Epidermal growth factor accelerates renal repair in mercuric chloride nephrotoxicity

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Abstract
Repair and recovery of ischemic or nephrotoxic acute renal failure (ARF) are dependent upon renal tubule cell regeneration. Because epidermal growth factor (EGF) is a potent growth promoter to renal tubule cells, experiments were undertaken to assess the effects of exogenous administration of EGF during the recovery phase of HgCl2-induced ARF. Rats were administered HgCl2 (5 mg/kg sc), and [3H]thymidine incorporation into renal tissue and blood urea nitrogen (BUN) and serum creatinine concentrations were measured at various times after toxin administration. EGF (20 microgram) was administered subcutaneously 2 or 4 h after HgCl2 injection. Exogenous EGF resulted in greater levels of renal [3H]thymidine incorporation into renal proximal tubule cells compared with those observed in nontreated animals at several time points in the first 48 h after toxic injury. Morphometric analysis of histoautoradiograph sections of renal tissue demonstrated that greater than 96% of labeled cells were tubular in all examined sections. This EGF-related acceleration in DNA synthesis was associated with significantly lower peak BUN and serum creatinine levels, averaging 213 +/- 23 and 6.54 +/- 0.72 (SE) mg/dl, respectively, at 3 days in EGF-treated nephrotoxic rats compared with peak levels of 359 +/- 40 and 9.92 +/- 1.67 mg/dl (P less than 0.001, n = 7-16) at 5 days in non-EGF-treated nephrotoxic rats. EGF treatment also was associated with a return to near normal BUN and serum creatinine levels approximately 4 days earlier than that observed in non-EGF-treated animals. These findings demonstrate that exogenous EGF accelerates the repair process of the kidney after a severe toxic insult.