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Microvascular (MIA) and Interstitial (i) Inflammation Influence Late Death-Censored Graft Failure (DCGF) After Kidney Transplantation

R. Gaston,1 A. Fieberg,2 R. Leduc,2 J. Connett,2 F. Cosio,3 S. Gourishankar,4 J. Grande,3 L. Hunsicker,5 B. Kasiske,6 J. Cecka,7 A. Matas,2 D. Rush.8

1UAB, Birmingham
2U Minnesota, Minneapolis
3Mayo Clinic, Rochester
4U Alberta, Edmonton, Canada
5U Iowa, Iowa City
6Hennepin County Med Ctr, Minneapolis
7UCLA Immunogenetics, Los Angeles
8U Manitoba, Winnipeg, Canada.

Meeting: 2015 American Transplant Congress

Abstract number: B97

Keywords: Antibodies, Inflammation, Kidney transplantation, Rejection

Session Information

Date: Sunday, May 3, 2015

Session Name: Poster Session B: Kidney Complications: Late Graft Failure

Session Time: 5:30pm-6:30pm

 Presentation Time: 5:30pm-6:30pm

Location: Exhibit Hall E

Related Abstracts
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We and others have shown late DCGF is due to ongoing, most often immune, injury. Though there is general agreement that antibody-mediated injury is a common cause of late DCGF, the impact of cell-mediated immunity remains controversial. In this prospective, multicenter study, 559 pts underwent for-cause biopsies 7.9±5.8 years post-txp for new-onset graft dysfunction or proteinuria, with 235 having both central DSA determination, and biopsy (bx) read by a blinded pathologist according to 2007 Banff criteria. MIA was characterized by quantitative g (glomerulitis) and ptc (peritubular capillaritis) scores; other inflammation by i (interstitial) and t (tubulitis) scores. Pts with DSA, C4d, or both were more likely to have g (p=0.04) and ptc (p<0.001) scores ≥ 1. By univariate analysis, DSA (HR=2.9), C4d (HR=3.1), both DSA/C4d (HR=4.3), g (HR≥1.8), ptc (HR≥2.4), combined g+ptc score (HR≥2.7), i (HR≥1.5), and t (HR≥1.8) were all associated with increased risk for DCGF, as were time after transplantation and serum creatinine at bx. Multivariate analysis demonstrated a significant, independent impact of DSA/C4d classification, MIA, and i, but not t, scores on risk for DCGF.

Multivariate analysis of impact on DCGF
  P value
C4d/DSA group 0.0001
g+ptc score 0.005
i score 0.005
t score 0.11
Serum creat at bx <0.0001
Years post txp 0.01
When cg score (transplant glomerulopathy) is added to the multivariate model, MIA loses its significance as a predictive variable, suggesting that with advanced microvascular injury, MIA no longer influences risk. These findings indicate that, even in the presence of C4d and DSA, microvascular and interstitial inflammation play a significant role in risk of DCGF, and imply both cell-mediated and humoral mechanisms are of operational significance.

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To cite this abstract in AMA style:

Gaston R, Fieberg A, Leduc R, Connett J, Cosio F, Gourishankar S, Grande J, Hunsicker L, Kasiske B, Cecka J, Matas A, Rush D. Microvascular (MIA) and Interstitial (i) Inflammation Influence Late Death-Censored Graft Failure (DCGF) After Kidney Transplantation [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/microvascular-mia-and-interstitial-i-inflammation-influence-late-death-censored-graft-failure-dcgf-after-kidney-transplantation/. Accessed April 15, 2021.

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