The role of macrophages and reactive oxygen species in experimental hydronephrosis.

A common feature to a number of immune and non-immune renal diseases of diverse etiology is the infiltration of the glomerular and tubulointerstitial compartments by infiltrating macrophages. This review will focus on experimental data supporting the role of the infiltrating renal macrophage as a mediator of interstitial fibrosis during the course of obstructive nephropathy as it pertains to the unilateral ureteral obstruction model in the rat. The mechanical disturbance resulting from complete ureteral obstruction causes tubular injury/dysfunction resulting in a florid pro-inflammatory and fibrogenic response. The central pathobiological theme drawn from data in this model is that macrophage-derived pro-inflammatory mediators, including fibrogenic cytokines and reactive oxygen species, represent pivotal links between the pro-inflammatory state of ureteral obstruction and the late development of interstitial fibrosis. We propose that increased intrarenal oxidant stress, owing to an overproduction of reactive oxygen species and dysregulated tubular antioxidant enzymes, can induce overexpression of fibrogenic cytokines and chemoattractants, as well as increased transcription and synthesis of extracellular matrix proteins, leading to tubular loss and fibrogenesis.