Tubular handling of filtered albumin

Albumin is the most abundant circulating protein in the plasma, playing key roles in maintaining colloid pressure, transporting multiple endogenous and exogenous ligands, and contributing to antioxidant processes. 1 Merlot A.M. Kalinowski D.S. Richardson D.R. Unraveling the mysteries of serum albumin-more than just a serum protein. Front Physiol. 2014; 5: 299 Crossref PubMed Scopus (460) Google Scholar Albumin is produced by hepatocytes and delivered into the bloodstream through interaction with the neonatal crystallizable fragment receptor (FcRn). 2 Pyzik M. Rath T. Kuo T.T. et al. Hepatic FcRn regulates albumin homeostasis and susceptibility to liver injury. Proc Natl Acad Sci U S A. 2017; 114: E2862-E2871 Crossref PubMed Scopus (70) Google Scholar 3 Dylewski J.F. Haddad G. Blaine J. Exploiting the neonatal Fc receptor to treat kidney disease. Kidney Int. Published online October 27, 2023; (https://doi.org/10.1016/j.kint.2023.09.024) Abstract Full Text Full Text PDF Scopus (1) Google Scholar The catabolism of albumin occurs mostly in the endothelial cells of the muscle, skin, and liver, as well as in the proximal tubule cells of the kidney. In the latter, the classical view is that the ultrafiltered albumin is reabsorbed through clathrin-dependent endocytosis involving the megalin-cubilin-amnionless receptor complex and then undergoing lysosomal degradation and recycling as free amino acids through the basolateral membrane into the bloodstream. This canonical view on the glomerular filtration and tubular processing of albumin has been debated in the last 2 decades, triggered by technological developments and use of specific animal models and cell systems. 4 Gburek J. Konopska B. Gołąb K. Renal handling of albumin—from early findings to current concepts. Int J Mol Sci. 2021; 22: 5809 Crossref Scopus (16) Google Scholar Tubular albumin uptake: is there evidence for a quantitatively important, receptor-independent mechanism?Kidney InternationalVol. 104Issue 6PreviewThe kidney proximal tubule plays an essential role in the recovery of filtered plasma proteins, including albumin. Within the last 20 years, the molecular mechanisms responsible for the proximal tubule reabsorption of filtered albumin have been extensively explored and elucidated. These studies have documented that receptor-mediated endocytosis involving the multiligand receptors megalin and cubilin is fundamental for this process. However, the role of the receptors for the handling of albumin in renal physiology and pathology continues to be a matter of controversy. Full-Text PDF Proximal tubule role in albumin homeostasis: controversy, species differences, and the contributions of intravital microscopyKidney InternationalVol. 104Issue 6PreviewAlbuminuria is a known risk factor for the development and progression of chronic kidney disease. Glomerular disease has been shown to result in increased glomerular permeability and albuminuria, but the role of the proximal tubule (PT) in albumin homeostasis under physiologic and disease conditions remains controversial. The controversy centers around the glomerular sieving coefficient of albumin (GSCa), the percentage of albumin filtered across the glomerulus, and the ability of the PT to reabsorb and transcytose the reabsorbed albumin across the basolateral membrane for reuse (reclamation). Full-Text PDF