Increased urinary hepatocyte growth factor excretion in human acute renal failure

Studies in animals suggest that hepatocyte growth factor (HGF) is an important mediator of kidney development, compensatory growth and tubule repair following acute injury, however, evidence for HGF action in human renal disease is scant. To determine whether increased renal production of HGF occurs in man, urine HGF excretion rate was measured in normals and in patients with a variety of acute and chronic renal diseases. Urine samples were collected from 9 healthy individuals, 25 individuals with acute tubular necrosis (ATN), 20 individuals with chronic glomerular disease, 9 patients with polycystic kidney disease and 10 individuals with severe chronic renal failure not yet receiving renal replacement therapy. Samples were initially frozen and then HGF content measured by ELISA and factored for creatinine concentration measured by autoanalyzer. Detectable but low levels of HGF were found in the urine of normals and in patients with chronic glomerular or polycystic disease. Levels were also not increased in patients with advanced, chronic renal insufficiency. In contrast, a marked increase in urine HGF was observed in patients with acute renal failure. In addition, HGF excretion tended to correlate with disease severity as higher levels were observed in patients with oliguric ATN. Urine HGF levels declined to control values in patients recovering from ATN, generally within one week. These findings are consistent with a role for HGF in promoting tubule cell proliferation, differentiation and recovery from acute tubular injury in man.