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Nephronophthisis: a pathological and genetic perspective.

Authors :
Wolf, Matthias T. F.
Bonsib, Stephen M.
Larsen, Christopher P.
Hildebrandt, Friedhelm
Source :
Pediatric Nephrology. Jul2024, Vol. 39 Issue 7, p1977-2000. 24p.
Publication Year :
2024

Abstract

Nephronophthisis (NPHP) is an autosomal recessive cystic kidney disease and is one of the most frequent genetic causes for kidney failure (KF) in children and adolescents. Over 20 genes cause NPHP and over 90 genes contribute to renal ciliopathies often involving multiple organs. About 15–20% of NPHP patients have additional extrarenal symptoms affecting other organs than the kidneys. The involvement of additional organ systems in syndromic forms of NPHP is explained by shared expression of most NPHP gene products in centrosomes and primary cilia, a sensory organelle present in most mammalian cells. This finding resulted in the classification of NPHP as a ciliopathy. If extrarenal symptoms are present in addition to NPHP, these disorders are defined as NPHP-related ciliopathies (NPHP-RC) and can involve the retina (e.g., with Senior-Løken syndrome), CNS (central nervous system) (e.g., with Joubert syndrome), liver (e.g., Boichis and Arima syndromes), or bone (e.g., Mainzer-Saldino and Sensenbrenner syndromes). This review focuses on the pathological findings and the recent genetic advances in NPHP and NPHP-RC. Different mechanisms and signaling pathways are involved in NPHP ranging from planar cell polarity, sonic hedgehog signaling (Shh), DNA damage response pathway, Hippo, mTOR, and cAMP signaling. A number of therapeutic interventions appear to be promising, ranging from vasopressin receptor 2 antagonists such as tolvaptan, cyclin-dependent kinase inhibitors such as roscovitine, Hh agonists such as purmorphamine, and mTOR inhibitors such as rapamycin. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
0931041X
Volume :
39
Issue :
7
Database :
Academic Search Index
Journal :
Pediatric Nephrology
Publication Type :
Academic Journal
Accession number :
177623333
Full Text :
https://doi.org/10.1007/s00467-023-06174-8