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Urinary concentration defects and mechanisms underlying nephronophthisis

Lookup NU author(s): Dr Lorraine Eley, Professor John SayerORCiD


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The cystic kidney disease nephronophthisis (NPHP) is the commonest genetic cause of end-stage renal failure in young people and children. Histologically the disease is characterized by interstitial fibrosis, tubular atrophy with corticomedullary cyst development and disruption of the tubular basement membrane. Affected children present with polydipsia and polyuria, secondary to a urinary concentration defect, before these structural changes develop. Recently, molecular genetic advances have identified several genes mutated in NPHP, providing novel insights into its pathophysiology for the first time in decades. Here we review the normal physiological mechanisms of urinary concentration and explain, in the context of recent discoveries, the possible mechanisms underlying urinary concentration defects in patients with NPHP. The pattern of a ciliary and adherens junction subcellular localization of nephrocystin proteins is discussed. Recent animal models of cystic kidney disease and treatment with vasopressin V2 receptor antagonists are reviewed and a hypothesis regarding urinary concentration defects in NPHP is proposed. Understanding the cellular mechanisms underlying NPHP and other cystic kidney diseases will provide the rationale for therapeutic interventions in this disease. Early urinary concentration defects provide both a clue to clinical diagnosis of NPHP and potential therapeutic targets for pharmacological treatment of this condition. Copyright © 2008 S. Karger AG.

Publication metadata

Author(s): Krishnan R, Eley L, Sayer JA

Publication type: Review

Publication status: Published

Journal: Kidney and Blood Pressure Research

Year: 2008

Volume: 31

Issue: 3

Pages: 152-162

ISSN (print): 1420-4096

ISSN (electronic): 1423-0143


DOI: 10.1159/000129648

PubMed id: 18460874