Developmental disorders in the normal formation of tubules, such as polycystic kidney diseases, can result in the formation of a tubulo-cystic epithelium (Wilson and Sherwood, 1991). The most common is autosomal recessive polycystic kidney disease (RPKD) which afflicts about 1: 1000 live births. Autosomal dominant polycystic kidney disease (ADPKD) occurs less frequently, about 1: 100,000 live births. In RPKD the cysts derive from distal collecting tubules while in ADPKD the cysts of derive from dilatations of proximal or distal segments (Baert, 1978; Faraggiana et al., 1985).

Mammalian kidneys also form cystic tubules following toxicant-induced injury. These cysts form from adult tubules and are not the result of alterations during development. We have recently found that the goldfish develops new nephrons following hexachloro-butadiene-induced (HCBD) nephrotoxicity (500 mg/kg) (Reimschuessel et al., 1990). In addition, fish exposed to a single dose of HCBD developed polycystic kidneys within 70 days. There was a massive increase in cell proliferation in the collecting ducts and collecting tubules during the regenerative response. It appears that collecting duct epithelium is the major source of new cells to repopulate the denuded tubular basement membrane. HCBD exposure (a single intraperitoneal injection) resulted in prolonged tubulo-necrosis. As the regenerating epithelium matured and differentiated it also underwent necrosis typical of the necrosis seen in the original epithelium. Large renal tubule cysts form within two months following HCBD exposure. These cysts appear to form from the epithelium that had undergone several rounds of regeneration and necrosis. Two and three year follow-up studies show that very large cysts can form.

The mechanism responsible for the formation of these cysts may be similar to that in ADPKD. Currently, ADPKD cysts are thought to form because of aberrant epithelial proliferation and fluid accumulation in proximal tubules (Wilson and Sherwood, 1991). The epithelium of the goldfish cysts has gamma-glutamyl-transpeptidase activity indicating that they are also of proximal tubule origin. The goldfish renal polycystic lesions induced by HCBD exposure may provide a useful model to investigate the mechanisms of polycystic tubule formation.

This work was funded in part by the Mayland Cancer Program/American Cancer Society Institutional, Research Grant IN-147, University of Maryland at Baltimore.

References

1.  Baert, L. 1978. Hereditary polycystic kidney disease (adult form): A microdissection study of two cases at an early stage of the disease. Kid. Int. 13:519-525.

2.  Faraggiana, T. J. Bernstein, L. Strauss, J. Chirg: Use of lectins in the study of histogenesis of renal cysts. Lab Inves. 53: 575-579.

3.  Reimschuessel, R., R.O. Bennett, E.B. May and M.M. Lipsky, 1990. Renal tubular cell regeneration, cell proliferation and chronic nephrotoxicity in the goldfish (Carassius auratus) following exposure to a single sublethal dose of hexachlorobutadiene. Diseases of Aquatic Organisms 8, 211-224. Wilson, P.D. and A.C. Sherwood. 1991. Tubulocystic epithelium. Kid. Int. 39: 450-463.