Exogenous Epidermal Growth Factor Fails to Accelerate Functional Recovery in the Autotransplanted Ischemic Pig Kidney

Abstract

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 factor (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 analogous to man. Group 1 animals underwent left autotransplant after 120 minutes of warm ischemia and received either a single intra-arterial dose of recombinant human EGF (EGF, 10(-7) M.) (N = 11) or vehicle alone (N = 6). Group 2 animals underwent left autotransplant after 72 hours of cold preservation with Collins' solution and received a similar 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 beneficial 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 125I-EGF revealed binding of EGF throughout the kidney. Immunohistochemistry showed significant tubular cell proliferation in response to ischemic injury, without further enhancement from EGF. Thus, although exogenous EGF bound to pig kidney cells and stimulated cell proliferation, we were unable to demonstrate a clinically significant acceleration of recovery from ischemic injury.