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Pediatric Nephrology (Berlin, Germany) Oct 2020Bartter and Gitelman syndromes are rare inherited tubulopathies characterized by hypokalaemic, hypochloraemic metabolic alkalosis. They are caused by mutations in at... (Review)
Review
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.
Topics: Bartter Syndrome; Chloride Channels; Gitelman Syndrome; Humans; Kidney Tubules, Distal; Loop of Henle; Mutation; Renal Reabsorption; Sodium
PubMed: 31664557
DOI: 10.1007/s00467-019-04371-y -
Cureus Apr 2023Milk-alkali syndrome is described by a triad of elevated levels of calcium, metabolic alkalosis, and acute kidney injury that historically occurred as a result of the...
Milk-alkali syndrome is described by a triad of elevated levels of calcium, metabolic alkalosis, and acute kidney injury that historically occurred as a result of the combined intake of large amounts of calcium and absorbable alkali. It is becoming common recently with the use of over-the-counter calcium supplements for osteoporosis treatment in postmenopausal women. We present a case of a 62-year-old female who presented with generalized weakness. She was noted to have severe hypercalcemia, and impaired renal function with a significant history of daily over-the-counter calcium supplement use and as-needed calcium carbonate use for gastroesophageal reflux disease (GERD). This case highlights the stepwise approach to the evaluation and management of hypercalcemia. She was appropriately treated with the resolution of hypercalcemia and presenting symptoms.
PubMed: 37252584
DOI: 10.7759/cureus.38171 -
Cureus May 2023Gitelman syndrome is a rare hereditary tubulopathy characterized by hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria. In this case report, we...
Gitelman syndrome is a rare hereditary tubulopathy characterized by hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria. In this case report, we describe a 21-year-old male who presented with myalgias, asthenia, general muscle weakness, and hypokalemia after receiving oral potassium supplementation for six months. Additional biochemical studies showed hypomagnesemia, metabolic alkalosis, and increased urinary potassium and magnesium excretion. Calcium urinary excretion was within the normal range, but 25-hydroxycholecalciferol levels were low. Systolic arterial hypertension was found, probably reflecting chronic hyperreninemic hyperaldosteronism. Genetic testing for mutations identified a pathogenic variant in homozygosity, which confirmed the Gitelman syndrome diagnosis. Treatment with chronic potassium and magnesium oral supplementation was started, as well as eplerenone and amiloride, with sustained correction of hypokalemia and hypomagnesemia.
PubMed: 37273382
DOI: 10.7759/cureus.38418 -
Frontiers in Medicine 2021The aim of the study was to describe the clinical characteristics of patients with or without respiratory alkalosis, and analyze the relationship of respiratory...
The aim of the study was to describe the clinical characteristics of patients with or without respiratory alkalosis, and analyze the relationship of respiratory alkalosis and the outcome of adult coronavirus disease 2019 (COVID-19) patients. Clinical and laboratory data of adult COVID-19 patients in a single center in China, were retrospectively collected and analyzed. The Kaplan-Meier (KM) curve and cox regression were adopted to analyze the association between respiratory alkalosis and prognosis of COVID-19 patients. Of 230 adult COVID-19 patients, 66 patients (28.7%) had respiratory alkalosis on admission. Of 66 patients, the median age was 53 years old (range, 21-84 years), and 43 (65.2%) were female. Compared with those without respiratory alkalosis, patients with respiratory alkalosis were significantly older ( = 0.002), had a higher proportion of female ( = 0.004), and showed higher ratios of underlying diseases including hypertension ( = 0.023) and cardiovascular disease ( = 0.028). Moreover, they demonstrated higher proportion of severe events ( = 0.001). Patients with respiratory alkalosis had a higher possibility of developing severe events compared with those without respiratory alkalosis (Log Rank = 0.001). After adjusting for gender, age, and comorbidities, patients with respiratory alkalosis still showed significantly elevated risks of developing to severe cases (HR 2.445, 95% CI 1.307-4.571, = 0.005) using cox regression analyses. Respiratory alkalosis as a common acid-base disorder in COVID-19 patients, was associated with a higher risk of developing severe event.
PubMed: 33981711
DOI: 10.3389/fmed.2021.564635 -
BJA Education Jun 2023
Review
PubMed: 37223696
DOI: 10.1016/j.bjae.2023.03.002 -
International Journal of Molecular... Aug 2023The Cl-transporting proteins CFTR, SLC26A9, and anoctamin (ANO1; ANO6) appear to have more in common than initially suspected, as they all participate in the pathogenic... (Review)
Review
The Cl-transporting proteins CFTR, SLC26A9, and anoctamin (ANO1; ANO6) appear to have more in common than initially suspected, as they all participate in the pathogenic process and clinical outcomes of airway and renal diseases. In the present review, we will therefore concentrate on recent findings concerning electrolyte transport in the airways and kidneys, and the role of CFTR, SLC26A9, and the anoctamins ANO1 and ANO6. Special emphasis will be placed on cystic fibrosis and asthma, as well as renal alkalosis and polycystic kidney disease. In essence, we will summarize recent evidence indicating that CFTR is the only relevant secretory Cl channel in airways under basal (nonstimulated) conditions and after stimulation by secretagogues. Information is provided on the expressions of ANO1 and ANO6, which are important for the correct expression and function of CFTR. In addition, there is evidence that the Cl transporter SLC26A9 expressed in the airways may have a reabsorptive rather than a Cl-secretory function. In the renal collecting ducts, bicarbonate secretion occurs through a synergistic action of CFTR and the Cl/HCO transporter SLC26A4 (pendrin), which is probably supported by ANO1. Finally, in autosomal dominant polycystic kidney disease (ADPKD), the secretory function of CFTR in renal cyst formation may have been overestimated, whereas ANO1 and ANO6 have now been shown to be crucial in ADPKD and therefore represent new pharmacological targets for the treatment of polycystic kidney disease.
Topics: Humans; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Polycystic Kidney, Autosomal Dominant; Polycystic Kidney Diseases; Anoctamins; Membrane Transport Proteins; Sulfate Transporters; Antiporters
PubMed: 37686084
DOI: 10.3390/ijms241713278 -
Journal of Translational Medicine Nov 2022Apparent mineralocorticoid excess is an autosomal recessive form of monogenic disease characterized by juvenile resistant low-renin hypertension, marked hypokalemic... (Review)
Review
Apparent mineralocorticoid excess is an autosomal recessive form of monogenic disease characterized by juvenile resistant low-renin hypertension, marked hypokalemic alkalosis, low aldosterone levels, and high ratios of cortisol to cortisone metabolites. It is caused by defects in the HSD11B2 gene, encoding the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which is primarily involved in the peripheral conversion of cortisol to cortisone. To date, over 50 deleterious HSD11B2 mutations have been identified worldwide. Multiple molecular mechanisms function in the lowering of 11β-HSD2 activity, including damaging protein stability, lowered affinity for the substrate and cofactor, and disrupting the dimer interface. Genetic polymorphism, environmental factors as well as epigenetic modifications may also offer an implicit explanation for the molecular pathogenesis of AME. A precise diagnosis depends on genetic testing, which allows for early and specific management to avoid the morbidity and mortality from target organ damage. In this review, we provide insights into the molecular genetics of classic and non-classic apparent mineralocorticoid excess and aim to offer a comprehensive overview of this monogenic disease.
Topics: Humans; Cortisone; 11-beta-Hydroxysteroid Dehydrogenase Type 2; Hydrocortisone; Hypertension; Molecular Biology; Mineralocorticoid Excess Syndrome, Apparent
PubMed: 36329487
DOI: 10.1186/s12967-022-03698-9 -
European Journal of Medical Research May 2024The base excess value (BE, mmol/L), not standard base excess (SBE), correctly calculated including pH, pCO (mmHg), sO (%) and cHb (g/dl) is a diagnostic tool for several... (Review)
Review
The base excess value (BE, mmol/L), not standard base excess (SBE), correctly calculated including pH, pCO (mmHg), sO (%) and cHb (g/dl) is a diagnostic tool for several in vivo events, e.g., mortality after multiple trauma or shock, acidosis, bleeding, clotting, artificial ventilation. In everyday clinical practice a few microlitres of blood (arterial, mixed venous or venous) are sufficient for optimal diagnostics of any metabolic acidosis or alkalosis.The same applies to a therapeutic tool-then referred to as potential base excess (BEpot)-for several in vitro assessments, e.g., solutions for infusion, sodium bicarbonate, blood products, packed red blood cells, plasma. Thus, BE or BEpot has been a parameter with exceptional clinical significance since 2007.
Topics: Humans; Acidosis; Acid-Base Imbalance; Acid-Base Equilibrium; Alkalosis
PubMed: 38735983
DOI: 10.1186/s40001-024-01796-6 -
BJA Education Apr 2023
Review
PubMed: 36960435
DOI: 10.1016/j.bjae.2023.01.002 -
Revista Medica de Chile Sep 2022Severe metabolic acidosis is defined by a pH < 7.2 with HCO3- < 8 mE- q/L in plasma. Its best treatment is to correct the underlying cause. However, acidemia produces... (Review)
Review
Severe metabolic acidosis is defined by a pH < 7.2 with HCO3- < 8 mE- q/L in plasma. Its best treatment is to correct the underlying cause. However, acidemia produces multiple complications such as resistance to the action of catecholamines, pulmonary vasoconstriction, impaired cardiovascular function, hyperkalemia, immunological dysregulation, respiratory muscle fatigue, neurological impairment, cellular dysfunction, and finally, it contributes to multisystemic failure. Intravenous NaHCO3 buffers severe acidemia, preventing the associated damage and gains time while the causal disease is corrected. Its indication requires a risk-benefit assessment, considering its complications. These are hypernatremia, hypokalemia, ionic hypocalcemia, rebound alkalosis, and intracellular acidosis. For this reason, therapy must be "adapted" and administered judiciously. The patient will require monitoring with serial evaluation of the internal environment, especially arterial blood gases, plasma electrolytes, and ionized calcium. Isotonic solutions should be preferred instead of hypertonic bicarbonate. The development of hypernatremia must be prevented, calcium must be provided for hypocalcemia to improve cardiovascular function. Furthermore, in mechanically ventilated patients, a respiratory response similar to the one that would develop physiologically, must be established to be able to extract excess CO2 and thus avoid intracellular acidosis. It is possible to estimate the bicarbonate deficit, speed, and volume of its infusion. However, the calculations are only for reference. More important is to start intravenous NaHCO3 when needed, administer it judiciously, manage its side effects, and continue it to a safe goal. In this review we address all the necessary elements to consider in the administration of intravenous NaHCO3, highlighting why it is the best buffer for the management of severe metabolic acidosis.
Topics: Humans; Acidosis; Sodium Bicarbonate; Administration, Intravenous; Risk Assessment; Severity of Illness Index
PubMed: 37358132
DOI: 10.4067/S0034-98872022000901214