Evidence for Antibody-Mediated Injury as a Major Determinant of Late Kidney Allograft Failure

被引:419
作者
Gaston, Robert S. [1 ]
Cecka, J. Michael [2 ]
Kasiske, Bert L. [3 ]
Fieberg, Ann M. [4 ]
Leduc, Robert [4 ]
Cosio, Fernando C. [5 ]
Gourishankar, Sita [6 ]
Grande, Joseph [9 ]
Halloran, Philip [6 ]
Hunsicker, Lawrence [7 ]
Mannon, Roslyn [1 ]
Rush, David [8 ]
Matas, Arthur J. [10 ]
机构
[1] Univ Alabama, Div Nephrol, Birmingham, AL USA
[2] Univ Calif Los Angeles, Sch Med, Immunogenet Lab, Los Angeles, CA USA
[3] Hennepin Cty Med Ctr, Div Nephrol, Minneapolis, MN 55415 USA
[4] Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA
[5] Mayo Clin, Div Nephrol, Rochester, MN USA
[6] Univ Alberta, Div Nephrol & Transplantat Immunol, Edmonton, AB, Canada
[7] Univ Iowa Hlth Care, Div Nephrol, Iowa City, IA USA
[8] Hlth Sci Ctr, Dept Internal Med, Winnipeg, MB, Canada
[9] Mayo Clin, Dept Pathol, Rochester, NY USA
[10] Univ Minnesota, Dept Surg, Minneapolis, MN 55455 USA
关键词
Kidney transplant; Chronic rejection; Immunosuppression; Donor-specific antibody; RENAL-TRANSPLANTATION; PROTOCOL BIOPSIES; MEDICAL PROGRESS; REJECTION; NEPHROPATHY; CYCLOSPORINE; STRATEGIES; DEPOSITION; RECIPIENTS; RISK;
D O I
10.1097/TP.0b013e3181e065de
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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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收藏
页码:68 / 74
页数:7
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