Thick Ascending Limb of the Loop of Henle

Mount, David B.

doi:10.2215/cjn.04480413

Cited by 140 publications

(123 citation statements)

References 106 publications

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“…A water-independent active Na + absorption along the thick ascending limb of the loop of Henle (TAL) on the outer medulla is critical for both diluting luminal fluid and accumulating electrolytes in the interstitium, leading to an osmotic disequilibrium between the lumen and the interstitium [28] . This mechanism is mediated by the furosemide-sensitive Na-K-2Cl cotransporter (NKCC2).…”

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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“…The first step in NaCl transport to the medulla is through the Na-K 1 -2Cl 2 cotransporter located in the apical membrane of the thick ascending limb of the loop of Henle cells. Loop diuretics inhibit this transporter, reducing NaCl delivered to the medulla and thereby, decreasing the medullary osmotic gradient necessary for water reabsorption in the CD and therefore, increasing free water excretion (57,58). The only clinical evidence for the efficacy of loop diuretics in the treatment of hyponatremia comes from case series, and all in combination with NaCl tablets (39,40,55,59).…”

Section: Recommended Fluidmentioning

confidence: 99%

Mild Chronic Hyponatremia in the Ambulatory Setting

Rondon‐Berrios

Berl

2015

Clinical Journal of the American Society of Nephrology

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Mild chronic hyponatremia, as defined by a persistent (>72 hours) plasma sodium concentration between 125 and 135 mEq/L without apparent symptoms, is common in ambulatory patients and generally perceived as being inconsequential. The association between increased mortality and hyponatremia in hospitalized patients in various settings and etiologies is widely recognized. This review analyzes the significance of mild chronic hyponatremia in ambulatory subjects and its effects on mortality and morbidity. It addresses whether this disorder should even be treated and if so, which patients are likely to benefit from treatment. The available approaches to correct hyponatremia in such patients in the context of recently published panel-generated recommendations and guidelines are described.

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“…For the reader who wishes additional information, the fundamentals of salt reabsorption in the distal tubule are discussed more extensively in the review by Seyberth and Schlingmann published in Pediatric Nephrology [2]. For more in-depth studies on the tubular system, the excellent Clinical Journal of the American Society of Nephrology series entitled BRenal Physiology for the Clinician^, which has just been published, is highly recommended [3][4][5][6][7][8].…”

Section: Physiology Of Salt and Water Reabsorption In The Distal Nephronmentioning

confidence: 99%

Pathophysiology and clinical presentations of salt-losing tubulopathies

Seyberth

2015

Pediatr Nephrol

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At least three renal tubular segments are involved in the pathophysiology of salt-losing tubulopathies (SLTs). Whether the pathogenesis starts either in the thick ascending limb of the loop of Henle (TAL) or in the distal convoluted tubule (DCT), it is the function of the downstream-localized aldosterone sensitive distal tubule (ASDT) to contribute to the adaptation process. In isolated TAL defects (loop disorders) ASDT adaptation is supported by upregulation of DCT, whereas in DCT disorders the ASDT is complemented by upregulation of TAL function. This upregulation has a major impact on the clinical presentation of SLT patients. Taking into account both the symptoms and signs of primary tubular defect and of the secondary reactions of adaptation, a clinical diagnosis can be made that eventually leads to an appropriate therapy. In addition to salt wasting, as occurs in all SLTs, characteristic features of loop disorders are hypo- or isosthenuric polyuria and hypercalciuria, whereas characteristics of DCT disorders are hypokalemia and (symptomatic) hypomagnesemia. In both SLT categories, replacement of urinary losses is the primary goal of treatment. In loop disorders COX inhibitors are also recommended to mitigate polyuria, and in DCT disorders magnesium supplementation is essential for effective treatment. Of note, the combination of a salt- and potassium-rich diet together with an adequate fluid intake is always the basis of long-term treatment in all SLTs.

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Thick Ascending Limb of the Loop of Henle

Cited by 140 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

Mild Chronic Hyponatremia in the Ambulatory Setting

Pathophysiology and clinical presentations of salt-losing tubulopathies

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