Glomerular filtration rate dependence of sieving of albumin and some neutral proteins in rat kidneys

Lund, Ulla; Rippe, Anna; Venturoli, Daniele; Tenstad, Olav; Grubb, Anders; Rippe, Bengt

doi:10.1152/ajprenal.00316.2002

Cited by 116 publications

(183 citation statements)

References 37 publications

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“…Nevertheless, filtration-dependent potentials likely are also generated in the mammalian kidney. (1) In an isolated perfused mammalian kidney, the sieving coefficient of albumin was observed to depend inversely on filtration pressures, 19 which is consistent with a filtration-dependent potential difference in our model. (2) Other experiments in isolated perfused mammalian kidneys are also consistent with our hypothesis.…”

supporting

confidence: 86%

Electrical Forces Determine Glomerular Permeability

Hausmann

Kuppe

Egger

et al. 2010

Journal of the American Society of Nephrology

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supporting

confidence: 86%

Electrical Forces Determine Glomerular Permeability

Hausmann

Kuppe

Egger

et al. 2010

Journal of the American Society of Nephrology

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“…[33][34][35][36][37][38] This has been attributed to the charge barrier and size selectivity at the glomerular filtration barrier. Previous in vivo rat filtration studies and noninvasive studies using isolated perfused rat kidneys showed a much higher GSC of albumin using [ 3 H]albumin.…”

Section: Importance Of Ptc Albumin Reabsorptionmentioning

confidence: 99%

The Proximal Tubule and Albuminuria

Dickson

Wagner

Sandoval

et al. 2014

Journal of the American Society of Nephrology

229

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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“…For this reason, protein bound Ca is not filterable during the renal filtration process. In addition, serum protein induced by IGF-1 can affect the permeability of filtering membrane in kidney (Lund et al 2003;Rippe 2004). Thus, filtering ability may be affected and consequently Ca filtration is altered.…”

Section: Resultsmentioning

confidence: 99%

A Theoretical Modeling for Suggesting Unique Mechanism of Adolescent Calcium Metabolism

Lee

Cho

Okos

2013

Journal of Biosystems Engineering

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Purpose: Modeling has been used for elucidating the mechanism of complex biosystems. In spite of importance and uniqueness of adolescent calcium (Ca) metabolism characterized by a threshold Ca intake, its regulatory mechanism has not been covered and even not proposed. Hence, this study aims at model-based proposing potential mechanisms regulating adolescent Ca metabolism. Methods: Two different hypothetic mechanisms were proposed. The main mechanism is conceived based on Ca-protein binding which induces renal Ca filtration, while additional mechanism assumed that active renal Ca re-absorption regulated Ca metabolism in adolescents. Mathematical models were developed to represent the proposed mechanism and simulated them whether they could produce adolescent Ca profiles in serum and urine. Results: Simulation showed that both mechanisms resulted in the unique behavior of Ca metabolism in adolescents. Based on the simulation insulin-like growth factor-1 (IGF-1) is suggested as a potential regulator because it is related to both growth, a remarkable characteristic of adolescence, and Ca metabolism including absorption and bone accretion. Then, descriptive modeling is employed to conceptualize the hypothesized mechanisms governing adolescent Ca metabolism. Conclusions: This study demonstrated that modeling is a powerful tool for elucidating an unknown mechanism by simulating potential regulatory mechanisms in adolescent Ca metabolism. It is expected that various analytic applications would be plausible in the study of biosystems, particularly with combination of experimental and modeling approaches.

show abstract

Glomerular filtration rate dependence of sieving of albumin and some neutral proteins in rat kidneys

Abstract: filtration rate dependence of sieving of albumin and some neutral proteins in rat kidneys.

Cited by 116 publications

References 37 publications

Electrical Forces Determine Glomerular Permeability

Electrical Forces Determine Glomerular Permeability

The Proximal Tubule and Albuminuria

A Theoretical Modeling for Suggesting Unique Mechanism of Adolescent Calcium Metabolism

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