Renal growth factors: past, present and future.

It is known that a series of mediators, so-called growth factors, are able to induce hypertrophy of the kidney in a patient after uninephrectomy. The first investigator who demonstrated this phenomenon was C. Sacerdotti, an Italian pathologist of Bizzozero's School in Turin, who published an important report in 1896. He attempted to explain how compensatory renal hypertrophy occurred and how this hypertrophy might be induced in a normal dog. Interestingly, he demonstrated that when the kidneys of a normal dog received a blood transfusion from uni- or binephrectomized dogs several mitoses appeared in the renal epithelium. These mitoses, expression of renal hypertrophy, were more evident in dogs receiving several blood transfusions for 6-7 days. He concluded that hypertrophy was induced by specific substances circulating in the blood of uni- or binephrectomized dogs. This hypothesis was in the next 100 years confirmed by the discovery of renal growth factors such as epidermal growth factor, insulin-like growth factor-1, hepatocyte growth factor, platelet-derived growth factor and others. The pathogenic role of these mediators is evident in the recovery of tubules after acute tubular necrosis and in the remnant glomeruli after glomerular damage. Today, attempts to use these growth factors for improving renal function in patients with acute tubular necrosis and to block their action in the progression of renal damage in chronic glomerulonephritides are under investigation. Future trends in these growth factors will be set by drug companies designing specific therapies such as gene therapy. In conclusion, the outstanding observation by Sacerdotti, over a century ago, remains an important step in nephrologic history for prognosis and therapy of renal diseases.