Elevated ischaemia-associated lysyl oxidase activity in delayed graft failure 6-12 months after renal transplantation.

What is the central question of this study? What potential biochemical changes are associated with renal parenchyma 6-12 months after renal transplantation and delayed graft failure? What is the main finding and its importance? Tissue fibrosis, mediated by tissue ischaemia-induced induction of hypoxia-inducible factor-1α and fibronectin and consequent activation of lysyl oxidase, is a major underlying pathophysiological mechanism that contributes to delayed graft failure several months after renal transplantation. The present investigation was undertaken to evaluate the potential biochemical changes associated with renal parenchyma 6-12 months after renal transplantation and delayed graft failure. Serum concentrations of transforming growth factor-β in these subjects always remained elevated. In addition, examination of tissue from needle biopsies confirmed that there were consistent changes in the enzyme lysyl oxidase, which functions as an amine oxidase, modifies lysine residues on collagen and cross-links in a process of modulation of the extracellular matrix. Parenchymal levels of hypoxia-inducible factor-1α and fibronectin were elevated, as detected by Western blotting. These findings indicate an ongoing ischaemic insult, which might result from increased tissue fibrosis or, in some cases, might be additive with pre-existing pathophysiological factors that constrain proper renal haemodynamics. Thus, increased lysyl oxidase activity, which we assayed, is a potential unfavourable mechanism occurring in these kidneys that are undergoing failure and probably causes increased fibrosis within the organ and causes ischaemia, renovascular hypertension and a cascade leading to renal dysfunction and failure.