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

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. Data on 466 patients with primary FSGS with proteinuria (urine...

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Veröffentlicht in:Clinical journal of the American Society of Nephrology Jg. 13; H. 3; S. 414
Hauptverfasser: Troost, Jonathan P, Trachtman, Howard, Nachman, Patrick H, Kretzler, Matthias, Spino, Cathie, Komers, Radko, Tuller, Sarah, Perumal, Kalyani, Massengill, Susan F, Kamil, Elaine S, Oh, Gia, Selewski, David T, Gipson, Patrick, Gipson, Debbie S
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 07.03.2018
Schlagworte:
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
Randomized Controlled Trials as Topic
ROC Curve
Treatment Outcome
Young Adult
Prognosis
glomerular filtration rate
Humans
proteinuria
Proportional Hazards Models
surrogate endpoint
Propensity Score
kidney
creatinine
Renal Insufficiency
FSGS
Kidney Failure, Chronic
Glomerulosclerosis, Focal Segmental
Goals
Cohort Studies
ISSN:1555-905X, 1555-905X
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Zusammenfassung: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. 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. 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; =0.01; month 8: hazard ratio, 0.30; =0.002). Reaching either a complete or partial remission using a novel or conventional definition was associated with better long-term outcomes in patients with FSGS. This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018_02_20_CJASNPodcast_18_3_T.mp3.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:1555-905X
1555-905X
DOI:10.2215/CJN.04780517