EXOGENOUS EPIDERMAL GROWTH-FACTOR FAILS TO ACCELERATE FUNCTIONAL RECOVERY IN THE AUTOTRANSPLANTED ISCHEMIC PIG-KIDNEY

The reversibility of ischemic renal injury is dependent on epithelial cell regeneration and repopulation of the nephron. Renal cells produce and respond to many growth factors. In the rat, epidermal growth fact or (EGF) is mitogenic for tubular cells and accelerates renal recovery after ischemia. We used a pig renal autotransplant model to evaluate the effect of exogenous EGF on renal recovery in a large animal more a nalogous to man. Group 1 animals underwent left autotransplant after 1 20 minutes of warm ischemia and received either a single intra-arteria l dose of recombinant human EGF (EGF, 10(-7) M.) (N = 11) or vehicle a lone (N = 6). Group 2 animals underwent left autotransplant after 72 h ours of cold preservation with Collins' solution and received a simila r intra-arterial dose plus a subcutaneous dose of EGF (0.5 ml. of 10(- 3) M.) (N = 8) or vehicle alone (N = 6). Contralateral nephrectomy was performed in all animals.Daily creatinine measurements revealed no be neficial effect from EGF on recovery of renal function in Group 1 or 2 animals. Studies of EGF on pig proximal tubular cells demonstrated in vitro mitogenesis; autoradiography with I-125-EGF revealed binding of EGF throughout the kidney. Immunohistochemistry showed significant tu bular cell proliferation in response to ischemic injury, without furth er enhancement from EGF. Thus, although exogenous EGF bound to pig kid ney cells and stimulated cell proliferation, we were unable to demonst rate a clinically significant acceleration of recovery from ischemic i njury.