Journal article
Mechanisms of podocyte injury in genetic kidney disease
Pediatric nephrology (Berlin, West), Vol.40(5), pp.1523-1538
05/2025
DOI: 10.1007/s00467-024-06551-x
PMCID: PMC11945604
PMID: 39485497
Abstract
Glomerular diseases are a leading cause of chronic kidney disease worldwide. Both acquired and hereditary glomerulopathies frequently share a common final disease mechanism: disruption of the glomerular filtration barrier, podocyte injury, and ultimately podocyte death and detachment. Over 70 monogenic causes of proteinuric kidney disease have been identified, and most of these genes are highly expressed in podocytes, regulating key processes such as maintenance of the slit diaphragm, regulation of actin cytoskeleton remodeling, and modulation of downstream transcriptional pathways. Collectively, these are increasingly being referred to as hereditary “podocytopathies,” in which podocyte injury is the central feature driving proteinuria and kidney dysfunction. In this review, we provide an overview of the monogenic podocytopathies and discuss the molecular mechanisms by which single-gene defects lead to podocyte injury and ultimately glomerulosclerosis. We review how advances in genomic technology and a better understanding of the cell biological basis of disease have led to the development of more targeted and personalized therapeutic strategies, including an overview of small molecule and gene therapy approaches.
Details
- Title: Subtitle
- Mechanisms of podocyte injury in genetic kidney disease
- Creators
- Nina Mann - Boston Children's HospitalHua Sun - University of IowaAmar J. Majmundar - Boston Children's Hospital
- Resource Type
- Journal article
- Publication Details
- Pediatric nephrology (Berlin, West), Vol.40(5), pp.1523-1538
- DOI
- 10.1007/s00467-024-06551-x
- PMID
- 39485497
- PMCID
- PMC11945604
- NLM abbreviation
- Pediatr Nephrol
- ISSN
- 0931-041X
- eISSN
- 1432-198X
- Publisher
- SPRINGER
- Grant note
- National Institutes of Health: 1K08DK125768-01A1, 1R01DK136563, K08-DK127011 American Society of Nephrology (Norman Siegel Research Scholar Career): 81542 Manton Center for Orphan Disease Research (Junior Faculty Award)
A.J.M. is supported by the National Institutes of Health (1K08DK125768-01A1), the American Society of Nephrology (Norman Siegel Research Scholar Career Grant 81542), and the Manton Center for Orphan Disease Research (Junior Faculty Award). H.S. is supported by the National Institutes of Health (1R01DK136563). N.M. is supported by the National Institutes of Health (K08-DK127011).
- Language
- English
- Electronic publication date
- 11/01/2024
- Date published
- 05/2025
- Academic Unit
- Nephrology, Dialysis and Transplantation; Stead Family Department of Pediatrics
- Record Identifier
- 9984742660002771
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