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Kidney International Feb 2021Bartter syndrome is a rare inherited salt-losing renal tubular disorder characterized by secondary hyperaldosteronism with hypokalemic and hypochloremic metabolic...
Diagnosis and management of Bartter syndrome: executive summary of the consensus and recommendations from the European Rare Kidney Disease Reference Network Working Group for Tubular Disorders.
Bartter syndrome is a rare inherited salt-losing renal tubular disorder characterized by secondary hyperaldosteronism with hypokalemic and hypochloremic metabolic alkalosis and low to normal blood pressure. The primary pathogenic mechanism is defective salt reabsorption predominantly in the thick ascending limb of the loop of Henle. There is significant variability in the clinical expression of the disease, which is genetically heterogenous with 5 different genes described to date. Despite considerable phenotypic overlap, correlations of specific clinical characteristics with the underlying molecular defects have been demonstrated, generating gene-specific phenotypes. As with many other rare disease conditions, there is a paucity of clinical studies that could guide diagnosis and therapeutic interventions. In this expert consensus document, the authors have summarized the currently available knowledge and propose clinical indicators to assess and improve quality of care.
Topics: Alkalosis; Bartter Syndrome; Consensus; Humans; Hypokalemia; Rare Diseases
PubMed: 33509356
DOI: 10.1016/j.kint.2020.10.035 -
Pediatric Clinics of North America Feb 2019Bartter and Gitelman syndromes are conditions characterized by renal salt-wasting. Clinical presentations range from severe antenatal disease to asymptomatic with... (Review)
Review
Bartter and Gitelman syndromes are conditions characterized by renal salt-wasting. Clinical presentations range from severe antenatal disease to asymptomatic with incidental diagnosis. Hypokalemic hypochloremic metabolic alkalosis is the common feature. Bartter variants may be associated with polyuria and weakness. Gitelman syndrome is often subtle, and typically diagnosed later life with incidental hypokalemia and hypomagnesemia. Treatment may involve fluid and electrolyte replenishment, prostaglandin inhibition, and renin-angiotensin-aldosterone system axis disruption. Investigators have identified causative mutations but genotypic-phenotypic correlations are still being characterized. Collaborative registries will allow improved classification schema and development of effective treatments.
Topics: Bartter Syndrome; Child; Diagnosis, Differential; Gitelman Syndrome; Humans
PubMed: 30454738
DOI: 10.1016/j.pcl.2018.08.010 -
World Journal of Pediatrics : WJP Feb 2021Bartter's syndrome (BS) is a rare group of salt losing tubulopathies due to the impairment of transport mechanisms at the thick ascending limb of the Henle's loop. (Review)
Review
BACKGOUND
Bartter's syndrome (BS) is a rare group of salt losing tubulopathies due to the impairment of transport mechanisms at the thick ascending limb of the Henle's loop.
DATA SOURCES
Literature reviews and original research articles were collected from database, including PubMed and Scopus.
RESULTS
According to the time of onset and symptoms, BS can be classified into antenatal and classic BS. Molecular studies have identified different subtypes of BS. BS types I, II and III are caused by mutations on genes encoding the luminal Na-K-2Cl co-transporter, the luminal K+ channel ROMK, and the basolateral chloride channel ClC-Kb (CLCNKB), respectively. Loss-of-function mutations of Barttin CLCNK type accessory beta subunit cause BS type IVa. Simultaneous mutations of CLCNKB and CLCNKA cause BS type IVb. BS type V consists in a novel transient form characterized by antenatal presentation due to mutations in the MAGE family member D2. Severe gain-of-function mutations of the extracellular calcium sensing receptor gene can result in an autosomal dominant condition of BS. Main clinical and biochemical alterations in BS include polyuria, dehydration, hypokalemia, hypochloremic metabolic alkalosis, hyperreninemia, high levels of prostaglandins, normal or low blood pressure, hypercalciuria and failure to thrive. Treatment focuses mainly at correcting dehydration and electrolyte disturbances and in measures to reduce polyuria, including the use of nonsteroidal anti-inflammatory medications to control excessive renal prostaglandin E2 production.
CONCLUSIONS
Early diagnosis and treatment of BS may prevent long-term consequences such as growth failure, nephrocalcinosis and end-stage renal disease.
Topics: Bartter Syndrome; Humans
PubMed: 32488762
DOI: 10.1007/s12519-020-00370-4 -
International Journal of Molecular... Oct 2021Gitelman and Bartter syndromes are rare inherited diseases that belong to the category of renal tubulopathies. The genes associated with these pathologies encode... (Review)
Review
Gitelman and Bartter syndromes are rare inherited diseases that belong to the category of renal tubulopathies. The genes associated with these pathologies encode electrolyte transport proteins located in the nephron, particularly in the Distal Convoluted Tubule and Ascending Loop of Henle. Therefore, both syndromes are characterized by alterations in the secretion and reabsorption processes that occur in these regions. Patients suffer from deficiencies in the concentration of electrolytes in the blood and urine, which leads to different systemic consequences related to these salt-wasting processes. The main clinical features of both syndromes are hypokalemia, hypochloremia, metabolic alkalosis, hyperreninemia and hyperaldosteronism. Despite having a different molecular etiology, Gitelman and Bartter syndromes share a relevant number of clinical symptoms, and they have similar therapeutic approaches. The main basis of their treatment consists of electrolytes supplements accompanied by dietary changes. Specifically for Bartter syndrome, the use of non-steroidal anti-inflammatory drugs is also strongly supported. This review aims to address the latest diagnostic challenges and therapeutic approaches, as well as relevant recent research on the biology of the proteins involved in disease. Finally, we highlight several objectives to continue advancing in the characterization of both etiologies.
Topics: Bartter Syndrome; Electrolytes; Gitelman Syndrome; Humans; Hyperaldosteronism; Hypercalciuria; Hypokalemia; Hyponatremia; Kidney Tubules, Distal; Loop of Henle; Nephrocalcinosis; Renal Tubular Transport, Inborn Errors; Water-Electrolyte Balance
PubMed: 34768847
DOI: 10.3390/ijms222111414 -
Nephrologie & Therapeutique Jul 2020Bartter-Gitelman syndromes are rare inherited autosomal recessive salt-losing tubulopathies characterized by severe and chronic hypokalemia associated with metabolic...
Bartter-Gitelman syndromes are rare inherited autosomal recessive salt-losing tubulopathies characterized by severe and chronic hypokalemia associated with metabolic alkalosis and secondary hyperaldosteronism. Bartter syndrome results from a furosemide-like defect in sodium reabsorption in the Henle's loop leading to hypercalciuria and defect in urinary concentration capacity. The antenatal Bartter syndrome is defined by polyhydramnios and an infantile polyuria with severe dehydration whereas classic Bartter syndrome appears during childhood or adulthood. Gitelman syndrome is a thiazide-like salt-losing tubulopathy. It is associated with hypomagnesemia, hypocalciuria without defect in urinary concentration capacity. The diagnosis is most often made in adolescents or adults. Clinical symptoms include tetany, delay in the height-weight growth curves, chronic tiredness, muscle weakness, myalgia and vertigo. Nephrocalcinosis in Bartter syndrome could lead to chronic kidney disease. Antenatal Bartter syndrome requires hospitalization in intensive care unit to manage the severe newborn dehydration. Chondrocalcinosis is the major complication in the Gitelman syndrome. The corner stones of treatment is the fluid and electrolyte management Bartter and Gitelman syndromes need lifelong oral supplementations of potassium, salt (Bartter) and magnesium (Gitelman). Indomethacin is efficient to reduce water and electrolyte loss in Bartter. In Gitelman, potassium-sparing diuretics may be helping for severe hypokaliemia but they will reinforce hypovolemia.
Topics: Bartter Syndrome; Gitelman Syndrome; Humans
PubMed: 32622651
DOI: 10.1016/j.nephro.2020.06.001 -
Nefrologia : Publicacion Oficial de La... 2005
Review
Topics: Bartter Syndrome; Hearing Loss, Sensorineural; Humans
PubMed: 16514898
DOI: No ID Found -
Casopis Lekaru Ceskych 2022Bartter and Gitelman syndromes belong to salt-losing tubulopathies. These rare diseases may be associated with severe electrolyte disorders. Early identification of... (Review)
Review
Bartter and Gitelman syndromes belong to salt-losing tubulopathies. These rare diseases may be associated with severe electrolyte disorders. Early identification of tubulopathies is essential for appropriate management. Progress in molecular genetics enabled the identification of genes and pathophysiologic mechanisms associated with these diseases. Here, we review etiology and diagnostics of these disorders from the light of current knowledge. Additionally, we discuss contemporary therapeutic approaches.
Topics: Bartter Syndrome; Gitelman Syndrome; Humans
PubMed: 36100451
DOI: No ID Found -
Current Opinion in Pediatrics Apr 2017The clinical presentations of Bartter's syndrome and Gitelman's syndrome will be reviewed including two most recently described hypokalemic salt-losing tubulopathies. By... (Review)
Review
PURPOSE OF REVIEW
The clinical presentations of Bartter's syndrome and Gitelman's syndrome will be reviewed including two most recently described hypokalemic salt-losing tubulopathies. By taking the quite heterogeneous presentations and the apparently different pathophysiologies as the basis, the applicability of the physiologic classification has been tested.
RECENT FINDINGS
According to the physiologic approach, salt-losing tubulopathies can be divided into two major groups (with completely different tubular defects): first, disorders of the thick ascending limb of Henle's loop (loop disorders); second, disorders of the distal convolute tubule (DCT disorders). A combination of these two groups with complety different tubular defects will finally lead to a third group: the combined loop/DCT disorders. On the basis of pharmacologic tests (pharmacotyping), it appears that the Bartter's syndrome V belongs to the DCT group, whereas the most recently described transient antenatal Bartter's syndrome best fits in the group with the loop and DCT combination.Besides secondary hyperaldosteronism, loop disorders present a whole spectrum of (secondary) pathophysiologic characteristics with significant diagnostic and therapeutic impact, such as polyhydramnios, hyperprostaglandinuria, nephrogenic diabetes insipidus, and nephrocalcinosis. Recent reports indicate that neonatal hyperparathyroidism has also to be added to the clinical presentation of isolated loop disorders.
SUMMARY
As long as gene therapy is not available, the overall therapeutic management follows the clinical presentation, which leads to the underlying pathophysiology of renal salt wasting. Thus, when dealing with Bartter's syndrome and Gitelman's syndrome, the correct physiologic and pharmacologic characterization appears to be essential for a sound diagnostic and therapeutic patient management.
Topics: Bartter Syndrome; Diagnosis, Differential; Female; Genetic Predisposition to Disease; Gitelman Syndrome; Humans; Kidney Tubules, Distal; Male; Risk Assessment; Sodium
PubMed: 27906863
DOI: 10.1097/MOP.0000000000000447 -
Kidney International Jan 2017Gitelman syndrome (GS) is a rare, salt-losing tubulopathy characterized by hypokalemic metabolic alkalosis with hypomagnesemia and hypocalciuria. The disease is...
Gitelman syndrome (GS) is a rare, salt-losing tubulopathy characterized by hypokalemic metabolic alkalosis with hypomagnesemia and hypocalciuria. The disease is recessively inherited, caused by inactivating mutations in the SLC12A3 gene that encodes the thiazide-sensitive sodium-chloride cotransporter (NCC). GS is usually detected during adolescence or adulthood, either fortuitously or in association with mild or nonspecific symptoms or both. The disease is characterized by high phenotypic variability and a significant reduction in the quality of life, and it may be associated with severe manifestations. GS is usually managed by a liberal salt intake together with oral magnesium and potassium supplements. A general problem in rare diseases is the lack of high quality evidence to inform diagnosis, prognosis, and management. We report here on the current state of knowledge related to the diagnostic evaluation, follow-up, management, and treatment of GS; identify knowledge gaps; and propose a research agenda to substantiate a number of issues related to GS. This expert consensus statement aims to establish an initial framework to enable clinical auditing and thus improve quality control of care.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents, Non-Steroidal; Bartter Syndrome; Calcium; Chloride Channels; Chondrocalcinosis; Consensus Development Conferences as Topic; Diagnosis, Differential; Dietary Supplements; Genetic Testing; Gitelman Syndrome; Humans; Hypokalemia; Magnesium; Mutation; Phenotype; Potassium; Practice Guidelines as Topic; Quality of Life; Rare Diseases; Sodium Chloride, Dietary; Solute Carrier Family 12, Member 3; Ultrasonography
PubMed: 28003083
DOI: 10.1016/j.kint.2016.09.046 -
Current Opinion in Nephrology and... Sep 2003This review describes recent advances in our understanding of the genetic heterogeneity, pathophysiology and treatment of Bartter syndrome, a group of autosomal... (Review)
Review
PURPOSE OF REVIEW
This review describes recent advances in our understanding of the genetic heterogeneity, pathophysiology and treatment of Bartter syndrome, a group of autosomal recessive disorders that are characterized by markedly reduced or absent salt transport by the thick ascending limb of Henle. Consequently, individuals with Bartter syndrome exhibit renal salt wasting and lowered blood pressure, hypokalemic metabolic alkalosis and hypercalciuria with a variable risk of renal stones.
RECENT FINDINGS
Previously, three genes (SLC12A2, the sodium-potassium-chloride co-transporter; KCNJ1, the ROMK potassium ion channel; ClC-Kb, the basolateral chloride ion channel) had been identified as causing antenatal and 'classic' Bartter syndrome. Two additional genes have now been identified. Barttin is a beta-subunit that is required for the trafficking of CLC-K (both ClC-Ka and ClC-Kb) channels to the plasma membrane in both the thick ascending limb and the marginal cells in the scala media of the inner ear that secrete potassium ion-rich endolymph. Loss-of-function mutations in barttin thus cause Bartter syndrome with sensorineural deafness. In addition, severe gain-of-function mutations in the extracellular calcium ion-sensing receptor can result in a Bartter phenotype because activation of this G protein-coupled receptor inhibits salt transport in the thick ascending limb (a furosemide-like effect).
SUMMARY
Five genes have been identified as causing Bartter syndrome (types I-V), with the unifying pathophysiology being the loss of salt transport by the thick ascending limb. Phenotypic differences in Bartter types I-V relate to the specific physiological roles of the individual genes in the kidney and other organ systems.
Topics: Bartter Syndrome; Humans; Ion Channels
PubMed: 12920401
DOI: 10.1097/00041552-200309000-00008