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Frontiers in Pediatrics 2022Bartter syndrome (BS) is a rare tubulopathy that causes polyuria, hypokalemia, hypochloremic metabolic alkalosis, and normotensive hyperreninemic hyperaldosteronism. It... (Review)
Review
Bartter syndrome (BS) is a rare tubulopathy that causes polyuria, hypokalemia, hypochloremic metabolic alkalosis, and normotensive hyperreninemic hyperaldosteronism. It is characterized by locus, clinical, and allelic heterogeneity. Types 1-4 of BS are inherited according to an autosomal recessive pattern, while type 5, which is transient, is X linked. There are specific correlations between the clinical expression and the molecular defect, but since it is a rare disease, such studies are rare. Therapeutic interventions are different, being correlated with types of BS.
PubMed: 35722471
DOI: 10.3389/fped.2022.908655 -
Seminars in Nephrology Jul 2023The tubular system of the kidneys is a complex series of morphologic and functional units orchestrating the content of tubular fluid as it flows along the nephron and... (Review)
Review
The tubular system of the kidneys is a complex series of morphologic and functional units orchestrating the content of tubular fluid as it flows along the nephron and collecting ducts. Renal tubules maintain body water, regulate electrolytes and acid-base balance, reabsorb precious organic solutes, and eliminate specific metabolites, toxins, and drugs. In addition, decisive mechanisms to adjust blood pressure are governed by the renal tubules. Genetic as well as acquired disorders of these tubular functions may cause serious diseases that manifest both in childhood and adulthood. This article addresses a selection of tubulopathies and the underlying pathomechanisms, while highlighting the important differences in pediatric and adult nephrology care. These range from rare monogenic conditions such as nephrogenic diabetes insipidus, cystinosis, and Bartter syndrome that present in childhood, to the genetic and acquired tubular pathologies causing hypertension or nephrolithiasis that are more prevalent in adults. Both pediatric and adult nephrologists must be aware of these conditions and the age-dependent manifestations that warrant close interaction between the two subspecialties.
Topics: Humans; Child; Nephrology; Kidney Tubules; Kidney; Diabetes Insipidus, Nephrogenic; Nephrons
PubMed: 37968178
DOI: 10.1016/j.semnephrol.2023.151437 -
Clinical Kidney Journal Jun 2018Bartter and Gitelman syndromes are autosomal recessive disorders of renal tubular salt handling. Due to their rarity, limited long-term data are available to inform...
BACKGROUND
Bartter and Gitelman syndromes are autosomal recessive disorders of renal tubular salt handling. Due to their rarity, limited long-term data are available to inform prognosis and management.
METHODS
Long-term longitudinal data were analysed for 45 children with pathogenic variants in ( = 8), ( = 8), ( = 17), ( = 2) and ( = 10) seen at a single centre between 1984 and 2014. Median follow-up was 8.9 [interquartile range (IQR) 0.7-18.1] years.
RESULTS
Polyhydramnios and prematurity were seen in children with and mutations. Patients with mutations had the lowest serum potassium and serum magnesium and the highest serum bicarbonate levels. Fractional excretion of chloride was >0.5% in all patients prior to supplementation. Nephrocalcinosis at presentation was present in the majority of patients with and mutations, while it was only present in one patient with and not in or mutations. Growth was impaired, but within the normal range (median height standard deviation score -1.2 at the last follow-up). Impaired estimated glomerular filtration rate (eGFR <90 mL/min/1.73 m) at the last follow-up was seen predominantly with [71 mL/min/1.73 m (IQR 46-74)] and [62 mL/min/1.73 m (IQR 48-72)] mutations. Pathological albuminuria was detected in 31/45 children.
CONCLUSIONS
Patients with Bartter and Gitelman syndromes had a satisfactory prognosis during childhood. However, decreased eGFR and pathologic proteinuria was evident in a large number of these patients, highlighting the need to monitor glomerular as well as tubular function. Electrolyte abnormalities were most severe in mutations both at presentation and during follow-up. Fractional excretion of chloride prior to supplementation is a useful screening investigation in children with hypokalaemic alkalosis to establish renal salt wasting.
PubMed: 29942493
DOI: 10.1093/ckj/sfx118 -
Journal of Eating Disorders Feb 2023Eating disorders are psychiatric disorders with significant and widespread medical complications, including renal disorders. Renal disease is not uncommon in patients... (Review)
Review
Eating disorders are psychiatric disorders with significant and widespread medical complications, including renal disorders. Renal disease is not uncommon in patients with eating disorders but is often unrecognized. It includes both acute renal injury and progression to chronic kidney disease requiring dialysis. Electrolyte abnormalities including hyponatremia, hypokalemia, and metabolic alkalosis are common in eating disorders and vary depending on whether patients engage in purging behaviors. Chronic hypokalemia due to purging in patients with anorexia nervosa-binge purge subtype or bulimia nervosa can lead to hypokalemic nephropathy and chronic kidney disease. Additional electrolyte derangements are seen during refeeding, including hypophosphatemia, hypokalemia, and hypomagnesemia. Patients can also develop Pseudo-Bartter's syndrome which leads to edema and rapid weight gain in patients who cease purging behavior. Clinicians and patients should be aware of these complications in order to provide education and early detection and prevention.
PubMed: 36803805
DOI: 10.1186/s40337-023-00751-w -
Nephrology, Dialysis, Transplantation :... Nov 2022Small cohort studies have reported high parathyroid hormone (PTH) levels in patients with Bartter syndrome and lower serum phosphate levels have anecdotally been...
BACKGROUND
Small cohort studies have reported high parathyroid hormone (PTH) levels in patients with Bartter syndrome and lower serum phosphate levels have anecdotally been reported in patients with Gitelman syndrome. In this cross-sectional study, we assessed PTH and phosphate homeostasis in a large cohort of patients with salt-losing tubulopathies.
METHODS
Clinical and laboratory data of 589 patients with Bartter and Gitelman syndrome were provided by members of the European Rare Kidney Diseases Reference Network (ERKNet) and the European Society for Paediatric Nephrology (ESPN).
RESULTS
A total of 285 patients with Bartter syndrome and 304 patients with Gitelman syndrome were included for analysis. Patients with Bartter syndrome type I and II had the highest median PTH level (7.5 pmol/L) and 56% had hyperparathyroidism (PTH >7.0 pmol/L). Serum calcium was slightly lower in Bartter syndrome type I and II patients with hyperparathyroidism (2.42 versus 2.49 mmol/L; P = .038) compared to those with normal PTH levels and correlated inversely with PTH (rs -0.253; P = .009). Serum phosphate and urinary phosphate excretion did not correlate with PTH. Overall, 22% of patients had low serum phosphate levels (phosphate-standard deviation score < -2), with the highest prevalence in patients with Bartter syndrome type III (32%). Serum phosphate correlated with tubular maximum reabsorption of phosphate/glomerular filtration rate (TmP/GFR) (rs 0.699; P < .001), suggesting renal phosphate wasting.
CONCLUSIONS
Hyperparathyroidism is frequent in patients with Bartter syndrome type I and II. Low serum phosphate is observed in a significant number of patients with Bartter and Gitelman syndrome and appears associated with renal phosphate wasting.
Topics: Child; Humans; Gitelman Syndrome; Parathyroid Hormone; Bartter Syndrome; Cross-Sectional Studies; Hyperparathyroidism; Phosphates; Homeostasis; Calcium
PubMed: 35137195
DOI: 10.1093/ndt/gfac029 -
Acta Biochimica Polonica 2000There are many diseases related to ion channels. Mutations in muscle voltage-gated sodium, potassium, calcium and chloride channels, and acetylcholine-gated channel may... (Review)
Review
There are many diseases related to ion channels. Mutations in muscle voltage-gated sodium, potassium, calcium and chloride channels, and acetylcholine-gated channel may lead to such physiological disorders as hyper- and hypokalemic periodic paralysis, myotonias, long QT syndrome, Brugada syndrome, malignant hyperthermia and myasthenia. Neuronal disorders, e.g., epilepsy, episodic ataxia, familial hemiplegic migraine, Lambert-Eaton myasthenic syndrome, Alzheimer's disease, Parkinson's disease, schizophrenia, hyperekplexia may result from dysfunction of voltage-gated sodium, potassium and calcium channels, or acetylcholine- and glycine-gated channels. Some kidney disorders, e.g., Bartter's syndrome, policystic kidney disease and Dent's disease, secretion disorders, e.g., hyperinsulinemic hypoglycemia of infancy and cystic fibrosis, vision disorders, e.g., congenital stationary night blindness and total colour-blindness may also be linked to mutations in ion channels.
Topics: Animals; Calcium Channels; Chloride Channels; Cystic Fibrosis Transmembrane Conductance Regulator; Epilepsy; Heart Diseases; Humans; Ion Channels; Malignant Hyperthermia; Metabolic Diseases; Muscular Diseases; Mutation; Potassium Channels; Receptors, Glycine; Receptors, Nicotinic; Sodium Channels
PubMed: 11310970
DOI: No ID Found -
Journal of the American Society of... Mar 2018Renal tubulopathies provide insights into the inner workings of the kidney, yet also pose therapeutic challenges. Because of the central nature of sodium in tubular... (Review)
Review
Renal tubulopathies provide insights into the inner workings of the kidney, yet also pose therapeutic challenges. Because of the central nature of sodium in tubular transport physiology, disorders of sodium handling may affect virtually all aspects of the homeostatic functions of the kidney. Yet, owing to the rarity of these disorders, little clinical evidence regarding treatment exists. Consequently, treatment can vary widely between individual physicians and centers and is based mainly on understanding of renal physiology, reported clinical observations, and individual experiences. Salt-losing tubulopathies can affect all tubular segments, from the proximal tubule to the collecting duct. But the more frequently observed disorders are Bartter and Gitelman syndrome, which affect salt transport in the thick ascending limb of Henle's loop and/or the distal convoluted tubule, and these disorders generate the greatest controversies regarding management. Here, we review clinical and molecular aspects of salt-losing tubulopathies and discuss novel insights provided mainly by genetic investigations and retrospective clinical reviews. Additionally, we discuss controversial topics in the management of these disorders to highlight areas of importance for future clinical trials. International collaboration will be required to perform clinical studies to inform the treatment of these rare disorders.
Topics: Adaptor Proteins, Signal Transducing; Adolescent; Antigens, Neoplasm; Bartter Syndrome; Child; Child, Preschool; Fanconi Syndrome; Gitelman Syndrome; Humans; Infant; Infant, Newborn; Kidney Tubules; Renal Reabsorption; Sodium Chloride; Solute Carrier Proteins
PubMed: 29237739
DOI: 10.1681/ASN.2017060600 -
Zhejiang Da Xue Xue Bao. Yi Xue Ban =... Apr 2023Renal calculus is a common disease with complex etiology and high recurrence rate. Recent studies have revealed that gene mutations may lead to metabolic defects which... (Review)
Review
Renal calculus is a common disease with complex etiology and high recurrence rate. Recent studies have revealed that gene mutations may lead to metabolic defects which are associated with the formation of renal calculus, and single gene mutation is involved in relative high proportion of renal calculus. Gene mutations cause changes in enzyme function, metabolic pathway, ion transport, and receptor sensitivity, causing defects in oxalic acid metabolism, cystine metabolism, calcium ion metabolism, or purine metabolism, which may lead to the formation of renal calculus. The hereditary conditions associated with renal calculus include primary hyperoxaluria, cystinuria, Dent disease, familial hypomagnesemia with hypercalciuria and nephrocalcinosis, Bartter syndrome, primary distal renal tubular acidosis, infant hypercalcemia, hereditary hypophosphatemic rickets with hypercalciuria, adenine phosphoribosyltransferase deficiency, hypoxanthine-guanine phosphoribosyltransferase deficiency, and hereditary xanthinuria. This article reviews the research progress on renal calculus associated with inborn error of metabolism, to provide reference for early screening, diagnosis, treatment, prevention and recurrence of renal calculus.
Topics: Infant; Humans; Hypercalciuria; Kidney Calculi; Urolithiasis; Nephrocalcinosis; Metabolism, Inborn Errors
PubMed: 37283101
DOI: 10.3724/zdxbyxb-2022-0698 -
Nephron. Physiology 2006Genetic studies into rare inborn errors of renal tubular sodium handling in man have brought many interesting, sometimes surprising insights into how we can maintain our... (Review)
Review
Genetic studies into rare inborn errors of renal tubular sodium handling in man have brought many interesting, sometimes surprising insights into how we can maintain our bodies' electrolytes and fluids homeostasis. The cloning and identification of sodium transporting genes and proteins like NHE3, NKCC2, ROMK, CLCNKB, NCC, and EnaC has considerably improved our understanding of renal salt handling. Subsequently, studies of genetically engineered animals provided even more insight into the complex renal physiology. The recent discovery of the WNK kinases as regulators and integrators of specific renal transport pathways helped elucidate this further and lets us start to appreciate the full complexity of renal sodium handling. We summarize recent findings in the field in the context of human diseases and a pathophysiologic basis for their treatment.
Topics: Animals; Bartter Syndrome; Humans; Hypokalemia; Kidney Tubules; Salts
PubMed: 16785747
DOI: 10.1159/000094001 -
Journal of Molecular Biology Apr 2017Melanoma antigen (MAGE) genes are conserved in all eukaryotes and encode for proteins sharing a common MAGE homology domain. Although only a single MAGE gene exists in... (Review)
Review
Melanoma antigen (MAGE) genes are conserved in all eukaryotes and encode for proteins sharing a common MAGE homology domain. Although only a single MAGE gene exists in lower eukaryotes, the MAGE family rapidly expanded in eutherians and consists of more than 50 highly conserved genes in humans. A subset of MAGEs initially garnered interest as cancer biomarkers and immunotherapeutic targets due to their antigenic properties and unique expression pattern that is primary restricted to germ cells and aberrantly reactivated in various cancers. However, further investigation revealed that MAGEs not only drive tumorigenesis but also regulate pathways essential for diverse cellular and developmental processes. Therefore, MAGEs are implicated in a broad range of diseases including neurodevelopmental, renal, and lung disorders, and cancer. Recent biochemical and biophysical studies indicate that MAGEs assemble with E3 RING ubiquitin ligases to form MAGE-RING ligases (MRLs) and act as regulators of ubiquitination by modulating ligase activity, substrate specification, and subcellular localization. Here, we present a comprehensive guide to MAGEs highlighting the molecular mechanisms of MRLs and their physiological roles in germ cell and neural development, oncogenic functions in cancer, and potential as therapeutic targets in disease.
Topics: Antigens, Neoplasm; Bartter Syndrome; Chromosome Mapping; Evolution, Molecular; Gene Expression Regulation, Developmental; Humans; Immunotherapy; Melanoma-Specific Antigens; Multigene Family; Neoplasms; Prader-Willi Syndrome; Ubiquitin-Protein Ligases; Ubiquitination
PubMed: 28300603
DOI: 10.1016/j.jmb.2017.03.005