ABSTRACT
Early renal interstitial fibrosis [IF] has been described in renal allografts and implicated in the progression of chronic allograft nephropathy [CAN]. The precise factors implicated in initiation and progression of early allograft fibrosis remain uncertain. Recent studies in experimental nephropathy have implicated the protein-crosslinking enzyme, tissue transglutaminase [tTg] in the progression of fibrosis by its action, on the ECM. To elucidate any changes in the levels of tTg and its cross-link product in renal allografts during the early post-transplantation [post-Tx] period, I have retrospectively studied 21 cadaveric renal allograft recipients, over a three years period [1996-1998, inclusive], with the intention of detecting early fibrotic changes. There was a significant increase in the IF score [MT staining] from implantation to early follow-up Ax [p=0.0027]. At implantation, tTg and E[y--glutamyl] lysine were hardly detected. I have detected a significant increase in both immunoreactive tTg [+266%, p<0.001] and s-[y-glutamyl] lysine [+256.3%. p<0.001] within 3 months of transplantation. These stainings were noted within the glomerular mesangium and the renal interstitium. The increased e-[y-glutamyl] lysine at the early post-Tx period was correlated significantly with its Level at implantation [r=0, 546, p=001 1] as well as with both. allograft function [r=0.542, p=0.01] and its fibrosis score [Masson s Trichrome] [r=0. 781, p=0.01] at follow-up. By multivariate analysis, both. tTg and e-[y-glutamyl] lysine were risk factors for the increased serum creatinine [468.5-283.9 mmol/ l] at follow-up biopsy [R2=0.484. p0.034 and=0.002, respectively] as was tTg at implantation [p=0.021]. By univaniate analysis of variance, delayed graft function [DGF] [R2=0.5 18. p=0.05] and acute rejection [AR] [R2=0.735, p=0.007] were risk factors for follow-up E-[y-glutamyl] lysine. In conclusion. implantation histology. and in particular tissue trnasglutaminase, Is a predictor of early IF in a subgroup of patients with DGF and AR. Further, tissue transglutaminase [tTg] and its cross link product E-[y--glutamyl] lysine progressed significantly in concert with the progression of scarring on biopsies from renal graft recipients during the early post-transplant period