Determinants of Renal Disease Variability in ADPKD

Peter C. Harris, Sandro Rossetti

Research output: Contribution to journalReview articlepeer-review

40 Scopus citations


In common with other Mendelian diseases, the presentation and progression of autosomal dominant polycystic kidney disease (ADPKD) vary widely in the population. The typical course is of adult-onset disease with ESRD in the 6th decade. However, a small proportion has adequate renal function into the 9th decade, whereas others present with enlarged kidneys as neonates. ADPKD is genetically heterogeneous, and the disease gene is a major determinant of severity; PKD1 on average is associated with ESRD 20 years earlier than PKD2. The majority of PKD1 and PKD2 mutations are likely fully inactivating although recent studies indicate that some alleles retain partial activity (hypomorphic alleles). Homozygotes for such alleles are viable and in combination with an inactivating allele can result in early-onset disease. Hypomorphic alleles and mosaicism may also account for some cases with unusually mild disease. The degree of phenotypic variation detected in families indicates that genetic background influences disease severity. Genome-wide association studies are planned to map common variants associated with severity. Although ADPKD is a simple genetic disease, fully understanding the phenotypic variability requires consideration of influences at the genic, allelic, and genetic background level, and so, ultimately, it is complex.

Original languageEnglish (US)
Pages (from-to)131-139
Number of pages9
JournalAdvances in Chronic Kidney Disease
Issue number2
StatePublished - Mar 2010

ASJC Scopus subject areas

  • Nephrology


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