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Multicenter Study
. 2010 Sep;10(9):2066-73.
doi: 10.1111/j.1600-6143.2010.03240.x.

Inflammation in areas of tubular atrophy in kidney allograft biopsies: a potent predictor of allograft failure

R B Mannon  1 , A J Matas, J Grande, R Leduc, J Connett, B Kasiske, J M Cecka, R S Gaston, F Cosio, S Gourishankar, P F Halloran, L Hunsicker, D Rush; DeKAF Investigators
Affiliations
Multicenter Study

Inflammation in areas of tubular atrophy in kidney allograft biopsies: a potent predictor of allograft failure

R B Mannon et al. Am J Transplant. 2010 Sep.

Abstract

The Banff scoring schema provides a common ground to analyze kidney transplant biopsies. Interstitial inflammation (i) and tubulitis (t) in areas of viable tissue are features in scoring acute rejection, but are excluded in areas of tubular atrophy (TA). We studied inflammation and tubulitis in a cohort of kidney transplant recipients undergoing allograft biopsy for new-onset late graft dysfunction (N = 337). We found inflammation ('iatr') and tubulitis ('tatr') in regions of fibrosis and atrophy to be strongly correlated with each other (p < 0.0001). Moreover, iatr was strongly associated with death-censored graft failure when compared to recipients whose biopsies had no inflammation, even after adjusting for the presence of interstitial fibrosis (Hazard Ratio = 2.31, [1.10-4.83]; p = 0.0262) or TA (hazard ratio = 2.42, [1.16-5.08]; p = 0.191), serum creatinine at the time of biopsy, time to biopsy and i score. Further, these results did not qualitatively change after additional adjustments for C4d staining or donor specific antibody. Stepwise regression identified the most significant markers of graft failure which include iatr score. We propose that a more global assessment of inflammation in kidney allograft biopsies to include inflammation in atrophic areas may provide better prognostic information. Phenotypic characterization of these inflammatory cells and appropriate treatment may ameliorate late allograft failure.

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Figures

Figure 1
Figure 1
Representative photomicrographs showing (A) inflammation in region of atrophy, and (B) tubulitis in atrophic tubules.
Figure 2
Figure 2
Time to death censored graft failure after allograft biopsy is dependent on the severity of scoring for iatr.
Figure 3
Figure 3
Time to death censored graft failure after allograft biopsy based on the presence or absence of iatr.
Figure 4
Figure 4
Time to death censored graft failure after allograft biopsy comparing biopsies with no inflammation (i=0, iatr=0; n=102), inflammation only in areas of fibrosis (i=0 and iatr≥1; n=108) and those with inflammation in both fibrotic and non-fibrotic areas (i≥1, iatr≥1; n=124 and i>0 and iatr=0; n=3) demonstrating the independent effect of iatr from Banff i score on allograft failure.
See this image and copyright information in PMC

Comment in

References

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