Nephromegaly relates to hepatocyte growth factor dysregulation in biliary atresia

To demonstrate nephromegaly in children with biliary atresia and children with compensatory renal hypertrophy and to examine their plasma hepatocyte growth factor (HGF), transforming growth factor β1 (TGF-β1), and the difference of total kidney volume, 11 children with biliary atresia (age range 5 months to 10 years), 11 with compensatory renal hypertrophy, and 11 age-matched healthy controls were investigated. Kidney volume was measured by renal ultrasonography and plasma HGF and TGF-β1 levels were studied. To clarify the significance of nephromegaly in biliary atresia, creatinine clearance was also measured in 9 children with biliary atresia and 9 healthy children. The unilateral kidney in biliary atresia and the solitary kidney in compensatory renal hypertrophy had significantly higher kidney volumes compared with those of healthy children (P<0.001 by analysis of covariance). However, a significant increase in total kidney volume was noted only in children with biliary atresia (P<0.001 by analysis of covariance). Although this was actually associated with increased creatinine clearance (117.3±22.0 ml/min per 1.73 m2 vs. 98.3±13.6 ml/min per 1.73 m2 in controls, P<0.05), corrected creatinine clearance was not correlated with total kidney volume (r=0.199, P=0.61) in biliary atresia. Plasma HGF levels and HGF/TGF-β1 ratios were elevated in children with biliary atresia (2,648±1,215 pg/ml and 233.8±139.1 pg/ng vs. 493±131 pg/ml and 35.9± 15.7 pg/ng in compensatory renal hypertrophy and 468±194 pg/ml and 24.0±19.6 pg/ng in controls, P<0.001) and had a positive correlation with total kidney volume by multiple regression analysis (P=0.006 and P=0.002, respectively). These results show that nephromegaly in biliary atresia is associated with increased total kidney volume and a higher glomerular filtration rate, and is positively correlated with plasma HGF and plasma HGF/TGF-β1 ratio, implying a role of HGF in this situation. However, nephromegaly in compensatory renal hypertrophy may have different mechanisms in terms of normal total kidney volume, transient elevation of plasma HGF followed by normal plasma HGF, and normal plasma HGF/TGF-β1 ratio. These data also suggest a common mechanism (HGF) for initial renal hypertrophy (as in compensatory renal growth), with dysregulation of control of this process later in the course (as in biliary atresia). The detailed mechanisms for nephromegaly in these two conditions should be further clarified.