scholarly journals Pathophysiological aspects of the thick ascending limb and novel genetic defects: HELIX syndrome and transient antenatal Bartter syndrome

2021 ◽  
Author(s):  
Rosa Vargas-Poussou
Keyword(s):  
Bartter Syndrome ◽  
Genetic Defects ◽  
Thick Ascending Limb

Type-5 Bartter syndrome presenting with metabolic seizure in adulthood

2021 ◽  
Vol 14 (2) ◽  
pp. e235349
Author(s):  
Aqeel Hussain ◽  
Mahendra Atlani ◽  
Abhishek Goyal ◽  
Alkesh Kumar Khurana
Keyword(s):  
Age Of Onset ◽  
Bartter Syndrome ◽  
Electrolyte Imbalance ◽  
Thick Ascending Limb ◽  
Calcium Sensing Receptor ◽  
Inherited Disorders ◽  
Calcium Sensing ◽  
Aged Woman ◽  
Middle Aged Woman ◽  
Renal Tubular

Bartter syndrome is a very rare and heterogeneous disease with variable age of onset and symptom severity. Genotypically they have inherited disorders of the thick ascending limb in the renal tubular system, which manifest phenotypically as electrolyte imbalance due to loss of sodium, chloride and potassium. Gain of function mutations in the calcium-sensing receptor has been described in some patients with Bartter’s syndrome (type-5 Bartter syndrome or autosomal dominant hypocalcaemia with Bartter syndrome) associated with hypocalcaemia and hypercalciuria differentiating it from Gitelman syndrome. This phenotype has been reported to present in adulthood with metabolic abnormalities. We present a case of a middle-aged woman who presented with metabolic seizures and on evaluation was found to have profound electrolyte abnormalities which were corrected with supplements and led to the resolution of symptoms.

scholarly journals Neonatal Bartter syndrome: A case report from Northern India

2021 ◽  
pp. 10-14
Author(s):  
Astitva Singh ◽  
Nishant Sharma ◽  
Prachi Agarwal ◽  
Bolledu Swaroop Anand ◽  
Akshay Shukla
Keyword(s):  
Case Report ◽  
Genetic Disorder ◽  
Failure To Thrive ◽  
Bartter Syndrome ◽  
Thick Ascending Limb ◽  
Older Children ◽  
Northern India ◽  
Tubular System ◽  
Renal Tubular ◽  
Neonatal Bartter Syndrome

Abstract. Bartter Syndrome is a rare genetic disorder affecting the renal tubular system causing a decreased absorption of sodium and chloride in the thick ascending limb of the Henle loop. Most children present in infancy with complaints of polyuria, polydipsia, vomiting, constipation and failure to thrive while older children present with recurrent episodes of dehydration, muscle weakness and cramps. The present study aimed to demonstrate a case of Bartter syndrome presenting as acute gastroenteritis.

scholarly journals Thick Ascending Limb Sodium Transport in the Pathogenesis of Hypertension

2019 ◽  
Vol 99 (1) ◽  
pp. 235-309 ◽  
Author(s):  
Agustin Gonzalez-Vicente ◽  
Fara Saez ◽  
Casandra M. Monzon ◽  
Jessica Asirwatham ◽  
Jeffrey L. Garvin
Keyword(s):  
Blood Pressure ◽  
Racial Differences ◽  
Current Knowledge ◽  
Renal Hypertension ◽  
Renal Medulla ◽  
Genetic Defects ◽  
Electrolyte Balance ◽  
Thick Ascending Limb ◽  
Paracrine Effects ◽  
The Rich

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.

ROMK is required for expression of the 70-pS K channel in the thick ascending limb

2004 ◽  
Vol 286 (3) ◽  
pp. F490-F495 ◽  
Author(s):  
Ming Lu ◽  
Tong Wang ◽  
Qingshang Yan ◽  
Wenhui Wang ◽  
Gerhard Giebisch ◽  
...  
Keyword(s):  
Functional Expression ◽  
Bartter Syndrome ◽  
Salt Transport ◽  
K Channel ◽  
Thick Ascending Limb ◽  
Channel Activity ◽  
Loss Of Function ◽  
High K ◽  
Hypokalemic Alkalosis ◽  
Severe Reduction

Apical potassium recycling is crucial for salt transport by the thick ascending limb (TAL). Loss-of-function mutations in the K channel, ROMK (Kir1.1; KCNJ1), cause Bartter syndrome, a genetically heterogeneous disorder characterized by severe reduction in salt absorption by the TAL, Na wasting, polyuria, and hypokalemic alkalosis. ROMK(-/-) null mice exhibit a Bartter phenotype and lack the small-conductance (30-pS) apical K channel (SK) in the TAL. However, a distinct 70-pS K channel can also significantly contribute to the apical conductance of TAL. We now examine the effect of ROMK deletion on the functional expression of the 70-pS K channel in the TAL. Functional expression of the 70-pS K channel was low [average channel acitivty ( NPo) = 0.02] in ROMK(+/+) mice on a control K diet but increased to 0.27 by high-K intake for 2 wk. In contrast, the high-K diet decreased NPo of SK by ∼30%, from 2.04 to 1.44. In ROMK heterozygous (+/-) mice on a control K diet, SK activity was about one-half of that observed in ROMK(+/+) mice (0.95 vs. 2.04). The high-K diet also reduced SK activity in ROMK(+/-) mice by ∼40% (from 0.95 to 0.55) but increased NPo of the 70-pS K channel from 0 to 0.09 in ROMK(+/-) mice. This corresponds to ∼30% of channel activity ( NPo = 0.27) observed in ROMK(+/+) mice. Neither the 70-pS nor the 30-pS K channels were observed in TAL cells from ROMK(-/-) mice on either the normal or high-K diets. Thus functional expression of the 70-pS K channel is enhanced by increasing dietary K and requires expression of ROMK. It is likely that ROMK forms a critical subunit of the 70-pS K channel, accounting for the loss of apical K secretory channel activity in ROMK Bartter syndrome.

scholarly journals Large deletion of the 5' end of the ROMK1 gene causes antenatal Bartter syndrome.

1998 ◽  
Vol 9 (12) ◽  
pp. 2357-2359
Author(s):  
D Feldmann ◽  
J L Alessandri ◽  
G Deschênes
Keyword(s):  
Homozygous Deletion ◽  
Large Deletion ◽  
Bartter Syndrome ◽  
Thick Ascending Limb ◽  
Consanguineous Family ◽  
Medullary Thick Ascending Limb ◽  
Untranslated Exon ◽  
Exon 1

Mutations in exon 5 of the ROMK1 gene (KCNJ1) have recently been observed in antenatal Bartter syndrome patients. This study describes a homozygous deletion removing KCNJ1 exons 1 and 2 observed in a consanguineous family with antenatal Bartter syndrome. Absence of the untranslated exon 1 led to the deletion of transcription elements located in this exon that may cause the disease. Deletion of exon 1 transcription elements should lead to the absence of hROMK2-K5 transcripts, whereas hROMK1 transcripts should normally be transcripted. Consequently, probably only hROMK2-K5 transcripts are expressed in the medullary thick ascending limb of Henle.

scholarly journals The Urinary Excretion of Uromodulin is Regulated by the Potassium Channel ROMK

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Guglielmo Schiano ◽  
Bob Glaudemans ◽  
Eric Olinger ◽  
Nadine Goelz ◽  
Michael Müller ◽  
...  
Keyword(s):  
Potassium Channel ◽  
Primary Cultures ◽  
Pressure Control ◽  
Bartter Syndrome ◽  
Thick Ascending Limb ◽  
Gene Encoding ◽  
Functional Link ◽  
Knock Out ◽  
Urinary Levels ◽  
Urinary Concentrating Ability

AbstractUromodulin, the most abundant protein in normal urine, is produced by cells lining the thick ascending limb (TAL) of the loop of Henle. Uromodulin regulates the activity of the potassium channel ROMK in TAL cells. Common variants in KCNJ1, the gene encoding ROMK, are associated with urinary levels of uromodulin in population studies. Here, we investigated the functional link between ROMK and uromodulin in Kcnj1 knock-out mouse models, in primary cultures of mouse TAL (mTAL) cells, and in patients with Bartter syndrome due to KCNJ1 mutations. Both global and kidney-specific Kcnj1 knock-out mice showed reduced urinary levels of uromodulin paralleled by increased levels in the kidney, compared to wild-type controls. Pharmacological inhibition and genetic deletion of ROMK in mTAL cells caused a reduction in apical uromodulin excretion, reflected by cellular accumulation. In contrast, NKCC2 inhibition showed no effect on uromodulin processing. Patients with Bartter syndrome type 2 showed reduced urinary uromodulin levels compared to age and gender matched controls. These results demonstrate that ROMK directly regulates processing and release of uromodulin by TAL cells, independently from NKCC2. They support the functional link between transport activity and uromodulin in the TAL, relevant for blood pressure control and urinary concentrating ability.

scholarly journals Adult presentation of Bartter syndrome type IV with erythrocytosis

2015 ◽  
Vol 13 (4) ◽  
pp. 604-606 ◽  
Author(s):  
Ita Pfeferman Heilberg ◽  
Cláudia Tótoli ◽  
Joaquim Tomaz Calado
Keyword(s):  
Late Onset ◽  
Bartter Syndrome ◽  
Sodium Reabsorption ◽  
Thick Ascending Limb ◽  
Syndrome Type ◽  
Loss Of Function ◽  
Mild Phenotype ◽  
Type Iv ◽  
Hypokalemic Alkalosis ◽  
A Subunit

Abstract Bartter syndrome comprises a group of rare autosomal-recessive salt-losing disorders with distinct phenotypes, but one unifying pathophysiology consisting of severe reductions of sodium reabsorption caused by mutations in five genes expressed in the thick ascending limb of Henle, coupled with increased urinary excretion of potassium and hydrogen, which leads to hypokalemic alkalosis. Bartter syndrome type IV, caused by loss-of-function mutations in barttin, a subunit of chloride channel CLC-Kb expressed in the kidney and inner ear, usually occurs in the antenatal-neonatal period. We report an unusual case of late onset presentation of Bartter syndrome IV and mild phenotype in a 20 years-old man who had hypokalemia, deafness, secondary hyperparathyroidism and erythrocytosis.

scholarly journals Bartter Syndrome in Children; A Cause of Severe Hypokalemic Metabolic Alkalosis: Clinical Case Report and Literature Review

2020 ◽  
pp. 1-7
Author(s):  
A. Radi ◽  
M. Akhrif ◽  
M. Kmari ◽  
A. Ourrai ◽  
A. Hassani ◽  
...  
Keyword(s):  
Metabolic Alkalosis ◽  
Clinical Case ◽  
Male Infant ◽  
High Plasma ◽  
Bartter Syndrome ◽  
Thick Ascending Limb ◽  
Triangular Face ◽  
Renal Tubular Disorder ◽  
Dysmorphic Syndrome ◽  
Renal Tubular

Bartter syndrome is an inherited renal tubular disorder caused by a defective salt reabsorption in the thick ascending limb of loop of Henle. It characterized by urinary loss of sodium, potassium, and chloride; hypokalemic metabolic alkalosis; normal blood pressure, high plasma levels of renin and aldosterone. There is phenotypical and genetic variability of Bartter syndrome since were identified five genes responsible for five different forms of Bartter syndrome. The objective of this work is to report a clinical case to study the pathophysiological, clinical, biological and therapeutic features of this syndrome. Materials and Methods: We reported a case of 04-month-old male infant admitted for acute dehydration secondary to polyuro-polydipsia syndrome and vomiting. In clinical presentation the patient had a dysmorphic syndrome with triangular face, protruding ears and flattened nasal root. Laboratory tests revealed hypokalemia, hyponatremia, metabolic alkalosis and hypercalciuria. Treatment with indomethacin was started at 1 mg/kg per day with favorable outcome.

Mutation of the Na+-K+-2Cl−cotransporter NKCC2 in mice is associated with severe polyuria and a urea-selective concentrating defect without hyperreninemia

2010 ◽  
Vol 298 (6) ◽  
pp. F1405-F1415 ◽  
Author(s):  
Elisabeth Kemter ◽  
Birgit Rathkolb ◽  
Lise Bankir ◽  
Anja Schrewe ◽  
Wolfgang Hans ◽  
...  
Keyword(s):  
Human Disease ◽  
Late Onset ◽  
Critical Role ◽  
Bartter Syndrome ◽  
Type I ◽  
Thick Ascending Limb ◽  
Mouse Line ◽  
Loss Of Function ◽  
Plasma Urea ◽  
Salt Wasting

The bumetanide-sensitive Na+-K+-2Cl−cotransporter NKCC2, located in the thick ascending limb of Henle's loop, plays a critical role in the kidney's ability to concentrate urine. In humans, loss-of-function mutations of the solute carrier family 12 member 1 gene ( SLC12A1), coding for NKCC2, cause type I Bartter syndrome, which is characterized by prenatal onset of a severe polyuria, salt-wasting tubulopathy, and hyperreninemia. In this study, we describe a novel chemically induced, recessive mutant mouse line termed Slc12a1I299Fexhibiting late-onset manifestation of type I Bartter syndrome. Homozygous mutant mice are viable and exhibit severe polyuria, metabolic alkalosis, marked increase in plasma urea but close to normal creatininemia, hypermagnesemia, hyperprostaglandinuria, hypotension,, and osteopenia. Fractional excretion of urea is markedly decreased. In addition, calcium and magnesium excretions are more than doubled compared with wild-type mice, while uric acid excretion is twofold lower. In contrast to hyperreninemia present in human disease, plasma renin concentration in homozygotes is not increased. The polyuria observed in homozygotes may be due to the combination of two additive factors, a decrease in activity of mutant NKCC2 and an increase in medullary blood flow, due to prostaglandin-induced vasodilation, that impairs countercurrent exchange of urea in the medulla. In conclusion, this novel viable mouse line with a missense Slc12a1 mutation exhibits most of the features of type I Bartter syndrome and may represent a new model for the study of this human disease.

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