Contraluminal serum albumin uptake in isolated perfused renal tubules

Je, Bourdeau; Fa, Carone

doi:10.1152/ajplegacy.1973.224.2.399

Cited by 23 publications

(12 citation statements)

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“…67,73,74 In addition, the rate of apical endocytosis is many times that of basolateral endocytosis in vivo, but the two are equivalent in cell culture. 67,74,75 Therefore, one must not overinterpret cell culture data. Finally, intravenously injected albumin remains intact within the serum and is partially catabolized within PTCs.…”

Section: Endocytosis By the Ptmentioning

confidence: 99%

The Proximal Tubule and Albuminuria

Dickson

Wagner

Sandoval

et al. 2014

Journal of the American Society of Nephrology

232

227

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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 apical membrane 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. Although the importance of urinary albumin in disease progression is known, the key mechanisms mediating the presence and toxic effects of albuminuria remain to be determined. Recently, the quantitative role of the glomerular filtration barrier (GFB) and the proximal tubule (PT) cell (PTC) in the development of albuminuria has been reexamined. Different lines of evidence, from multiple investigative teams, now suggest that the filtration of albumin, under physiologic conditions, is greater than previously determined. These data suggest an increased clinical role for the PT in minimizing albuminuria through the reabsorption of albumin. Emerging data also suggest that both glomerular permeability and PTCs play fundamental, physiologic, synergistic, interactive, and dynamic roles in the renal handling of albumin. Furthermore, it appears that PTCs, especially in the S1 segment, have specific mechanisms for efficiently and effectively reabsorbing and transcytosing albumin (reclamation). Therefore, the purpose of this review is to describe the emerging data regarding PTC albumin handling and provide a framework for considering future exciting, insightful, and novel studies with direct clinical relevance.This review is not intended to debate the important role of the GFB but to emphasize that the PT should be considered important both under physiologic and pathologic conditions. We believe that glomerular or PTC defects can and do result in proteinuria. Specifically, we outline current data supporting PT uptake of albumin and mechanisms of reabsorption and transcytosis, and we propose a mechanism for intracellular sorting between degradation and transcytotic pathways based on pH-dependent binding. DYSFUNCTIONAL PTCS LE...

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Section: Endocytosis By the Ptmentioning

confidence: 99%

The Proximal Tubule and Albuminuria

Dickson

Wagner

Sandoval

et al. 2014

Journal of the American Society of Nephrology

232

227

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“…5,6) Accordingly, we suggested that the high urinary albumin excretion in rats with high P intake may arise from diminished proximal tubular function, 5,6) because most albumin reabsorption is in the proximal tubules. 14) That is, proximal tubular function is an important factor in the change in urinary albumin excretion in rats given high-P feed.…”

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confidence: 99%

Sex Differences in Kidney Mineral Concentrations and Urinary Albumin Excretion in Rats Given High-phosphorus Feed

Matsuzaki

Katsumata

Masuyama

et al. 2002

Bioscience, Biotechnology, and Biochemistry

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We examined sex diŠerences in kidney mineral concentrations and urinary albumin excretion in rats given feed containing various phosphorus (P) levels. With feed that was 0.6%, 0.9%, 1.2%, and 1.5%P, kidney calcium and P concentrations were higher in female rats than in male rats. With 1.2% or 1.5%P, urinary albumin excretion was higher in the female rats. The sex of the animal aŠected the kidney mineral concentrations and urinary albumin excretion in rats with a high P intake.

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“…Furthermore, the increase in urinary albumin excretion may be related to the proximal tubular function, since albumin reabsorption occurs mainly in the proximal tubules. 18) This study demonstrates that renal tubular injury was induced in rats fed the Mg-deˆcient diet. The results suggest that the renal tubular injury induces diminished proximal tubular function, and diminished proximal tubular function leads to an obstruction of proximal tubular albumin reabsorption.…”

Section: Kidney Function In Magnesium Deˆcient Ratsmentioning

confidence: 71%