2008 Homer W. Smith award: Insights into the pathogenesis of polycystic kidney disease from gene discovery

Research output: Contribution to journalReview articlepeer-review

47 Scopus citations


Polycystic kidney diseases (PKD) are a group of inherited disorders characterized by morbidity-associated development of renal cysts. Three forms of PKD are described here: The common, late onset, autosomal dominant PKD (ADPKD); the mainly infantile, autosomal recessive PKD (ARPKD); and the lethal, syndromic, Meckel syndrome that also includes central nervous system and digital defects. Positional cloning approaches based on genetic linkage have identified the disease genes in these disorders. Completion of the Human Genome Project, cases with atypical mutation, and animal models have greatly aided gene identification, and characterization of the disease genes has allowed establishment of molecular diagnostics. Genetic and allelic heterogeneity, plus genetic modification, underlie the significant phenotypic variability in each disorder. Positional cloning identified novel disease-associated protein families: The polycystins (ADPKD); fibrocystins (ARPKD); and meckelin. A common feature of pathogenesis in each disorder seems to be the primary cilia, implicating detection of fluid flow and the developmental process of planar cell polarity. Identifying the primary defect has contributed to our understanding of defective cellular processes and highlights potential therapeutic targets. A number of agents are now in Phase 3 trials, and many others show promise preclinically, providing hope of effective treatments for ADPKD in the foreseeable future.

Original languageEnglish (US)
Pages (from-to)1188-1198
Number of pages11
JournalJournal of the American Society of Nephrology
Issue number6
StatePublished - Jun 2009

ASJC Scopus subject areas

  • Nephrology


Dive into the research topics of '2008 Homer W. Smith award: Insights into the pathogenesis of polycystic kidney disease from gene discovery'. Together they form a unique fingerprint.

Cite this