PROLIFERATIVE ACTIVITY OF CYST EPITHELIUM IN HUMAN RENAL CYSTIC DISEASES

Increased proliferative activity of the renal tubular epithelium is th ought to be a prerequisite for renal cyst formation by many investigat ors. However, in humans, the exact in vivo proliferation rate of epith elial cells lining these cysts is not known. In this study, which used immunohistochemical methods with an antibody to proliferating cell nu clear antigen (PCNA), the proliferation index (PI) (percentage of PCNA positive cell nuclei among epithelial cells lining the renal cysts) w as determined in 10 cases of autosomal dominant polycystic kidney dise ase (ADPKD), 8 cases of autosomal recessive polycystic kidney disease (ARPKD), and 8 cases of acquired cystic kidney disease (ACKD). Cysts w ith proximal and distal nephron phenotype and cysts with markedly thic kened basement membranes, as well as cysts lined by atrophic (flattene d), ''regular'' (cuboidal or cylindrical), and hyperplastic epithelium , were evaluated separately. The overall PI of cyst epithelium (exclud ing hyperplastic cysts) was 2.58 in ADPKD, was 10.5 in ARPKD, and was 3.61 in ACKD. Overall, there were only minor differences in the PI bet ween the various types of cysts. Cysts with hyperplastic epithelium in ACKD (unlike in ADPKD) showed a high PI (9.1). For comparison, the PI of two renal cell carcinomas occurring in two ACKD cases was also det ermined (13.70 and 8.67%). The PI of tubular epithelium in normal kidn eys was only 0.22 to 0.33%, depending on the tubule segment. In contra st, in polycystic kidneys, those noncystic segments of the nephron fro m which the cysts are thought to originate (distal nephron (specifical ly collecting duct)) in ARPKD, primarily distal in ADPKD, proximal and distal in ACKD) had PI values similar to those of the cyst epithelium . In summary, these results suggest that (1) increased renal tubular e pithelial cell proliferation might precede cyst formation; and/or that (2) increased epithelial cell proliferation by itself may not be suff icient for cyst formation to occur. Hyperplastic renal cyst epithelium may be a precursor of renal epithelial neoplasia in ACKD.