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 |
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07.03.2018
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| Abstract | 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. |
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| AbstractList | 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.BACKGROUND AND OBJECTIVESProteinuria 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.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTSData 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; P=0.01; month 8: hazard ratio, 0.30; P=0.002).RESULTSIn 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).Reaching either a complete or partial remission using a novel or conventional definition was associated with better long-term outcomes in patients with FSGS.CONCLUSIONSReaching 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.PODCASTThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018_02_20_CJASNPodcast_18_3_T.mp3. 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. |
| Author | Gipson, Patrick Komers, Radko Massengill, Susan F Oh, Gia Selewski, David T Gipson, Debbie S Tuller, Sarah Kamil, Elaine S Spino, Cathie Perumal, Kalyani Kretzler, Matthias Nachman, Patrick H Troost, Jonathan P Trachtman, Howard |
| Author_xml | – sequence: 1 givenname: Jonathan P surname: Troost fullname: Troost, Jonathan P organization: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material – sequence: 2 givenname: Howard surname: Trachtman fullname: Trachtman, Howard – sequence: 3 givenname: Patrick H surname: Nachman fullname: Nachman, Patrick H – sequence: 4 givenname: Matthias surname: Kretzler fullname: Kretzler, Matthias – sequence: 5 givenname: Cathie surname: Spino fullname: Spino, Cathie – sequence: 6 givenname: Radko surname: Komers fullname: Komers, Radko – sequence: 7 givenname: Sarah surname: Tuller fullname: Tuller, Sarah – sequence: 8 givenname: Kalyani surname: Perumal fullname: Perumal, Kalyani – sequence: 9 givenname: Susan F surname: Massengill fullname: Massengill, Susan F – sequence: 10 givenname: Elaine S surname: Kamil fullname: Kamil, Elaine S – sequence: 11 givenname: Gia surname: Oh fullname: Oh, Gia – sequence: 12 givenname: David T surname: Selewski fullname: Selewski, David T – sequence: 13 givenname: Patrick surname: Gipson fullname: Gipson, Patrick – sequence: 14 givenname: Debbie S orcidid: 0000-0003-4473-9045 surname: Gipson fullname: Gipson, Debbie S |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/29167190$$D View this record in MEDLINE/PubMed |
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| Keywords | 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 |
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| SubjectTerms | 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 |
| Title | An Outcomes-Based Definition of Proteinuria Remission in Focal Segmental Glomerulosclerosis |
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