Aim: Better understanding of early onset of interstitial fibrosis and tubular atrophy (IF/TA), as the morphological surrogate of renal allograft deterioration might improve outcome after renal transplantation.
Material and methods: We quantified mRNA expression of 3 profibrotic (transforming growth factor-beta (TGF-beta), tissue transglutaminase (tTG), tissue inhibitor of matrix metalloproteases (TIMP-1)) and 1 antifibrotic (matrix metalloprotease-2 (MMP-2)) molecule in protocol biopsies from renal allografts. From 107 transplants, two sequential protocol biopsies (6 weeks and 6 months) were analyzed. We evaluated a control group showing no IF/TA in both biopsies (n = 65) and a IF/TA group developing IF/TA at 6 months (n = 42). Expression data were correlated with clinical and histological risk factors for IF/TA and allograft function.
Results: The expression of the genes correlated strongly with each other, particularly the profibrotic genes and in patients who developed IF/TA. Analyzing protocol biopsies from stable grafts, not all patients in both groups showed increased gene expression. In patients with increased gene expression a significantly higher tTG expression (matrix stabilization) at 6 weeks and a significantly lower MMP-2 expression (failure in matrix degradation) at 6 months were observed in the IFTA group compared to controls. Multivariate logistic regression revealed donor age positively and TIMP-1 expression at 6 weeks inversely correlated with IF/TA at 6 months.
Conclusions: We conclude that a disturbance in the equilibrium of pro- and antifibrotic pathways is decisive for early onset of IF/TA in renal allografts: insufficient degradation of exaggerated matrix production apparently changes the balance in the direction of IF/TA.