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Antibody-Mediated Injury Is the Major Cause of Late Kidney Allograft Failure

R. Gaston, R. Leduc, F. Cosio, S. Gourishankar, J. Grande, L. Hunsicker, B. Kasiske, R. Mannon, A. Matas, D. Rush, M. Cecka

UAB, Birmingham
U Minnesota, Minneapolis
Mayo Clinic, Rochester
U Alberta, Edmonton, Canada
U Iowa, Iowa City
Hennepin County Med Ctr, Minneapolis
U Manitoba, Winnipeg, Canada
UCLA Immunogenetics Laboratory, Los Angeles

Meeting: 2013 American Transplant Congress

Abstract number: 34

DeKAF is NIH-funded multicenter observational study of late kidney graft failure with over 4500 recs enrolled from 2006-10. The Cross-Sectional cohort (CS, N=559) includes recs transplanted at any time with serum creat ≤ 2.0mg/dl on 1/1/06. In data from 173 CS recs with 2 years followup after for-cause biopsies (bx) (Transplantation 90:68, 2010), c4d+ was associated with greater strength of DSA response and worse outcomes than in recs with DSA and no c4d staining. We now report data from 469 patients with up to 6 years followup after bx. Histology and DSA were determined from tissue and sera obtained at entry bx. 4 groups were defined based on c4d and DSA status.

  Group A (C4d-/DSA-) Group B (C4d-/DSA+) Group C (C4d+/DSA-) Group D (C4d+/DSA+)
N (%) 220 (47) 98 (21) 55 (12) 96 (20)
Time to biopsy, years 8.1±6.1 7.6±5.4 7.6±5.8 7.0±4.9
Serum cr @ bx (mg/dl, mean±SD)* 2.3±1.0 2.2±1.2 2.6±1.3 3.0±1.9
Strength of DSA (Sum MFI, Class I and II)* NA 7.95±6.9 NA 14.35±10.9
*P<0.05 between groups

The groups did not differ with respect to rec or donor age or donor type (living vs. deceased). HLA match differed between groups. The time to graft loss differed significantly by group (Log-rank p<0.0001).

In adjusted Cox models, Groups B, C, and D had a higher risk of graft loss than Group A (Group B: HR=2.4 (95% CI 1.5−3.8), Group C: HR=2.6 (1.5−4.4), Group D: HR=3.0 (2.0−4.7). C4d and DSA were each independently associated with increased risk of graft loss [C4d HR=1.7 (1.2−2.4), DSA HR=1.8 (1.3−2.5)]

Conclusion: Among patients with late allograft dysfunction, evidence of antibody-mediated injury is common and negatively influences outcome. The impact of DSA alone may take longer to manifest, but the ultimate result is similar with or without c4d at initial biopsy. Antibody-mediated injury is the major cause of late kidney allograft failure.

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To cite this abstract in AMA style:

Gaston R, Leduc R, Cosio F, Gourishankar S, Grande J, Hunsicker L, Kasiske B, Mannon R, Matas A, Rush D, Cecka M. Antibody-Mediated Injury Is the Major Cause of Late Kidney Allograft Failure [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/antibody-mediated-injury-is-the-major-cause-of-late-kidney-allograft-failure/. Accessed May 17, 2025.

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