TIME-COURSE OF GROWTH-FACTOR EXPRESSION IN MERCURIC-CHLORIDE ACUTE-RENAL-FAILURE

Background. Renal EGF expression decreases in varying models of acute renal failure (ARF). We found previously that the loss of distal tubul ar EGF during gentamicin ARF is strongest in the cortex, where proxima l tubular injury was most severe. To gain more insight into the mechan ism underlying this apparent anatomical association, renal growth fact or expression was investigated during mercuric chloride ARF, in which proximal tubular injury is most severe in the outer stripe of the oute r medulla (OSOM). Methods. Endogenous renal growth factor expression w as investigated by RNA hybridization and by immunohistochemistry in a rat model of mercuric chloride ARF. In addition we determined temporal and spatial profiles of tubular injury, cell proliferation, and monon uclear cell infiltration during the 3-week observation period. Results . Serum creatinine values were maximal 2 days after treatment and were again normalized at day 6. Tubular injury was most severe in the PST and maximal at day 2. Cell proliferation was also highest in the PST a nd maximal at day 4. Three weeks after treatment, normal renal morphol ogy was restored. Increased numbers of mononuclear cells appeared tran siently in the renal interstitium from day 1 on. Most of these cells w ere macrophages and T lymphocytes; macrophages surrounded preferential ly the severely injured PST in the OSOM. In analogy to gentamicin ARF, renal EGF and IGF-I gene expression were decreased early in the setti ng of mercuric chloride ARF. The decrease in distal tubular EGF staini ng was most pronounced in the OSOM, i.e. the anatomical area where mer curic-chloride-induced proximal tubular injury was most severe. Conclu sions. Renal EGF and IGF-I gene expression decreases strongly during m ercuric chloride ARF. The spatial association between the initial decr ease of distal tubular EGF expression and the zone of major proximal t ubular injury could originate from metabolic alterations secondary to oxygen starvation. A possible role of mononuclear cells remains to be determined.