uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Renal phenotypic investigations of megalin-deficient patients: novel insights into tubular proteinuria and albumin filtration
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
Show others and affiliations
2013 (English)In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 28, no 3, 585-591 p.Article in journal (Refereed) Published
Abstract [en]

Background

The reabsorption of filtered plasma proteins, hormones and vitamins by the renal proximal tubules is vital for body homeostasis. Studies of megalin-deficient mice suggest that the large multi-ligand endocytic receptor megalin plays an essential role in this process. In humans, dysfunctional megalin causes the extremely rare Donnai-Barrow/Facio-Oculo-Acustico-Renal (DB/FOAR) syndrome characterized by a characteristic and multifaceted phenotype including low-molecular-weight proteinuria. In this study, we examined the role of megalin for tubular protein reabsorption in humans through analysis of proximal tubular function in megalin-deficient patients.

Methods

Direct sequencing of the megalin-encoding gene (LRP2) was performed in a family in which three children presented with classical DB/FOAR manifestations. Renal consequences of megalin deficiency were investigated through immunohistochemical analyses of renal biopsy material and immunoblotting of urine samples.

Results

In the patients, a characteristic urinary protein profile with increased urinary excretion of vitamin D-binding protein, retinol-binding protein and albumin was associated with absence of, or reduced, proximal tubular endocytic uptake as shown by renal immunohistochemistry. In the absence of tubular uptake, urinary albumin excretion was in the micro-albuminuric range suggesting that limited amounts of albumin are filtered in human glomeruli.

Conclusions

This study demonstrated that megalin plays an essential role for human proximal tubular protein reabsorption and suggests that only limited amounts of albumin is normally filtered in the human glomeruli. Finally, we propose that the characteristic urinary protein profile of DB/FOAR patients may be utilized as a diagnostic marker of megalin dysfunction.

Place, publisher, year, edition, pages
2013. Vol. 28, no 3, 585-591 p.
National Category
Clinical Laboratory Medicine Basic Medicine
Research subject
Pathology
Identifiers
URN: urn:nbn:se:uu:diva-183402DOI: 10.1093/ndt/gfs462ISI: 000316120000015PubMedID: 23048173OAI: oai:DiVA.org:uu-183402DiVA: diva2:562661
Available from: 2012-10-25 Created: 2012-10-25 Last updated: 2017-12-07

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Authority records BETA

Frykholm, CarinaNevéus, TryggveHolmström, Gerd

Search in DiVA

By author/editor
Frykholm, CarinaNevéus, TryggveHolmström, Gerd
By organisation
Department of Immunology, Genetics and PathologyDepartment of Women's and Children's HealthOphthalmologyMolecular and Morphological Pathology
In the same journal
Nephrology, Dialysis and Transplantation
Clinical Laboratory MedicineBasic Medicine

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 687 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf