2,825 results on '"Acidosis, renal tubular"'
Search Results
102. Screening and function discussion of a hereditary renal tubular acidosis family pathogenic gene
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Jie-Wei Luo, Yao-Bin Zhu, Zhao Jin, Jianbin Huang, Xin-Fu Lin, Han-Lu Wang, Zhu-Ting Fang, and Li Chen
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Male ,0301 basic medicine ,Heterozygote ,Vacuolar Proton-Translocating ATPases ,Cancer Research ,Hearing Loss, Sensorineural ,Immunology ,030232 urology & nephrology ,Biology ,Kidney ,Article ,Renal tubular acidosis ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Exon ,symbols.namesake ,0302 clinical medicine ,Distal renal tubular acidosis ,medicine ,Humans ,lcsh:QH573-671 ,Gene ,Sanger sequencing ,Kidney diseases ,lcsh:Cytology ,DNA damage and repair ,HEK 293 cells ,Heterozygote advantage ,Acidosis, Renal Tubular ,Exons ,Cell Biology ,Transfection ,medicine.disease ,Molecular biology ,030104 developmental biology ,Mutation ,symbols ,Female - Abstract
Hereditary distal renal tubular acidosis (dRTA) is a rare disease of H+ excretion defect of α-intercalated cells in renal collecting duct, caused by decreased V-ATPase function due to mutations in the ATP6V1B1 or ATP6V0A4 genes. In the present study, a genetic family with 5 members of the complete dRTA phenotype were found with distal tubule H+ secretion disorder, hypokalemia, osteoporosis, and kidney stones. A variant NM_020632.2:c.1631C > T (p.Ser544Leu) in exon 16 on an ATP6V0A4 gene associated with dRTA was detected by next generation sequencing target region capture technique and verified by Sanger sequencing, which suggested that except for one of the patients who did not receive the test, the other four patients all carried the p.S544L heterozygote. In transfected HEK293T cells, cells carrying p.S544L-mut showed early weaker ATPase activity and a slower Phi recovery rate after rapid acidification. By immunofluorescence localization, it was observed that the expression level of p.S544L-mut on the cell membrane increased and the distribution was uneven. Co-immunoprecipitation showed the a4 subunit of ATP6V0A4/p.S544L-mut could not bind to the B1 subunit, which might affect the correct assembly of V-ATPase. The present study of dRTA family suggests that the p.S544L variant may be inherited in a dominant manner.
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- 2020
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103. [The 475th case: renal tubular acidosis, renal failure, anemia, and lactic acidosis]
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G, Chen, D, Wu, and M X, Li
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Vomiting ,Biopsy ,Lymphoma, Non-Hodgkin ,Pneumonia, Pneumocystis ,Anemia ,Antineoplastic Agents ,Nausea ,Acidosis, Renal Tubular ,Middle Aged ,Treatment Refusal ,Sodium Bicarbonate ,Creatinine ,Humans ,Prednisone ,Acidosis, Lactic ,Female ,Renal Insufficiency ,Erythropoietin - Abstract
A 47-year-old female patient presented nausea and vomiting for half a year and elevated serum creatinine for 3 days. Proximal renal tubular acidosis (RTA) complicated with anemiawas confirmed after admission. Secondary factors, such as autoimmune disease, drugs, poison, monoclonal gammopathy, were excluded. Renal biopsy revealed acute interstitial nephritis. The patient was administrated with daily prednisone 50 mg, sodium bicarbonate 4 g, 3 times per day, erythropoietin 3 000 U, 2 times per week, combined with potassium, calcium, and calcitriol tablets. Serum creatinine reduced to 90 μmol/L. However nausea and vomiting deteriorated with lactic acidosis. Bone marrow biopsy indicated the diagnosis of non-Hodgkin lymphoma, therefore the patient was treated with chemotherapy. Although metabolic acidosis improved gradually after chemotherapy, severe pneumocystis carinii pneumonia developed two weeks later. The patient refused further treatment and was discharged.患者女性,47岁。因恶心、呕吐半年,发现肾功能异常(血肌酐255 μmol/L)3 d就诊,入院检查发现近端肾小管酸中毒合并贫血,排除自身免疫病、药物、毒物、单克隆免疫球蛋白病等继发因素,肾脏穿刺活检组织病理提示急性间质性肾炎,予泼尼松50 mg/d;碳酸氢钠4 g,3次/d;促红细胞生成素3 000 U,2次/周;氯化钾缓释片500 mg,3次/d;碳酸钙500 mg,3次/d;骨化三醇0.5 μg,1次/d。患者血肌酐恢复至90 μmol/L,但随诊期间患者恶心呕吐加重,再次检查发现合并乳酸酸中毒(乳酸14.1 mmol/L)。骨髓穿刺提示非霍奇金淋巴瘤,予CHOP方案化疗,期间乳酸酸中毒逐步好转(乳酸由14.5 mmol/L降至3.1 mmol/L),半个月后发生重症耶氏肺孢子菌肺炎,最终放弃治疗出院。.
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- 2020
104. ATP6V1B1 recurrent mutations in Algerian deaf patients associated with renal tubular acidosis
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Crystel Bonnet, Sonia Talbi, Christine Petit, Fatima Ammar-Khodja, Merieme Djebbar, Farid Boudjenah, Malika Dahmani, Sofiane Ouhab, Université des Sciences et de la Technologie Houari Boumediene = University of Sciences and Technology Houari Boumediene [Alger] (USTHB), Établissement Public Hospitalier Bachir Mentouri, Service ORL [Tizi Ouzou], Centre Hospitalier Universitaire Mohamed Nedir, Institut de la Vision, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique et Physiologie de l'Audition, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Collège de France - Chaire Génétique et physiologie cellulaire, Collège de France (CdF (institution)), We are grateful to the family members for their participation in this study. The study was supported by National Veterinary School and the Algerian Ministry of Higher Education and Scientific research., Université des Sciences et de la Technologie Houari Boumediene [Alger] (USTHB), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Chaire Génétique et physiologie cellulaire
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Male ,MESH: Acidosis, Renal Tubular ,MESH: Introns ,[SDV]Life Sciences [q-bio] ,Gene mutation ,Gastroenterology ,Renal tubular acidosis ,Sensorineural hearing loss (SNHL) ,0302 clinical medicine ,Distal renal tubular acidosis ,030223 otorhinolaryngology ,Frameshift Mutation ,education.field_of_study ,Enlarged vestibular aqueduct (EVA) ,MESH: Vestibular Aqueduct ,Homozygote ,MESH: Frameshift Mutation ,General Medicine ,Acidosis, Renal Tubular ,Exons ,MESH: Infant ,3. Good health ,Child, Preschool ,Sensorineural hearing loss ,Female ,MESH: Algeria ,MESH: Homozygote ,medicine.medical_specialty ,Vacuolar Proton-Translocating ATPases ,Distal renal tubular acidosis (dRTA) ,Hearing Loss, Sensorineural ,Population ,MESH: Vacuolar Proton-Translocating ATPases ,Frameshift mutation ,Vestibular Aqueduct ,03 medical and health sciences ,030225 pediatrics ,Internal medicine ,medicine ,otorhinolaryngologic diseases ,Humans ,education ,ATP6V1B1 ,MESH: Humans ,business.industry ,MESH: Child, Preschool ,Infant ,Metabolic acidosis ,medicine.disease ,Introns ,MESH: Male ,Otorhinolaryngology ,MESH: Hearing Loss, Sensorineural ,Algeria ,Pediatrics, Perinatology and Child Health ,business ,MESH: Exons ,MESH: Female ,Enlarged vestibular aqueduct - Abstract
International audience; Hereditary distal renal tubular acidosis (dRTA) is a rare disorder characterized by metabolic acidosis due to impaired renal acid excretion. To date, three genes (ATP6V1B1, ATP6V0A4 and SLC4A1) have been reported to be responsible for this genetic disorder. Notably, mutations of ATP6V1B1 gene, which encode B1-subunit of H + -ATPase pump cause distal renal tubular acidosis often, associated with sensorineural hearing loss (SNHL). Furthermore, enlarged vestibular aqueduct (EVA) was also described in some patients with ATP6V1B1 mutations. Four Algerian unrelated patients presented with dRTA and SNHL were recruited. The ATP6V1B1 gene was preferentially analyzed in all these patients by Sanger sequencing. We identified two previously reported variants in ATP6V1B1 gene: a frameshift mutation (c.1155dupC: p.(Ile386Hisfs*56) in exon 12 and a splicing mutation in intron 2 (c.175-1G > C: p?). Both mutations were homozygous in affected members. Interestingly, one patient with p.(Ile386Hisfs*56) mutation presented profound SNHL and bilateral enlarged vestibular aqueduct (EVA). Our study indicates the importance contribution of ATP6V1B1 gene mutations to the pathogenesis of the dRTA in the Algerian population and will contribute to introducing principles to predict the characteristics of the dRTA in patients. Thus, screening for this gene could allow rapid patient management and provide adequate genetic counseling.
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- 2020
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105. Tenofovir disoproxil fumarate-induced distal renal tubular acidosis: A case report
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Sudha Vidyasagar, Danturulu Muralidhar Varma, Rozhin Salimi, Radhakrishnan Rajesh, B. Nandakrishna, and Ishmath Begum
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Drug ,medicine.medical_specialty ,Tenofovir ,Anti-HIV Agents ,viruses ,media_common.quotation_subject ,Urology ,Human immunodeficiency virus (HIV) ,HIV Infections ,Dermatology ,medicine.disease_cause ,030226 pharmacology & pharmacy ,Nephrotoxicity ,Renal tubular acidosis ,03 medical and health sciences ,0302 clinical medicine ,Distal renal tubular acidosis ,Proximal rta ,medicine ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,media_common ,business.industry ,Public Health, Environmental and Occupational Health ,Acidosis, Renal Tubular ,biochemical phenomena, metabolism, and nutrition ,Middle Aged ,medicine.disease ,Infectious Diseases ,Treatment Outcome ,Female ,business ,Adverse drug reaction ,medicine.drug - Abstract
Tenofovir disoproxil fumarate (TDF) is an anti-retroviral drug that is known to cause nephrotoxicity including renal tubular acidosis (RTA). With increasing literature on proximal RTA caused by TDF, reports on distal RTA are scarce, with only one case reported so far. We report a case of distal RTA in patient living with human immunodeficiency virus, who presented with nausea and fatigue giving a history of TDF-based therapy for two years. Laboratory investigations revealed non-anion gap metabolic acidosis, positive urine anion gap, hyperchloremia, and hypokalemia. The patient improved after discontinuing TDF and supportive management.
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- 2020
106. Hypophosphataemic osteomalacia due to cadmium exposure in the silver industry
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Johan Paul, Thomas V Paul, Nihal Thomas, and Kripa Elizabeth Cherian
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Adult ,Male ,Cadmium Poisoning ,Silver ,Hypophosphatemia ,chemistry.chemical_element ,India ,030204 cardiovascular system & hematology ,010501 environmental sciences ,01 natural sciences ,03 medical and health sciences ,0302 clinical medicine ,Environmental health ,Medicine ,Humans ,0105 earth and related environmental sciences ,Cadmium ,Osteomalacia ,business.industry ,Public Health, Environmental and Occupational Health ,Heavy metals ,Acidosis, Renal Tubular ,medicine.disease ,Occupational Diseases ,CADMIUM EXPOSURE ,chemistry ,business - Abstract
Chronic heavy metal exposure and the health hazards that ensue are important public-health problems. We highlight the occurrence of hypophosphataemic osteomalacia due to chronic cadmium exposure in the silver industry in India. Three silversmiths presented similarly with clinical, biochemical and radiological evidence of hypophosphataemic osteomalacia. Considering their occupation, their blood samples were screened for heavy metals and were found to have toxic levels of cadmium. They were initiated on neutral phosphate and calcitriol. On follow-up, they reported significant reduction in severity of symptoms. It is essential to maintain a high index of suspicion in diagnosing this condition. A thorough knowledge of the occupational background of patients, as well as ambient conditions at the workplace is of utmost importance in contemplating the possibility of such rare occurrences. Moreover, regulatory agencies and policy makers ought to survey the silver industry and ensure that the metals used are within permissible safe limits of exposure.
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- 2020
107. A rare case of autosomal recessive ATP6V0A4 variant of distal renal tubular acidosis in a young female with recurrent nephrolithiasis
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Priya Haridas Anupama, Sneha Haridas Anupama, Lakshmi Shanmugasundaram, and Georgi Abraham
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Adult ,medicine.medical_specialty ,Vacuolar Proton-Translocating ATPases ,Nonsense mutation ,lcsh:Medicine ,Anion gap ,Gene mutation ,Nephrolithiasis ,Distal renal tubular acidosis ,Recurrence ,Internal medicine ,medicine ,Humans ,Hypercalciuria ,Acidosis ,Transplantation ,business.industry ,lcsh:R ,Acidosis, Renal Tubular ,medicine.disease ,Hypokalemia ,Endocrinology ,Nephrology ,Female ,medicine.symptom ,Nephrocalcinosis ,business - Abstract
Homozygous autosomal recessive distal renal tubular acidosis (dRTA) is a rare entity. The intercalated cells in the collecting ducts are defective in apical proton secretion or basolateral bicarbonate reabsorption, due to mutations in genes encoding for proteins in a4 and B1 subunits of the V-ATPase and the anion exchanger Cl-/HCO- (kAE1). This results in decreased ammonium (NH4+) excretion and defective urine acidification. dRTA is characterized by hyperchloremic metabolic acidosis with normal anion gap, hypokalemia, hypercalciuria, hypocitranuria, and nephrocalcinosis. Autosomal recessive dRTA is associated with mutation in ATP6V1B1 (2p13) or ATP6V0A4 (7q34) genes. ATP6V1B1 mutation is associated with early – onset sensory neural hearing loss (SNHL), whereas ATP6V0A4 gene mutation may be associated with early-to late-onset SNHL. We report the case of a 30-year-old married woman diagnosed with dRTA at three months of age with mild SNHL, showing homogygous nonsense mutation in exon 3 of the ATP6V0A4 gene that resulted in a stop codon and premature truncation of the protein at codon 6.
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- 2020
108. Five Novel Mutations in Chinese Children with Primary Distal Renal Tubular Acidosis
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Xiangzhong Zhao, Cui Wang, Yanhua Lang, Ruixiao Zhang, Yanxia Gao, Zeqing Chen, Jingru Lu, and Leping Shao
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Adult ,Male ,0301 basic medicine ,China ,Vacuolar Proton-Translocating ATPases ,Pathology ,medicine.medical_specialty ,Adolescent ,DNA Mutational Analysis ,Mutation, Missense ,030232 urology & nephrology ,03 medical and health sciences ,0302 clinical medicine ,Asian People ,Distal renal tubular acidosis ,Anion Exchange Protein 1, Erythrocyte ,Humans ,Medicine ,Child ,Genetic Association Studies ,Genetics (clinical) ,business.industry ,High-Throughput Nucleotide Sequencing ,Infant ,Acidosis, Renal Tubular ,Exons ,General Medicine ,Middle Aged ,medicine.disease ,Pedigree ,030104 developmental biology ,Child, Preschool ,Mutation ,Female ,business ,Novel mutation - Abstract
To analyze the variants of the potential causative genes in five Chinese patients with primary distal renal tubular acidosis (dRTA) from five unrelated families, and to explore their possible genotype-phenotype correlations, so as to raise the awareness of the disease.Variants were identified by next generation sequencing. Clinical features and biochemical findings at the first presentation, as well as at follow-up visits were also investigated. One hundred unrelated healthy subjects were selected to evaluate each of the novel mutations found in this study.A total of seven different mutations in the ATP6V0A4, ATP6V1B1, and SLC4A1 genes, the three main causative genes of dRTA, were detected in 4/5 patients. In patient I a novel heterozygous intronic mutation (c.639 + 1GA) in the ATP6V0A4 gene was identified along with a heterozygous nonsense variant (c.580CT, p.Arg194*). Two novel heterozygous missense mutations of the ATP6V1B1 gene (c.409CT, p.Pro137Ser; c.904CT, p.Arg302Trp) were identified in patient II. In patient III 2 novel heterozygous duplications (c.1504dupT, p.Tyr502Leufs*22; c.2351dupT, p.Phe785Ilefs*28) were found. Thus, these three patients all were compound heterozygotes leading to dRTA. These findings are consistent with the known autosomal recessive inheritance pattern of this disease. Furthermore, a de novo heterozygous missense mutation previously reported (c.1765CA, p.Arg589Ser) in the SLC4A1 gene was observed in patient IV. No mutations in any of the known dRTA-related causative genes were found in the patient V.In the present study we identified 7 mutations, including 5 novel variants, in the three genes previously correlated with dRTA, enriching the human gene mutation database (HGMD). In addition, our lack of findings in these three genes for patient V suggests that other genes may contribute to dRTA in some cases.
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- 2018
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109. Clinical and genetic analysis of distal renal tubular acidosis in three Chinese children
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Jiaojiao Liu, Guomin Li, Xiaoyan Fang, Qian Shen, Yihui Zhai, and Hong Xu
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Male ,China ,Vacuolar Proton-Translocating ATPases ,medicine.medical_specialty ,ATP6V0A4 ,SLC4A1 ,growth ,Hearing Loss, Sensorineural ,Mutation, Missense ,030232 urology & nephrology ,distal renal tubular acidosis ,Hypokalemia ,lcsh:RC870-923 ,Critical Care and Intensive Care Medicine ,Genetic analysis ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Distal renal tubular acidosis ,Alkaline urine ,Anion Exchange Protein 1, Erythrocyte ,Internal medicine ,Humans ,Medicine ,030212 general & internal medicine ,recombinant human growth hormone ,Growth Disorders ,ATP6V1B1 ,Growth retardation ,urogenital system ,business.industry ,Infant ,Metabolic acidosis ,Acidosis, Renal Tubular ,General Medicine ,lcsh:Diseases of the genitourinary system. Urology ,medicine.disease ,Nephrocalcinosis ,Nephrology ,Child, Preschool ,Growth Hormone ,Female ,business - Abstract
Objective: Primary distal renal tubular acidosis (dRTA) is a rare genetic disease characterized by distal tubular dysfunction leading to metabolic acidosis and alkaline urine. Growth retardation is a major concern in these children. The disease is caused by defects in at least three genes (SLC4A1, ATP6V0A4, and ATP6V1B1) involved in urinary distal acidification. Several series of dRTA patients from different ethnic backgrounds have been genetically studied, but genetic studies regarding Chinese population is rare. Our aim was to investigate the clinical features and genetic basis of primary dRTA in Chinese children. Methods: Three unrelated patients with dRTA participated in our study. Next-generation sequencing was performed, and the findings were validated using the Sanger sequencing method. Results: All patients exhibited hyperchloraemic metabolic acidosis, abnormally high urine pH, hypokalemia, and nephrocalcinosis. Growth retardation was observed in all patients. During the follow-up (range 1–4 years), alkali replacement therapy corrected the systemic metabolic acidosis, and two patients demonstrated normal growth. rhGH therapy was administered to patient-3 at the age of 6 years, and his growth rate was significantly improved (growth velocity 9.6 cm/yr). In total, 5 mutations were identified in our cohort of three patients, and four mutations were novel. Conclusions: We report the clinical and molecular characteristics of dRTA patients from China. The four novel mutations detected in our study extend the spectrum of gene mutations associated with primary dRTA. Furthermore, our study confirms the effect of early treatment in improving growth for dRTA patient and provides insight into the effects of rhGH on dRTA patients who were diagnosed late and exhibiting a persistent growth delay despite appropriate therapy.
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- 2018
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110. Distal renal tubular acidosis caused bytryptophan-aspartate repeat domain 72(WDR72) mutations
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Choochai Nettuwakul, Nanyawan Rungroj, Pasena A, Sittideth Sangnual, Pa-thai Yenchitsomanus, Nunghathai Sawasdee, Suchai Sritippayawan, Sukachart Kirdpon, Nipaporn Deejai, Misgar Ra, Somkiat Vasuvattakul, and Sookkasem Khositseth
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Adult ,Male ,Models, Molecular ,0301 basic medicine ,Adolescent ,Genotype ,Protein Conformation ,DNA Mutational Analysis ,Nonsense mutation ,030232 urology & nephrology ,Tryptophan-Aspartate Repeat ,Biology ,Compound heterozygosity ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Protein structure ,Distal renal tubular acidosis ,Exome Sequencing ,Genetics ,Homologous chromosome ,medicine ,Humans ,Genetic Predisposition to Disease ,Amino Acid Sequence ,Child ,Gene ,Genetic Association Studies ,Genetics (clinical) ,Exome sequencing ,Computational Biology ,Proteins ,Acidosis, Renal Tubular ,medicine.disease ,Pedigree ,Phenotype ,030104 developmental biology ,Case-Control Studies ,Mutation ,Female ,Biomarkers - Abstract
Hereditary distal renal tubular acidosis (dRTA) is a rare genetic disease that is caused by mutations in SLC4A1, ATP6V1B1, or ATP6V0A4. However, there are many families with hereditary dRTA in whom the disease-causing genes are unknown. Accordingly, we performed whole exome sequencing and genetic studies of the members of a family with autosomal recessive dRTA of an unknown genetic etiology. Here, we report compound heterozygous pathogenic variations in tryptophan-aspartate repeat domain 72 (WDR72) (c.1777A>G [p.R593G] and c.2522T>A [p.L841Q]) in three affected siblings of a family with dRTA. Both variants segregated with dRTA in the family and were not observed in normal control subjects. Homologous modeling and in silico mutagenesis indicated that R593G and L841Q alter the H-bond formations in the nearby residues, affecting the WDR72 protein structure. All these evidences indicate that the identified WDR72 variations were probably to have caused hereditary dRTA in the reported family. In addition, homozygous nonsense mutation (c.2686C>T [p.R896X]) was identified in another family, strongly supporting the causal role of WDR72 in dRTA. Based on our literature review, WDR72 mutations associated with dRTA have not been previously described. This is the first identification of pathogenic variations in WDR72 as a cause of hereditary dRTA.
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- 2018
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111. Clinical Approach to Proximal Renal Tubular Acidosis in Children
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Gal Finer and Daniel Landau
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medicine.medical_specialty ,Cystinosis ,030232 urology & nephrology ,Anion gap ,Dent Disease ,030204 cardiovascular system & hematology ,Gastroenterology ,Kidney Tubules, Proximal ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Child ,Wasting ,business.industry ,nutritional and metabolic diseases ,Fanconi syndrome ,Acidosis, Renal Tubular ,Fanconi Syndrome ,medicine.disease ,Oculocerebrorenal Syndrome ,chemistry ,Nephrology ,Uric acid ,medicine.symptom ,Differential diagnosis ,business ,Proximal renal tubular acidosis - Abstract
Proximal renal tubular acidosis (pRTA) is an inherited or acquired clinical syndrome in which there is a decreased bicarbonate reclamation in the proximal tubule resulting in normal anion gap hyperchloremic metabolic acidosis. In children, pRTA may be isolated but is often associated with a general proximal tubular dysfunction known as Fanconi syndrome which frequently heralds an underlying systemic disorder from which it arises. When accompanied by Fanconi syndrome, pRTA is characterized by additional renal wasting of phosphate, glucose, uric acid, and amino acids. The most common cause of inherited Fanconi syndrome in the pediatric age group is cystinosis, a disease with therapeutic implications. In this article, we summarize the clinical presentation and differential diagnosis of pRTA and Fanconi syndrome and provide a practical approach to their evaluation in children.
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- 2018
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112. Hypokalemic Distal Renal Tubular Acidosis
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Daniel Batlle and Patricia G. Vallés
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Vacuolar Proton-Translocating ATPases ,DISTAL RTA ,medicine.medical_specialty ,CIENCIAS MÉDICAS Y DE LA SALUD ,Urinary system ,GROWTH FAILURE ,030232 urology & nephrology ,Ciencias de la Salud ,Hypokalemia ,030204 cardiovascular system & hematology ,Carbonic Anhydrase II ,Excretion ,03 medical and health sciences ,0302 clinical medicine ,Distal renal tubular acidosis ,Anion Exchange Protein 1, Erythrocyte ,Internal medicine ,medicine ,Humans ,Hypercalciuria ,Kidney Tubules, Distal ,Acidosis ,ACID EXCRETION ,HYPOKALEMIA ,business.industry ,Biological Transport ,Metabolic acidosis ,Acidosis, Renal Tubular ,medicine.disease ,HYPERCHLOREMIC METABOLIC ACIDOSIS ,Otras Ciencias de la Salud ,Endocrinology ,Nephrology ,Mutation ,Potassium ,medicine.symptom ,Nephrocalcinosis ,business ,Glomerular Filtration Rate - Abstract
Distal renal tubular acidosis (DRTA) is defined as hyperchloremic, non-anion gap metabolic acidosis with impaired urinary acid excretion in the presence of a normal or moderately reduced glomerular filtration rate. Failure in urinary acid excretion results from reduced H+ secretion by intercalated cells in the distal nephron. This results in decreased excretion of NH4 + and other acids collectively referred as titratable acids while urine pH is typically above 5.5 in the face of systemic acidosis. The clinical phenotype in patients with DRTA is characterized by stunted growth with bone abnormalities in children as well as nephrocalcinosis and nephrolithiasis that develop as the consequence of hypercalciuria, hypocitraturia, and relatively alkaline urine. Hypokalemia is a striking finding that accounts for muscle weakness and requires continued treatment together with alkali-based therapies. This review will focus on the mechanisms responsible for impaired acid excretion and urinary potassium wastage, the clinical features, and diagnostic approaches of hypokalemic DRTA, both inherited and acquired. Fil: Garramuño, Patricia. Universidad del Aconcagua. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina Fil: Battle, Daniel. Northwestern University; Estados Unidos
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- 2018
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113. Pseudo-Renal Tubular Acidosis: Conditions Mimicking Renal Tubular Acidosis
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Jerry Yee and Junior Uduman
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medicine.medical_specialty ,030232 urology & nephrology ,Urology ,Anion gap ,Urinalysis ,Urinary Diversion ,Diagnosis, Differential ,Renal tubular acidosis ,03 medical and health sciences ,0302 clinical medicine ,Hyperchloremia ,medicine ,Humans ,030212 general & internal medicine ,Hyperchloremic metabolic acidosis ,Acid-Base Equilibrium ,business.industry ,Osmolar Concentration ,food and beverages ,Acidosis, Renal Tubular ,medicine.disease ,Bicarbonates ,Carbon dioxide content ,Nephrology ,Respiratory alkalosis ,Urine anion gap ,business ,Alkalosis, Respiratory - Abstract
Hyperchloremic metabolic acidosis, particularly renal tubular acidosis, can pose diagnostic challenges. The laboratory phenotype of a low total carbon dioxide content, normal anion gap, and hyperchloremia may be misconstrued as hypobicarbonatemia from renal tubular acidosis. Several disorders can mimic renal tubular acidosis, and these must be appropriately diagnosed to prevent inadvertent and inappropriate application of alkali therapy. Key physiologic principles and limitations in the assessment of renal acid handling that can pose diagnostic challenges are enumerated.
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- 2018
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114. SLC4A4 compound heterozygous mutations in exon–intron boundary regions presenting with severe proximal renal tubular acidosis and extrarenal symptoms coexisting with Turner’s syndrome: a case report
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Tulay Simsek, Shoji Tsuji, Atsushi Suzuki, Nilgun Yildirim, Shoko Horita, Motonobu Nakamura, Tomohito Mizuno, Masaomi Nangaku, Hiroyuki Ishiura, Enver Simsek, George Seki, Hiroyuki Tsukada, and Nobuhiko Satoh
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0301 basic medicine ,Proband ,medicine.medical_specialty ,SLC4A4 ,lcsh:Internal medicine ,lcsh:QH426-470 ,Nonsense-mediated decay ,Turner Syndrome ,Case Report ,NBCe1 ,medicine.disease_cause ,Compound heterozygosity ,03 medical and health sciences ,Exon ,mRNA surveillance ,Proximal renal tubular acidosis ,Internal medicine ,Genetics ,medicine ,Humans ,Child ,lcsh:RC31-1245 ,Genetics (clinical) ,Acidosis ,Mutation ,biology ,business.industry ,Sodium-Bicarbonate Symporters ,Compound heterozygous mutations ,Acidosis, Renal Tubular ,Exons ,medicine.disease ,Introns ,lcsh:Genetics ,030104 developmental biology ,Endocrinology ,Kidney Tubules ,biology.protein ,Female ,medicine.symptom ,business - Abstract
Background Congenital NBCe1A deficiency with the SLC4A4 mutation causes severe proximal renal tubular acidosis, which often comprises extrarenal symptoms, such as intellectual disability and developmental delay, glaucoma, cataract and band keratopathy. To date, almost all mutations have been found to be homozygous mutations located in exons. Case presentation We performed direct nucleotide sequencing analysis of exons and exon–intron boundary regions of the SLC4A4 in a patient presenting with severe renal proximal tubule acidosis, glaucoma and intellectual disability and her parents without these signs. The examination revealed compound heterozygous mutations in exon–intron boundary regions, c.1076 + 3A > C and c.1772 − 2A > T, neither of which have been reported previously. While the former mutation was found in the mother, the latter was found in the father. The transcript of the SLC4A4 gene was almost undetectable, and the patient was also diagnosed with Turner’s syndrome. Conclusions We identified two novel SLC4A4 mutations, c.1076 + 3A > C and c.1772 − 2A > T. When presented in a compound heterozygous state, these mutations caused a phenotype of severe renal proximal tubular acidosis along with glaucoma and mental retardation. This is the first report of congenital proximal renal tubular acidosis carrying compound heterozygous SLC4A4 mutations in exon–intron boundary regions. We suggest that an mRNA surveillance mechanism, nonsense-mediated RNA decay, following aberrant splicing was the reason that the SLC4A4 transcript was almost undetectable in the proband.
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- 2018
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115. Proximal Muscle Weakness With Overlying Hypokalemic Periodic Paralysis in Sjögren Syndrome
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Anmol Singh Rai, Ritu Verma, Vimal Kumar Paliwal, Surendra Kumar, and Vikas Agarwal
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Adult ,Male ,Pathology ,medicine.medical_specialty ,Proximal muscle weakness ,Calcium-Regulating Hormones and Agents ,Hypokalemic Periodic Paralysis ,030232 urology & nephrology ,Sjögren syndrome ,Diagnosis, Differential ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Hypokalemic periodic paralysis ,Humans ,Medicine ,Autoantibodies ,030203 arthritis & rheumatology ,Muscle Weakness ,Electromyography ,business.industry ,Acidosis, Renal Tubular ,medicine.disease ,Sjogren's Syndrome ,Sodium Bicarbonate ,Treatment Outcome ,Potassium ,Calcium ,Female ,business - Published
- 2018
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116. Genotype–Phenotype Analysis in Pediatric Patients with Distal Renal Tubular Acidosis
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Hye Sun Hyun, Myung Hyun Cho, Hyun-Jin Choi, Young Seo Park, Eujin Park, Jae Il Shin, Hee Gyung Kang, Joo H. Lee, and Hae Il Cheong
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Male ,0301 basic medicine ,Candidate gene ,lcsh:Diseases of the circulatory (Cardiovascular) system ,DNA Mutational Analysis ,030232 urology & nephrology ,Growth ,lcsh:RC870-923 ,Gastroenterology ,0302 clinical medicine ,Distal renal tubular acidosis ,Anion Exchange Protein 1, Erythrocyte ,Chronic kidney disease ,lcsh:Dermatology ,Child ,Kidney Tubules, Distal ,Genetic disorder ,Acidosis, Renal Tubular ,General Medicine ,Sensorineural hearing loss ,Nephrocalcinosis ,Nephrology ,Child, Preschool ,Female ,Cardiology and Cardiovascular Medicine ,Mutations ,Vacuolar Proton-Translocating ATPases ,medicine.medical_specialty ,Adolescent ,Hearing Loss, Sensorineural ,03 medical and health sciences ,Internal medicine ,Republic of Korea ,medicine ,Humans ,Genetic Association Studies ,business.industry ,Metabolic acidosis ,lcsh:RL1-803 ,medicine.disease ,Growth retardation ,lcsh:Diseases of the genitourinary system. Urology ,030104 developmental biology ,lcsh:RC666-701 ,Mutation ,Age of onset ,business ,Kidney disease - Abstract
Background/Aims: Primary distal renal tubular acidosis (dRTA) in children is a rare genetic disorder, and three causative mutated genes have been identified: SLC4A1, ATP6V1B1, and ATP6V0A4. We analyzed the prevalence and phenotypic differences of genetic mutations in children with dRTA. Methods: A total of 17 children with dRTA were enrolled in the study. All patients underwent genetic testing for all three candidate genes. Results: Pathogenic mutations, including six novel mutations, were detected in 15 (88.2%) patients: dominant SLC4A1 mutations in ten (58.8%) patients, recessive ATP6V0A4 mutations in three (17.6%) patients, and recessive ATP6V1B1 mutations in two (11.8%) patients. Compared to other patients, patients with SLC4A1 mutations showed an older age of onset (3.7 ± 2.6 years) and less severe metabolic acidosis at initial presentation. All patients developed nephrocalcinosis, and sensorineural hearing loss was observed in two patients with ATP6V1B1 mutations. Three (17.6%) patients had decreased renal function (chronic kidney disease stage 2), and five (29.4%) patients had persistent growth retardation at the last follow-up. Long-term prognosis showed no genotype–phenotype correlation. Conclusions: SLC4A1 is the most common defective gene in Korean children with dRTA. Patients with SLC4A1 mutations show later onset and milder disease severity. Long-term follow-up of hearing ability, renal function, and growth is necessary for patients with dRTA.
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- 2018
117. Molecular mechanisms of cutis laxa– and distal renal tubular acidosis–causing mutations in V-ATPase a subunits, ATP6V0A2 and ATP6V0A4
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Morris F. Manolson, Yeqi Yao, Joo Wan Kim, Reinhart A. F. Reithmeier, Norbert Kartner, and Sally Esmail
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Models, Molecular ,0301 basic medicine ,Proteasome Endopeptidase Complex ,Vacuolar Proton-Translocating ATPases ,Glycosylation ,Recombinant Fusion Proteins ,Protein subunit ,Mutation, Missense ,Golgi Apparatus ,Protein degradation ,Endoplasmic Reticulum ,Kidney ,medicine.disease_cause ,Biochemistry ,Cutis Laxa ,03 medical and health sciences ,symbols.namesake ,Enzyme Stability ,medicine ,Humans ,V-ATPase ,Protein Interaction Domains and Motifs ,Molecular Biology ,Mutation ,Chemistry ,Endoplasmic reticulum ,Cell Membrane ,HEK 293 cells ,Molecular Bases of Disease ,Acidosis, Renal Tubular ,Cell Biology ,Golgi apparatus ,medicine.disease ,Cell biology ,Protein Transport ,Proton-Translocating ATPases ,HEK293 Cells ,030104 developmental biology ,Amino Acid Substitution ,Proteolysis ,symbols ,Protein Multimerization ,Protein Processing, Post-Translational ,Cutis laxa - Abstract
The a subunit is the largest of 15 different subunits that make up the vacuolar H(+)-ATPase (V-ATPase) complex, where it functions in proton translocation. In mammals, this subunit has four paralogous isoforms, a1–a4, which may encode signals for targeting assembled V-ATPases to specific intracellular locations. Despite the functional importance of the a subunit, its structure remains controversial. By studying molecular mechanisms of human disease–causing missense mutations within a subunit isoforms, we may identify domains critical for V-ATPase targeting, activity and/or regulation. cDNA-encoded FLAG-tagged human wildtype ATP6V0A2 (a2) and ATP6V0A4 (a4) subunits and their mutants, a2(P405L) (causing cutis laxa), and a4(R449H) and a4(G820R) (causing renal tubular acidosis, dRTA), were transiently expressed in HEK 293 cells. N-Glycosylation was assessed using endoglycosidases, revealing that a2(P405L), a4(R449H), and a4(G820R) were fully N-glycosylated. Cycloheximide (CHX) chase assays revealed that a2(P405L) and a4(R449H) were unstable relative to wildtype. a4(R449H) was degraded predominantly in the proteasomal pathway, whereas a2(P405L) was degraded in both proteasomal and lysosomal pathways. Immunofluorescence studies disclosed retention in the endoplasmic reticulum and defective cell-surface expression of a4(R449H) and defective Golgi trafficking of a2(P405L). Co-immunoprecipitation studies revealed an increase in association of a4(R449H) with the V(0) assembly factor VMA21, and a reduced association with the V(1) sector subunit, ATP6V1B1 (B1). For a4(G820R), where stability, degradation, and trafficking were relatively unaffected, 3D molecular modeling suggested that the mutation causes dRTA by blocking the proton pathway. This study provides critical information that may assist rational drug design to manage dRTA and cutis laxa.
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- 2018
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118. Distal renal tubular acidosis secondary to vesico-ureteric reflux: A case report with review of literature
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Tanmay Bharani, Anjali Bharani, and Rajesh Bharani
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Male ,medicine.medical_specialty ,Adolescent ,Urinary system ,Urology ,Anion gap ,Administration, Oral ,lcsh:Medicine ,Hypokalemia ,Alkalies ,urologic and male genital diseases ,Tubulopathy ,Renal tubular dysfunction ,Distal renal tubular acidosis ,medicine ,Humans ,Kidney Tubules, Distal ,Acidosis ,Ultrasonography ,Vesico-Ureteral Reflux ,business.industry ,lcsh:R ,Metabolic acidosis ,General Medicine ,Acidosis, Renal Tubular ,medicine.disease ,Sodium Bicarbonate ,Treatment Outcome ,Dietary Supplements ,Potassium ,medicine.symptom ,business - Abstract
Vesicoureteric reflux (VUR) is the most common congenital anomaly of the urinary tract that occurs in 30%-50% of children presenting with recurrent urinary tract infections. Long-standing untreated VUR results in renal scarring and hydronephrotic changes ultimately leading to chronic renal failure and arterial hypertension. However, it may also result in diffuse tubulopathy compromising the concentrating capacity of tubules and urinary acidification defects. Renal tubular dysfunction should be considered in all children with VUR presenting with failure to thrive, rickets, bony deformity/pain, hypokalemia, and metabolic acidosis. We report such a case of a 16-year-old male adolescent who presented with rickets, failure to gain weight and height, bony pains, and muscle weakness with a history of VUR. On investigation, he was found to have normal anion gap metabolic acidosis with hypokalemia suggestive of distal renal tubular acidosis. He responded well to oral alkali and potassium replacement therapy.
- Published
- 2018
119. Renal Tubular Acidosis Presenting as Nephrogenic Diabetes Insipidus
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Debaditya Das, Rajiv Sinha, and Subrata Dey
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Vacuolar Proton-Translocating ATPases ,medicine.medical_specialty ,Hearing loss ,Urology ,Diabetes Insipidus, Nephrogenic ,urologic and male genital diseases ,Renal tubular acidosis ,03 medical and health sciences ,0302 clinical medicine ,Nephropathic Cystinosis ,030225 pediatrics ,medicine ,Humans ,030212 general & internal medicine ,Acidosis ,business.industry ,Infant ,Fanconi syndrome ,Acidosis, Renal Tubular ,medicine.disease ,Nephrogenic diabetes insipidus ,Amino Acid Transport Systems, Neutral ,Mutation ,Pediatrics, Perinatology and Child Health ,Diabetes insipidus ,Female ,medicine.symptom ,business ,Proximal renal tubular acidosis - Abstract
Background Nephrogenic diabetes insipidus (DI) can be primary or secondary to various causes. Case characteristics One child with Fanconi syndrome with proximal renal tubular acidosis (RTA) due to nephropathic cystinosis, and other with Distal RTA with hearing loss. Observation Both cases showed features of nephrogenic DI, which resolved after treating the primary pathology. Message Renal Tubular acidosis may cause nephrogenic DI.
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- 2019
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120. MELAS syndrome: an acute stroke-like episode complicated by renal tubular acidosis
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Dearbhail Ni Cathain, Kieran Skehan, Emmet Browne, and Karl Boyle
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Pediatrics ,medicine.medical_specialty ,Ataxia ,business.industry ,Metabolic acidosis ,Acidosis, Renal Tubular ,General Medicine ,Arginine ,medicine.disease ,MELAS syndrome ,Stroke ,Renal tubular acidosis ,MELAS Syndrome ,medicine ,Humans ,medicine.symptom ,business ,Acute stroke ,Confusion - Abstract
MELAS, a mitochondrially inherited multisystem disorder, can present with acute stroke-like episodes. The literature thus far supports the use of L-arginine therapy in acute MELAS flares to alleviate and shorten the duration of symptoms. This is the case of a patient who presented with ataxia and worsening confusion on a background of genetically confirmed MELAS syndrome. In this instance, intravenous L-arginine therapy, along with corticosteroids, was administered in keeping with best practice. However, in a metabolically vulnerable patient, L-arginine therapy resulted in a further deterioration in his clinical status and the development of a non-anion gap metabolic acidosis.
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- 2021
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121. Genetic and clinical profile of patients with hypophosphatemic rickets.
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Marik B, Bagga A, Sinha A, Khandelwal P, Hari P, and Sharma A
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- Fibroblast Growth Factors genetics, Fibroblast Growth Factors metabolism, Humans, PHEX Phosphate Regulating Neutral Endopeptidase genetics, PHEX Phosphate Regulating Neutral Endopeptidase metabolism, Vitamin D, Acidosis, Renal Tubular, Familial Hypophosphatemic Rickets diagnosis, Familial Hypophosphatemic Rickets genetics, Rickets, Hypophosphatemic genetics, Vacuolar Proton-Translocating ATPases metabolism
- Abstract
Nutritional vitamin D deficiency is the most frequent cause of rickets followed by genetic causes, that include entities like classic hypophosphatemic rickets (FGF23 related), Dent disease, Fanconi syndrome, renal tubular acidosis, and vitamin D dependent rickets. Hypophosphatemia is a feature in all these forms. The diagnosis relies on a combination of clinical, biochemical and radiological features, but genetic testing is required to confirm the diagnosis. We screened 66 patients with hypophosphatemic rickets referred to this center between May 2015 and July 2019 using whole exome sequencing (WES) in addition to the measurement of their intact serum fibroblast growth factor 23 (FGF23) levels. WES revealed 36 pathogenic and 28 likely pathogenic variants in 16 different genes (PHEX, FGF23, DMP1, ENPP1, CLCN5, CTNS, SLC2A2, GATM, SLC34A1, EHHADH, SLC4A1, ATP6V1B1, ATP6V0A4, CYP27B1, VDR and FGFR1) in 63 patients which helped differentiate between the various forms of hypophosphatemic rickets. Intact serum FGF23 levels were significantly higher in patients with variations in PHEX, FGF23, DMP1 or ENPP1 genes. The major genetic causes of rickets were classic hypophosphatemic rickets with elevated FGF23 levels, distal renal tubular acidosis, and vitamin D dependent rickets. Based on the present results, we propose a customized gene panel for targeted exome sequencing, which will be useful for confirming the diagnosis in most patients with hypophosphatemic rickets., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)
- Published
- 2022
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122. Diagnóstico de Anomalías Dentarias en Pacientes Pediátricos con Acidosis Tubular Distal mediante Radiografía Panorámica.
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Acosta, María Gabriela, M, Quevedo, and Hernández, Zuleima
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DENTAL caries ,ACIDOSIS ,CROSS-sectional method ,PEDIATRIC nephrology ,TAURODONTISM ,MOLAR abnormalities ,TOOTH erosion ,RADIOGRAPHY - Abstract
Copyright of Pesquisa Brasileira em Odontopediatria e Clinica Integrada is the property of Pesquisa Brasileira em Odontopediatria e Clinica Integrada Journal (Brazil) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2012
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123. Hypokalaemic quadriparesis with respiratory failure due to latent Sjogren syndrome
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Manoj Lakhotia, Mudita Gupta, Archita Makharia, and Pradeep Lalwani
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0301 basic medicine ,Pathology ,medicine.medical_specialty ,Hypokalemia ,Sjögren syndrome ,Quadriplegia ,Asymptomatic ,03 medical and health sciences ,0302 clinical medicine ,Distal renal tubular acidosis ,medicine ,Humans ,Sequence (medicine) ,Autoimmune disease ,business.industry ,Acidosis, Renal Tubular ,General Medicine ,Middle Aged ,medicine.disease ,Connective tissue disease ,stomatognathic diseases ,Sjogren's Syndrome ,030104 developmental biology ,Respiratory failure ,Female ,medicine.symptom ,Respiratory Insufficiency ,business ,030217 neurology & neurosurgery ,Sudden onset - Abstract
Sjogren’s syndrome (SS) is an autoimmune disease with involvement of multiple organs, including both glandular and extraglandular organs. Usually involvement of glandular organs manifests before the extraglandular ones, but when the sequence is reversed, diagnosis may be missed. Hypokalaemic quadriparesis in SS is not uncommon. Respiratory failure in hypokalaemia is not usually seen, but in SS, it has been reported. We report a case of a 55-year-old woman who presented with sudden onset flaccid quadriparesis and respiratory muscle paralysis secondary to severe hypokalaemia. On detailed investigation, she was detected to have distal renal tubular acidosis secondary to clinically inapparent and asymptomatic SS.
- Published
- 2021
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124. Bartter syndrome and hypothyroidism masquerading cystinosis in a 3-year-old girl: rare manifestation of a rare disease
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Pamali Nanda, Anupriya Kaur, Rajesh Kumar, and Gargi Das
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0301 basic medicine ,Pediatrics ,medicine.medical_specialty ,endocrine system diseases ,Cystinosis ,Metabolic alkalosis ,Bartter syndrome ,Renal tubular acidosis ,03 medical and health sciences ,Rare Diseases ,0302 clinical medicine ,Hypothyroidism ,Renal tubular dysfunction ,030225 pediatrics ,medicine ,Humans ,Child ,business.industry ,Bartter Syndrome ,Acidosis, Renal Tubular ,General Medicine ,medicine.disease ,030104 developmental biology ,Cystinosin ,Child, Preschool ,Failure to thrive ,Female ,medicine.symptom ,business ,Rare disease - Abstract
Cystinosis is a multisystem disorder with varied presentations secondary to deposition of cystine crystals in different organ systems. Children with cystinosis typically present with renal tubular acidosis and failure to thrive. We report a 3-year-old girl, born to a third-degree consanguineous couple, who presented with failure to thrive and polyuria. Laboratory investigations showed metabolic alkalosis suggestive of a Bartter-like syndrome and acquired hypothyroidism. Although metabolic alkalosis is a rare manifestation of cystinosis, the presence of renal tubular dysfunction and hypothyroidism prompted consideration of a probable diagnosis of cystinosis in the index child. Slit-lamp examination revealed cystine crystals in the cornea and genetic analysis showed a mutation in exon 9 of the CTNS (cystinosin, lysosomal cystine transporter) gene on chromosome 17. We highlight the importance of considering cystinosis as a differential diagnosis for Bartter syndrome and hypothyroidism.
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- 2021
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125. Unilateral Ureteral Obstruction Alters Expression of Acid-Base Transporters in Rat Kidney.
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Wang, Guixian, Ring, Troels, Li, Chunling, Kim, Soo Wan, Wen, Jianguo, Djurhuus, Jens Christian, Nielsen, Søren, and Frøkiær, Jørgen
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URINARY obstructions ,GENE expression ,RENAL tubular transport ,ACID-base imbalances ,LABORATORY rats ,IMMUNOHISTOCHEMISTRY ,ADENOSINE triphosphatase - Abstract
Purpose: Unilateral ureteral obstruction is a common clinical problem that is often associated with a urinary acidification defect caused by decreased net H
+ secretion and/or HCO3 − reabsorption. To clarify the molecular mechanisms of these defects we examined expression levels of key acid-base transporters along the renal nephron segments and collecting duct. Materials and Methods: Wistar rats (Møllegard Breeding Centre, Eiby, Denmark) underwent 24-hour unilateral ureteral obstruction, unilateral ureteral obstruction release followed for 4 days or unilateral ureteral obstruction release followed for 4 days plus experimental acidosis induced by NH4 Cl oral administration. After sacrifice kidneys were processed for immunoblotting and immunohistochemistry. Results: Semiquantitative immunoblotting revealed that unilateral ureteral obstruction caused significant mean ± SE down-regulation of type 3 Na+ /H+ exchanger to 53% ± 9%, electrogenic Na+ /HCO3 − cotransporter to 60% ± 9%, type 1 bumetanide sensitive Na+ -K+ (NH4 + ) -2Cl− cotransporter to 64% ± 7%, electroneutral Na+ /HCO3 − cotransporter to 43% ± 4% and anion exchanger (pendrin) to 53% ± 10% in the obstructed kidney, which was confirmed by immunohistochemistry. After release of unilateral ureteral obstruction down-regulation of these transporters persisted together with marked down-regulation of H+ -adenosine triphosphatase in the obstructed kidney. In rats with unilateral ureteral obstruction release followed for 4 days with experimental acidosis induced by NH4 Cl oral administration plasma pH and HCO3 − were dramatically decreased in response to NH4 Cl for 2 days compared with those in sham operated rats with acid loading, indicating a defect in H+ excretion and HCO3 − reabsorption after obstruction release. Expression of these transporters did not change in the contralateral nonobstructed kidney of rats with unilateral ureteral obstruction and unilateral ureteral obstruction release followed for 4 days. Conclusions: The expression of renal acid-base transporters is markedly decreased in the obstructed kidney, which may be responsible for the contribution of impaired renal H+ excretion and HCO3 − reabsorption to the urinary acidification defect in response to unilateral ureteral obstruction. [Copyright &y& Elsevier]- Published
- 2009
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126. Near and Far
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Sean Lockwood, Aibek E. Mirrakhimov, Reza Manesh, Adam Gray, and Allan C. Gelber
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Adult ,Muscle Weakness ,Leadership and Management ,business.industry ,Health Policy ,Acidosis, Renal Tubular ,General Medicine ,Assessment and Diagnosis ,Data science ,Text mining ,Humans ,Medicine ,Female ,Fundamentals and skills ,business ,Care Planning - Published
- 2017
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127. Acidosis and Deafness in Patients with Recessive Mutations in FOXI1
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Carsten A. Wagner, Mikael Heglind, John A. Sayer, Sumaya Alkanderi, William van’t Hoff, Stephen B. Walsh, Detlef Bockenhauer, Daniel Nilsson, Abdulrahim R.A. Bakhsh, Emma Ashton, Sven Enerbäck, Arezoo Daryadel, Feras E.B. Kokash, Noel Edwards, Robert Kleta, Felice D'Arco, Soline Bourgeois, and Asma Deeb
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Male ,0301 basic medicine ,Mutation, Missense ,030232 urology & nephrology ,Deafness ,Nephropathy ,Renal tubular acidosis ,Consanguinity ,03 medical and health sciences ,0302 clinical medicine ,Distal renal tubular acidosis ,Clinical Research ,medicine ,Humans ,Missense mutation ,Hearing Loss, Central ,Child ,Kidney Tubules, Distal ,Cells, Cultured ,Kidney ,business.industry ,Homozygote ,Chronic metabolic acidosis ,Infant ,Forkhead Transcription Factors ,Acidosis, Renal Tubular ,DNA ,General Medicine ,medicine.disease ,Pedigree ,030104 developmental biology ,medicine.anatomical_structure ,FOXI1 ,Nephrology ,Cancer research ,Collecting duct system ,Female ,business - Abstract
Maintenance of the composition of inner ear fluid and regulation of electrolytes and acid-base homeostasis in the collecting duct system of the kidney require an overlapping set of membrane transport proteins regulated by the forkhead transcription factor FOXI1. In two unrelated consanguineous families, we identified three patients with novel homozygous missense mutations in FOXI1 (p.L146F and p.R213P) predicted to affect the highly conserved DNA binding domain. Patients presented with early-onset sensorineural deafness and distal renal tubular acidosis. In cultured cells, the mutations reduced the DNA binding affinity of FOXI1, which hence, failed to adequately activate genes crucial for normal inner ear function and acid-base regulation in the kidney. A substantial proportion of patients with a clinical diagnosis of inherited distal renal tubular acidosis has no identified causative mutations in currently known disease genes. Our data suggest that recessive mutations in FOXI1 can explain the disease in a subset of these patients.
- Published
- 2017
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128. Urine Anion Gap to Predict Urine Ammonium and Related Outcomes in Kidney Disease
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Joachim H. Ix, Kalani L. Raphael, and Sarah Gilligan
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Male ,Epidemiology ,030232 urology & nephrology ,Urine ,030204 cardiovascular system & hematology ,Critical Care and Intensive Care Medicine ,Urine collection device ,chemistry.chemical_compound ,0302 clinical medicine ,Risk Factors ,Ammonium Compounds ,Medicine ,Randomized Controlled Trials as Topic ,Acid-Base Equilibrium ,Proteinuria ,Sulfates ,Acidosis, Renal Tubular ,Middle Aged ,Prognosis ,Nephrology ,Urine anion gap ,Female ,Kidney Diseases ,Acid–base reaction ,medicine.symptom ,Adult ,Adolescent ,Sodium ,chemistry.chemical_element ,Urinalysis ,Risk Assessment ,Phosphates ,Excretion ,Young Adult ,03 medical and health sciences ,Predictive Value of Tests ,Humans ,Ammonium ,Renal Insufficiency, Chronic ,Aged ,Transplantation ,Chromatography ,business.industry ,Editorials ,Original Articles ,United States ,Black or African American ,Cross-Sectional Studies ,chemistry ,Kidney Failure, Chronic ,business ,Biomarkers - Abstract
Background and objectives Low urine ammonium excretion is associated with ESRD in CKD. Few laboratories measure urine ammonium, limiting clinical application. We determined correlations between urine ammonium, the standard urine anion gap, and a modified urine anion gap that includes sulfate and phosphate and compared risks of ESRD or death between these ammonium estimates and directly measured ammonium. Design, setting, participants, & measurements We measured ammonium, sodium, potassium, chloride, phosphate, and sulfate from baseline 24-hour urine collections in 1044 African-American Study of Kidney Disease and Hypertension participants. We evaluated the cross-sectional correlations between urine ammonium, the standard urine anion gap (sodium + potassium − chloride), and a modified urine anion gap that includes urine phosphate and sulfate in the calculation. Multivariable-adjusted Cox models determined the associations of the standard urine anion gap and the modified urine anion gap with the composite end point of death or ESRD; these results were compared with results using urine ammonium as the predictor of interest. Results The standard urine anion gap had a weak and direct correlation with urine ammonium ( r =0.18), whereas the modified urine anion gap had a modest inverse relationship with urine ammonium ( r =−0.58). Compared with the highest tertile of urine ammonium, those in the lowest urine ammonium tertile had higher risk of ESRD or death (hazard ratio, 1.46; 95% confidence interval, 1.13 to 1.87) after adjusting for demographics, GFR, proteinuria, and other confounders. In comparison, participants in the corresponding standard urine anion gap tertile did not have higher risk of ESRD or death (hazard ratio, 0.82; 95% confidence interval, 0.64 to 1.07), whereas the risk for those in the corresponding modified urine anion gap tertile (hazard ratio, 1.32; 95% confidence interval, 1.03 to 1.68) approximated that of directly measured urine ammonium. Conclusions Urine anion gap is a poor surrogate of urine ammonium in CKD unless phosphate and sulfate are included in the calculation. Because the modified urine anion gap merely estimates urine ammonium and requires five measurements, direct measurements of urine ammonium are preferable in CKD.
- Published
- 2017
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129. Management of the Metabolic Acidosis of Chronic Kidney Disease
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Donald E. Wesson and Nimrit Goraya
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medicine.medical_specialty ,030232 urology & nephrology ,Renal function ,030204 cardiovascular system & hematology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Vegetables ,medicine ,Animals ,Humans ,Renal Insufficiency, Chronic ,Adverse effect ,Acidosis ,Acid-Base Equilibrium ,Sodium bicarbonate ,business.industry ,Chronic metabolic acidosis ,Metabolic acidosis ,Acidosis, Renal Tubular ,medicine.disease ,Diet ,Bicarbonates ,Sodium Bicarbonate ,Endocrinology ,chemistry ,Nephrology ,Fruit ,Dietary Proteins ,Acid–base reaction ,medicine.symptom ,business ,Glomerular Filtration Rate ,Kidney disease - Abstract
Subjects with CKD and reduced glomerular filtration rate are at risk for chronic metabolic acidosis, and CKD is its most common cause. Untreated metabolic acidosis, even in its mildest forms, is associated with increased mortality and morbidity and should therefore be treated. If reduced glomerular filtration rate or the tubule abnormality causing chronic metabolic acidosis cannot be corrected, it is typically treated with dietary acid (H+) reduction using Na+-based alkali, usually NaHCO3. Dietary H+ reduction can also be accomplished with the addition of base-producing foods such as fruits and vegetables and limiting intake of H+-producing foods like animal-sourced protein. The optimal dose of Na+-based alkali that prevents the untoward effects of metabolic acidosis while minimizing adverse effects and the appropriate combination of this traditional therapy with dietary strategies remain to be determined by ongoing studies. Recent emerging evidence supports a phenomenon of H+ retention, which precedes the development of metabolic acidosis by plasma acid-base parameters, but further studies will be needed to determine how best to identify patients with this phenomenon and whether they too should be treated with dietary H+ reduction.
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- 2017
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130. γ-COPI mediates the retention of kAE1 G701D protein in Golgi apparatus – a mechanistic explanation of distal renal tubular acidosis associated with the G701D mutation
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Komgrid Charngkaew, Pa-thai Yenchitsomanus, Nunghathai Sawasdee, Thawornchai Limjindaporn, Suratchanee Phadngam, Mutita Junking, Natapol Duangtum, Andrea Castiglioni, and Ciro Isidoro
- Subjects
0301 basic medicine ,Protein subunit ,Mutant ,Golgi Apparatus ,Biology ,Kidney ,Coatomer Protein ,Models, Biological ,Biochemistry ,03 medical and health sciences ,symbols.namesake ,0302 clinical medicine ,Anion Exchange Protein 1, Erythrocyte ,Calnexin ,Humans ,RNA, Small Interfering ,Molecular Biology ,Secretory pathway ,Adaptor Proteins, Signal Transducing ,Endoplasmic reticulum ,Acidosis, Renal Tubular ,Cell Biology ,COPI ,Golgi apparatus ,Apical membrane ,Molecular biology ,Cell biology ,Protein Subunits ,HEK293 Cells ,030104 developmental biology ,Gene Knockdown Techniques ,030220 oncology & carcinogenesis ,Mutation ,symbols ,Mutant Proteins ,Protein Binding - Abstract
Mutations of the solute carrier family 4 member 1 (SLC4A1) gene encoding kidney anion (chloride/bicarbonate ion) exchanger 1 (kAE1) can cause genetic distal renal tubular acidosis (dRTA). Different SLC4A1 mutations give rise to mutant kAE1 proteins with distinct defects in protein trafficking. The mutant kAE1 protein may be retained in endoplasmic reticulum (ER) or Golgi apparatus, or mis-targeted to the apical membrane, failing to display its function at the baso-lateral membrane. The ER-retained mutant kAE1 interacts with calnexin chaperone protein; disruption of this interaction permits the mutant kAE1 to reach the cell surface and display anion exchange activity. However, the mechanism of Golgi retention of mutant kAE1 G701D protein, which is otherwise functional, is still unclear. In the present study, we show that Golgi retention of kAE1 G701D is due to a stable interaction with the Golgi-resident protein, coat protein complex I (COPI), that plays a role in retrograde vesicular trafficking and Golgi-based quality control. The interaction and co-localization of kAE1 G701D with the γ-COPI subunit were demonstrated in human embryonic kidney (HEK-293T) cells by co-immunoprecipitation and immunofluorescence staining. Small interference RNA (siRNA) silencing of COPI expression in the transfected HEK-293T cells increased the cell surface expression of transgenic kAE1 G701D, as shown by immunofluorescence staining. Our data unveil the molecular mechanism of Golgi retention of kAE1 G701D and suggest that disruption of the COPI-kAE1 G701D interaction could be a therapeutic strategy to treat dRTA caused by this mutant.
- Published
- 2017
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131. Hearing loss without overt metabolic acidosis in ATP6V1B1 deficient MRL mice, a new genetic model for non-syndromic deafness with enlarged vestibular aqueducts
- Author
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Susan Sheehan, Jaclynn M. Lett, Kevin K. Ohlemiller, Cong Tian, Chantal M. Longo-Guess, Kenneth R. Johnson, Angela D. Schrader, Leona H. Gagnon, and Ron Korstanje
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Male ,0301 basic medicine ,Vacuolar Proton-Translocating ATPases ,medicine.medical_specialty ,Genetic Linkage ,Hearing loss ,030232 urology & nephrology ,Deafness ,Biology ,Vestibular Aqueduct ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Distal renal tubular acidosis ,Internal medicine ,Genetic model ,otorhinolaryngologic diseases ,Genetics ,medicine ,Animals ,Humans ,Nonsyndromic deafness ,Profound hearing impairment ,Hearing Loss ,Molecular Biology ,Genetics (clinical) ,Mice, Knockout ,Metabolic acidosis ,Articles ,Acidosis, Renal Tubular ,General Medicine ,medicine.disease ,Mice, Inbred C57BL ,Disease Models, Animal ,Phenotype ,030104 developmental biology ,Endocrinology ,Ear, Inner ,Mutation ,Knockout mouse ,Female ,medicine.symptom ,Acidosis ,Enlarged vestibular aqueduct - Abstract
Mutations of the human ATP6V1B1 gene cause distal renal tubular acidosis (dRTA; OMIM #267300) often associated with sensorineural hearing impairment; however, mice with a knockout mutation of Atp6v1b1 were reported to exhibit a compensated acidosis and normal hearing. We discovered a new spontaneous mutation (vortex, symbol vtx) of Atp6v1b1 in an MRL/MpJ (MRL) colony of mice. In contrast to the reported phenotype of the knockout mouse, which was developed on a primarily C57BL/6 (B6) strain background, MRL-Atp6v1b1vtx/vtx mutant mice exhibit profound hearing impairment, which is associated with enlarged endolymphatic compartments of the inner ear. Mutant mice have alkaline urine but do not exhibit overt metabolic acidosis, a renal phenotype similar to that of the Atpbv1b1 knockout mouse. The abnormal inner ear phenotype of MRL- Atp6v1b1vtx/vtx mice was lost when the mutation was transferred onto the C57BL/6J (B6) background, indicating the influence of strain-specific genetic modifiers. To genetically map modifier loci in Atp6v1b1vtx/vtx mice, we analysed ABR thresholds of progeny from a backcross segregating MRL and B6 alleles. We found statistically significant linkage with a locus on Chr 13 that accounts for about 20% of the hearing threshold variation in the backcross mice. The important effect that genetic background has on the inner ear phenotype of Atp6v1b1 mutant mice provides insight into the hearing loss variability associated with dRTA caused by ATP6V1B1 mutations. Because MRL-Atp6v1b1vxt/vtx mice do not recapitulate the metabolic acidosis of dRTA patients, they provide a new genetic model for nonsyndromic deafness with enlarged vestibular aqueduct (EVA; OMIM #600791).
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- 2017
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132. Identification of the Causes for Chronic Hypokalemia: Importance of Urinary Sodium and Chloride Excretion
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Chih-Chen Sung, Yu-Juei Hsu, Shih-Hua Lin, Sung-Sen Yang, Ming-Hua Tseng, Chih-Jen Cheng, Kun-Lin Wu, and Tom Chau
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Adult ,Male ,medicine.medical_specialty ,Anorexia Nervosa ,Substance-Related Disorders ,030232 urology & nephrology ,Hypokalemia ,Urine ,Anorexia ,Bartter syndrome ,Gastroenterology ,Urine sodium ,Body Mass Index ,Excretion ,03 medical and health sciences ,Sex Factors ,0302 clinical medicine ,Chlorides ,Distal renal tubular acidosis ,Internal medicine ,medicine ,Humans ,Prospective Studies ,030212 general & internal medicine ,Bulimia ,Diuretics ,business.industry ,Sodium ,Bartter Syndrome ,Acidosis, Renal Tubular ,General Medicine ,Gitelman syndrome ,medicine.disease ,Endocrinology ,Laxatives ,Chronic Disease ,Female ,medicine.symptom ,business ,Gitelman Syndrome - Abstract
Background Uncovering the correct diagnosis of chronic hypokalemia with potassium (K+) wasting from the kidneys or gut can be fraught with challenges. We identified clinical and laboratory parameters helpful for differentiating the causes of chronic hypokalemia. Methods Normotensive patients referred to our tertiary academic medical center for the evaluation of chronic hypokalemia were prospectively enrolled over 5 years. Clinical features, laboratory examinations-including blood and spot urine electrolytes, acid-base status, biochemistries, and hormones-as well as genetic analysis, were determined. Results Ninety-nine patients with chronic normotensive hypokalemia (serum K+ 2.8 ± 0.4 mmol/L, duration 4.1 ± 0.9 years) were enrolled. Neuromuscular symptoms were the most common complaints. Although Gitelman syndrome (n = 33), Bartter syndrome (n = 10), and distal renal tubular acidosis (n = 12) were the predominant renal tubular disorders, 44 patients (44%) were diagnosed with anorexia/bulimia nervosa (n = 21), surreptitious use of laxatives (n = 11), or diuretics (n = 12). Patients with gastrointestinal causes and surreptitious diuretics use exhibited a female predominance, lower body mass index, and less K+ supplementation. High urine K+ excretion (transtubular potassium gradient >3, urine K+/Cr >2 mmol/mmol) was universally present in patients with renal tubular disorders, but also found in >50% patients with gastrointestinal causes. Of interest, while urine sodium (Na+) and chloride (Cl-) excretions were high and coupled (urine Na+/Cl- ratio ∼1) in renal tubular disorders and "on" diuretics use, skewed or uncoupled urine Na+ and Cl- excretions were found in anorexia/bulimia nervosa and laxatives abuse (urine Na+/Cl- ratio: 5.0 ± 2.2, 0.4 ± 0.2, respectively) and low urine Na+ and Cl- excretions with fixed Na+/Cl- ratios (0.9 ± 0.2) when "off" diuretics. Conclusion Besides body mass index, sex, and blood acid-base status, integrated interpretation of the urine Na+:Cl- excretion and their ratio is important to make an accurate diagnosis and treatment plan for patients with chronic normotensive hypokalemia.
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- 2017
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133. A Case of Kidney Involvement in Primary Sjögren’s Syndrome
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Mohammad Kamgar, Niloofar Nobakht, Hania Shakeri, Farid Arman, and Anjay Rastogi
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medicine.medical_specialty ,endocrine system diseases ,Hypokalemia ,030204 cardiovascular system & hematology ,Nephrolithiasis ,urologic and male genital diseases ,Gastroenterology ,Renal tubular acidosis ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,stomatognathic system ,Polyuria ,Distal renal tubular acidosis ,Internal medicine ,Humans ,Medicine ,030203 arthritis & rheumatology ,business.industry ,Fanconi syndrome ,Acidosis, Renal Tubular ,Articles ,General Medicine ,medicine.disease ,Nephrogenic diabetes insipidus ,eye diseases ,stomatognathic diseases ,Sjogren's Syndrome ,Endocrinology ,Diabetes insipidus ,Nephritis, Interstitial ,Female ,medicine.symptom ,business ,Polydipsia ,Diabetes Insipidus ,Sjögren’s Syndrome - Abstract
Patient: Female, 24 Final Diagnosis: Primary Sjögren syndrome Symptoms: Kidney stones • nocturia • polyuria Medication: — Clinical Procedure: — Specialty: Nephrology Objective: Rare co-existance of disease or pathology Background: Sjögren’s syndrome is an autoimmune disorder caused by the infiltration of monocytes in epithelial glandular and extra-glandular tissues. Hallmark presentations include mouth and eye dryness. Although renal involvement is uncommon in primary Sjögren’s syndrome (pSS), patients may experience renal tubular acidosis type I (RTA I), tubulointerstitial nephritis, diabetes insipidus (DI), nephrolithiasis, and Fanconi syndrome. However, it is atypical to see more than 1 of these manifestations in a single patient. Case Report: We present the case of a 24-year-old woman with polyuria and polydipsia, who was initially diagnosed with nephrogenic diabetes insipidus. She also had chronic hypokalemia and nephrolithiasis. Based on clinical presentation and work up, she was diagnosed with pSS and treated accordingly. Conclusions: This was a pSS patient with tubulointerstitial nephritis, diabetes insipidus, renal tubular acidosis, hypokalemia, and nephrolithiasis, who was receiving symptomatic treatment for diabetes insipidus. Diagnosis and treatment of pSS led to significant improvement in systemic and renal presentations of the patient. pSS should be considered as one of the differential diagnoses in patients with diabetes insipidus and renal tubular acidosis.
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- 2017
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134. Expression of Acid-Sensing Ion Channels in Renal Tubular Epithelial Cells and Their Role in Patients with Henoch-Schönlein Purpura Nephritis
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Li-ping Yuan, Gui Ming, Zhang Qin, Yan Bo, Hua Ran, Wang Li, and Yu-fei Li
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Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Pathology ,Adolescent ,IgA Vasculitis ,Kidney ,03 medical and health sciences ,Glomerulonephritis ,0302 clinical medicine ,Lab/In Vitro Research ,Internal medicine ,medicine ,Extracellular ,Humans ,RNA, Messenger ,030212 general & internal medicine ,Child ,Acid-sensing ion channel ,Ion channel ,Purpura, Schoenlein-Henoch ,Messenger RNA ,Nephritis ,Chemistry ,RNA ,Epithelial Cells ,Acidosis, Renal Tubular ,General Medicine ,medicine.disease ,Epithelium ,Acid Sensing Ion Channels ,Kidney Tubules ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,Female - Abstract
BACKGROUND Acid-sensing ion channels (ASICs) are ligand-gated cation channels activated by extracellular protons. However, the role of ASICs in kidney diseases remains uncertain. This study investigated ASICs expression in kidney tissues and their role in the development of Henoch-Schönlein purpura nephritis (HSPN). MATERIAL AND METHODS The expression of ASIC subunits was examined by immunochemical techniques in the kidney tissue from HSPN patients. Acid-induced ASICs expression in cultured renal tubular epithelial cells was determined by quantitative RT-PCR analysis. The expression of K7 and K18 protein in renal tubular epithelial cells was used to evaluate acid-induced cell injury. In addition, we observed the effect of blocking ASICs on acid-induced cell injury to assess the role of ASICs in renal tubular epithelial cell injury. RESULTS The results showed that ASIC1, ASIC2, and ASIC3 proteins were obviously expressed in renal tubular cells from HSPN patients. ASIC1 expression and 24-h urine protein level were higher in the pathological grade ISKD III group than in the ISKD II group. ASIC1, ASIC2, and ASIC3 mRNA, and K7 and K18 protein expression in cultured renal tubular epithelial cells were increased when exposed to pH 6.5. K7 and K18 protein expression was closely related to ASIC1 expression, and ASICs blockers reduced K7 and K18 protein expression in tubular epithelial cells. CONCLUSIONS These findings suggest ASICs are most highly expressed in renal tubular cells of HSPN patients, which is closely related to renal tubular injury. ASICs might be involved in the development of HSPN.
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- 2017
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135. Marble brain disease: a rare cause of renal tubular acidosis
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Aghilès Hamroun, Mehdi Maanaoui, Rémi Lenain, and Arnaud Lionet
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Adult ,Male ,Nephrology ,medicine.medical_specialty ,Pathology ,business.industry ,Osteopetrosis ,Acidosis, Renal Tubular ,medicine.disease ,Renal tubular acidosis ,Marble brain disease ,Internal medicine ,medicine ,Humans ,business ,Urea Cycle Disorders, Inborn ,Carbonic Anhydrases - Published
- 2020
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136. Renal Tubular Acidosis, Sjögren Syndrome, and Bone Disease.
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Fulop, Milford and Mackay, Meggan
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RENAL tubular transport , *ACIDOSIS , *BONE diseases , *OSTEOMALACIA , *VITAMIN D deficiency , *HEALTH surveys - Abstract
Background: There has been disagreement about whether osteomalacia (adult rickets) occurs in adults with type 1 (distal) renal tubular acidosis (RTA1). Therefore, after finding scapular pseudofractures in a patient with RTA1 and Sjögren syndrome, we decided to survey other patients with RTA to learn whether osteomalacia occurred in others and, if it did, whether it was necessarily associated with the presence of Sjögren syndrome. Methods: We examined the hospital records and laboratory findings of 250 patients with codes for RTA, 124 with codes for osteomalacia, and 20 with codes for Sjögren syndrome who were seen at a university-affiliated acute care municipal hospital since 1990. Further detailed survey was then limited to patients older than 15 years and excluded those with potentially confounding causes of bone disease such as chronic renal insufficiency or sickle cell disease. Seven adults with RTA1 were thereby identified. Results: Two adults with RTA1 had radiological and biochemical findings compatible with osteomalacia, and 1 had findings compatible with Sjögren syndrome. A third patient without Sjögren syndrome had biochemical findings suggestive of osteomalacia. Conclusions: Osteomalacia seems to occur in some adult patients with RTA1, and not only in association with Sjögren syndrome. We found no biochemical evidence of osteomalacia in the patients with Sjögren syndrome who did not have RTA. [ABSTRACT FROM AUTHOR]
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- 2004
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137. Sjogren’s with distal renal tubular acidosis complicating pregnancy
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Georgi Abraham, Anand Yuvaraj, Sudakshina Ghosh, and Lakshmi Shanmugasundaram
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Adult ,medicine.medical_specialty ,Anion gap ,Gestational Age ,Gastroenterology ,Ultrasonography, Prenatal ,Renal tubular acidosis ,03 medical and health sciences ,0302 clinical medicine ,Distal renal tubular acidosis ,Pregnancy ,Potassium Citrate ,Internal medicine ,medicine ,Humans ,Hyperchloremic metabolic acidosis ,Acidosis ,030219 obstetrics & reproductive medicine ,Cesarean Section ,urogenital system ,business.industry ,Pregnancy Outcome ,Obstetrics and Gynecology ,Acidosis, Renal Tubular ,Heart Rate, Fetal ,medicine.disease ,Pregnancy Complications ,Nephrocalcinosis ,Sjogren's Syndrome ,Sodium Bicarbonate ,030220 oncology & carcinogenesis ,Female ,Sjogren s ,Ultrasonography ,medicine.symptom ,business - Abstract
Renal tubular acidosis (RTA) is a heterogenous group of relatively uncommon tubular disorders which are characterised by hyperchloremic metabolic acidosis with a normal anion gap. It usually worsen...
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- 2018
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138. The Case | Hypokalemia and severe renal loss of sodium
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Philippe Froguel, Dominique Eladari, Sandrine Lemoine, Laurent Juillard, Amélie Bonnefond, Laurence Dubourg, Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), Université Lille Nord de France (COMUE), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie Tissulaire et d'ingénierie Thérapeutique UMR 5305 (LBTI), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
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medicine.medical_specialty ,Sodium ,[SDV]Life Sciences [q-bio] ,MEDLINE ,chemistry.chemical_element ,Hypokalemia ,030204 cardiovascular system & hematology ,Kidney ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Text mining ,Internal medicine ,medicine ,Humans ,030304 developmental biology ,0303 health sciences ,business.industry ,Acidosis, Renal Tubular ,chemistry ,Nephrology ,Potassium ,medicine.symptom ,business - Published
- 2019
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139. Impaired consciousness, hypokalaemia and renal tubular acidosis in sustained Nurofen Plus abuse
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Jerome Cockings, Luke Armstrong, Rebecca Li, and Neda Hasan
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Adult ,Substance-Related Disorders ,Hypokalemia ,Ibuprofen ,Renal tubular acidosis ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,030212 general & internal medicine ,Adverse effect ,Unexpected Outcome (Positive or Negative) Including Adverse Drug Reactions ,business.industry ,Codeine ,030208 emergency & critical care medicine ,Metabolic acidosis ,Conscious State ,General Medicine ,Acidosis, Renal Tubular ,medicine.disease ,Impaired consciousness ,Drug Combinations ,Anesthesia ,Consciousness Disorders ,Over-the-counter ,Female ,Opiate ,business ,medicine.drug - Abstract
Ibuprofen-induced renal tubular acidosis is a rare but important diagnosis which should be considered in patients presenting with hypokalaemia and metabolic acidosis. This case report details the case of a 33-year-old woman presenting with reduced conscious state, metabolic acidosis and profound hypokalaemia without an obvious cause. With correction of the patient’s electrolyte and acid-base disturbance, her conscious state improved allowing disclosure of her use of Nurofen Plus for its euphoric opiate effects. The diagnosis of renal tubular acidosis had been considered and subsequent disclosure of excessive chronic ingestion of ibuprofen suggested this to be the underlying cause. The striking feature of our patient was the insidious development of the problem and delayed accurate drug history. An important safety message arising from our case is the composite risk of dependence on the opiate component of over the counter analgesics, such as Nurofen Plus, and adverse events related to the ibuprofen component.
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- 2019
140. The natural history of solitary post-nephrectomy kidney in a pediatric population
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Sánchez Basto Catalina, Fernandez Nicolas, Espitaleta Vergara Zilac, Pérez Niño Jaime, Puerto Niño Angie Katherine, Ana María Quintero Gómez, and Castillo Mariangel
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Male ,medicine.medical_treatment ,030232 urology & nephrology ,urologic and male genital diseases ,Nephrectomy ,Renal tubular acidosis ,Solitary Kidney ,0302 clinical medicine ,Risk Factors ,Prevalence ,Postoperative Period ,Renal Insufficiency ,Age of Onset ,Child ,Kidney ,Proteinuria ,Medical record ,Acidosis, Renal Tubular ,Prognosis ,Natural history ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Child, Preschool ,Hypertension ,Female ,Original Article ,medicine.symptom ,Glomerular Filtration Rate ,medicine.medical_specialty ,Adolescent ,Urology ,Renal function ,Colombia ,03 medical and health sciences ,medicine ,Humans ,Renal Insufficiency, Chronic ,Retrospective Studies ,business.industry ,Infant, Newborn ,Infant ,medicine.disease ,Diseases of the genitourinary system. Urology ,Blood pressure ,RC870-923 ,business ,Follow-Up Studies - Abstract
Introduction: Children with a solitary post-nephrectomy kidney (SNK) are at potential risk of developing kidney disease later in life. In response to the global decline in the number of nephrons, adaptive mechanisms lead to renal injury. The aim of this study was to determine the prevalence and time of onset of high blood pressure (HBP), proteinuria, glomerular filtration rate (GFR) disruption and renal tubular acidosis (RTA) in children with SNK. Materials and methods: After obtaining the approval from our institution's ethics committee, we reviewed the medical records of patients under 18 years of age who underwent unilateral nephrectomy between January 2005 and December 2015 in three university hospitals. Results: We identified 43 patients, 35 (81.4%) cases of unilateral nephrectomy (UNP) were due to a non-oncologic pathology and Wilm's tumor was identified in 8 (18.6%) cases. In patients with non-oncologic disease, 9.3% developed de novo hypertension, with an average time of onset of 7.1 years, 25% developed proteinuria de novo, with an average time of onset of 2.2 years. For GFR, 21.8% presented deterioration of the GFR in an average time of 3.4 years. Ten (43.5%) patients developed some type of de novo renal injury after UNP. Patients with oncologic disease developed the conditions slowly and none of them developed proteinuria. Conclusions: Taking into account the high rate of long term postoperative renal injury, it can be considered that nephrectomy does not prevent this disease. The follow-up of children with SNK requires a multidisciplinary approach and long-term surveillance to detect renal injury.
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- 2019
141. Molecular modelling and dynamics of CA2 missense mutations causative to carbonic anhydrase 2 deficiency syndrome
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Babajan Banaganapalli, Ramu Elango, Noor Ahmad Shaik, Tariq Ahmed Masoodi, Hifaa A. Bokhari, Ghada Ajabnoor, and Preetha J. Shetty
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Enzyme deficiency ,Deficiency syndrome ,biology ,Cerebral calcification ,Mutation, Missense ,Osteopetrosis ,General Medicine ,Acidosis, Renal Tubular ,Gene mutation ,medicine.disease ,Molecular biology ,Carbonic Anhydrase II ,Renal tubular acidosis ,Structural Biology ,Carbonic anhydrase ,medicine ,biology.protein ,Missense mutation ,Humans ,Molecular Biology ,Urea Cycle Disorders, Inborn ,Carbonic Anhydrases - Abstract
Carbonic anhydrase 2 (CA2) enzyme deficiency caused by CA2 gene mutations is an inherited disorder characterized by symptoms like osteopetrosis, renal tubular acidosis, and cerebral calcification. This study has collected the CA2 deficiency causal missense mutations and assessed their pathogenicity using diverse computational programs. The 3D protein models for all missense mutations were built, and analyzed for structural divergence, protein stability, and molecular dynamics properties. We found M-CAP as the most sensitive prediction method to measure the deleterious potential of CA2 missense mutations. Free energy dynamics of tertiary structure models of CA2 mutants with DUET, mCSM, and SDM based consensus methods predicted only 50% of the variants as destabilizing. Superimposition of native and mutant CA2 models revealed the minor structural fluctuations at the amino acid residue level but not at the whole protein structure level. Near native molecular dynamic simulation analysis indicated that CA2 causative missense variants result in residue level fluctuation pattern in the protein structure. This study expands the understanding of genotype-protein phenotype correlations underlying CA2 variant pathogenicity and presents a potential avenue for modifying the CA2 deficiency by targeting biophysical structural features of CA2 protein. Communicated by Ramaswamy H. Sarma.
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- 2019
142. Familial hyperkalemia and hypertension and a hypothesis to explain proximal renal tubular acidosis
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Haim Mayan, Steven J.D. Karlish, and Zvi Farfel
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medicine.medical_specialty ,Letter ,Hyperkalemia ,Pseudohypoaldosteronism ,Mice, Transgenic ,Protein Serine-Threonine Kinases ,chemistry.chemical_compound ,Mice ,Hyperchloremia ,Chlorides ,Internal medicine ,Hyperchloremic acidosis ,medicine ,Humans ,Animals ,Distal convoluted tubule ,Aldosterone ,Acidosis ,Multidisciplinary ,urogenital system ,business.industry ,Acidosis, Renal Tubular ,medicine.disease ,WNK4 ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Hypertension ,Potassium ,medicine.symptom ,business ,Proximal renal tubular acidosis - Abstract
Familial hyperkalemia and hypertension (FHHt) is an inherited disease characterized by hyperkalemia, hypertension, and hyperchloremic acidosis (1, 2). The primary defect is a hyperactive sodium chloride cotransporter (NCC), expressed exclusively in renal distal convoluted tubule (DCT). FHHt is caused by a mutation in 1 of 4 genes, WNK1, WNK4, KLHL3, and Cul3, which leads to activation of NCC (2). A recent publication in PNAS (3) shows that a mutation of WNK4 prevents specific modulation by Cl− ions, inhibits its activity, and produces a FHHt phenotype. This emphasizes the significant role of WNK4 in renal Cl− handling in pathogenesis of FHHt and the question of the mechanism of hyperchloremic metabolic acidosis (4). Is hyperchloremia in FHHt a primary abnormality … [↵][1]1To whom correspondence may be addressed. Email: farfel{at}post.tau.ac.il. [1]: #xref-corresp-1-1
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- 2019
143. Hyperchloremic normal gap metabolic acidosis
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Biff F. Palmer and Deborah J. Clegg
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Diarrhea ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Bicarbonate ,Anion gap ,030209 endocrinology & metabolism ,Hypokalemia ,Buffers ,Urinary Diversion ,Kidney ,Models, Biological ,Renal tubular acidosis ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,Postoperative Complications ,Distal renal tubular acidosis ,Chlorides ,Ammonia ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Renal Insufficiency, Chronic ,Aldosterone ,Acidosis ,Acid-Base Equilibrium ,business.industry ,Kidney metabolism ,Metabolic acidosis ,Acidosis, Renal Tubular ,medicine.disease ,Bicarbonates ,Kidney Tubules ,chemistry ,030220 oncology & carcinogenesis ,Urine anion gap ,medicine.symptom ,Protons ,business ,Glomerular Filtration Rate - Abstract
Metabolic acidosis is defined as a pathologic process that, when unopposed, increases the concentration of hydrogen ions (H+) in the body and reduces the bicarbonate (HCO3-) concentration. Metabolic acidosis can be of a kidney origin or an extrarenal cause. Assessment of urinary ammonium excretion by calculating the urine anion gap or osmolal gap is a useful method to distinguish between these two causes. Extrarenal processes include increased endogenous acid production and accelerated loss of bicarbonate from the body. Metabolic acidosis of renal origin is due to a primary defect in renal acidification with no increase in extrarenal hydrogen ion production. This situation can occur because either the renal input of new bicarbonate is insufficient to regenerate the bicarbonate lost in buffering endogenous acid as with distal renal tubular acidosis (RTA) or the RTA of renal insufficiency, or the filtered bicarbonate is lost by kidney wasting as in proximal RTA. In either condition, because of loss of either NaHCO3 (proximal RTA) or NaA (distal RTA), effective extracellular volume is reduced and as a result the avidity for chloride reabsorption derived from the diet is increased and results in a hyperchloremic normal gap metabolic acidosis. The RTA of renal insufficiency is also characterized by a normal gap acidosis, however, with severe reductions in the glomerular filtration rate an anion gap metabolic acidosis eventually develops.
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- 2019
144. Molecular Pathophysiology of Acid-Base Disorders
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Carsten A. Wagner, Soline Bourgeois, Pedro Henrique Imenez Silva, University of Zurich, and Wagner, Carsten A
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0301 basic medicine ,medicine.medical_specialty ,Carbonic anhydrase II ,030232 urology & nephrology ,610 Medicine & health ,Nephron ,Kidney ,10052 Institute of Physiology ,Renal tubular acidosis ,03 medical and health sciences ,0302 clinical medicine ,Distal renal tubular acidosis ,Ammonia ,Internal medicine ,medicine ,Animals ,Homeostasis ,Humans ,Acid-Base Equilibrium ,2727 Nephrology ,biology ,Kidney metabolism ,Acidosis, Renal Tubular ,medicine.disease ,Bicarbonates ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,Nephrology ,biology.protein ,570 Life sciences ,SLC4A4 ,Proximal renal tubular acidosis - Abstract
Acid-base balance is critical for normal life. Acute and chronic disturbances impact cellular energy metabolism, endocrine signaling, ion channel activity, neuronal activity, and cardiovascular functions such as cardiac contractility and vascular blood flow. Maintenance and adaptation of acid-base homeostasis are mostly controlled by respiration and kidney. The kidney contributes to acid-base balance by reabsorbing filtered bicarbonate, regenerating bicarbonate through ammoniagenesis and generation of protons, and by excreting acid. This review focuses on acid-base disorders caused by renal processes, both inherited and acquired. Distinct rare inherited monogenic diseases affecting acid-base handling in the proximal tubule and collecting duct have been identified. In the proximal tubule, mutations of solute carrier 4A4 (SLC4A4) (electrogenic Na+/HCO3--cotransporter Na+/bicarbonate cotransporter e1 [NBCe1]) and other genes such as CLCN5 (Cl-/H+-antiporter), SLC2A2 (GLUT2 glucose transporter), or EHHADH (enoyl-CoA, hydratase/3-hydroxyacyl CoA dehydrogenase) causing more generalized proximal tubule dysfunction can cause proximal renal tubular acidosis resulting from bicarbonate wasting and reduced ammoniagenesis. Mutations in adenosine triphosphate ATP6V1 (B1 H+-ATPase subunit), ATPV0A4 (a4 H+-ATPase subunit), SLC4A1 (anion exchanger 1), and FOXI1 (forkhead transcription factor) cause distal renal tubular acidosis type I. Carbonic anhydrase II mutations affect several nephron segments and give rise to a mixed proximal and distal phenotype. Finally, mutations in genes affecting aldosterone synthesis, signaling, or downstream targets can lead to hyperkalemic variants of renal tubular acidosis (type IV). More common forms of renal acidosis are found in patients with advanced stages of chronic kidney disease and are owing, at least in part, to a reduced capacity for ammoniagenesis.
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- 2019
145. Clinical features, genetic background, and outcome in infants with urinary tract infection and type IV renal tubular acidosis
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Min-Hua, Tseng, Jing-Long, Huang, Shih-Ming, Huang, Jeng-Daw, Tsai, Tai-Wei, Wu, Wen-Lang, Fan, Jhao-Jhuang, Ding, and Shih-Hua, Lin
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Cohort Studies ,Male ,Receptors, Mineralocorticoid ,Mutation ,Renin ,Urinary Tract Infections ,Humans ,Infant ,Female ,Acidosis, Renal Tubular ,Aldosterone - Abstract
Type IV renal tubular acidosis (RTA) is a severe complication of urinary tract infection (UTI) in infants. A detailed clinical and molecular analysis is still lacking.Infants with UTI who exhibited features of type IV RTA were prospectively enrolled. Clinical, laboratory, and image characteristics and sequencing of genes responsible for phenotype were determined with follow-up.The study cohort included 12 infants (9 males, age 1-8 months). All exhibited typical type IV RTA such as hyperkalemia with low transtubular potassium gradient, hyperchloremic metabolic acidosis with positive urine anion gap, hypovolemic hyponatremia with renal salt wasting, and high plasma renin and aldosterone levels. Seven had hyperkalemia-related arrhythmia and two of them developed life-threatening ventricular tachycardia. With prompt therapy, all clinical and biochemical abnormalities resolved within 1 week. Five had normal urinary tract anatomy, and three of them carried genetic variants on NR3C2. Three variants, c.1645TG (S549A), c.538GA (V180I), and c.1-2CG, on NR3C2 were identified in four patients. During follow-up, none of them had recurrent type IV RTA, but four developed renal scaring.Genetic mutation on NR3C2 may contribute to the development of type IV RTA as a complication of UTI in infants without identifiable risk factors, such as urinary tract anomalies.
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- 2019
146. Metabolic alkalosis in patients with distal renal tubular acidosis
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Toru, Watanabe
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metabolic alkalosis ,Humans ,distal renal tubular acidosis ,Alkalosis ,Case Report ,Acidosis, Renal Tubular ,urologic and male genital diseases ,Diuretics ,hydrochlorothiazide - Abstract
Introduction: Distal renal tubular acidosis is a rare genetic disease, characterised by deficit in renal tubular transport. Clinical features are metabolic acidosis with hypercloraemia and hypokalemia, and inability in urine acidification. Hypercalciuria may also be present, often treated with the use of a diuretic therapy with thiazides. Case Presentation: We present a severe disease onset in a neonate with consanguineous parents, both autosomal-recessive for an ATP6VOA4 gene mutation, and a nevertheless severe episode of metabolic alkalosis, occurred in the same patient after few months, during the diuretic therapy. Conclusion: Biochemical results lead us to hypothesize a susceptibility to the treatment that need further investigations. (www.actabiomedica.it)
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- 2019
147. Tenofovir and Severe Symptomatic Hypophosphatemia
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Asim Kichloo, Ghazaleh Emedis Goldar, Jay Panday, Sanjeev Gupta, and Savneek Chugh
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medicine.medical_specialty ,Organic anion transporter 1 ,Anti-HIV Agents ,Epidemiology ,Lumen (anatomy) ,Case Report ,HIV Infections ,urologic and male genital diseases ,Kidney Tubules, Proximal ,Renal tubular acidosis ,tubular acidosis ,Internal medicine ,medicine ,lcsh:Pathology ,Humans ,Safety, Risk, Reliability and Quality ,hypophosphatemia ,lcsh:R5-920 ,biology ,business.industry ,Multidrug resistance-associated protein 2 ,Acidosis, Renal Tubular ,Middle Aged ,Apical membrane ,Fanconi Syndrome ,medicine.disease ,tenofovir ,Endocrinology ,Fanconi’s syndrome ,Tubular proteinuria ,Aminoaciduria ,biology.protein ,Female ,business ,lcsh:Medicine (General) ,Safety Research ,Hypophosphatemia ,lcsh:RB1-214 - Abstract
Tenofovir is a broadly used drug used for the treatment of human immunodeficiency virus (HIV). Although the initial results of the clinical trials supported the renal safety of Tenofovir, clinical use of it has caused a low, albeit a significant, risk of renal damage either in the form of AKI or CKD. The pathophysiology has been linked to the effect of this medication on the proximal tubular cell. Although the exact mechanism is unknown, studies have suggested that Tenofovir accumulates in proximal tubular cells which are rich in mitochondria. It is both filtered in the glomerulus and actively secreted in the tubules for elimination and is excreted unchanged in the urine. Studies have shown an active transportation of 20-30% of this drug into the renal proximal tubule (PCT) cells via the organic anion transporters in the baso-lateral membrane (primarily hOAT1, and OAT3 to a lesser extent) and ultimate excretion of the drug into the tubular lumen via the transporters in the proximal tubular apical membrane MRP4 and MRP2 (multidrug resistance-associated proteins 2 & 4). Subsequently, the mitochondrial injury caused by Tenofovir can lead to the development of Fanconi’s syndrome which causes renal tubular acidosis, phosphaturia, aminoaciduria, glucosuria with normoglycemia, and tubular proteinuria. Here we present a case where Tenofovir treatment resulted in severe hypophosphatemia requiring hospitalization for parentral phosphate repletion.
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- 2019
148. Extrarenal Signs of Proximal Renal Tubular Acidosis Persist in Nonacidemic Nbce1b/c-Null Mice
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Thamer A. Alsufayan, Bianca N. Quade, Emily E Salerno, Cheikh S. Alassane Mballo, Jordan Marshall, Aniko Marshall, Mark D. Parker, and Sangita P Patel
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0301 basic medicine ,medicine.medical_specialty ,Mutation, Missense ,Corneal dystrophy ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Internal medicine ,Medicine ,Animals ,Mice, Knockout ,Analysis of Variance ,biology ,business.industry ,Sodium-Bicarbonate Symporters ,Enamel organ ,Chronic metabolic acidosis ,Metabolic acidosis ,General Medicine ,Acidosis, Renal Tubular ,Tooth enamel ,medicine.disease ,Bicarbonates ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,Basic Research ,Phenotype ,Gene Expression Regulation ,Nephrology ,Failure to thrive ,biology.protein ,Acidosis, Respiratory ,medicine.symptom ,Blood Gas Analysis ,business ,SLC4A4 ,Acidosis ,Proximal renal tubular acidosis ,030217 neurology & neurosurgery - Abstract
Background The SLC4A4 gene encodes electrogenic sodium bicarbonate cotransporter 1 (NBCe1). Inheritance of recessive mutations in SLC4A4 causes proximal renal tubular acidosis (pRTA), a disease characterized by metabolic acidosis, growth retardation, ocular abnormalities, and often dental abnormalities. Mouse models of pRTA exhibit acidemia, corneal edema, weak dental enamel, impacted colons, nutritional defects, and a general failure to thrive, rarely surviving beyond weaning. Alkali therapy remains the preferred treatment for pRTA, but it is unclear which nonrenal signs are secondary to acidemia and which are a direct consequence of NBCe1 loss from nonrenal sites (such as the eye and enamel organ) and therefore require separate therapy. SLC4A4 encodes three major NBCe1 variants: NBCe1-A, NBCe1-B, and NBCe1-C. NBCe1-A is expressed in proximal tubule epithelia; its dysfunction causes the plasma bicarbonate insufficiency that underlies acidemia. NBCe1-B and NBCe1-C exhibit a broad extra-proximal-tubular distribution. Methods To explore the consequences of Nbce1b/c loss in the absence of acidemia, we engineered a novel strain of Nbce1b/c-null mice and assessed them for signs of pRTA. Results Nbce1b/c-null mice have normal blood pH, but exhibit increased mortality, growth retardation, corneal edema, and tooth enamel defects. Conclusions The correction of pRTA-related acidemia should not be considered a panacea for all signs of pRTA. The phenotype of Nbce1b/c-null mice highlights the physiologic importance of NBCe1 variants expressed beyond the proximal tubular epithelia and potential limitations of pH correction by alkali therapy in pRTA. It also suggests a novel genetic locus for corneal dystrophy and enamel hypomineralization without acidemia.
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- 2019
149. Hyperchloremic metabolic acidosis in the kidney transplant patient
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Candela Iommi, Carlos G. Musso, Debora Avila-Poletti, Leticia De Azevedo, and Kristian Heldal
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medicine.medical_specialty ,Hyperparathyroidism ,Hyperkalemia ,business.industry ,Urology ,030209 endocrinology & metabolism ,General Medicine ,Acidosis, Renal Tubular ,030204 cardiovascular system & hematology ,medicine.disease ,urologic and male genital diseases ,Kidney ,Kidney Transplantation ,Pathophysiology ,Calcineurin ,Renal tubular acidosis ,03 medical and health sciences ,0302 clinical medicine ,Medicine ,Humans ,Renal osteodystrophy ,medicine.symptom ,business ,Complication ,Kidney transplantation - Abstract
Hyperchloremic metabolic acidosis of renal origin results from a defect in renal tubular acidification mechanism, and this tubular dysfunction can consist of an altered tubular proton secretion or bicarbonate reabsorption capability. Studies have documented that all forms of renal tubular acidosis (RTA), type I to IV, are documented in kidney transplant patients. Among RTA pathophysiologic mechanisms have been described the renal mass reduction, hyperkalemia, hyperparathyroidism, graft rejection, immunologic diseases, and some drugs such as renin-angiotensin-aldosterone blockers, and calcineurin inhibitors. RTA can lead to serious complications as is the case of muscle protein catabolism, muscle protein synthesis inhibition, renal osteodystrophy, renal damage progression, and anemia promotion. RTA should be treated by suppressing its etiologic factor (if it is possible), avoiding hyperkalemia, and/or supplying bicarbonate or a precursor (citrate). In conclusion: Hyperchloremic metabolic acidosis of renal origin is a relatively frequent complication in kidney transplantation patients, which can be harmful, and should be adequately treated in order to avoid its renal and systemic adverse effects.
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- 2019
150. [Accidentally diagnosed distal renal tubular acidosis with nephrocalcinosis - a case report]
- Author
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Agnieszka, Turczyn, Piotr, Skrzypczyk, Małgorzata, Mizerska-Wasiak, Michał, Brzewski, and Małgorzata, Pańczyk-Tomaszewska
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Male ,Nephrocalcinosis ,Child, Preschool ,Mutation ,Humans ,Hypokalemia ,Acidosis, Renal Tubular ,Glomerular Filtration Rate - Abstract
Distal renal tubular acidosis is a defect of acidification of urine in distal tubule. Full-blown form is characterized by polyuria, growth deficiency, nephrolithiasis or nephrocalcinosis. Mutations in genes encoding Cl-/HCO3 - exchanger (autosomal dominant) or H+-ATPase (autosomal recessive) are the most frequent in children.In a boy aged 2,5 years, healthy, with proper development, metabolic acidosis with hyperchloremia, hypokalaemia, normal glomerular filtration rate and alkaline urine was discovered during hospitalization because of pneumonia. USG showed normal length kidney with nephrocalcinosis type IIB. The family history revealed nephrocalcinosis on the part of the boy's father. He also had metabolic acidosis in blood gas test. Genetic test in a boy and his father showed mutation of SLC4A1(17q21-q22) gene encoding Cl-/HCO3 - exchanger. The boy was treated with 8,4% NaHCO3 - orally (1mEq/kg/24h) and KCl (0,3 mEq/kg/24h). We obtained normalization of blood gas test and potassium concentration.Every child, with accidentally discovered metabolic acidosis, even with normal development, should be diagnosed in case of renal tubular acidosis. Electrolytes, gas blood test, urinalysis and USG are needed in the closest family members of child with diagnosed renal tubular acidosis.
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- 2019
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