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Drugs

, Volume 64, Issue 12, pp 1285–1294 | Cite as

Recent Advances in Understanding the Pathogenesis of Polycystic Kidney Disease

Therapeutic Implications
Leading Article

Abstract

Hereditary polycystic kidney disease (PKD) is a common cause of renal failure. Increasing knowledge is available regarding mechanisms of cyst development and progression, and renal functional deterioration in PKD. On the basis of this information and theories regarding the pathophysiology of these processes, studies to alter progression and potentially treat PKD have been reported. Cyst development and progression requires epithelial cell proliferation, transepithelial fluid secretion and extracellular matrix remodelling. Several interventions designed to inhibit cell proliferation or alter fluid secretion modify the progression of PKD in selected animal models. Renal functional deterioration appears to involve interstitial inflammation and fibrosis, and tubular apoptosis. Glucocorticoids with anti-inflammatory and antifibrotic properties slow the progression of cystic disease and renal functional deterioration in animal models of PKD. Other interventions, such as dietary modification and angiotensin antagonism, shown to be of benefit in non-PKD models of slowly progressive renal disease, are also of benefit in animal models of PKD. Caution should be used in extrapolating interventional studies in one animal model to another model and certainly to human disease, since examples exist in which treatments in one model of PKD have different effects in another model. Nonetheless, early attempts to determine whether potential treatments are tolerated and of potential benefit in patients with PKD are beginning to appear. Ultimately, treatment of PKD may involve efforts to identify patients at greatest risk for disease progression, thus allowing targeted therapy, use of surrogate markers for disease progression to assist assessment of therapeutic efficacy, and combination therapy to retard disease progression and renal functional deterioration in this common hereditary cause of chronic renal failure.

Keywords

Polycystic Kidney Disease Renal Cystic Disease Dietary Protein Restriction Renal Functional Deterioration Progressive Renal Dysfunction 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

The author receives support from the University of Oklahoma Foundation as The John Gammill Chair in Polycystic Kidney Disease. Various studies discussed were supported by Baxter Healthcare, The Polycystic Kidney Foundation, The University of Kansas Medical Center Research Institute and The Presbyterian Health Foundation of Oklahoma.

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© Adis data information BV 2004

Authors and Affiliations

  1. 1.Nephrology/WP2250University of Oklahoma Health Sciences CenterOklahoma CityUSA

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