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Single Cell Transcriptomics identifies Focal Segmental Glomerulosclerosis Remission Endothelial Biomarker

ABSTRACT: Intrinsic nephron cell types and tissue resident immune cells were recovered from renal biopsy specimens using a scRNAseq protocol for the Kidney Precision Medicine Project (KPMP), designed for deployment in a multicenter research network. Combined processing of 24 samples including 16 tumor-nephrectomy, 5 surveillance and 3 pre-perfusion biopsies using the scRNAseq protocol yielded 22,268 cells (4690 from surveillance biopsies, 16,491 from tumor-nephrectomies and 2834 cells from pre-perfusion biopsies) .

ORGANISM(S): Homo sapiens

PROVIDER: GSE140989 | GEO | 2020/03/03

REPOSITORIES: GEO

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Project description: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.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.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).ConclusionsReaching either a complete or partial remission using a novel or conventional definition was associated with better long-term outcomes in patients with FSGS.PodcastThis 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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Single Cell Transcriptomics identifies Focal Segmental Glomerulosclerosis Remission Endothelial Biomarker

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­Single Cell Transcriptomics identifies Focal Segmental Glomerulosclerosis Remission Endothelial Biomarker

Dataset's files

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OmicsDI is part of the ELIXIR infrastructure

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Single Cell Transcriptomics identifies Focal Segmental Glomerulosclerosis Remission Endothelial Biomarker