Urinary excretion of human epidermal growth factor in the various stages of diabetic nephropathy

Epidermal growth factor (EGF) is a polypeptide mitogen first isolated from mouse submaxillary glands and later from human urine. We have examined the pattern of urinary excretion of human EGF (hEGF) in normal subjects and in diabetic patients with varying degrees of nephropathy. hEGF was measured by homologous radioimmunoassay and expressed in terms of urinary creatinine excretion. On the basis of their albumin excretion rate, the diabetic patients were divided into those with normoalbuminuria (albumin excretion rate 3.5 (1.4-9.8) micrograms/min; mean (range)), microalbuminuria (albumin excretion rate 75 (30-128) micrograms/min) and macroalbuminuria (289 (169-879) micrograms/min). The albumin excretion rate for the normal subjects was 3.7 (1.6-9.7) micrograms/min. The mean (range) hEGF excretion (nmol hEGF/mmol creatinine) was 0.69 (0.47-1.29) for 19 healthy subjects, 0.60 (0.16-1.36) for the normoalbuminuric group (n = 18; NS), 0.47 (0.10-0.83) for the microalbuminuric patients (n = 19; P less than 0.001 vs controls and normoalbuminuric diabetics) and 0.38 (0.10-0.63) for the macroalbuminuric group (n = 18; P less than 0.001 vs controls and normoalbuminuric diabetics). There was an inverse correlation between albumin excretion rate and hEGF: creatinine ratio (r = -0.49; P = 0.02). These results show a progressive decline in hEGF excretion in diabetic patients with varying degrees of nephropathy and do not support the hypothesis that increased kidney size seen in early nephropathy is due to excessive amounts of EGF in the urine.