Evidence for antibody-mediated injury as a Major determinant of late kidney allograft failure

Robert S. Gaston, J. Michael Cecka, Bert L. Kasiske, Ann M. Fieberg, Robert Leduc, Fernando G Cosio, Sita Gourishankar, Joseph Peter Grande, Philip Halloran, Lawrence Hunsicker, Roslyn Mannon, David Rush, Arthur J. Matas

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Abstract

Background: Late graft failure (LGF) is believed to be the consequence of immunologic and nonimmunologic insults leading to progressive deterioration in kidney function. We studied recipients with new onset late kidney graft dysfunction (n=173) to determine the importance of C4d staining and circulating donor-specific antibody (DSA) in subsequent LGF. Methods: One hundred seventy-three subjects transplanted before October 1, 2005 (mean time after transplant 7.3±6.0 years) had a baseline serum creatinine level of 1.4±0.3 mg/dL before January 1, 2006 and underwent biopsy for new onset graft dysfunction after that date (mean creatinine at biopsy 2.7±1.6 mg/dL). Statistical analysis was based on central DSA and blinded pathology determinations. Results: Subjects were divided into four groups based on C4d and DSA: no C4d, no DSA (group A; n=74); only DSA (group B; n=31); only C4d (group C; n=28); and both C4d and DSA (group D; n=40). Among DSA+ recipients (groups B and D), group D had broader reactivity and a stronger DSA response. After 2 years, groups C and D (C4d+) were at significantly greater risk for LGF than groups A and B. Adjusting for inflammation (Banff i, t, g, and ptc scores) did not change the outcome. Local diagnosis of calcineurin inhibitor nephrotoxicity was spread across all four subgroups and did not impact risk of LGF. ConclusionS: Evidence of antibody-mediated injury (DSA or C4d) is common (57%) in patients with new onset late kidney allograft dysfunction. The risk of subsequent graft failure is significantly worse in the presence of C4d+ staining.

Original languageEnglish (US)
Pages (from-to)68-74
Number of pages7
JournalTransplantation
Volume90
Issue number1
DOIs
StatePublished - Jul 15 2010

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Renal Insufficiency
Allografts
Tissue Donors
Transplants
Antibodies
Wounds and Injuries
Kidney
Creatinine
Staining and Labeling
Biopsy
Antibody Formation
Pathology
Inflammation
Serum

Keywords

  • Chronic rejection
  • Donor-specific antibody.
  • Immunosuppression
  • Kidney transplant

ASJC Scopus subject areas

  • Transplantation

Cite this

Gaston, R. S., Cecka, J. M., Kasiske, B. L., Fieberg, A. M., Leduc, R., Cosio, F. G., ... Matas, A. J. (2010). Evidence for antibody-mediated injury as a Major determinant of late kidney allograft failure. Transplantation, 90(1), 68-74. https://doi.org/10.1097/TP.0b013e3181e065de

Evidence for antibody-mediated injury as a Major determinant of late kidney allograft failure. / Gaston, Robert S.; Cecka, J. Michael; Kasiske, Bert L.; Fieberg, Ann M.; Leduc, Robert; Cosio, Fernando G; Gourishankar, Sita; Grande, Joseph Peter; Halloran, Philip; Hunsicker, Lawrence; Mannon, Roslyn; Rush, David; Matas, Arthur J.

In: Transplantation, Vol. 90, No. 1, 15.07.2010, p. 68-74.

Research output: Contribution to journalArticle

Gaston, RS, Cecka, JM, Kasiske, BL, Fieberg, AM, Leduc, R, Cosio, FG, Gourishankar, S, Grande, JP, Halloran, P, Hunsicker, L, Mannon, R, Rush, D & Matas, AJ 2010, 'Evidence for antibody-mediated injury as a Major determinant of late kidney allograft failure', Transplantation, vol. 90, no. 1, pp. 68-74. https://doi.org/10.1097/TP.0b013e3181e065de
Gaston, Robert S. ; Cecka, J. Michael ; Kasiske, Bert L. ; Fieberg, Ann M. ; Leduc, Robert ; Cosio, Fernando G ; Gourishankar, Sita ; Grande, Joseph Peter ; Halloran, Philip ; Hunsicker, Lawrence ; Mannon, Roslyn ; Rush, David ; Matas, Arthur J. / Evidence for antibody-mediated injury as a Major determinant of late kidney allograft failure. In: Transplantation. 2010 ; Vol. 90, No. 1. pp. 68-74.
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abstract = "Background: Late graft failure (LGF) is believed to be the consequence of immunologic and nonimmunologic insults leading to progressive deterioration in kidney function. We studied recipients with new onset late kidney graft dysfunction (n=173) to determine the importance of C4d staining and circulating donor-specific antibody (DSA) in subsequent LGF. Methods: One hundred seventy-three subjects transplanted before October 1, 2005 (mean time after transplant 7.3±6.0 years) had a baseline serum creatinine level of 1.4±0.3 mg/dL before January 1, 2006 and underwent biopsy for new onset graft dysfunction after that date (mean creatinine at biopsy 2.7±1.6 mg/dL). Statistical analysis was based on central DSA and blinded pathology determinations. Results: Subjects were divided into four groups based on C4d and DSA: no C4d, no DSA (group A; n=74); only DSA (group B; n=31); only C4d (group C; n=28); and both C4d and DSA (group D; n=40). Among DSA+ recipients (groups B and D), group D had broader reactivity and a stronger DSA response. After 2 years, groups C and D (C4d+) were at significantly greater risk for LGF than groups A and B. Adjusting for inflammation (Banff i, t, g, and ptc scores) did not change the outcome. Local diagnosis of calcineurin inhibitor nephrotoxicity was spread across all four subgroups and did not impact risk of LGF. ConclusionS: Evidence of antibody-mediated injury (DSA or C4d) is common (57{\%}) in patients with new onset late kidney allograft dysfunction. The risk of subsequent graft failure is significantly worse in the presence of C4d+ staining.",
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T1 - Evidence for antibody-mediated injury as a Major determinant of late kidney allograft failure

AU - Gaston, Robert S.

AU - Cecka, J. Michael

AU - Kasiske, Bert L.

AU - Fieberg, Ann M.

AU - Leduc, Robert

AU - Cosio, Fernando G

AU - Gourishankar, Sita

AU - Grande, Joseph Peter

AU - Halloran, Philip

AU - Hunsicker, Lawrence

AU - Mannon, Roslyn

AU - Rush, David

AU - Matas, Arthur J.

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N2 - Background: Late graft failure (LGF) is believed to be the consequence of immunologic and nonimmunologic insults leading to progressive deterioration in kidney function. We studied recipients with new onset late kidney graft dysfunction (n=173) to determine the importance of C4d staining and circulating donor-specific antibody (DSA) in subsequent LGF. Methods: One hundred seventy-three subjects transplanted before October 1, 2005 (mean time after transplant 7.3±6.0 years) had a baseline serum creatinine level of 1.4±0.3 mg/dL before January 1, 2006 and underwent biopsy for new onset graft dysfunction after that date (mean creatinine at biopsy 2.7±1.6 mg/dL). Statistical analysis was based on central DSA and blinded pathology determinations. Results: Subjects were divided into four groups based on C4d and DSA: no C4d, no DSA (group A; n=74); only DSA (group B; n=31); only C4d (group C; n=28); and both C4d and DSA (group D; n=40). Among DSA+ recipients (groups B and D), group D had broader reactivity and a stronger DSA response. After 2 years, groups C and D (C4d+) were at significantly greater risk for LGF than groups A and B. Adjusting for inflammation (Banff i, t, g, and ptc scores) did not change the outcome. Local diagnosis of calcineurin inhibitor nephrotoxicity was spread across all four subgroups and did not impact risk of LGF. ConclusionS: Evidence of antibody-mediated injury (DSA or C4d) is common (57%) in patients with new onset late kidney allograft dysfunction. The risk of subsequent graft failure is significantly worse in the presence of C4d+ staining.

AB - Background: Late graft failure (LGF) is believed to be the consequence of immunologic and nonimmunologic insults leading to progressive deterioration in kidney function. We studied recipients with new onset late kidney graft dysfunction (n=173) to determine the importance of C4d staining and circulating donor-specific antibody (DSA) in subsequent LGF. Methods: One hundred seventy-three subjects transplanted before October 1, 2005 (mean time after transplant 7.3±6.0 years) had a baseline serum creatinine level of 1.4±0.3 mg/dL before January 1, 2006 and underwent biopsy for new onset graft dysfunction after that date (mean creatinine at biopsy 2.7±1.6 mg/dL). Statistical analysis was based on central DSA and blinded pathology determinations. Results: Subjects were divided into four groups based on C4d and DSA: no C4d, no DSA (group A; n=74); only DSA (group B; n=31); only C4d (group C; n=28); and both C4d and DSA (group D; n=40). Among DSA+ recipients (groups B and D), group D had broader reactivity and a stronger DSA response. After 2 years, groups C and D (C4d+) were at significantly greater risk for LGF than groups A and B. Adjusting for inflammation (Banff i, t, g, and ptc scores) did not change the outcome. Local diagnosis of calcineurin inhibitor nephrotoxicity was spread across all four subgroups and did not impact risk of LGF. ConclusionS: Evidence of antibody-mediated injury (DSA or C4d) is common (57%) in patients with new onset late kidney allograft dysfunction. The risk of subsequent graft failure is significantly worse in the presence of C4d+ staining.

KW - Chronic rejection

KW - Donor-specific antibody.

KW - Immunosuppression

KW - Kidney transplant

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