Salt-Losing Tubulopathies in Children: What’s New, What’s Controversial?

Kleta, Robert; Böckenhauer, Detlef

doi:10.1681/asn.2017060600

Cited by 60 publications

(75 citation statements)

References 101 publications

(111 reference statements)

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“…However, in the more distal DCT and the CD, also known as the aldosterone-sensitive part of the nephron, potassium can be actively secreted. Inherited or acquired factors (the latter including drugs) that disrupt the function of specific transporters in these nephron segments can cause a range of symptoms, the most common being polyuria and polydipsia, electrolyte abnormalities, and acid-base disturbances [1][2][3][4].…”

Section: Physiology and Pathophysiologymentioning

confidence: 99%

“…This recycling establishes the lumen-positive transepithelial potential that is needed for the paracellular uptake of cations, including calcium and magnesium via claudins ( Fig. 1) [2][3][4]. It is important to note that the macula densa, the site of tubuloglomerular feedback (TGF) is part of the TAL.…”

Section: Salt Reabsorption In the Talmentioning

confidence: 99%

“…Magnesium is imported by the luminal transient receptor potential cation channel subfamily M member 6 (TRPM6). The basolateral exit pathways are thought to include a basolateral Na/Mg exchanger [2][3][4][16][17][18].…”

Section: Salt Transport In the Dctmentioning

confidence: 99%

“…Patients present with polyuria (which, depending on the subtype, can manifest antenatally with polyhydramnios and preterm birth), hypokalaemic, hypochloraemic metabolic alkalosis and normal blood pressure in the context of elevated renin and aldosterone levels. On a genetic basis, 5 different subtypes are currently distinguished (Table 1) [3,4,21].…”

Section: Bartter Syndromesmentioning

confidence: 99%

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Bartter and Gitelman syndromes: Questions of class

2019

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Bartter and Gitelman syndromes are rare inherited tubulopathies characterized by hypokalaemic, hypochloraemic metabolic alkalosis. They are caused by mutations in at least 7 genes involved in the reabsorption of sodium in the thick ascending limb (TAL) of the loop of Henle and/or the distal convoluted tubule (DCT). Different subtypes can be distinguished and various classifications have been proposed based on clinical symptoms and/or the underlying genetic cause. Yet, the clinical phenotype can show remarkable variability, leading to potential divergences between classifications. These problems mostly relate to uncertainties over the role of the basolateral chloride exit channel CLCNKB, expressed in both TAL and DCT and to what degree the closely related paralogue CLCNKA can compensate for the loss of CLCNKB function. Here, we review what is known about the physiology of the transport proteins involved in these disorders. We also review the various proposed classifications and explain why a gene-based classification constitutes a pragmatic solution.

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Section: Physiology and Pathophysiologymentioning

confidence: 99%

Section: Salt Reabsorption In the Talmentioning

confidence: 99%

Section: Salt Transport In the Dctmentioning

confidence: 99%

Section: Bartter Syndromesmentioning

confidence: 99%

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Bartter and Gitelman syndromes: Questions of class

2019

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“…Moreover, because the diagnosis may be the same after genetic testing in most antenatal/neonatal cases with “Bartter syndrome” as well as in most adult‐onset “Gitelman syndrome” cases with hypomagnesemia, a diagnosis of “BS” or “GS” in such cases would generally be acceptable before genetic testing. Furthermore, the term “salt‐losing tubulopathy” has been used in reference to broader renal tubular disorders including Fanconi syndrome and pseudohypoaldosteronism type I, which are caused by abnormalities in molecules associated with sodium handling in the proximal tubule and collecting duct, respectively …”

mentioning

confidence: 99%

A case to use “salt‐losing tubulopathy” instead of “Bartter/Gitelman syndrome”

Miura

Hattori

2020

Pediatrics International

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A novel homozygous CLCNKB variant: An early presentation of classic Bartter syndrome in a neonate

Yaprak,

Kara,

Calisici

et al. 2023

Birth Defects Research

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BackgroundBartter syndrome (BS) is a rare congenital salt‐losing renal tubular transport disorder, characterized by salt wasting, polyuria, biochemical abnormalities, and acid–base homeostasis imbalance. The syndrome has five different genetic forms, and novel mutations of CLCNKB gene lead to type 3 BS also known as classic BS. In this case, we report clinical and molecular findings from a newborn baby with BS.CaseA 10‐day‐old male infant born at 37 weeks of gestation by cesarean section following a pregnancy complicated with polyhydramnios, and fetal distress to a 30‐year‐old gravida 3, para 3 mother, with a 2500 g birth weight was brought to the pediatric emergency department due to weight loss and jaundice. The neonate was referred to the neonatal intensive care unit (NICU) with a preliminary diagnosis of hyponatremic dehydration (Na: 122 mmol/L, 10% dehydration) and hypokalemic hypochloremic metabolic alkalosis (K: 2.13 mmol/L, Cl: 63 mmol/L, pH: 7.62, pCO2: 39 mmHg, HCO3: 40.8 mmol/L, BE: 16.9 mmol/L), and hypocalcemia (ionized Ca: 0.72 mmol/L). On arrival to the NICU, symptomatic focal seizures, and polyuria complicated his course. Spot urine biochemistry revealed a renal salt wasting and hypercalciuria: Creatine 11.4 mg/dL Na: 51 mmol/L (54–150), K: 26 mmol/L (20–80), Cl: 164 mmol/L, fractional excretion of sodium (FENa): 3% (0.9–1.6), fractional excretion of chloride (FECl): 17% (<0.5%) and Ca/Cr: 0.33 (<0.2). Biochemical abnormalities disappeared through intravenous fluid and electrolyte therapy, but he could not achieve adequate weight gain, and polyuric urine output (6.5 cc/kg/h), and metabolic alkalosis continued as the enteral feedings advance. Patient's serum renin: 184 pg/mL (5–27 pg/mL) and aldosterone: 1670 pg/mL (1–180 ng/dL) were elevated. Polyuria, renal salt wasting, electrolyte and acid–base disturbances, and hyperreninemic hyperaldosteronism established the diagnosis as Bartter syndrome. An oral indomethacin (1 mg/kg/day) treatment, on the 8th day. ensured the weight gain, and normalized daily urine output. He achieved the goal of birth weight on the 30th day and he was 3520 g weight at discharge on day 42. The genetic tests of the patient as KCNJ1 SLC12A1 gene sequence analysis revealed a novel homozygous mutation in the 14th exon of the CLCNKB gene, the c.1334_1338del CTTTT (p. Ser445fs*4) variant was identified.DiscussionThe diagnosis of BS should be considered in the presence of a medical history of severe polyhydramnios of fetal origin. Postnatally, polyuria, signs of dehydration, renal salt wasting, and hypokalemic‐metabolic alkalosis should prompt the clinician to request genetic testing for BS in the neonatal period. This case is presented to emphasize that early diagnosis of BS should be considered in newborns presenting with electrolyte abnormalities and metabolic alkalosis accompanying dehydration and favorable growth results can be achieved by starting indomethacin treatment in the early neonatal period. The clinical exome sequencing illustrated a novel missense variant in the CLCNKB gene leading to the molecular diagnosis of BS type 3.

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Salt-Losing Tubulopathies in Children: What’s New, What’s Controversial?

Cited by 60 publications

References 101 publications

Bartter and Gitelman syndromes: Questions of class

Bartter and Gitelman syndromes: Questions of class

A case to use “salt‐losing tubulopathy” instead of “Bartter/Gitelman syndrome”

A novel homozygous CLCNKB variant: An early presentation of classic Bartter syndrome in a neonate

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