Chronic hypomagnesemia and hypokalemia due to renal wasting in siblings

Iwata, Fujihiko; Hanawa, Yoshio; Takashima, H

doi:10.1111/j.1442-200x.1993.tb03047.x

Cited by 9 publications

(3 citation statements)

References 18 publications

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“…Symptoms include the development of antenatal polyhydramnios (48,66), salt and volume loss after birth accompanied by hypokalemic alkalosis (2), hypercalciuria (43), excessive prostanoid formation (10,64), and hyperreninemia (18,63). Patients, especially infants, suffer from dehydration and low blood pressure (4) and are affected to various degrees by muscle weakness, fever, tetany, seizures, and growth and mental retardation (27,30,42,69).…”

Section: Functional Characteristics Of Nkcc2 Isoforms: Deletion Studiesmentioning

confidence: 99%

Isoforms of renal Na-K-2Cl cotransporter NKCC2: expression and functional significance

Castrop¹,

Schnermann²

2008

American Journal of Physiology-Renal Physiology

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The renal Na-K-2Cl cotransporter (NKCC2, BSC1) is selectively expressed in the apical membrane of cells of the thick ascending limb of the loop of Henle (TAL) and macula densa. NKCC2-dependent salt transport constitutes the major apical entry pathway for transepithelial salt reabsorption in the TAL. Although NKCC2 is encoded by a single gene (Slc12a1), differential splicing of the NKCC2 pre-mRNA results in the formation of several alternate transcripts. Thus three full-length splice isoforms of NKCC2 differ in their variable exon 4, resulting in transcripts for NKCC2B, NKCC2A, and NKCC2F. In addition to full-length isoforms, variants with truncated COOH-terminal ends have been described. The various splice isoforms of NKCC2 differ in their localization along the TAL and in their transport characteristics. Data in the literature are reviewed to assess the principles of NKCC2 differential splicing, the localization of NKCC2 splice isoforms along the TAL in various species, and the functional characteristics of the splice isoforms. In addition, we discuss the functional significance of NKCC2 isoforms for TAL salt retrieval and for the specific salt sensor function of macula densa cells based on studies using isoform-specific NKCC2-knockout mice. We suggest that different NKCC2 splice variants cooperate in salt retrieval along the TAL and that the coexpression of two splice variants (NKCC2B and NKCC2A) in the macula densa cells facilitates efficient salt sensing over wide ranges of fluctuating salt concentrations.

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Section: Functional Characteristics Of Nkcc2 Isoforms: Deletion Studiesmentioning

confidence: 99%

Isoforms of renal Na-K-2Cl cotransporter NKCC2: expression and functional significance

Castrop¹,

Schnermann²

2008

American Journal of Physiology-Renal Physiology

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“…The relationship of cellular potassium and magnesium metabolism is complex and far from understood. Potassium depletion sometimes results in increased urinary magnesium and calcium excretion (87,154,179,348). The increase in urinary excretion of divalent cations may be explained by the known effects of potassium depletion on the thick ascending limb of the loop.…”

Section: A Potassium Depletionmentioning

confidence: 99%

Magnesium Transport in the Renal Distal Convoluted Tubule

Dai

Ritchie

Kerstan

et al. 2001

Physiological Reviews

293

252

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The distal tubule reabsorbs approximately 10% of the filtered Mg(2+), but this is 70-80% of that delivered from the loop of Henle. Because there is little Mg(2+) reabsorption beyond the distal tubule, this segment plays an important role in determining the final urinary excretion. The distal convoluted segment (DCT) is characterized by a negative luminal voltage and high intercellular resistance so that Mg(2+) reabsorption is transcellular and active. This review discusses recent evidence for selective and sensitive control of Mg(2+) transport in the DCT and emphasizes the importance of this control in normal and abnormal renal Mg(2+) conservation. Normally, Mg(2+) absorption is load dependent in the distal tubule, whether delivery is altered by increasing luminal Mg(2+) concentration or increasing the flow rate into the DCT. With the use of microfluorescent studies with an established mouse distal convoluted tubule (MDCT) cell line, it was shown that Mg(2+) uptake was concentration and voltage dependent. Peptide hormones such as parathyroid hormone, calcitonin, glucagon, and arginine vasopressin enhance Mg(2+) absorption in the distal tubule and stimulate Mg(2+) uptake into MDCT cells. Prostaglandin E(2) and isoproterenol increase Mg(2+) entry into MDCT cells. The current evidence indicates that cAMP-dependent protein kinase A, phospholipase C, and protein kinase C signaling pathways are involved in these responses. Steroid hormones have significant effects on distal Mg(2+) transport. Aldosterone does not alter basal Mg(2+) uptake but potentiates hormone-stimulated Mg(2+) entry in MDCT cells by increasing hormone-mediated cAMP formation. 1,25-Dihydroxyvitamin D(3), on the other hand, stimulates basal Mg(2+) uptake. Elevation of plasma Mg(2+) or Ca(2+) inhibits hormone-stimulated cAMP accumulation and Mg(2+) uptake in MDCT cells through activation of extracellular Ca(2+)/Mg(2+)-sensing mechanisms. Mg(2+) restriction selectively increases Mg(2+) uptake with no effect on Ca(2+) absorption. This intrinsic cellular adaptation provides the sensitive and selective control of distal Mg(2+) transport. The distally acting diuretics amiloride and chlorothiazide stimulate Mg(2+) uptake in MDCT cells acting through changes in membrane voltage. A number of familial and acquired disorders have been described that emphasize the diversity of cellular controls affecting renal Mg(2+) balance. Although it is clear that many influences affect Mg(2+) transport within the DCT, the transport processes have not been identified.

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“…14 Both adults and children describe a range of symptoms (box FB2). 15 16 Classically, patients are normotensive or hypotensive with elevated plasma renin and aldosterone concentrations. Both syndromes have a subnormal responsiveness to infused angiotensin II, and there is often an increase in urinary prostaglandin E 2 excretion in Bartter's patients 17.…”

Section: Clinical Aspectsmentioning

confidence: 99%

The pathophysiological and molecular basis of Bartter's and Gitelman's syndromes

Bhandari

1999

Postgraduate Medical Journal

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SummaryMolecular defects aVecting the transport of sodium, potassium and chloride in the nephron through the ROMK K + channel, Na-cotransporter, the Na + / Cl -cotransporter and chloride channel have been identified in patients with Bartter's and Gitelman's syndromes. Defects of the angiotensin II type I receptor and CFTR have also being described. These defects are simple (ie, most are single amino acid substitutions) but aVect key elements in tubular transport. The simplicity of the genetic defects may explain why the inheritance of these conditions remains unclear in most kindreds (ie, not just recessive or dominant) and emphasises the crucial importance of the conformational structure of these channels. Application of this molecular information will allow the early genetic identification of patients with these syndromes and enable us to diVerentiate between the various disorders at a functional level. It may also identify a subgroup in which the heterozygous form may make patients potentially exquisitely sensitive to diuretics.Keywords: Bartter's syndrome; Gitelman's syndrome; hypokalaemic alkalosesThe inherited hypokalaemic alkaloses are typified by a constellation of metabolic abnormalities, including metabolic alkalosis, hypokalaemia, chloride wasting, hypomagnesaemia, and hyper-or hypocalciuria.

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Chronic hypomagnesemia and hypokalemia due to renal wasting in siblings

Cited by 9 publications

References 18 publications

Isoforms of renal Na-K-2Cl cotransporter NKCC2: expression and functional significance

Isoforms of renal Na-K-2Cl cotransporter NKCC2: expression and functional significance

Magnesium Transport in the Renal Distal Convoluted Tubule

The pathophysiological and molecular basis of Bartter's and Gitelman's syndromes

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