Recent advances in understanding the pathogenesis of polycystic kidney disease: therapeutic implications

Drugs. 2004;64(12):1285-94. doi: 10.2165/00003495-200464120-00002.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Polycystic Kidney Diseases / complications
  • Polycystic Kidney Diseases / genetics
  • Polycystic Kidney Diseases / physiopathology*
  • Polycystic Kidney Diseases / therapy
  • Renal Insufficiency / etiology
  • Renal Insufficiency / prevention & control
  • Risk Factors