George W Burke1, Jayanthi Chandar2, Junichiro Sageshima3, Mariella Ortigosa-Goggins4, Pooja Amarapurkar5, Alla Mitrofanova6, Marissa J Defreitas7, Chryso P Katsoufis7, Wacharee Seeherunvong7, Alexandra Centeno8, Javier Pagan4, Lumen A Mendez-Castaner4, Adela D Mattiazzi4, Warren L Kupin4, Giselle Guerra4, Linda J Chen9, Mahmoud Morsi9, Jose M G Figueiro9, Rodrigo Vianna9,10, Carolyn L Abitbol7, David Roth4, Alessia Fornoni11, Phillip Ruiz12, Gaetano Ciancio9, Eduardo H Garin13. 1. Division of Kidney-Pancreas Transplantation, Department of Surgery, Miami Transplant Institute, University of Miami Miller School of Medicine, 1801 NW 9th Ave, Highland Professional Building, Miami, FL, 33136, USA. gburke@med.miami.edu. 2. Division of Pediatric Kidney Transplantation, Department of Pediatrics, Miami Transplant Institute, University of Miami Miller School of Medicine, Miami, FL, 33136, USA. 3. Division of Transplant Surgery, Department of Surgery, University of California Davis School of Medicine, Sacramento, CA, 95817, USA. 4. Katz Family Division of Nephrology and Hypertension, Department of Medicine, and the Miami Transplant Institute, University of Miami Miller School of Medicine, Miami, FL, 33136, USA. 5. Division of Nephrology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, 30309, USA. 6. Research, Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, 33136, USA. 7. Division of Pediatric Nephrology, Department of Pediatrics, University of Miami Miller School of Medicine, Miami, FL, 33136, USA. 8. Transplant Clinical Pharmacy Services, Miami Transplant Institute, Jackson Memorial Hospital, Miami, FL, 33136, USA. 9. Division of Kidney-Pancreas Transplantation, Department of Surgery, Miami Transplant Institute, University of Miami Miller School of Medicine, 1801 NW 9th Ave, Highland Professional Building, Miami, FL, 33136, USA. 10. Division of Liver and GI Transplantation, Department of Surgery, Miami Transplant Institute, University of Miami Miller School of Medicine, Miami, FL, 33136, USA. 11. Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, 33136, USA. 12. Transplant Pathology, Department of Surgery, Miami Transplant Institute, University of Miami Miller School of Medicine, Miami, FL, 33136, USA. 13. Division of Nephrology, Department of Pediatrics, University of Florida School of Medicine, Gainesville, FL, 32610, USA.
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. A higher resolution version of the Graphical abstract is available as Supplementary information.
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. A higher resolution version of the Graphical abstract is available as Supplementary information.
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