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

被引:16
作者
Burke, George W., III [1 ]
Chandar, Jayanthi [2 ]
Sageshima, Junichiro [3 ]
Ortigosa-Goggins, Mariella [4 ,5 ]
Amarapurkar, Pooja [6 ]
Mitrofanova, Alla [7 ]
Defreitas, Marissa J. [8 ]
Katsoufis, Chryso P. [8 ]
Seeherunvong, Wacharee [8 ]
Centeno, Alexandra [9 ]
Pagan, Javier [4 ,5 ]
Mendez-Castaner, Lumen A. [4 ,5 ]
Mattiazzi, Adela D. [4 ,5 ]
Kupin, Warren L. [4 ,5 ]
Guerra, Giselle [4 ,5 ]
Chen, Linda J. [1 ]
Morsi, Mahmoud [1 ]
Figueiro, Jose M. G. [1 ]
Vianna, Rodrigo [1 ,10 ]
Abitbol, Carolyn L. [8 ]
Roth, David [4 ,5 ]
Fornoni, Alessia [4 ]
Ruiz, Phillip [11 ]
Ciancio, Gaetano [1 ]
Garin, Eduardo H. [12 ]
机构
[1] Univ Miami, Miami Transplant Inst, Dept Surg, Div Kidney Pancreas Transplantat,Miller Sch Med, 1801 NW 9th Ave,Highland Profess Bldg, Miami, FL 33136 USA
[2] Univ Miami, Miami Transplant Inst, Dept Pediat, Div Pediat Kidney Transplantat,Miller Sch Med, Miami, FL 33136 USA
[3] Univ Calif Davis, Dept Surg, Div Transplant Surg, Sch Med, Sacramento, CA 95817 USA
[4] Univ Miami, Katz Family Div Nephrol & Hypertens, Dept Med, Miller Sch Med, Miami, FL 33136 USA
[5] Univ Miami, Miami Transplant Inst, Miller Sch Med, Miami, FL 33136 USA
[6] Emory Univ, Dept Med, Div Nephrol, Sch Med, Atlanta, GA 30309 USA
[7] Univ Miami, Dept Med, Katz Family Div Nephrol & Hypertens, Res,Miller Sch Med, Miami, FL 33136 USA
[8] Univ Miami, Dept Pediat, Div Pediat Nephrol, Miller Sch Med, Miami, FL 33136 USA
[9] Jackson Mem Hosp, Miami Transplant Inst, Transplant Clin Pharm Serv, Miami, FL 33136 USA
[10] Univ Miami, Miami Transplant Inst, Dept Surg, Div Liver & GI Transplantat,Miller Sch Med, Miami, FL 33136 USA
[11] Univ Miami, Miami Transplant Inst, Dept Surg, Transplant Pathol,Miller Sch Med, Miami, FL 33136 USA
[12] Univ Florida, Dept Pediat, Div Nephrol, Sch Med, Gainesville, FL 32610 USA
关键词
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;
D O I
10.1007/s00467-022-05549-7
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
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.
引用
收藏
页码:145 / 159
页数:15
相关论文
共 44 条
[21]   Belatacept in recurrent focal segmental glomerulosclerosis after kidney transplantation [J].
Grellier, Jimmy ;
Del Bello, Arnaud ;
Milongo, David ;
Guilbeau-Frugier, Celine ;
Rostaing, Lionel ;
Kamar, Nassim .
TRANSPLANT INTERNATIONAL, 2015, 28 (09) :1109-1110
[22]   Efficacy of abatacept treatment for focal segmental glomerulosclerosis and minimal change disease: A systematic review of case reports, case series, and observational studies [J].
Hansrivijit, Panupong ;
Puthenpura, Max M. ;
Ghahramani, Nasrollah .
CLINICAL NEPHROLOGY, 2020, 94 (03) :117-126
[23]   Recurrent focal glomerulosclerosis in pediatric renal allografts:: the Miami experience [J].
Hubsch, H ;
Montané, B ;
Abitbol, C ;
Chandar, J ;
Shariatmadar, S ;
Ciancio, G ;
Burke, G ;
Miller, J ;
Strauss, J ;
Zilleruelo, G .
PEDIATRIC NEPHROLOGY, 2005, 20 (02) :210-216
[24]   Recurrent Glomerulonephritis after Renal Transplantation: The Clinical Problem [J].
Infante, Barbara ;
Rossini, Michele ;
Leo, Serena ;
Troise, Dario ;
Netti, Giuseppe Stefano ;
Ranieri, Elena ;
Gesualdo, Loreto ;
Castellano, Giuseppe ;
Stallone, Giovanni .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2020, 21 (17) :1-23
[25]   Abatacept in Steroid-Dependent Minimal Change Disease and CD80-uria [J].
Isom, Robert ;
Shoor, Stanford ;
Higgins, John ;
Cara-Fuentes, Gabriel ;
Johnson, Richard J. .
KIDNEY INTERNATIONAL REPORTS, 2019, 4 (09) :1349-1353
[26]   Disease Recurrence-The Sword of Damocles in Kidney Transplantation for Primary Focal Segmental Glomerulosclerosis [J].
Kienzl-Wagner, Katrin ;
Waldegger, Siegfried ;
Schneeberger, Stefan .
FRONTIERS IN IMMUNOLOGY, 2019, 10
[27]   B7-1 Immunostaining in Proteinuric Kidney Disease [J].
Larsen, Christopher P. ;
Messias, Nidia C. ;
Walker, Patrick D. .
AMERICAN JOURNAL OF KIDNEY DISEASES, 2014, 64 (06) :1001-1003
[28]   SMPDL3b modulates insulin receptor signaling in diabetic kidney disease [J].
Mitrofanova, A. ;
Mallela, S. K. ;
Ducasa, G. M. ;
Yoo, T. H. ;
Rosenfeld-Gur, E. ;
Zelnik, I. D. ;
Molina, J. ;
Santos, J. Varona ;
Ge, M. ;
Sloan, A. ;
Kim, J. J. ;
Pedigo, C. ;
Bryn, J. ;
Volosenco, I. ;
Faul, C. ;
Zeidan, Y. H. ;
Hernandez, C. Garcia ;
Mendez, A. J. ;
Leibiger, I. ;
Burke, G. W. ;
Futerman, A. H. ;
Barisoni, L. ;
Ishimoto, Y. ;
Inagi, R. ;
Merscher, S. ;
Fornoni, A. .
NATURE COMMUNICATIONS, 2019, 10 (1)
[29]   Costimulatory blockade in patients with rheumatoid arthritis a pilot, dose-finding, double-blind, placebo-controlled clinical trial evaluating CTLA-4Ig and LEA29Y eighty-five days after the first infusion [J].
Moreland, LW ;
Alten, R ;
Van den Bosch, F ;
Appelboom, T ;
Leon, M ;
Emery, P ;
Cohen, S ;
Luggen, M ;
Shergy, W ;
Nuamah, I ;
Becker, JC .
ARTHRITIS AND RHEUMATISM, 2002, 46 (06) :1470-1479
[30]   Podocyte-Targeted Treatment for Proteinuric Kidney Disease [J].
Mundel, Peter .
SEMINARS IN NEPHROLOGY, 2016, 36 (06) :459-462