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NDT Advance Access originally published online on April 4, 2007
Nephrology Dialysis Transplantation 2007 22(8):2133-2135; doi:10.1093/ndt/gfm178
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© The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Prime time for polycystic kidney disease: does one shot of roscovitine bring the cure?*

E. Wolfgang Kuehn and Gerd Walz

Renal Division, University Hospital Freiburg, Hugstetter Strasse 55, 79104 Freiburg, Germany

Correspondence and offprint requests to: Gerd Walz, Renal Division, Hugstetter Strasse 55 79104 Freiburg, Germany. Email: gerd.walz@uniklinik-freiburg.de

Keywords: ADPKD; mTOR; polycystic kidney disease; roscovitine; therapy; vasopressin-2-receptor antagonists

The first 10% of the full text of this article appears below.



   Introduction
 
Autosomal dominant polycystic kidney disease (ADPKD), caused by either PKD1 or PKD2 mutations, relentlessly progresses to end-stage renal disease (ESRD) in more than half of the affected patients. Although the pathogenesis is still incompletely understood, several potential therapies are now emerging that promise to effectively prevent cyst formation and progression. In a lifelong disease, therapeutics with a long-lasting effect after a brief application appear particularly attractive. (R)-roscovitine, a protein kinase inhibitor with preferential selectivity for cyclin-dependent kinases (CDKs), may be just such a drug. A recent report demonstrates that roscovitine blocks cyst progression in two animal models of PKD, the jck (NEK8) and cpk (cystin) mouse. Roscovitine prevents phosphorylation of the retinoblastoma protein (Rb) through inhibition of CDKs, and normalizes the levels of several cyclins, thereby preventing cell proliferation. In addition, roscovitine ameliorates cyst progression, through inhibition of transcription and . . . [Full Text of this Article]



   Subjects and methods
 
The pathogenesis of polycystic kidney disease
Vasopressin-2-receptor antagonists and mTOR inhibitors
CDK inhibitors


   Discussion and conclusion
 
Can ADPKD patients benefit from CDK inhibitors?

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