Ciliopathies and the Kidney: A Review

Am J Kidney Dis. 2021 Mar;77(3):410-419. doi: 10.1053/j.ajkd.2020.08.012. Epub 2020 Oct 9.

Abstract

Primary cilia are specialized sensory organelles that protrude from the apical surface of most cell types. During the past 2 decades, they have been found to play important roles in tissue development and signal transduction, with mutations in ciliary-associated proteins resulting in a group of diseases collectively known as ciliopathies. Many of these mutations manifest as renal ciliopathies, characterized by kidney dysfunction resulting from aberrant cilia or ciliary functions. This group of overlapping and genetically heterogeneous diseases includes polycystic kidney disease, nephronophthisis, and Bardet-Biedl syndrome as the main focus of this review. Renal ciliopathies are characterized by the presence of kidney cysts that develop due to uncontrolled epithelial cell proliferation, growth, and polarity, downstream of dysregulated ciliary-dependent signaling. Due to cystic-associated kidney injury and systemic inflammation, cases result in kidney failure requiring dialysis and transplantation. Of the handful of pharmacologic treatments available, none are curative. It is important to determine the molecular mechanisms that underlie the involvement of the primary cilium in cyst initiation, expansion, and progression for the development of novel and efficacious treatments. This review updates research progress in defining key genes and molecules central to ciliogenesis and renal ciliopathies.

Keywords: BBSome; Bardet-Biedl syndrome (BBS); Joubert syndrome; Meckel-Gruber syndrome (MKS); Primary cilia; Senior-Loken syndrome (SLS); ciliary signaling; fibrocystin; kidney failure; nephronophthisis (NPHP); polycystic kidney disease (PKD); polycystins; renal ciliopathy; renal cystogenesis; review.

Publication types

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

MeSH terms

  • Abnormalities, Multiple / genetics
  • Abnormalities, Multiple / metabolism
  • Abnormalities, Multiple / physiopathology
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Vesicular Transport / genetics
  • Bardet-Biedl Syndrome / genetics*
  • Bardet-Biedl Syndrome / metabolism
  • Bardet-Biedl Syndrome / physiopathology
  • Cerebellum / abnormalities
  • Cerebellum / metabolism
  • Cerebellum / physiopathology
  • Chaperonins / genetics
  • Cilia / metabolism*
  • Cilia / physiology
  • Ciliary Motility Disorders / genetics
  • Ciliary Motility Disorders / metabolism
  • Ciliary Motility Disorders / physiopathology
  • Ciliopathies / genetics*
  • Ciliopathies / metabolism
  • Ciliopathies / physiopathology
  • Cytoskeletal Proteins / genetics
  • Encephalocele / genetics
  • Encephalocele / metabolism
  • Encephalocele / physiopathology
  • Eye Abnormalities / genetics
  • Eye Abnormalities / metabolism
  • Eye Abnormalities / physiopathology
  • Humans
  • Kidney Diseases, Cystic / genetics
  • Kidney Diseases, Cystic / metabolism
  • Kidney Diseases, Cystic / physiopathology
  • Leber Congenital Amaurosis / genetics
  • Leber Congenital Amaurosis / metabolism
  • Leber Congenital Amaurosis / physiopathology
  • Membrane Proteins / genetics
  • Microtubule-Associated Proteins / genetics
  • Optic Atrophies, Hereditary / genetics
  • Optic Atrophies, Hereditary / metabolism
  • Optic Atrophies, Hereditary / physiopathology
  • Polycystic Kidney Diseases / genetics*
  • Polycystic Kidney Diseases / metabolism
  • Polycystic Kidney Diseases / physiopathology
  • Proteins / genetics
  • Retina / abnormalities
  • Retina / metabolism
  • Retina / physiopathology
  • Retinitis Pigmentosa / genetics
  • Retinitis Pigmentosa / metabolism
  • Retinitis Pigmentosa / physiopathology
  • TRPP Cation Channels / genetics

Substances

  • AHI1 protein, human
  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport
  • BBS10 protein, human
  • Bbs1 protein, human
  • Bbs2 protein, human
  • Cytoskeletal Proteins
  • MKS1 protein, human
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • NPHP1 protein, human
  • Proteins
  • TMEM216 protein, human
  • TMEM67 protein, human
  • TRPP Cation Channels
  • polycystic kidney disease 1 protein
  • polycystic kidney disease 2 protein
  • Chaperonins

Supplementary concepts

  • Agenesis of Cerebellar Vermis
  • Meckel syndrome type 1
  • Senior Loken Syndrome