The importance of the thick ascending limb of Henle&amp;rsquo;s loop in renal physiology and pathophysiology

Zacchia, Miriam; Capolongo, Giovanna; Rinaldi, Luca; Capasso, Giovambattista

doi:10.2147/ijnrd.s154000

Cited by 21 publications

(24 citation statements)

References 115 publications

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“…60% of patients showed hypercalciuria in the absence of hypercalcemia. In adults, the mean maximal urine osmolality was 669 mOsm/kg, with 50% showing a defective ability to concentrate the urine, defined as a urine osmolality < 750 mOsm/kg (an arbitrary cut-off based on the literature) [25,26]. After overnight fasting, urine pH was > 6.5 in 20% of the patients analyzed, and > 80% of patients had a urine α 1microglobulin concentration > 15 mg/g creatinine, indicating defective tubular reabsorption.…”

Section: Renal and Tubular Functionmentioning

confidence: 99%

Urinary Metabolic Profile of Patients with Transfusion-Dependent β-Thalassemia Major Undergoing Deferasirox Therapy

Capolongo

Zacchia

Beneduci

et al. 2020

Kidney Blood Press Res

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Introduction: Renal dysfunction is a frequent complication in patients suffering from β-thalassemia major (β-TM). The aim of this study was to analyze the renal function and urine metabolomic profile of β-TM patients undergoing transfusions and deferasirox (DFX) therapy, in order to better characterize and shed light on the pathogenesis of renal disease in this setting. Methods and Subjects: 40 patients affected by β-TM treated with DFX and 35 age-and gender-matched healthy controls were enrolled in the study. Renal function was assessed. Glomerular filtration rate (GFR) was estimated with CKD-EPI and Schwartz formula for adults and children, respectively. Renal tubular function and maximal urine concentration ability were tested. Urine specimens were analyzed by nuclear magnetic resonance spectroscopy to identify the urinary metabolite profiles. Results: The study of renal function in β-TM patients revealed normal estimated (e)GFR mean values and the albumin-to-creatinine ratio was < 30 mg/g. The analysis of tubular function showed normal basal plasma electrolyte levels; 60% of patients presented hypercalciuria and many subjects showed defective urine concentration. Several amino acids, N-methyl compounds, and organic acids were overexcreted in the urine of thalassemic patients compared with controls. Discussion: The major finding of this work is that β-TM patients and controls exhibit different concentrations of some metabolites in the urine. Early recognition of urinary abnormalities may be useful to detect and prevent kidney damage.

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Section: Renal and Tubular Functionmentioning

confidence: 99%

Urinary Metabolic Profile of Patients with Transfusion-Dependent β-Thalassemia Major Undergoing Deferasirox Therapy

Capolongo

Zacchia

Beneduci

et al. 2020

Kidney Blood Press Res

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“…In the first part of this section, we will discuss racial differences in Na ϩ handling by thick ascending limbs, whereas in the second part we will discuss a wide spectrum of mutations in thick ascending limb genes causing a multitude of symptoms, including hypertension, hypotension, and salt waste (321,415,626,635,637,645,766).…”

Section: Human Hypertensionmentioning

confidence: 99%

Thick Ascending Limb Sodium Transport in the Pathogenesis of Hypertension

Gonzalez‐Vicente

Sáez

Monzón

et al. 2019

Physiological Reviews

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The thick ascending limb plays a key role in maintaining water and electrolyte balance. The importance of this segment in regulating blood pressure is evidenced by the effect of loop diuretics or local genetic defects on this parameter. Hormones and factors produced by thick ascending limbs have both autocrine and paracrine effects, which can extend prohypertensive signaling to other structures of the nephron. In this review, we discuss the role of the thick ascending limb in the development of hypertension, not as a sole participant, but one that works within the rich biological context of the renal medulla. We first provide an overview of the basic physiology of the segment and the anatomical considerations necessary to understand its relationship with other renal structures. We explore the physiopathological changes in thick ascending limbs occurring in both genetic and induced animal models of hypertension. We then discuss the racial differences and genetic defects that affect blood pressure in humans through changes in thick ascending limb transport rates. Throughout the text, we scrutinize methodologies and discuss the limitations of research techniques that, when overlooked, can lead investigators to make erroneous conclusions. Thus, in addition to advancing an understanding of the basic mechanisms of physiology, the ultimate goal of this work is to understand our research tools, to make better use of them, and to contextualize research data. Future advances in renal hypertension research will require not only collection of new experimental data, but also integration of our current knowledge.

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“…The loop of Henle is a peculiar nephron site with a characteristic anatomic configuration and specific properties. In normal subjects, the TAL reabsorbs 25–30% of filtered NaCl and plays a crucial role in calcium (Ca 2+ ) reabsorption and urine concentration [18,19,20].…”

Section: The Role Of Erk12 Signalling Along the Thick Ascending Lmentioning

confidence: 99%

ERK1,2 Signalling Pathway along the Nephron and Its Role in Acid-base and Electrolytes Balance

Capolongo

Suzumoto

D’Acierno

et al. 2019

IJMS

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Mitogen-activated protein kinases (MAPKs) are intracellular molecules regulating a wide range of cellular functions, including proliferation, differentiation, apoptosis, cytoskeleton remodeling and cytokine production. MAPK activity has been shown in normal kidney, and its over-activation has been demonstrated in several renal diseases. The extracellular signal-regulated protein kinases (ERK 1,2) signalling pathway is the first described MAPK signaling. Intensive investigations have demonstrated that it participates in the regulation of ureteric bud branching, a fundamental process in establishing final nephron number; in addition, it is also involved in the differentiation of the nephrogenic mesenchyme, indicating a key role in mammalian kidney embryonic development. In the present manuscript, we show that ERK1,2 signalling mediates several cellular functions also in mature kidney, describing its role along the nephron and demonstrating whether it contributes to the regulation of ion channels and transporters implicated in acid-base and electrolytes homeostasis.

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The importance of the thick ascending limb of Henle’s loop in renal physiology and pathophysiology

Cited by 21 publications

References 115 publications

Urinary Metabolic Profile of Patients with Transfusion-Dependent β-Thalassemia Major Undergoing Deferasirox Therapy

Urinary Metabolic Profile of Patients with Transfusion-Dependent β-Thalassemia Major Undergoing Deferasirox Therapy

Thick Ascending Limb Sodium Transport in the Pathogenesis of Hypertension

ERK1,2 Signalling Pathway along the Nephron and Its Role in Acid-base and Electrolytes Balance

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