Modeling Transport and Flow Regulatory Mechanisms of the Kidney

Layton, Anita T.

doi:10.5402/2012/170594

Cited by 18 publications

(14 citation statements)

References 106 publications

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“…Accordingly, hereditary disorders affecting salt absorption along the TAL, as in Bartter syndrome, result in a urine concentrating defect and are classified as secondary inherited nephrogenic diabetes insipidus [29] . The osmotic gradient generated by active NaCl absorption along the TAL is enhanced by the countercurrent anatomical arrangement of the 2 branches of the loop of Henle, rising from the corticomedullary junction to the outer-inner medullary boundary, in a process defined as countercurrent multiplication [30] . The vasa recta, paralleling the loop of Henle, operate into the countercurrent mechanism, minimizing washout of solutes from the interstitium.…”

Section: Pathophysiology Of Urine Concentration and Dilutionmentioning

confidence: 99%

The Kidney in Bardet-Biedl Syndrome: Possible Pathogenesis of Urine Concentrating Defect

et al. 2017

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Background: The ciliopathies are a growing number of disorders caused by mutations in genes involved in the function of the primary cilium. Bardet-Biedl syndrome (BBS) belongs to this group of disorders. In this setting, kidney dysfunction is highly variable, and urine concentrating defect, a common feature of multiple ciliopathies, has been described as the most frequent defect. Here we review the mechanism of urine concentration and describe the possible mechanism underling this defect in ciliopathies and especially BBS, based on the current body of literature. Summary: Active Na⁺ absorption along the thick ascending limb of the loop of Henle (TAL) is critical for generating the corticomedullary osmotic gradient, and the countercurrent anatomical arrangement of the 2 branches of the loop of Henle enhances this gradient. The vasa recta, paralleling the loop of Henle, operate into the countercurrent mechanism, minimizing washout of solutes from the interstitium. Final water reabsorption is mediated by the aquaporin 2 (AQP2) water channels along the distal nephron, and it is under hormonal control. Several studies demonstrated that hyposthenuria in BBS patients relies on kidney resistance to desmopressin, suggesting a renal origin. We recently showed that the majority of hyposthenuric BBS patients have also a defect regarding maximal urine dilution. Independent studies showed that BBS10 deficiency caused AQP2 mistrafficking in vitro; accordingly, we demonstrated impaired urinary AQP2 excretion in BBS patients with combined concentrating and diluting defect. Whether receptor signaling pathways or downstream events cause AQP2 deregulation is still unclear. In addition, reduced urinary uromodulin excretion in BBS patients opens the possibility that TAL dysfunction may also play a pathogenic role. Key Message: Impaired water handling in BBS is associated with AQP2 mistrafficking. The potential role of additional factors, such as the dissipation of the medullary osmotic gradient due to TAL dysfunction and/or structural anomalies, remains to be elucidated.

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Section: Pathophysiology Of Urine Concentration and Dilutionmentioning

confidence: 99%

The Kidney in Bardet-Biedl Syndrome: Possible Pathogenesis of Urine Concentrating Defect

et al. 2017

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“…In this study, we focused our attention on the axial concentration gradient and the FIC, previously defined in Section (2), which are significant factors in the urinary concentration mechanism, [11,12]. The axial gradient is an important determinant of urinary concentration capacity.…”

Section: Discussionmentioning

confidence: 99%

On the role of the epithelium in a model of sodium exchange in renal tubules

Marulli

Edwards

Milisic

et al. 2020

Mathematical Biosciences

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In this study we present a mathematical model describing the transport of sodium in a fluid circulating in a counter-current tubular architecture, which constitutes a simplified model of Henle's loop in a kidney nephron. The model explicitly takes into account the epithelial layer at the interface between the tubular lumen and the surrounding interstitium. In a specific range of parameters, we show that explicitly accounting for transport across the apical and basolateral membranes of epithelial cells, instead of assuming a single barrier, affects the axial concentration gradient, an essential determinant of the urinary concentrating capacity. We present the solution related to the stationary system, and we perform numerical simulations to understand the physiological behaviour of the system. We prove that when time grows large, our dynamic model converges towards the stationary system at an exponential rate. In order to prove rigorously this global asymptotic stability result, we study eigenproblems of an auxiliary linear operator and its dual. .In these equations, r i , i = 1, 2, denotes the inner radius of tubule i, whereas r i,e denotes the outer radius of tubule i, which includes the epithelial layer. The fluxes J i describe the ionic exchanges between the different domains. They are modeled in the following way:Lumen. In the lumen, we consider the diffusion of Na + towards the epithelium. Then, J 1 = 2πr 1 P 1 (q 1 − u 1 ), J 2 = 2πr 2 P 2 (q 2 − u 2 ).

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“…Further, since the cortex is highly perfused and exhibits PO 2 levels similar to other organs' (30-60 mmHg), its oxygenation has been considered unlimited. Finally, the cortical apparent disorder (cortical tubular labyrinth, entangled with the peritubular capillary network), is less amenable to geometric treatment than the highly organized medullary regions [32].Recently though, a few modeling studies of oxygen use and distribution in the renal cortex have been proposed. These MS studies follow either one of two conceptual lines: one focuses on nephron segmentation and epithelial polarity and transport, while the other ignores epithelial "details" but integrates vascular anatomical features to describe delivery and consumption all along the renal vascular tree.…”

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confidence: 99%

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A Computer Model of Oxygen Dynamics in the Cortex of the Rat Kidney at the Cell-Tissue Level

Aubert

Kaminski

Guillaud

et al. 2019

IJMS

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The renal cortex drives renal function. Hypoxia/reoxygenation are primary factors in ischemia-reperfusion (IR) injuries, but renal oxygenation per se is complex and awaits full elucidation. Few mathematical models address this issue: none captures cortical tissue heterogeneity. Using agent-based modeling, we develop the first model of cortical oxygenation at the cell-tissue level (RCM), based on first principles and careful bibliographical analysis. Entirely parameterized with Rat data, RCM is a morphometrically equivalent 2D-slice of cortical tissue, featuring peritubular capillaries (PTC), tubules and interstitium. It implements hemoglobin/O 2 binding-release, oxygen diffusion, and consumption, as well as capillary and tubular flows. Inputs are renal blood flow RBF and PO 2 feeds; output is average tissue PO 2 (tPO 2 ). After verification and sensitivity analysis, RCM was validated at steady-state (tPO 2 37.7 ± 2.2 vs. 36.9 ± 6 mmHg) and under transients (ischemic oxygen half-time: 4.5 ± 2.5 vs. 2.3 ± 0.5 s in situ). Simulations confirm that PO 2 is largely independent of RBF, except at low values. They suggest that, at least in the proximal tubule, the luminal flow dominantly contributes to oxygen delivery, while the contribution of capillaries increases under partial ischemia. Before addressing IR-induced injuries, upcoming developments include ATP production, adaptation to minutes-hours scale, and segmental and regional specification. Int. J. Mol. Sci. 2019, 20, 6246 2 of 35heterogeneities [19]. This complexity pushed physiologists to resort to mathematical modeling and computer simulation (MS), as a complement to the experimental approaches [10,[20][21][22][23].Renal oxygen distribution started to be addressed under the MS angle in the late 90's [12,20]. The AV oxygen shunt has been long hinted and its mathematical descriptions are based on careful anatomic determinations. However, its physiological relevance and quantification remain debated [23][24][25][26]. Finally, oxygen distribution within the medulla, with its countercurrent system and complex organization, has been modeled with attention and a great level of histological detail [27][28][29][30].Conversely, oxygen distribution in the cortex has been addressed only lately, in the mid-2010's. Likely, the urine concentration and NaCl reabsorption role of the medulla have somewhat eclipsed the cortex [30,31]. Further, since the cortex is highly perfused and exhibits PO 2 levels similar to other organs' (30-60 mmHg), its oxygenation has been considered unlimited. Finally, the cortical apparent disorder (cortical tubular labyrinth, entangled with the peritubular capillary network), is less amenable to geometric treatment than the highly organized medullary regions [32].Recently though, a few modeling studies of oxygen use and distribution in the renal cortex have been proposed. These MS studies follow either one of two conceptual lines: one focuses on nephron segmentation and epithelial polarity and transport, while the other ignores epithelial "details" b...

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Modeling Transport and Flow Regulatory Mechanisms of the Kidney

Cited by 18 publications

References 106 publications

The Kidney in Bardet-Biedl Syndrome: Possible Pathogenesis of Urine Concentrating Defect

The Kidney in Bardet-Biedl Syndrome: Possible Pathogenesis of Urine Concentrating Defect

On the role of the epithelium in a model of sodium exchange in renal tubules

A Computer Model of Oxygen Dynamics in the Cortex of the Rat Kidney at the Cell-Tissue Level

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