Mast Cell Quantitation in Renal Biopsies as a Potential Marker for the Cumulative Burden of Tissue Injury

Abstract

Background: Mast cells (MC) in kidney allograft biopsies have been associated with late biopsy scarring and poor outcomes. No specific quantitative studies or correlation with other histological parameters have been performed previously. Methods: Using the CD117 immunostain, MC were counted in the most inflamed area at 200 Magnification in 461 consecutive kidney allograft biopsies. The number of MC were correlated with the presence and severity of acute and chronic rejection features, including tubular, vascular and microvascular inflammation as well as glomerulitis, C4d positivity, transplant glomerulopathy, peritubular multilamellation, active transplant arteriopathy, high number of glomerular macrophages (>12) and the presence of interstitial fibrosis-tubular atrophy. Results: 275 (59.65%) KBx had 0-10 MC (Group 1), 102 (22.13%) had >10- 20 MC (Group 2) and 84 (18.22%) had >20 MC (Group C). No correlation was found between the number of MC and the presence or degree of T-cell mediated rejection or with parameters defining acute or chronic antibody mediated rejection. Significant correlation was found, however, with time post transplantation of the KBx: Group 1: 13.07 27.58; Group 2:31.27 33.57 and Group 3: 55.33 48.44 months post transplantation, p=.000. Typically MC were completely absent in biopsies performed within the first 10 days post transplantation. MC very rarely permeated tubular basement membranes (tubulitis) and were not found in glomeruli or vessels. Although increased concentration of MC was seen in inflamed scars, no statistical correlation was found between their number and the overall degree of interstitial fibrosis. Peritubular C4d+ correlated negatively with the number of MC as follows. No C4d+: 13.19 12.01 MC, Focal C4d+ (< 50%): 12.40 12.21 and diffuse C4d+ (>50%): 10.36 12.01 MD, p=.000. Conclusions: MC represent a somewhat unique cellular infiltrative component that does not correlate (or correlates negatively) with parameters of cellular or antibody mediated rejection. MC correlates strongly with the time post transplantation and could be potentially valuable as a surrogate marker for the cumulative burden of tissue injury that could supplement the notoriously unreliable (due to sampling variation) estimation of the degree of interstitial fibrosis/scarring.