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

Autor: Burke GW 3rd; 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., Chandar J; Division of Pediatric Kidney Transplantation, Department of Pediatrics, Miami Transplant Institute, University of Miami Miller School of Medicine, Miami, FL, 33136, USA., Sageshima J; Division of Transplant Surgery, Department of Surgery, University of California Davis School of Medicine, Sacramento, CA, 95817, USA., Ortigosa-Goggins M; 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., Amarapurkar P; Division of Nephrology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, 30309, USA., Mitrofanova A; Research, Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, 33136, USA., Defreitas MJ; Division of Pediatric Nephrology, Department of Pediatrics, University of Miami Miller School of Medicine, Miami, FL, 33136, USA., Katsoufis CP; Division of Pediatric Nephrology, Department of Pediatrics, University of Miami Miller School of Medicine, Miami, FL, 33136, USA., Seeherunvong W; Division of Pediatric Nephrology, Department of Pediatrics, University of Miami Miller School of Medicine, Miami, FL, 33136, USA., Centeno A; Transplant Clinical Pharmacy Services, Miami Transplant Institute, Jackson Memorial Hospital, Miami, FL, 33136, USA., Pagan J; 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., Mendez-Castaner LA; 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., Mattiazzi AD; 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., Kupin WL; 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., Guerra G; 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., Chen LJ; 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., Morsi M; 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., Figueiro JMG; 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., Vianna R; 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.; Division of Liver and GI Transplantation, Department of Surgery, Miami Transplant Institute, University of Miami Miller School of Medicine, Miami, FL, 33136, USA., Abitbol CL; Division of Pediatric Nephrology, Department of Pediatrics, University of Miami Miller School of Medicine, Miami, FL, 33136, USA., Roth D; 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., Fornoni A; Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, 33136, USA., Ruiz P; Transplant Pathology, Department of Surgery, Miami Transplant Institute, University of Miami Miller School of Medicine, Miami, FL, 33136, USA., Ciancio G; 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., Garin EH; Division of Nephrology, Department of Pediatrics, University of Florida School of Medicine, Gainesville, FL, 32610, USA.
Jazyk: angličtina
Zdroj: Pediatric nephrology (Berlin, Germany) [Pediatr Nephrol] 2023 Jan; Vol. 38 (1), pp. 145-159. Date of Electronic Publication: 2022 May 04.
DOI: 10.1007/s00467-022-05549-7
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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