Elevated ischemia associated lysyl oxidase activity in delayed graft failure 6 -12 months post-renal transplantation

Abstract

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 TGF beta concentrations of these subjects always remained elevated. In addition, tissue examination 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 and fibronectin were elevated, as detected by western blotting. These indicates an ongoing ischemic insult, which may result from increased tissue fibrosis, or in some cases, may be additive from pre-existing pathophysiologic factors that constrain proper renal hemodynamics. Thus, increased lysyl oxidase activity, which we assayed, is a potential unfavorable mechanism occurring in these kidneys undergoing failure and which probably causes increased fibrosis within the organ, causes ischemia, renovascular hypertension, and a cascade leading to renal dysfunction and failure.

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