Association between genes conditioning low renin angiotensin system activity (ras) and severe hypodysplastic congenital nephropathy.

Hypo-dysplastic renal dysgenesis, a frequent cause of chronic renal failure in childhood, can have a familial nature, suggesting a role for genetic conditioning factors. Among the many genes currently under study, a particular interest is focused on the RAS genes for their important role in nephrogenesis, as they are among the major regulators of apoptosis and cellular proliferation in the developing kidney. A previous investigation on the impact of ACE l/D gene polymorphism on congenital renal malformations (Ped Nephrol 2001) failed to prove any association, however the group of children investigated was not homogeneous, including also reflux nephropathies and other urological abnormalities. Moreover, the patients were compared with controls not matched for the geographical area of origin. Aim of this study was to investigate the polymorphisms of the genes encoding for angiotensin converting enzyme (ACE:D/l), angiotensin I receptor (ATR1 1C/A) and angiotensinogen (AGT:C/T) in a highly selected series of 19 children (15 M/4 F) with severe bilateral renal dysplasia and global renal function <50% than normal. These data show a possible association, never reported in the literature, among genotypes considered able to negatively modulate the RAS and severe renal hypodysplasia. These data are in agreement with the observations in man and in experimental models of a primary role of angiotensin ll defects in abnormal nephrogenesis, such as dysplasia in fetal kidneys due to ACE inhibitors treatment during pregnancy and severe kidney malformations in mice with deletions of the RAS genes.