Polycystic kidney disease

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Abstract

Cystic kidneys are common causes of end-stage renal disease, both in children and in adults. Autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) are cilia-related disorders and the two main forms of monogenic cystic kidney diseases. ADPKD is a common disease that mostly presents in adults, whereas ARPKD is a rarer and often more severe form of polycystic kidney disease (PKD) that usually presents perinatally or in early childhood. Cell biological and clinical research approaches have expanded our knowledge of the pathogenesis of ADPKD and ARPKD and revealed some mechanistic overlap between them. A reduced ‘dosage’ of PKD proteins is thought to disturb cell homeostasis and converging signalling pathways, such as Ca2+, cAMP, mechanistic target of rapamycin, WNT, vascular endothelial growth factor and Hippo signalling, and could explain the more severe clinical course in some patients with PKD. Genetic diagnosis might benefit families and improve the clinical management of patients, which might be enhanced even further with emerging therapeutic options. However, many important questions about the pathogenesis of PKD remain. In this Primer, we provide an overview of the current knowledge of PKD and its treatment.

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Fig. 1: Renal and extrarenal manifestations in polycystic kidney disease.
Fig. 2: Domain organization of proteins implicated in polycystic kidney disease.
Fig. 3: The dosage model of cystogenesis in autosomal dominant polycystic kidney disease.
Fig. 4: Mechanisms of cyst formation and expansion.
Fig. 5: Renal fibrosis in autosomal dominant polycystic kidney disease.
Fig. 6: Hepatobiliary lesions in hepatorenal disease.
Fig. 7: Diagnosis of autosomal dominant polycystic kidney disease using different imaging techniques.
Fig. 8: Diagnosis of autosomal recessive polycystic kidney disease using MRI.

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Acknowledgements

C.B. receives research support for his laboratory from the Deutsche Forschungsgemeinschaft (DFG) Collaborative Research Centre (SFB) KIDGEM 1140 and the Federal Ministry of Education and Research (BMBF, 01GM1515C). L.M.G.-W. is supported by US National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) funding of the University of Alabama–Birmingham Hepato-Renal Fibrocystic Disease Core Center (DK074038). D.J.M.P. receives financial support from the Dutch Kidney Foundation and the Netherlands Organisation for Scientific Research. S.H. is supported by the Japan Society for the Promotion of Science KAKENHI grant number JP15K10632. P.C.H. and V.E.T. are supported by NIDDK funding of the Mayo Translational Polycystic Kidney Disease Center (DK090728). The authors thank J. Smith, T. Kline and M. Edwards (all at the Mayo Clinic, MN, USA) for their assistance with figures 1 and 7.

Reviewer information

Nature Reviews Disease Primers thanks J. Calvet and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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Introduction (C.B.); Epidemiology (S.H.); Mechanisms/pathophysiology (D.J.M.P. and L.M.G.-W.); Diagnosis, screening and prevention (P.C.H. and C.B.); Management (V.E.T.); Quality of life (S.H.); Outlook (P.C.H.); Overview of Primer (C.B.).

Correspondence to Carsten Bergmann.

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C.B. is an employee of Bioscientia/Sonic Healthcare and holds a part-time faculty appointment at the University of Freiburg, Germany.

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Related links

ADPKD Mutation Database (PKDB): http://pkdb.mayo.edu/

Genome aggregation database (gnomAD): http://gnomad.broadinstitute.org/

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