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

Springer Science and Business Media LLC - Tập 38 - Trang 145-159 - 2022
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. Chen1, Mahmoud Morsi1, Jose M. G. Figueiro1, Rodrigo Vianna1,9, Carolyn L. Abitbol7, David Roth4, Alessia Fornoni10, Phillip Ruiz11, Gaetano Ciancio1, Eduardo H. Garin12
1Division of Kidney-Pancreas Transplantation, Department of Surgery, Miami Transplant Institute, University of Miami Miller School of Medicine, Miami, USA
2Division of Pediatric Kidney Transplantation, Department of Pediatrics, Miami Transplant Institute, University of Miami Miller School of Medicine, Miami, USA
3Division of Transplant Surgery, Department of Surgery, University of California Davis School of Medicine, Sacramento, USA
4Katz Family Division of Nephrology and Hypertension, Department of Medicine, and the Miami Transplant Institute, University of Miami Miller School of Medicine, Miami, USA
5Division of Nephrology, Department of Medicine, Emory University School of Medicine, Atlanta, USA
6Research, Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, USA
7Division of Pediatric Nephrology, Department of Pediatrics, University of Miami Miller School of Medicine, Miami, USA
8Transplant Clinical Pharmacy Services, Miami Transplant Institute, Jackson Memorial Hospital, Miami, USA
9Division of Liver and GI Transplantation, Department of Surgery, Miami Transplant Institute, University of Miami Miller School of Medicine, Miami, USA
10Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, USA
11Transplant Pathology, Department of Surgery, Miami Transplant Institute, University of Miami Miller School of Medicine, Miami, USA
12Division of Nephrology, Department of Pediatrics, University of Florida School of Medicine, Gainesville, USA

Tóm tắt

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. 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. 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. 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

Tài liệu tham khảo

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Springer Science and Business Media LLC

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