Cargando…

Albumin uptake and processing by the proximal tubule: physiological, pathological, and therapeutic implications

For nearly 50 years the proximal tubule (PT) has been known to reabsorb, process, and either catabolize or transcytose albumin from the glomerular filtrate. Innovative techniques and approaches have provided insights into these processes. Several genetic diseases, nonselective PT cell defects, chron...

Descripción completa

Detalles Bibliográficos
Autores principales: Molitoris, Bruce A., Sandoval, Ruben M., Yadav, Shiv Pratap S., Wagner, Mark C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Physiological Society 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9255719/
https://www.ncbi.nlm.nih.gov/pubmed/35378997
http://dx.doi.org/10.1152/physrev.00014.2021
_version_ 1784740974501560320
author Molitoris, Bruce A.
Sandoval, Ruben M.
Yadav, Shiv Pratap S.
Wagner, Mark C.
author_facet Molitoris, Bruce A.
Sandoval, Ruben M.
Yadav, Shiv Pratap S.
Wagner, Mark C.
author_sort Molitoris, Bruce A.
collection PubMed
description For nearly 50 years the proximal tubule (PT) has been known to reabsorb, process, and either catabolize or transcytose albumin from the glomerular filtrate. Innovative techniques and approaches have provided insights into these processes. Several genetic diseases, nonselective PT cell defects, chronic kidney disease (CKD), and acute PT injury lead to significant albuminuria, reaching nephrotic range. Albumin is also known to stimulate PT injury cascades. Thus, the mechanisms of albumin reabsorption, catabolism, and transcytosis are being reexamined with the use of techniques that allow for novel molecular and cellular discoveries. Megalin, a scavenger receptor, cubilin, amnionless, and Dab2 form a nonselective multireceptor complex that mediates albumin binding and uptake and directs proteins for lysosomal degradation after endocytosis. Albumin transcytosis is mediated by a pH-dependent binding affinity to the neonatal Fc receptor (FcRn) in the endosomal compartments. This reclamation pathway rescues albumin from urinary losses and cellular catabolism, extending its serum half-life. Albumin that has been altered by oxidation, glycation, or carbamylation or because of other bound ligands that do not bind to FcRn traffics to the lysosome. This molecular sorting mechanism reclaims physiological albumin and eliminates potentially toxic albumin. The clinical importance of PT albumin metabolism has also increased as albumin is now being used to bind therapeutic agents to extend their half-life and minimize filtration and kidney injury. The purpose of this review is to update and integrate evolving information regarding the reabsorption and processing of albumin by proximal tubule cells including discussion of genetic disorders and therapeutic considerations.
format Online
Article
Text
id pubmed-9255719
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher American Physiological Society
record_format MEDLINE/PubMed
spelling pubmed-92557192022-07-18 Albumin uptake and processing by the proximal tubule: physiological, pathological, and therapeutic implications Molitoris, Bruce A. Sandoval, Ruben M. Yadav, Shiv Pratap S. Wagner, Mark C. Physiol Rev Review For nearly 50 years the proximal tubule (PT) has been known to reabsorb, process, and either catabolize or transcytose albumin from the glomerular filtrate. Innovative techniques and approaches have provided insights into these processes. Several genetic diseases, nonselective PT cell defects, chronic kidney disease (CKD), and acute PT injury lead to significant albuminuria, reaching nephrotic range. Albumin is also known to stimulate PT injury cascades. Thus, the mechanisms of albumin reabsorption, catabolism, and transcytosis are being reexamined with the use of techniques that allow for novel molecular and cellular discoveries. Megalin, a scavenger receptor, cubilin, amnionless, and Dab2 form a nonselective multireceptor complex that mediates albumin binding and uptake and directs proteins for lysosomal degradation after endocytosis. Albumin transcytosis is mediated by a pH-dependent binding affinity to the neonatal Fc receptor (FcRn) in the endosomal compartments. This reclamation pathway rescues albumin from urinary losses and cellular catabolism, extending its serum half-life. Albumin that has been altered by oxidation, glycation, or carbamylation or because of other bound ligands that do not bind to FcRn traffics to the lysosome. This molecular sorting mechanism reclaims physiological albumin and eliminates potentially toxic albumin. The clinical importance of PT albumin metabolism has also increased as albumin is now being used to bind therapeutic agents to extend their half-life and minimize filtration and kidney injury. The purpose of this review is to update and integrate evolving information regarding the reabsorption and processing of albumin by proximal tubule cells including discussion of genetic disorders and therapeutic considerations. American Physiological Society 2022-10-01 2022-04-04 /pmc/articles/PMC9255719/ /pubmed/35378997 http://dx.doi.org/10.1152/physrev.00014.2021 Text en Copyright © 2022 The Authors https://creativecommons.org/licenses/by/4.0/Licensed under Creative Commons Attribution CC-BY 4.0 (https://creativecommons.org/licenses/by/4.0/) . Published by the American Physiological Society.
spellingShingle Review
Molitoris, Bruce A.
Sandoval, Ruben M.
Yadav, Shiv Pratap S.
Wagner, Mark C.
Albumin uptake and processing by the proximal tubule: physiological, pathological, and therapeutic implications
title Albumin uptake and processing by the proximal tubule: physiological, pathological, and therapeutic implications
title_full Albumin uptake and processing by the proximal tubule: physiological, pathological, and therapeutic implications
title_fullStr Albumin uptake and processing by the proximal tubule: physiological, pathological, and therapeutic implications
title_full_unstemmed Albumin uptake and processing by the proximal tubule: physiological, pathological, and therapeutic implications
title_short Albumin uptake and processing by the proximal tubule: physiological, pathological, and therapeutic implications
title_sort albumin uptake and processing by the proximal tubule: physiological, pathological, and therapeutic implications
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9255719/
https://www.ncbi.nlm.nih.gov/pubmed/35378997
http://dx.doi.org/10.1152/physrev.00014.2021
work_keys_str_mv AT molitorisbrucea albuminuptakeandprocessingbytheproximaltubulephysiologicalpathologicalandtherapeuticimplications
AT sandovalrubenm albuminuptakeandprocessingbytheproximaltubulephysiologicalpathologicalandtherapeuticimplications
AT yadavshivprataps albuminuptakeandprocessingbytheproximaltubulephysiologicalpathologicalandtherapeuticimplications
AT wagnermarkc albuminuptakeandprocessingbytheproximaltubulephysiologicalpathologicalandtherapeuticimplications