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Peer-reviewedCC BY-NC-ND 4.0Kidney Medicine

Kidney Pathology of Megalin Deficiency in Adulthood

  • Alexis Cassard1
  • Magali Colombat2,3
  • Thomas Perier1,2
  • Joost Schanstra3,4
  • Stanislas Faguer1,3,4
4 affiliations
  1. 1Department of Nephrology and Organ Transplantation, National Reference Centre for Rare Kidney Diseases and European Rare Kidney Diseases Network, University Hospital of Toulouse, France
  2. 2Department of Pathology, University Institute for Cancer of Toulouse-Oncopole, University Hospital of Toulouse, France
  3. 3University of Toulouse, Toulouse, France
  4. 4Unit 1297, National Institute of Health and Medical Research, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France
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Abstract

Megalin belongs to the large low-density lipoprotein receptor--related protein subfamily and is pivotal in the tubular reabsorption of low-molecular-weight proteins freely filtered through the glomerular filter. Megalin deficiency is an ultrarare inherited disease (faciooculoacousticorenal or Donnay-Barrow syndrome) mostly diagnosed in childhood. In this study, we report an exceptional case of biallelic mutations in LRP2, the gene encoding the endocytic receptor megalin, diagnosed in a 51-year-old woman and characterized by chronic kidney disease (CKD) with incomplete proximal tubule dysfunction, moderate sensorineural hearing loss, severe myopia, and convergent strabismus. Kidney biopsy showed mild interstitial fibrosis with tubular atrophy but severe glomerulosclerosis. Other causes of CKD were ruled out. This case highlights the following aspects: (1) although megalin is mainly recognized as a key factor of proximal tubule physiology, megalin deficiency was associated with predominantly glomerular scarring lesions in humans, promoting slowly progressive CKD similar to mouse models; (2) megalin can contribute to podocyte physiology; and (3) LRP2 should be included in kidney gene panels for the evaluation of nephropathy of unknown origin, even in adulthood.

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Cite

BibTeXRIS
BibTeX
@article{cassard2026kidney,
  title = {{Kidney Pathology of Megalin Deficiency in Adulthood}},
  author = {Alexis Cassard and Magali Colombat and Thomas Perier and Joost Schanstra and Stanislas Faguer},
  journal = {Kidney Medicine},
  year = {2026},
  month = sep,
  doi = {10.1016/j.xkme.2026.101533},
  url = {https://doi.org/10.1016/j.xkme.2026.101533},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Kidney Pathology of Megalin Deficiency in Adulthood
AU  - Alexis Cassard
AU  - Magali Colombat
AU  - Thomas Perier
AU  - Joost Schanstra
AU  - Stanislas Faguer
PY  - 2026
DA  - 2026/09/12
JO  - Kidney Medicine
DO  - 10.1016/j.xkme.2026.101533
UR  - https://doi.org/10.1016/j.xkme.2026.101533
AB  - Megalin belongs to the large low-density lipoprotein receptor--related protein subfamily and is pivotal in the tubular reabsorption of low-molecular-weight proteins freely filtered through the glomerular filter. Megalin deficiency is an ultrarare inherited disease (faciooculoacousticorenal or Donnay-Barrow syndrome) mostly diagnosed in childhood. In this study, we report an exceptional case of biallelic mutations in LRP2, the gene encoding the endocytic receptor megalin, diagnosed in a 51-year-old woman and characterized by chronic kidney disease (CKD) with incomplete proximal tubule dysfunction, moderate sensorineural hearing loss, severe myopia, and convergent strabismus. Kidney biopsy showed mild interstitial fibrosis with tubular atrophy but severe glomerulosclerosis. Other causes of CKD were ruled out. This case highlights the following aspects: (1) although megalin is mainly recognized as a key factor of proximal tubule physiology, megalin deficiency was associated with predominantly glomerular scarring lesions in humans, promoting slowly progressive CKD similar to mouse models; (2) megalin can contribute to podocyte physiology; and (3) LRP2 should be included in kidney gene panels for the evaluation of nephropathy of unknown origin, even in adulthood.
SN  - 2590-0595
ER  -