Polycystic kidney diseases (PKD) are the most common
hereditary diseases of the human kidney and account for ten per cent of patients requiring
renal transplantation or dialysis. Renal
cyst formation has been attributed to enhanced cell proliferation, unbalanced cell death, abnormal targeting of
membrane proteins, aberrant kidney development and tubular obstruction, but there is no treatment that blocks the formation and enlargement of renal
cysts. We have now developed an in vitro model of spontaneous
cyst formation that distinguishes
polycystic kidney epithelium from its normal counterpart. Inhibitors of
DNA,
RNA and
protein synthesis did not prevent in vitro
cyst formation, but this was reversibly inhibited by
ouabain,
amiloride and the microtubule-specific agents
colchicine,
vinblastine and
taxol. The cpk mouse is a well-characterized recessive PKD model and we find that cpk/cpk mice develop PKD and die from uraemia by 4-5 weeks of age, but when treated weekly with
taxol they survive for more than 200 days with minimal loss of renal function, show limited collecting-dust
cyst enlargement, and attain adult size. Our results indicate that the microtubule cytoskeleton has a central role in the pathogenesis of PKD in cpk mice and that
taxol may also be useful in treating human PKD.