[Cystic kidney disease--genetics, pathogenesis and clinical aspects in children]

This paper reviews recent studies producing insight into genetics and cellular abnormalities causing kidney cysts, their growth and development. Clinical features of various cystic kidney diseases in our patients are described. Special attention has been paid to those rarely reported in our literature. Important discovery concerns location of the gene for autosomal dominant polycystic kidney disease (ADPKD) 1 and 2 on the short arms of chromosome 16 and 4 respectively, as well as for autosomal recessive polycystic kidney disease (ARPKD) on chromosome 6 and for juvenile nephronophtisis on the short arm of chromosome 2. Two basic abnormalities necessary for cyst formation are increased: epithelial cell proliferation and altered fluid transport. Mitogenic action of epidermal growth factor (EGF) is significantly increased and EGF receptors have been demonstrated on apical as well as on basal surface of cyst lining epithelium. TGF-beta shows marked loos of inhibitory activity with regard to EGF. Cystic epithelium has altered polarity; Na-K-ATP-ase is located exclusively on the apical cell membrane. Tubular basement membrane shows alteration in structural components. Complex medullar cystic disease--nephronophtisis, complex as well as the hepatorenal complex of nephoronophtisis--congenital hepatic fibrosis are emphasized in this paper. The later has proved to be rather frequent in our population. We described a distinctive variant of hepato-renal disorder in 4 patients and reviewed 5 similar patients in the literature. The main characteristics are progressive tubulointerstitial nephritis and cholestatic liver disease. We strongly suggest that this variant represents a new syndrome (Popović-Rolović M, Kostić M, Sindić M. et al Progressive tubulointerstitialnephritis and chronic cholestatic liver disease.