The proximal tubule and albuminuria: Really!

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

Research output: Contribution to journalReview article

132 Scopus citations

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

ASJC Scopus subject areas

  • Nephrology

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