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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Vydané v:	Clinical journal of the American Society of Nephrology Ročník 13; číslo 3; s. 414
Hlavní autori:	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
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States 07.03.2018
Predmet:	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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Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Undefined-3
ISSN:	1555-905X 1555-905X
DOI:	10.2215/CJN.04780517