria definitions associated with long-term kidney survival.

Design, setting, participants, & measurements: Data on 466 patients with primary FSGS with proteinuria (urine protein-to-creatinine ratio >1 g/g) were analyzed from five independent cohorts. Proteinuria by months 1, 4, and 8 after study baseline was categorized by conventional definitions of complete (<0.3 g/g) and partial remission (<3.5 g/g and 50% reduction in proteinuria). Novel remission definitions were explored using receiver operating curves. Kaplan-Meier methods were used to estimate the associations of proteinuria with progression to ESRD or a 50% loss in kidney function. Propensity score-adjusted Cox proportional hazards models were used to adjust for baseline proteinuria, eGFR, and therapy.

Results: In the initial derivation cohort, conventional partial remission was not associated with kidney survival. A novel definition of partial remission (40% proteinuria reduction and proteinuria<1.5 g/g) on the basis of receiver operating curve analyses of 89 patients was identified (Sensitivity=0.70; Specificity=0.77). In the validation cohort analyses, complete remission was associated with better prognosis (6 out of 41 patients progressed to kidney failure; 6.6 per 100 patient-years) as was the novel partial remission (13 out of 71 progressed; 8.5 per 100 patient-years), compared with those with no response (51 out of 116 progressed; 20.1 per 100 patient-years). Conventional partial remission at month 8, but not month 4, was also associated with better response (19 out of 85 patients progressed; risk=10.4 per 100 patient-years). Propensity score-adjusted analyses showed the novel partial remission was associated with less progression at months 4 and 8 (month 4: hazard ratio, 0.50; P=0.01; month 8: hazard ratio, 0.30; P=0.002).

Conclusions: Reaching either a complete or partial remission using a novel or conventional definition was associated with better long-term outcomes in patients with FSGS.

Podcast: This article contains a podcast at

Keywords: Cohort Studies; FSGS; Glomerulosclerosis, Focal Segmental; Goals; Humans; Kidney Failure, Chronic; Prognosis; Propensity Score; Proportional Hazards Models; Renal Insufficiency; creatinine; glomerular filtration rate; kidney; proteinuria; surrogate endpoint.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / urine
  • Child
  • Creatinine / urine
  • Disease Progression
  • Endpoint Determination*
  • Female
  • Glomerular Filtration Rate
  • Glomerulosclerosis, Focal Segmental / complications
  • Glomerulosclerosis, Focal Segmental / drug therapy
  • Glomerulosclerosis, Focal Segmental / physiopathology
  • Glomerulosclerosis, Focal Segmental / urine*
  • Humans
  • Kaplan-Meier Estimate
  • Kidney Failure, Chronic / etiology
  • Kidney Failure, Chronic / urine*
  • Male
  • Middle Aged
  • Observational Studies as Topic
  • Prognosis
  • Proportional Hazards Models
  • Proteinuria / etiology
  • Proteinuria / urine*
  • ROC Curve
  • Randomized Controlled Trials as Topic
  • Treatment Outcome
  • Young Adult


  • Biomarkers
  • Creatinine