Hereditary kidney diseases associated with hypomagnesemia

Claverie-Martı́n, Félix; Perdomo‐Ramirez, Ana; García‐Nieto, Victor

doi:10.23876/j.krcp.21.112

Cited by 5 publications

(3 citation statements)

References 103 publications

(209 reference statements)

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“…How does decreased Mg 2+ reabsorption occur in EAST/SeSAME syndrome? The exact mechanisms underlying this are the subject of debate ( Bandulik et al, 2011 ; Claverie-Martin et al, 2021 ). Interestingly, reduced NaCl transport, as also seen in thiazide treatment or Gitelman syndrome, leads to shortening of the DCT segment and downregulation of the Mg 2+ influx pathway ( Maeoka and McCormick, 2020 ; Franken et al, 2021 ).…”

Section: East/sesame Syndrome: a Pleiotropic Monogenetic Disease Caus...mentioning

confidence: 99%

EAST/SeSAME Syndrome and Beyond: The Spectrum of Kir4.1- and Kir5.1-Associated Channelopathies

Forst

Warth

et al. 2022

Front. Physiol.

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In 2009, two groups independently linked human mutations in the inwardly rectifying K+ channel Kir4.1 (gene name KCNJ10) to a syndrome affecting the central nervous system (CNS), hearing, and renal tubular salt reabsorption. The autosomal recessive syndrome has been named EAST (epilepsy, ataxia, sensorineural deafness, and renal tubulopathy) or SeSAME syndrome (seizures, sensorineural deafness, ataxia, intellectual disability, and electrolyte imbalance), accordingly. Renal dysfunction in EAST/SeSAME patients results in loss of Na+, K+, and Mg2+ with urine, activation of the renin–angiotensin–aldosterone system, and hypokalemic metabolic alkalosis. Kir4.1 is highly expressed in affected organs: the CNS, inner ear, and kidney. In the kidney, it mostly forms heteromeric channels with Kir5.1 (KCNJ16). Biallelic loss-of-function mutations of Kir5.1 can also have disease significance, but the clinical symptoms differ substantially from those of EAST/SeSAME syndrome: although sensorineural hearing loss and hypokalemia are replicated, there is no alkalosis, but rather acidosis of variable severity; in contrast to EAST/SeSAME syndrome, the CNS is unaffected. This review provides a framework for understanding some of these differences and will guide the reader through the growing literature on Kir4.1 and Kir5.1, discussing the complex disease mechanisms and the variable expression of disease symptoms from a molecular and systems physiology perspective. Knowledge of the pathophysiology of these diseases and their multifaceted clinical spectrum is an important prerequisite for making the correct diagnosis and forms the basis for personalized therapies.

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Section: East/sesame Syndrome: a Pleiotropic Monogenetic Disease Caus...mentioning

confidence: 99%

EAST/SeSAME Syndrome and Beyond: The Spectrum of Kir4.1- and Kir5.1-Associated Channelopathies

Forst

Warth

et al. 2022

Front. Physiol.

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“…CLCNKB is predominantly expressed in the TAL but the distal convoluted tubule (DCT) and CD as well. Therefore, symptoms of BS3 sometimes overlap with those of Gitelman syndrome; hypomagnesemia may or may not occur, as well as hypercalciuria and nephrocalcinosis 18 19) . Although they are usually diagnosed later than antenatal BS, BS3 is known to be more severe than antenatal BS 3) .…”

Section: Presentation Of Bartter Syndromementioning

confidence: 99%

Bartter Syndrome: Perspectives of a Pediatric Nephrologist

Choi

Kang

2022

Electrolyte Blood Press

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Bartter syndrome (BS) is one of the most well-known hereditary tubular disorders, characterized by hypokalemic, hypochloremic metabolic alkalosis, and polyuria/polydipsia. This disease usually presents before or during infancy, and adult nephrologists often inherit the patients from pediatric nephrologists since this is a life-long condition. Here, a few case scenarios will be presented to recount how they first got diagnosed and how their clinical courses were during childhood until adulthood, in addition to a brief review of the disease and its treatment.

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“…Mg 2+ is found in foods such as nuts, whole grains, and seeds, and is an important co-factor for hundreds of enzymatic reactions in the body ( Mathew and Panonnummal, 2021 ; Jahnen-Dechent and Ketteler, 2012 ). In plasma, ∼60–70% of Mg 2+ is ionized ( Rosanoff et al, 2022 ), and homeostasis is regulated primarily by Mg 2+ absorption in the small intestine and reabsorption in the kidneys ( Schuchardt and Hahn, 2017 ; Claverie-Martin et al, 2021 ). Hypomagnesemia (<.7 mml/L) can lead to cardiac arrhythmias, and seizures ( de Baaij et al, 2015 ) and is implicated in the pathogenesis of obesity, insulin resistance, and type 2 diabetes mellitus (T2DM) [reviewed in Pelczynska et al, 2022 ].…”

Section: Introductionmentioning

confidence: 99%

Gene-nutrient interactions that impact magnesium homeostasis increase risk for neural tube defects in mice exposed to dolutegravir

Gelineau-van Waes,

van Waes,

Hallgren

et al. 2023

Front. Cell Dev. Biol.

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In 2018, data from a surveillance study in Botswana evaluating adverse birth outcomes raised concerns that women on antiretroviral therapy (ART) containing dolutegravir (DTG) may be at increased risk for neural tube defects (NTDs). The mechanism of action for DTG involves chelation of Mg2+ ions in the active site of the viral integrase. Plasma Mg2+ homeostasis is maintained primarily through dietary intake and reabsorption in the kidneys. Inadequate dietary Mg2+ intake over several months results in slow depletion of plasma Mg2+ and chronic latent hypomagnesemia, a condition prevalent in women of reproductive age worldwide. Mg2+ is critical for normal embryonic development and neural tube closure. We hypothesized that DTG therapy might slowly deplete plasma Mg2+ and reduce the amount available to the embryo, and that mice with pre-existing hypomagnesemia due to genetic variation and/or dietary Mg2+ insufficiency at the time of conception and initiation of DTG treatment would be at increased risk for NTDs. We used two different approaches to test our hypothesis: 1) we selected mouse strains that had inherently different basal plasma Mg2+ levels and 2) placed mice on diets with different concentrations of Mg2+. Plasma and urine Mg2+ were determined prior to timed mating. Pregnant mice were treated daily with vehicle or DTG beginning on the day of conception and embryos examined for NTDs on gestational day 9.5. Plasma DTG was measured for pharmacokinetic analysis. Our results demonstrate that hypomagnesemia prior to conception, due to genetic variation and/or insufficient dietary Mg2+ intake, increases the risk for NTDs in mice exposed to DTG. We also analyzed whole-exome sequencing data from inbred mouse strains and identified 9 predicted deleterious missense variants in Fam111a that were unique to the LM/Bc strain. Human FAM111A variants are associated with hypomagnesemia and renal Mg2+ wasting. The LM/Bc strain exhibits this same phenotype and was the strain most susceptible to DTG-NTDs. Our results suggest that monitoring plasma Mg2+ levels in patients on ART regimens that include DTG, identifying other risk factors that impact Mg2+ homeostasis, and correcting deficiencies in this micronutrient might provide an effective strategy for mitigating NTD risk.

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Hereditary kidney diseases associated with hypomagnesemia

Cited by 5 publications

References 103 publications

EAST/SeSAME Syndrome and Beyond: The Spectrum of Kir4.1- and Kir5.1-Associated Channelopathies

EAST/SeSAME Syndrome and Beyond: The Spectrum of Kir4.1- and Kir5.1-Associated Channelopathies

Bartter Syndrome: Perspectives of a Pediatric Nephrologist

Gene-nutrient interactions that impact magnesium homeostasis increase risk for neural tube defects in mice exposed to dolutegravir

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