The proximal tubule and albuminuria: Really!

Landon E. Dickson, Mark Wagner, Ruben M. Sandoval, Bruce Molitoris

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

Recent data highlight the role of the proximal tubule (PT) in reabsorbing, processing, and transcytosing urinary albumin from the glomerular filtrate. Innovative techniques and approaches have provided exciting insights into these processes, and numerous investigators have shown that selective PT cell defects lead to significant albuminuria, even reaching nephrotic range in animal models. Thus, the mechanisms of albumin reabsorption and transcytosis are undergoing intense study. Working in concert with megalin and cubilin, a nonselective multireceptor complex that predominantly directs proteins for lysosomal degradation, the neonatal Fc receptor (FcRn) located at the brush border of the apicalmembrane has been implicated as the "receptor" mediating albumin transcytosis. The FcRn pathway facilitates reabsorption and mediates transcytosis by its pH-dependent binding affinity in endosomal compartments. This also allows for selective albumin sorting within the PT cell. This reclamation pathway minimizes urinary losses and catabolism of albumin, thus prolonging its serum half-life. It may also serve as a molecular sorter to preserve and reclaim normal albumin while allowing "altered" albumin to be catabolized via lysosomal pathways. Here, we critically review the data supporting this novel mechanism.

Original languageEnglish
Pages (from-to)443-453
Number of pages11
JournalJournal of the American Society of Nephrology
Volume25
Issue number3
DOIs
StatePublished - Mar 2014

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Albuminuria
Albumins
Transcytosis
Albumin Receptors
Low Density Lipoprotein Receptor-Related Protein-2
Microvilli
Proteolysis
Half-Life
Animal Models
Research Personnel
Serum

ASJC Scopus subject areas

  • Nephrology

Cite this

The proximal tubule and albuminuria : Really! / Dickson, Landon E.; Wagner, Mark; Sandoval, Ruben M.; Molitoris, Bruce.

In: Journal of the American Society of Nephrology, Vol. 25, No. 3, 03.2014, p. 443-453.

Research output: Contribution to journalArticle

Dickson, Landon E. ; Wagner, Mark ; Sandoval, Ruben M. ; Molitoris, Bruce. / The proximal tubule and albuminuria : Really!. In: Journal of the American Society of Nephrology. 2014 ; Vol. 25, No. 3. pp. 443-453.
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