Benefit of B7-1 staining and abatacept for treatment-resistant post-transplant focal segmental glomerulosclerosis in a predominantly pediatric cohort: time for a reappraisal

• Authors: George W Burke, University of Miami; Jayanthi Chandar, University of Miami; Junichiro Sageshima, University of California Davis; Mariella Ortigosa-Goggins, University of Miami; Pooja Amarapurkar, Emory University; Alla Mitrofanova, University of Miami; Marissa J Defreitas, University of Miami; Chryso P Katsoufis, University of Miami; Wacharee Seeherunvong, University of Miami; Alexandra Centeno, Jackson Memorial Hospital; Javier Pagan, University of Miami; Lumen A Mendez-Castaner, University of Miami; Adela D Mattiazzi, University of Miami; Warren L Kupin, University of Miami; Giselle Guerra, University of Miami; Linda J Chen, University of Miami; Mahmoud Morsi, University of Miami; Jose MG Figueiro, University of Miami; Rodrigo Vianna, University of Miami; Carolyn L Abitbol, University of Miami; David Roth, University of Miami; Alessia Fornoni, University of Miami; Phillip Ruiz, University of Miami; Gaetano Ciancio, University of Miami; Eduardo H Garin, University of Florida
• Journal Title: PEDIATRIC NEPHROLOGY
• Volume: Volume 38, Number 1
• Publisher: SPRINGER | 2022-05-04, Pages 145-159
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1007/s00467-022-05549-7
• Subjects: Health Sciences, Medicine and Surgery
• Keywords: Science & Technology; Life Sciences & Biomedicine; Pediatrics; Urology & Nephrology; Podocyte; Proteinuria; Nephrotic syndrome; Focal segmental glomerulosclerosis; Kidney transplantation; B7-1; Abatacept; FOOT PROCESS EFFACEMENT; MINIMAL CHANGE DISEASE; RECURRENT GLOMERULONEPHRITIS; KIDNEY-TRANSPLANTATION; PODOCYTES; BELATACEPT; EXPRESSION; RITUXIMAB; BLOCKADE

Abstract

Background: Primary FSGS manifests with nephrotic syndrome and may recur following KT. Failure to respond to conventional therapy after recurrence results in poor outcomes. Evaluation of podocyte B7-1 expression and treatment with abatacept (a B7-1 antagonist) has shown promise but remains controversial. Methods: From 2012 to 2020, twelve patients developed post-KT FSGS with nephrotic range proteinuria, failed conventional therapy, and were treated with abatacept. Nine/twelve (< 21 years old) experienced recurrent FSGS; three adults developed de novo FSGS, occurring from immediately, up to 8 years after KT. KT biopsies were stained for B7-1. Results: Nine KTRs (75%) responded to abatacept. Seven of nine KTRs were B7-1 positive and responded with improvement/resolution of proteinuria. Two patients with rFSGS without biopsies resolved proteinuria after abatacept. Pre-treatment UPCR was 27.0 ± 20.4 (median 13, range 8–56); follow-up UPCR was 0.8 ± 1.3 (median 0.2, range 0.07–3.9, p < 0.004). Two patients who were B7-1 negative on multiple KT biopsies did not respond to abatacept and lost graft function. One patient developed proteinuria while receiving belatacept, stained B7-1 positive, but did not respond to abatacept. Conclusions: Podocyte B7-1 staining in biopsies of KTRs with post-transplant FSGS identifies a subset of patients who may benefit from abatacept. Graphical abstract: A higher resolution version of the Graphical abstract is available as Supplementary information [Figure not available: see fulltext.]