Case series: CTLA4-IgG1 therapy in minimal change disease and focal segmental glomerulosclerosis

Eduardo H. Garin, Jochen Reiser, Gabriel Cara-Fuentes, Changli Wei, Dany Matar, Heiman Wang, Nada Alachkar, Richard J. Johnson

Research output: Contribution to journalArticle

Abstract

Background: Minimal Change Disease (MCD) in relapse is associated with increased podocyte CD80 expression and elevated urinary CD80 excretion, whereas focal segmental glomerulosclerosis (FSGS) has mild or absent CD80 podocyte expression and normal urinary CD80 excretion. Methods: One patient with MCD, one patient with primary FSGS and three patients with recurrent FSGS after transplantation received CD80 blocking antibodies (abatacept or belatacept). Urinary CD80 and CTLA-4 levels were measured by ELISA. Glomeruli were stained for CD80. Results: After abatacept therapy, urinary CD80 became undetectable with a concomitant transient resolution of proteinuria in the MCD patient. In contrast, proteinuria remained unchanged after abatacept or belatacept therapy in the one patient with primary FSGS and in two of the three patients with recurrent FSGS despite the presence of mild CD80 glomerular expression but normal urinary CD80 excretion. The third patient with recurrent FSGS after transplantation had elevated urinary CD80 excretion immediately after surgery which fell spontaneously before the initiation of abatacept therapy; after abatacept therapy, his proteinuria remained unchanged for 5 days despite normal urinary CD80 excretion. Conclusion: These observations are consistent with a role of podocyte CD80 in the development of proteinuria in MCD. In contrast, CD80 may not play a role in recurrent FSGS since the urinary CD80 of our three patients with recurrent FSGS was only increased transiently after surgery and normalization of urinary CD80 did not result in resolution of proteinuria.

Original languageEnglish (US)
Pages (from-to)469-477
Number of pages9
JournalPediatric Nephrology
Volume30
Issue number3
DOIs
StatePublished - 2014

Fingerprint

Lipoid Nephrosis
Focal Segmental Glomerulosclerosis
Immunoglobulin G
Proteinuria
Podocytes
Therapeutics
Transplantation
Blocking Antibodies
Abatacept
Enzyme-Linked Immunosorbent Assay
Recurrence

Keywords

  • CD80
  • CTLA-4
  • Focal segmental glomerulosclerosis
  • Minimal change disease
  • Nephrotic syndrome

ASJC Scopus subject areas

  • Nephrology
  • Pediatrics, Perinatology, and Child Health

Cite this

Garin, E. H., Reiser, J., Cara-Fuentes, G., Wei, C., Matar, D., Wang, H., ... Johnson, R. J. (2014). Case series: CTLA4-IgG1 therapy in minimal change disease and focal segmental glomerulosclerosis. Pediatric Nephrology, 30(3), 469-477. https://doi.org/10.1007/s00467-014-2957-6

Case series : CTLA4-IgG1 therapy in minimal change disease and focal segmental glomerulosclerosis. / Garin, Eduardo H.; Reiser, Jochen; Cara-Fuentes, Gabriel; Wei, Changli; Matar, Dany; Wang, Heiman; Alachkar, Nada; Johnson, Richard J.

In: Pediatric Nephrology, Vol. 30, No. 3, 2014, p. 469-477.

Research output: Contribution to journalArticle

Garin, EH, Reiser, J, Cara-Fuentes, G, Wei, C, Matar, D, Wang, H, Alachkar, N & Johnson, RJ 2014, 'Case series: CTLA4-IgG1 therapy in minimal change disease and focal segmental glomerulosclerosis', Pediatric Nephrology, vol. 30, no. 3, pp. 469-477. https://doi.org/10.1007/s00467-014-2957-6
Garin, Eduardo H. ; Reiser, Jochen ; Cara-Fuentes, Gabriel ; Wei, Changli ; Matar, Dany ; Wang, Heiman ; Alachkar, Nada ; Johnson, Richard J. / Case series : CTLA4-IgG1 therapy in minimal change disease and focal segmental glomerulosclerosis. In: Pediatric Nephrology. 2014 ; Vol. 30, No. 3. pp. 469-477.
@article{286c7d2532974653999656066bb2e7a0,
title = "Case series: CTLA4-IgG1 therapy in minimal change disease and focal segmental glomerulosclerosis",
abstract = "Background: Minimal Change Disease (MCD) in relapse is associated with increased podocyte CD80 expression and elevated urinary CD80 excretion, whereas focal segmental glomerulosclerosis (FSGS) has mild or absent CD80 podocyte expression and normal urinary CD80 excretion. Methods: One patient with MCD, one patient with primary FSGS and three patients with recurrent FSGS after transplantation received CD80 blocking antibodies (abatacept or belatacept). Urinary CD80 and CTLA-4 levels were measured by ELISA. Glomeruli were stained for CD80. Results: After abatacept therapy, urinary CD80 became undetectable with a concomitant transient resolution of proteinuria in the MCD patient. In contrast, proteinuria remained unchanged after abatacept or belatacept therapy in the one patient with primary FSGS and in two of the three patients with recurrent FSGS despite the presence of mild CD80 glomerular expression but normal urinary CD80 excretion. The third patient with recurrent FSGS after transplantation had elevated urinary CD80 excretion immediately after surgery which fell spontaneously before the initiation of abatacept therapy; after abatacept therapy, his proteinuria remained unchanged for 5 days despite normal urinary CD80 excretion. Conclusion: These observations are consistent with a role of podocyte CD80 in the development of proteinuria in MCD. In contrast, CD80 may not play a role in recurrent FSGS since the urinary CD80 of our three patients with recurrent FSGS was only increased transiently after surgery and normalization of urinary CD80 did not result in resolution of proteinuria.",
keywords = "CD80, CTLA-4, Focal segmental glomerulosclerosis, Minimal change disease, Nephrotic syndrome",
author = "Garin, {Eduardo H.} and Jochen Reiser and Gabriel Cara-Fuentes and Changli Wei and Dany Matar and Heiman Wang and Nada Alachkar and Johnson, {Richard J.}",
year = "2014",
doi = "10.1007/s00467-014-2957-6",
language = "English (US)",
volume = "30",
pages = "469--477",
journal = "Pediatric Nephrology",
issn = "0931-041X",
publisher = "Springer Verlag",
number = "3",

}

TY - JOUR

T1 - Case series

T2 - CTLA4-IgG1 therapy in minimal change disease and focal segmental glomerulosclerosis

AU - Garin, Eduardo H.

AU - Reiser, Jochen

AU - Cara-Fuentes, Gabriel

AU - Wei, Changli

AU - Matar, Dany

AU - Wang, Heiman

AU - Alachkar, Nada

AU - Johnson, Richard J.

PY - 2014

Y1 - 2014

N2 - Background: Minimal Change Disease (MCD) in relapse is associated with increased podocyte CD80 expression and elevated urinary CD80 excretion, whereas focal segmental glomerulosclerosis (FSGS) has mild or absent CD80 podocyte expression and normal urinary CD80 excretion. Methods: One patient with MCD, one patient with primary FSGS and three patients with recurrent FSGS after transplantation received CD80 blocking antibodies (abatacept or belatacept). Urinary CD80 and CTLA-4 levels were measured by ELISA. Glomeruli were stained for CD80. Results: After abatacept therapy, urinary CD80 became undetectable with a concomitant transient resolution of proteinuria in the MCD patient. In contrast, proteinuria remained unchanged after abatacept or belatacept therapy in the one patient with primary FSGS and in two of the three patients with recurrent FSGS despite the presence of mild CD80 glomerular expression but normal urinary CD80 excretion. The third patient with recurrent FSGS after transplantation had elevated urinary CD80 excretion immediately after surgery which fell spontaneously before the initiation of abatacept therapy; after abatacept therapy, his proteinuria remained unchanged for 5 days despite normal urinary CD80 excretion. Conclusion: These observations are consistent with a role of podocyte CD80 in the development of proteinuria in MCD. In contrast, CD80 may not play a role in recurrent FSGS since the urinary CD80 of our three patients with recurrent FSGS was only increased transiently after surgery and normalization of urinary CD80 did not result in resolution of proteinuria.

AB - Background: Minimal Change Disease (MCD) in relapse is associated with increased podocyte CD80 expression and elevated urinary CD80 excretion, whereas focal segmental glomerulosclerosis (FSGS) has mild or absent CD80 podocyte expression and normal urinary CD80 excretion. Methods: One patient with MCD, one patient with primary FSGS and three patients with recurrent FSGS after transplantation received CD80 blocking antibodies (abatacept or belatacept). Urinary CD80 and CTLA-4 levels were measured by ELISA. Glomeruli were stained for CD80. Results: After abatacept therapy, urinary CD80 became undetectable with a concomitant transient resolution of proteinuria in the MCD patient. In contrast, proteinuria remained unchanged after abatacept or belatacept therapy in the one patient with primary FSGS and in two of the three patients with recurrent FSGS despite the presence of mild CD80 glomerular expression but normal urinary CD80 excretion. The third patient with recurrent FSGS after transplantation had elevated urinary CD80 excretion immediately after surgery which fell spontaneously before the initiation of abatacept therapy; after abatacept therapy, his proteinuria remained unchanged for 5 days despite normal urinary CD80 excretion. Conclusion: These observations are consistent with a role of podocyte CD80 in the development of proteinuria in MCD. In contrast, CD80 may not play a role in recurrent FSGS since the urinary CD80 of our three patients with recurrent FSGS was only increased transiently after surgery and normalization of urinary CD80 did not result in resolution of proteinuria.

KW - CD80

KW - CTLA-4

KW - Focal segmental glomerulosclerosis

KW - Minimal change disease

KW - Nephrotic syndrome

UR - http://www.scopus.com/inward/record.url?scp=84924964566&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84924964566&partnerID=8YFLogxK

U2 - 10.1007/s00467-014-2957-6

DO - 10.1007/s00467-014-2957-6

M3 - Article

C2 - 25239302

AN - SCOPUS:84924964566

VL - 30

SP - 469

EP - 477

JO - Pediatric Nephrology

JF - Pediatric Nephrology

SN - 0931-041X

IS - 3

ER -