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American Journal of Physiology. Renal... Apr 2013The study of human physiology is paramount to understanding disease and developing rational and targeted treatments. Conversely, the study of human disease can teach us... (Review)
Review
The study of human physiology is paramount to understanding disease and developing rational and targeted treatments. Conversely, the study of human disease can teach us a lot about physiology. Investigations into primary inherited nephrogenic diabetes insipidus (NDI) have contributed enormously to our understanding of the mechanisms of urinary concentration and identified the vasopressin receptor AVPR2, as well as the water channel aquaporin-2 (AQP2), as key players in water reabsorption in the collecting duct. Yet, there are also secondary forms of NDI, for instance as a complication of lithium treatment. The focus of this review is secondary NDI associated with inherited human diseases, such as Bartter syndrome or apparent mineralocorticoid excess. Currently, the underlying pathophysiology of this inherited secondary NDI is unclear, but there appears to be true AQP2 deficiency. To better understand the underlying mechanism(s), collaboration between clinical and experimental physiologists is essential to further investigate these observations in appropriate experimental models.
Topics: Aquaporin 2; Bartter Syndrome; Diabetes Insipidus, Nephrogenic; Fanconi Syndrome; Humans; Hypercalciuria; Hypokalemia; Receptors, Vasopressin
PubMed: 23364801
DOI: 10.1152/ajprenal.00639.2012 -
American Journal of Physiology. Renal... May 2016Since its identification as the underlying molecular cause of Bartter's syndrome type 3, ClC-Kb (ClC-K2 in rodents, henceforth it will be referred as ClC-Kb/2) is... (Review)
Review
Since its identification as the underlying molecular cause of Bartter's syndrome type 3, ClC-Kb (ClC-K2 in rodents, henceforth it will be referred as ClC-Kb/2) is proposed to play an important role in systemic electrolyte balance and blood pressure regulation by controlling basolateral Cl(-) exit in the distal renal tubular segments from the cortical thick ascending limb to the outer medullary collecting duct. Considerable experimental and clinical effort has been devoted to the identification and characterization of disease-causing mutations as well as control of the channel by its cofactor, barttin. However, we have only begun to unravel the role of ClC-Kb/2 in different tubular segments and to reveal the regulators of its expression and function, e.g., insulin and IGF-1. In this review we discuss recent experimental evidence in this regard and highlight unexplored questions critical to understanding ClC-Kb/2 physiology in the kidney.
Topics: Animals; Bartter Syndrome; Chloride Channels; Humans; Insulin; Insulin-Like Growth Factor I; Kidney Tubules, Collecting; Kidney Tubules, Distal
PubMed: 26792067
DOI: 10.1152/ajprenal.00577.2015 -
Journal of Cellular Physiology Mar 2021Na -K -Cl cotransporter 2 (NKCC2; SLC12A1) is an integral membrane protein that comes as three splice variants and mediates the cotranslocation of Na , K , and Cl ions... (Review)
Review
Na -K -Cl cotransporter 2 (NKCC2; SLC12A1) is an integral membrane protein that comes as three splice variants and mediates the cotranslocation of Na , K , and Cl ions through the apical membrane of the thick ascending loop of Henle (TALH). In doing so, and through the involvement of other ion transport systems, it allows this nephron segment to reclaim a large fraction of the ultrafiltered Na , Cl , Ca , Mg , and HCO loads. The functional relevance of NKCC2 in human is illustrated by the many abnormalities that result from the inactivation of this transport system through the use of loop diuretics or in the setting of inherited disorders. The following presentation aims at discussing the physiological roles and molecular characteristics of Na -K -Cl cotransport in the TALH and those of the individual NKCC2 splice variants more specifically. Many of the historical and recent data that have emerged from the experiments conducted will be outlined and their larger meaning will also be placed into perspective with the aid of various hypotheses.
Topics: Alternative Splicing; Amino Acid Sequence; Animals; Humans; Ion Transport; Loop of Henle; Models, Biological; Solute Carrier Family 12, Member 3
PubMed: 32776569
DOI: 10.1002/jcp.29997 -
International Journal of Clinical and... 2017Potassium is the most abundant cation in the intracellular fluid and it plays a vital role in the maintenance of normal cell functions. Thus, potassium homeostasis...
Potassium is the most abundant cation in the intracellular fluid and it plays a vital role in the maintenance of normal cell functions. Thus, potassium homeostasis across the cell membrane, is very critical because a tilt in this balance can result in different diseases that could be life threatening. Both Oxidative stress (OS) and potassium imbalance can cause life threatening health conditions. OS and abnormalities in potassium channel have been reported in neurodegenerative diseases. This review highlights the major factors involved in potassium homeostasis (dietary, hormonal, genetic, and physiologic influences), and discusses the major diseases and abnormalities associated with potassium imbalance including hypokalemia, hyperkalemia, hypertension, chronic kidney disease, and Gordon's syndrome, Bartter syndrome, and Gitelman syndrome.
PubMed: 29218312
DOI: 10.4103/ijcep.ijcep_43_17 -
Indian Journal of Critical Care... Feb 2022Bartter-like syndrome (BLS) is a constellation of biochemical abnormalities which include metabolic alkalosis, hypokalemia, hypocalcemia, hypomagnesemia with normal...
UNLABELLED
Bartter-like syndrome (BLS) is a constellation of biochemical abnormalities which include metabolic alkalosis, hypokalemia, hypocalcemia, hypomagnesemia with normal kidney function. BLS is a very rare syndrome and can be induced by certain diseases, antibiotics, diuretics, and antineoplastic drugs. Colistin is a polymicrobial bactericidal drug and currently re-emerged as the only salvation therapy against multidrug resistant bacilli especially in critically ill patients at intensive care units. Only an anecdotal case report of colistin-induced Bartter-like syndrome has been reported. We here report a case series of four critically ill patients who were on treatment with colistin and presented with serious metabolic disturbances.
HOW TO CITE THIS ARTICLE
Kumari A, Gupta P, Verma H, Kumar A, Thakur P, Sharma K. Colistin-induced Bartter-like Syndrome: Ponder before Treatment! Indian J Crit Care Med 2022;26(2):239-243.
PubMed: 35712740
DOI: 10.5005/jp-journals-10071-24117 -
The Turkish Journal of Pediatrics 2022Bartter syndrome (BS) is a group of autosomal-recessive tubular disorders and it is classified into five genetic subtypes. BS can also be classified by phenotype...
INTRODUCTION
Bartter syndrome (BS) is a group of autosomal-recessive tubular disorders and it is classified into five genetic subtypes. BS can also be classified by phenotype (antenatal, classic). Patients with mutations in the same gene can present different phenotypes. In the present study, target gene sequencing was performed to evaluate the genotype-phenotype relationship.
METHODS
Biochemical, clinical and renal ultrasonography results were collected at presentation and the last clinic visit. Genetic analyses were performed. The findings of patients with classical BS (cBS) and antenatal BS (aBS) at presentation and the last visit were compared.
RESULTS
Our study included 21 patients (12 female, 57.1%) from 20 families with BS. The median age at diagnosis was 8 months and the median follow-up period was 39 months. The most frequent complaint was growth failure. We have found 18 different types of mutations in four genes, including nine in the CLCNKB gene, seven in the SLCA12A1 gene, one in the KCNJ1 gene and one in the BSND gene. In ten patients, nine different types of CLCNKB gene mutations were detected, five of them were novel. Seven different mutations in the SLC12A1 gene were detected in eight patients, five of them were novel. Compared to patients with aBS and cBS, prematurity was significantly higher in the group with aBS. Nephrocalcinosis was present in only one patient with cBS, all the ten hypercalciuric patients with aBS had nephrocalcinosis at the time of diagnosis and the last visit. The mean height standard deviation score (SDS) of patients with aBS were significantly lower than the cBS group at the time of presentation. The mean weight SDS at the time of presentation was worse in patients with aBS than in patients with cBS. The mean plasma potassium and chloride concentrations were significantly lower in the patients with cBS at the time of diagnosis.
CONCLUSIONS
This investigation revealed the mutation characteristics and phenotype-genotype relationship of our patients and provided valuable data for genetic counseling.
Topics: Female; Humans; Pregnancy; Bartter Syndrome; Chloride Channels; Genotype; Mutation; Nephrocalcinosis; Phenotype
PubMed: 36305432
DOI: 10.24953/turkjped.2021.4697 -
American Journal of Physiology. Renal... Jun 2015The mutations in the CLCNKB gene encoding the ClC-Kb chloride channel are responsible for Bartter syndrome type 3, one of the four variants of Bartter syndrome in the... (Review)
Review
The mutations in the CLCNKB gene encoding the ClC-Kb chloride channel are responsible for Bartter syndrome type 3, one of the four variants of Bartter syndrome in the genetically based nomenclature. All forms of Bartter syndrome are characterized by hypokalemia, metabolic alkalosis, and secondary hyperaldosteronism, but Bartter syndrome type 3 has the most heterogeneous presentation, extending from severe to very mild. A relatively large number of CLCNKB mutations have been reported, including gene deletions and nonsense or missense mutations. However, only 20 CLCNKB mutations have been functionally analyzed, due to technical difficulties regarding ClC-Kb functional expression in heterologous systems. This review provides an overview of recent progress in the functional consequences of CLCNKB mutations on ClC-Kb chloride channel activity. It has been observed that 1) all ClC-Kb mutants have an impaired expression at the membrane; and 2) a minority of the mutants combines reduced membrane expression with altered pH-dependent channel gating. Although further investigation is needed to fully characterize disease pathogenesis, Bartter syndrome type 3 probably belongs to the large family of conformational diseases, in which the mutations destabilize channel structure, inducing ClC-Kb retention in the endoplasmic reticulum and accelerated channel degradation.
Topics: Animals; Anion Transport Proteins; Bartter Syndrome; Chloride Channels; DNA Mutational Analysis; Genetic Predisposition to Disease; Humans; Mutation
PubMed: 25810436
DOI: 10.1152/ajprenal.00004.2015 -
Journal of Nephrology Apr 2021
Topics: Bartter Syndrome; COVID-19; Comorbidity; Disease Management; Gitelman Syndrome; Humans; Italy; Pandemics; SARS-CoV-2
PubMed: 33387334
DOI: 10.1007/s40620-020-00951-6 -
Kidney & Blood Pressure Research 2022
Topics: Humans; Angiotensin II; COVID-19; Bartter Syndrome
PubMed: 36063794
DOI: 10.1159/000526791 -
The Open Ophthalmology Journal 2017Sclerochoroidal calcification (SCC) is a rare and benign condition found mostly in middle-aged and elderly Caucasian men, characterized by multiple yellow-white lesions...
BACKGROUND
Sclerochoroidal calcification (SCC) is a rare and benign condition found mostly in middle-aged and elderly Caucasian men, characterized by multiple yellow-white lesions seen most commonly in the temporal regions of the fundus. While they may be concerning for benign tumors, primary neoplasias or metastases, SCCs most commonly present as asymptomatic findings during routine ophthalmologic testing and have a very good prognosis as they rarely cause visual deficits.
OBJECTIVE
To report and describe the findings in a case of bilateral idiopathic sclerochoroidal calcifications.
METHODS
A retrospective case report.
RESULTS
Repeated ophthalmological exams, including fundoscopic examination, ultrasonography, optical coherence tomography and fluorescein angiography, were all consistent bilateral idiopathic sclerochoroidal calcifications.
CONCLUSION
While most cases of idiopathic sclerochoroidal calcifications represent a benign ophthalmological condition, there are known associations with other systemic conditions, such as hyperthyroidism, hyperparathyroidism, Bartter's syndrome and Gitelman's syndrome. It is for this reason that these patients warrant a full systemic work-up in addition to careful ophthalmological monitoring.
PubMed: 28553424
DOI: 10.2174/1874364101711010076