EPIDERMAL GROWTH-FACTOR IN ACUTE-RENAL-FAILURE

Epidermal growth factor (EGF) is produced in large amounts in the kidn ey in the form of a membrane-bound high molecular weight precursor. Th is precursor is inserted in the apical plasma membrane of the EGF-prod ucing cells, which are localized in the thick ascending limb and dista l convoluted tubule in mouse and rat kidney, and probably also in huma n kidney. High levels of EGF are excreted in urine, although renal tis sue contains little mature EGF. It modulates renal cell proliferation and differentiation in vitro, but the role of the distal tubular EGF a nd/or its precursor in vivo is unknown. The expression of EGF in the k idney and its liberation into the urine are quickly abolished during s everal types of drug- or ischemia-induced acute renal failure and also in ureteral obstruction. Moreover, its expression is restored only af ter morphological and functional recovery of the kidney. This absence of EGF in conditions in which its mitogenic properties would be most a ppropriate suggests that the EGF of renal origin is not acting as a mi togen during kidney regeneration. Nevertheless, since the number of EG F receptors, which are localized at the basolateral cell surface in mo st nephron segments, is increased in regenerating renal epithelia, EGF of systemic origin or other members of the EGF family of growth facto rs, released from infiltrated inflammatory cells at the sites of injur y, could enhance cellular proliferation by interacting with the EGF re ceptor. Administration of EGF indeed has a mildly beneficial effect on recovery from acute renal injury.