Mechanisms of Disease: autosomal dominant and recessive polycystic kidney diseases

Nat Clin Pract Nephrol. 2006 Jan;2(1):40-55; quiz 55. doi: 10.1038/ncpneph0070.


Autosomal dominant polycystic kidney disease and autosomal recessive polycystic kidney disease are the best known of a large family of inherited diseases characterized by the development of renal cysts of tubular epithelial cell origin. Autosomal dominant and recessive polycystic kidney diseases have overlapping but distinct pathogeneses. Identification of the causative mutated genes and elucidation of the function of their encoded proteins is shedding new light on the mechanisms that underlie tubular epithelial cell differentiation. This review summarizes recent literature on the role of primary cilia, intracellular calcium homeostasis, and signaling involving Wnt, cyclic AMP and Ras/MAPK, in the pathogenesis of polycystic kidney disease. Improved understanding of pathogenesis and the availability of animal models orthologous to the human diseases provide an excellent opportunity for the development of pathophysiology-based therapies. Some of these have proven effective in preclinical studies, and clinical trials have begun.

Publication types

  • Review

MeSH terms

  • Animals
  • Calcium / physiology
  • Cell Differentiation / genetics
  • Cyclic AMP / physiology
  • Disease Models, Animal
  • Epithelial Cells / metabolism
  • Homeostasis / physiology
  • Humans
  • Kidney Concentrating Ability / physiology
  • Kidney Tubules / physiopathology
  • Mutation, Missense
  • Phosphorylation
  • Polycystic Kidney, Autosomal Dominant / genetics
  • Polycystic Kidney, Autosomal Dominant / physiopathology*
  • Polycystic Kidney, Autosomal Recessive / genetics
  • Polycystic Kidney, Autosomal Recessive / physiopathology*
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptor Protein-Tyrosine Kinases / physiology
  • Receptors, Cell Surface / metabolism
  • Receptors, Vasopressin / physiology
  • TRPP Cation Channels / metabolism
  • Transforming Growth Factor alpha / metabolism
  • Wnt Proteins / physiology
  • ras Proteins / physiology


  • PKHD1 protein, human
  • Receptors, Cell Surface
  • Receptors, Vasopressin
  • TRPP Cation Channels
  • Transforming Growth Factor alpha
  • Wnt Proteins
  • polycystic kidney disease 1 protein
  • polycystic kidney disease 2 protein
  • Cyclic AMP
  • Receptor Protein-Tyrosine Kinases
  • ras Proteins
  • Calcium