Hipomineralización Incisivo Molar en paciente pediátrico con acidosis tubular renal distal. Reporte de caso. Control y seguimiento por 14 años

Introducción: la hipomineralización incisivo molar es un defecto sistémico del desarrollo que afecta a uno o más primeros molares permanentes, se asocia con frecuencia a los incisivos permanentes, de etiología multifactorial y con diversas opciones de tratamiento. Objetivo: se presenta el caso de un paciente que presenta hipomineralización incisivo molar en sus primeros molares permanentes con antecedentes de haber padecido de acidosis tubular renal distal, dicha entidad puede ocasionar defectos en el esmalte. Reporte del caso: masculino de 7 años de edad diagnosticado con acidosis tubular distal a los 4 meses de edad, al momento de la consulta ya superado. En sus primeros molares permanentes se observan lesiones sugestivas de hipomineralización incisivo molar. Se evalúa clínica y radiográficamente. Se le realizan restauraciones con vidrio ionomérico revisadas en controles semestrales y a los 10 años se decide colocar resinas compuestas en los molares afectados. Se indican controles periódicos a los cuales asiste regularmente por 14 años. Conclusión: la identificación temprana de la Hipomineralización incisivo molar permitirá la aplicación de medidas preventivas para asegurar la permanencia de los dientes afectados en boca. Es Importante afianzar las prácticas higiénicas especialmente en las superficies afectadas, concomitantemente con la aplicación de materiales restauradores.

Introdução: a hipomineralização molar incisivo é um defeito sistémico do desenvolvimento que afeta um ou mais primeiros molares permanentes, está frequentemente associada a incisivos permanentes, de etiologia multifatorial e com várias opções de tratamento. Objetivo: é apresentado o caso de um paciente que apresenta hipomineralização molar incisivo em seus primeiros molares permanentes com histórico de ter sofrido acidose tubular renal distal, esta entidade pode causar defeitos de esmalte. Relato de caso: menino de 7 anos de idade diagnosticado com acidose tubular distal aos 4 meses de idade, à época da consulta já ultrapassado. Em seus primeiros molares permanentes, foram observadas lesões sugestivas de hipomineralização molar incisivo. É avaliado clínica e radiograficamente. Restaurações de ionômero de vidro foram realizadas, revisadas em controles semestrais, e aos 10 anos foi decidido colocar resinas compostas nos molares afetados. São indicados controles periódicos, que frequenta regularmente há 14 anos. Conclusão: a identificação precoce da hipomineralização molar incisivo permitirá a aplicação de medidas preventivas para garantir a permanência dos dentes acometidos na boca. É importante reforçar as práticas de higiene, principalmente nas superfícies afetadas, então com a aplicação de materiais restauradores.

Summary Introduction: molar incisor hypomineralization is a systemic developmental defect that affects one or more permanent first molars, is frequently associated with permanent incisors, of multifactorial etiology and with various treatment options. Objective: the case of a patient who presents molar incisor hypomineralization in his first permanent molars with a history of having suffered from distal renal tubular acidosis is presented, this entity can cause enamel defects Case report: 7-year-old male diagnosed with distal tubular acidosis at 4 months of age, at the time of the consultation he had already passed. In his first permanent molars, lesions suggestive of molar incisor hypomineralization were observed. It is evaluated clinically and radiographically. Glass ionomer restorations were performed, reviewed at six-monthly controls, and at 10 years it was decided to place composite resins on the affected molars. Periodic controls are indicated, which he regularly attends for 14 years. Conclusion: early identification of molar incisor hypomineralization will allow the application of preventive measures to ensure the permanence of affected teeth in the mouth. It is important to strengthen hygienic practices, especially on affected surfaces, concomitantly with the application of restorative materials.

Mutation analysis and phenotypic investigation in patients with primary distal renal tubular acidosis / 中华肾脏病杂志

Objective:To analyze the gene variants in patients with primary distal renal tubular acidosis (dRTA), and explore the correlation between the genotype and phenotype.Methods:The Sanger direct sequencing or whole-exome sequencing was used to identify causal variants and the variation pathogenicity was evaluated according to 2015 American College of Medical Genetics and Genomics (ACMG) standards and guidelines in 44 dRTA patients (37 families) diagnosed in the Affiliated Qingdao Municipal Hospital of Qingdao University and the Affiliated Hospital of Qingdao University from April 2010 to September 2020. The clinical features of the patients were summarized, and the correlation between the genotype and phenotype was investigated.Results:Seven variants of SLC4A1 gene, 17 variants of ATP6V0A4 gene, and 15 variants of ATP6V1B1 gene were identified in 44 patients with dRTA, and of which 11 variants were new ones. According to ACMG guidelines, the pathogenic, likely pathogenic, benign variants among the 39 variants were 22, 16 and 1, respectively. Nine patients were autosomal dominant hereditary dRTA caused by SLC4A1 gene mutation, 4 patients with autosomal recessive hereditary dRTA complicated with Southeast Asian ovalocytosis and anemia were caused by SLC4A1 gene mutation, and 14 patients caused by ATP6V0A4 gene mutation and 8 patients caused by ATP6V1B1 gene mutation were autosomal recessive hereditary dRTA; Two children with dRTA were found to carry one monoallelic defect in ATP6V1B1, and no causal gene mutation was identified in 7 patients. One patient showed incomplete dRTA, and the other 43 patients showed complete dRTA. The prevalence of sensory neural hearing loss caused by ATP6V0A4 and ATP6V1B1 mutation were 2/14 and 6/10 respectively. The frequency of chronic kidney disease in adults, children and infants were 4/4, 2/4, and 1/36, separately. After the drug treatment based on potassium citrate and sodium citrate, the growth and development (28/40) and electrolyte disturbance (41/44) of most patients were significantly improved. Conclusions:The present study has identified 39 variants of SLC4A1, ATP6V0A4 and ATP6V1B1 genes in 44 patients with dRTA, including 11 novel ones. There is a close relationship between genotype and phenotype in dRTA patients and most patients' conditions were improved after proper treatment. This study enriches the human gene mutation database and provides valuable references for diagnosis, treatment and genetic counseling in patients with dRTA.

Síndrome de Sjögren juvenil con acidosis tubular renal distal de debut / Juvenile Sjögren's syndrome with a presentation of renal distal tubular acidosis

RESUMEN Introducción: el Síndrome de Sjögren es una exocrinopatía autoinmune caracterizada por un infiltrado inflamatorio, con predominio de linfocitos en glándulas exocrinas y tejidos extraglandulares. La lesión glandular se caracteriza por la hiposecreción en mucosa oral y ocular. Caso Clínico: paciente femenina de 13 años de edad, procedente del municipio de Consolación del Sur, en la provincia de Pinar del Río, con Síndrome de Sjögren, cuya manifestación clínica inicial fue extraglandular, con el riñón como principal órgano afectado bajo la forma de acidosis tubular renal distal tipo I. Conclusiones: se demuestra que la realización de una minuciosa anamnesis, exploración clínica y la utilización de distintas herramientas diagnósticas, hacen posible un diagnóstico precoz de la enfermedad y de sus manifestaciones extraglandulares.

ABSTRACT Introduction: the Syndrome of Sjögren is an exocrinopatía autoinmune characterized by an infiltrated inflammatory, with linfocitos prevalence in glands exocrinas and knitted extraglandulares. The glandular lesion is characterized by the hiposecreción in mucous oral and ocular. Clinical case: a 13-year-old female adolescent with Sjögren's Syndrome is presented, whose initial clinical manifestation was extra-glandular, with the kidney as the main affected organ in type-I distal renal tubular acidosis. Conclusions: it is demonstrated that the realization of a meticulous anamnesis, clinical exploration and the use of different diagnostic tools, they make possible a precocious diagnosis of the illness and of their manifestations extraglandulares.

Atypical clinical presentation of distal renal tubular acidosis: a case report registered in Amazonas, Brazil / Apresentação clínica atípica da acidose tubular renal distal: relato de caso registrado no Amazonas, Brasil

ABSTRACT We report an unusual case of a 24-year-old girl with a history of recurrent hypokalemic paralysis episodes and skin lesions on the lower limbs and buttocks, both of which had an acute evolution. In subsequent investigations, the patient also had nephrocalcinosis, nephrolithiasis, hyperchloremic metabolic acidosis and persistent alkaline urinary pH. The findings were consistent with distal renal tubular acidosis as the cause of hypokalemic paralysis. Clinical findings, immunological tests and the result of skin biopsy suggested primary Sjögren's syndrome as an underlying cause. The patient developed azotemia due to obstructive nephrolithiasis. All the features presented in this case are an unusual manifestation of distal renal tubular acidosis; so far, we are not aware of a similar report in the literature.

RESUMO Relatamos um caso incomum de uma jovem de 24 anos com história de episódios recorrentes de paralisia hipocalêmica e lesões cutâneas em membros inferiores e nádegas, ambas de evolução aguda. Em investigações subsequentes, verificou-se que a paciente apresentava nefrocalcinose, nefrolitíase, acidose metabólica hiperclorêmica e pH urinário persistentemente alcalino. Os achados foram consistentes com acidose tubular renal distal como causa da paralisia hipocalêmica. Achados clínicos, exames imunológicos e o resultado da biópsia de pele foram compatíveis com a síndrome de Sjögren primária como causa subjacente. A paciente evoluiu com azotemia em decorrência da nefrolitíase obstrutiva. Todas as características apresentadas nesse caso são uma manifestação incomum de acidose tubular renal distal; até o momento, não temos conhecimento de um relato semelhante na literatura.

The 475th case: renal tubular acidosis, renal failure, anemia, and lactic acidosis / 中华内科杂志

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.

A physiology-based approach to a patient with hyperkalemic renal tubular acidosis / Abordagem diagnóstica de um paciente com acidose tubular renal hipercalêmica

ABSTRACT Hyperkalemic renal tubular acidosis is a non-anion gap metabolic acidosis that invariably indicates an abnormality in potassium, ammonium, and hydrogen ion secretion. In clinical practice, it is usually attributed to real or apparent hypoaldosteronism caused by diseases or drug toxicity. We describe a 54-year-old liver transplant patient that was admitted with flaccid muscle weakness associated with plasma potassium level of 9.25 mEq/L. Additional investigation revealed type 4 renal tubular acidosis and marked hypomagnesemia with high fractional excretion of magnesium. Relevant past medical history included a recent diagnosis of Paracoccidioidomycosis, a systemic fungal infection that is endemic in some parts of South America, and his outpatient medications contained trimethoprim-sulfamethoxazole, tacrolimus, and propranolol. In the present acid-base and electrolyte case study, we discuss a clinical approach for the diagnosis of hyperkalemic renal tubular acidosis and review the pathophysiology of this disorder.

RESUMO A acidose tubular renal hipercalêmica é uma acidose metabólica de ânion gap normal que invariavelmente indica anormalidade na secreção de íons potássio, amônio e hidrogênio. Na prática clínica, está geralmente atribuída a um estado de hipoaldosteronismo real ou aparente, causado por doenças ou toxicidade por drogas. Descrevemos um paciente de 54 anos, transplantado hepático, que foi admitido com fraqueza muscular associada à hipercalemia, potássio plasmático de 9,25 mEq/L. A investigação adicional revelou acidose tubular renal tipo 4 e importante hipomagnesemia com elevada fração de excreção de magnésio. A história patológica pregressa incluía um diagnóstico recente de Paracoccidioidomicose - uma infecção sistêmica fúngica endêmica que ocorre em algumas partes da América do Sul -, e as medicações de uso habitual continham sulfametoxazol-trimetoprim, tacrolimus e propranolol. No presente relato de caso, discutiremos uma abordagem clínico-laboratorial para o diagnóstico da acidose tubular renal hipercalêmica, assim como da hipomagnesemia, revisando a fisiopatologia desses transtornos.

Clinical characteristics of renal tubular acidosis in adults and children / 中华肾脏病杂志

Objective To view and compare the clinical characteristics of renal tubular acidosis in adults and children.Methods Clinical data of patients with renal tubular acidosis diagnosed by Shandong Provincial Hospital affiliated to Shandong University from Jan 1991 to Sep 2017 were reviewed.The difference and consistency in clinical characteristics of renal tubular acidosis between adults and children were analyzed.Results Data from 206 adults and 60 children were analyzed.89.81％ cases in adults were secondary to other diseases,mainly primary Sjogren's syndrome.Most children patients (81.67％) were idiopathic,others largely originated from inherited metabolic diseases.The most common subtype of both was distal renal tubular acidosis.Proximal renal tubular acidosis was easier to be found in idiopathic renal tubular diseases of children.Chief complaints or starting symptoms were mainly composed of polydipsia with polyuria (41.4％) and fatigue (35.3％).Children were typical of growth retardation,rickets and digestive symptoms.The rate of missed diagnosis and misdiagnosis was 41.4 percent.Routine therapy consisted of healing metabolic acidosis and electrolyte disorders,treating underlying diseases and preventing complications.The majority of patients (95.5％) improved after treatments.Conclusions Renal tubular acidosis possesses various underlying diseases,diverse clinical manifestation and high rate of misdiagnosis.Given the high incident of secondary types,investigation of underlying disease,especially autoimmune diseases such as Sjogren's syndrome,is of great importance in adults.Most children patients suffer from primary renal tubular acidosis.Attention should be paid to them in order to reduce the rate of misdiagnosis and teratogenicity.

Mutation analysis of 5 children with primary distal renal tubular acidosis / 中华肾脏病杂志

Objective To analyze the mutations of causal genes in 5 children with primary distal renal tubular acidosis (dRTA),and explore their association of genotype and phenotype,so as to raise the awareness of the disease.Methods The whole exome sequencing was used to identify mutations in these 5 children from 5 families.Results A total of 4 different mutations of ATP6V0A4 gene were found in 2 dRTA children,including a novel heterozygous intron mutation (c.639 + 1G＞ A),a reported heterozygous nonsense variant (c.580C ＞T,p.Arg194*) and 2 novel heterozygous duplications (c.1504dupT,p.Tyr502Leufs*22;c.2351dupT,p.Phe785Ilefs*28).Two novel heterozygous missense mutations of ATP6V 1B 1 gene (c.409C ＞ T,p.Pro 137Ser;c.904C ＞ T,p.Arg302Trp) were identified in the third child,and a heterozygous missense mutation of SLC4A1 gene (c.1765C ＞ A,p.Arg589Ser) previously reported was found in the fourth child.No mutation of the dRTA-related causal genes was found in the fifth child.Furthermore,the mutations of causal genes in each of the first three children were compound heterozygous,which were consistent with the autosomal recessive inheritance pattern,and the variant from the fourth child was de novo.Conclusions The present study has found 7 mutations,including 5 novel variants,which enriches the human gene mutation database (HGMD) and contributes to a better understanding of the disease mechanisms.

Diabetes mellitus and hyperkalemic renal tubular acidosis: case reports and literature review / Diabetes mellitus e acidose tubular renal hipercalêmica: relatos de caso e revisão da literatura

ABSTRACT Hyporeninemic hypoaldosteronism, despite being common, remains an underdiagnosed entity that is more prevalent in patients with diabetes mellitus. It presents with asymptomatic hyperkalemia along with hyperchloraemic metabolic acidosis without significant renal function impairment. The underlying pathophysiological mechanism is not fully understood, but it is postulated that either aldosterone deficiency (hyporeninemic hypoaldosteronism) and/or target organ aldosterone resistance (pseudohypoaldosteronism) may be responsible. Diagnosis is based on laboratory parameters. Treatment strategy varies according to the underlying pathophysiological mechanism and etiology and aims to normalize serum potassium. Two clínical cases are reported and the relevant literature is revisited.

RESUMO Apesar de comum, o hipoaldosteronismo hiporeninêmico continua a ser uma entidade sub-diagnosticada, com maior prevalência em pacientes com diabetes mellitus. A doença cursa com hipercalemia assintomática acompanhada de acidose metabólica hiperclorêmica sem disfunção renal significativa. O mecanismo fisiopatológico subjacente não é entendido em sua totalidade, mas postula-se que a deficiência de aldosterona (hipoaldosteronismo hiporeninêmico) e/ou a resistência à aldosterona no órgão-alvo (pseudo-hipoaldosteronismo) possam ser responsáveis. O diagnóstico é fundamentado em parâmetros laboratoriais. A estratégia terapêutica varia de acordo com o mecanismo fisiopatológico subjacente e a etiologia, mas seu objetivo é normalizar o potássio sérico. O presente artigo relata dois casos e analisa a literatura relevante sobre o assunto.

Two Cases of Distal Renal Tubular Acidosis accompanied by Sjogren's Syndrome / 대한내과학회지

Renal tubular acidosis (RTA) is a syndrome characterized by hyperchloremic metabolic acidosis and an inability to excrete highly acid urine, in which the impaired acid excretion is disproportional to the reduction in the glomerular filtration rate. Distal renal tubular acidosis (dRTA) is frequently associated with immune-mediated disease, including Sjogren's syndrome. Sjogren's syndrome is a systemic autoimmune disease that mainly affects exocrine glands, such as the lacrimal and salivary glands, resulting in xerophthalmia and xerostomia. Extraglandular manifestations are frequent and may include renal involvement. Recently, we experienced two cases of renal tubular acidosis in patients with Sjogren's syndrome. The first patient had lower extremity weakness and hypokalemia and the second had nephrocalcinosis. We discuss the frequency and pathogenesis of dRTA in Sjogren's syndrome.

Aspectos clínicos, fisiopatológicos e genéticos das tubulopatias hereditárias na infância / Clinical, pathophysiological and genetic aspects of inherited tubular disorders in childhood

ResumoNesta revisão, descrevemos a função tubular de cada segmento do néfron seguida das descrições das principais alterações moleculares que possam ocorrer nos transportadores expressos nestes locais. Assim, o conhecimento das modificações na função tubular renal permite o entendimento e o reconhecimento clínico das doenças tubulares renais que podem causar a morte fetal, neonatal ou infantil. Além disso, as crianças com tubulopatias podem evoluir para doença renal crônica terminal numa fase precoce da vida e também podem apresentar distúrbios do crescimento e do desenvolvimento acompanhados ou não de alterações neurológicas. Então, nós utilizamos o unitermo "inherited tubular disorders" a fim de selecionar na base de dados do PubMed os estudos publicados desde 2006. Esperamos que a leitura desta revisão auxilie no rápido diagnóstico dos pacientes com tubulopatias, o que poderá permitir o tratamento especializado e a possível melhora do prognóstico e qualidade de vida destes indivíduos.

AbstractIn this review, we described the tubular function of each nephron segment followed by the most important changes that may occur in the transporters expressed therein. Thus, knowledge of the changes in renal tubular function allows the understanding and recognition of renal tubular diseases that can cause stillbirth or death in newborns or in childhood. Moreover, children with tubular disorders may progress to chronic renal disease at an early stage of life and they may also show disturbances of growth and development associate or not with neurological dysfunction. Therefore, we used the keyword "inherited tubular disorders" to select the children studies that have been published in the PubMed database since 2006. We hope that this review may help physicians to perform an early diagnosis in patients with tubular disorders allowing a specialized treatment and an improvement in their prognosis and quality of life.

Acidose tubular renal tipo IV no pronto atendimento / Renal tubular acidosis type IV in emergency medical services

No Hospital de Base de São José do Rio Preto, uma paciente com diabetes melito tipo 2, apresentando quadro de acidose metabólica, foi tratada na emergência da clínica médica. Foi seguido inicialmente protocolo de cetoacidose diabética. Após um dia sem melhora clínica, com a hipótese diagnóstica de acidose tubular renal tipo IV, confirmada pela acidose metabólica hipercalêmica e hiperclorêmica, foi optado por introduzir fludrocortisona no tratamento. Devido à melhora clínica e laboratorial fechou-se o diagnóstico e a paciente encontra-se em acompanhamento no ambulatório.

At the Hospital de Base hospital in São José do Rio Preto, a type II diabetic patient presenting metabolic acidosis was treated at the internal medicine ER. Initially the diabetic ketoacidosis treatment protocol was followed. Due to no improvement after one day of treatment, the diagnostic hypothesis of renal tubular acidosis type IV was confirmed by the hyperkalemic and hyperchloremic metabolic acidosis. We treated the patient with fludrocortisone. Due to clinical recovery and improvement of laboratory results, the patient was discharged and is now an outpatient in our institution.

Distal Renal Tubular Acidosis Caused by Tacrolimus in a Systemic Lupus Erythematosus Patient: A Case Report / 대한내과학회지

Renal tubular acidosis (RTA) refers to a group of disorders involving transport defects in bicarbonate reabsorption or hydrogen excretion. Features like metabolic acidosis with a normal anion gap, neurological symptoms, and electrolyte imbalances indicate RTA. Kidney transplantation, cirrhosis, sickle cell anemia, medications, and autoimmune diseases, particularly Sjogren's syndrome and rheumatoid arthritis, are related to RTA. We encountered a rare case of a patient with systemic lupus erythematosus accompanied by RTA secondary to tacrolimus administration, who had muscle weakness and paralysis. Her symptoms improved after discontinuing tacrolimus and correcting the acidosis and potassium levels. Here, we report on this case and review the relevant literature.

Expression of integrin linked kinase in obstructive nephropathy with renal tubular acidosis / 重庆医学

Objective To observe integrin linked kinase(ILK)expression in obstructive nephropathy with renal tubular acidosis, and investigate the function of renal tubular acidosis on renal interstitial fibrosis.Methods 75 rate were divided into control group and unilateral ureteral obstruction(unilateral ureteral obstruction(UUO,n=25)group,and other 50 rats in UUO group.UUO group was divided into renal tubular acidosis (UUO1 group,n=31)group and non-renal tubular acidosis(UUO2,n=19)group,re-nal function and histology test was carried at the same time.7,14,21,28 days later after operation,the rats were killed in batches, then measured the expression of ILK in renal tissue by immunohistochemistry and western blot.Results Inflammatory cell infiltra-tion and interstitial fibrosis of UUO1 group were more serious under the light microscope than that of UUO2 group;there was only a small amount of ILK protein expression in control group,almost no FN protein deposition,expression of ILK and FN protein pre-cipitation of UUO2 group increased,and UUO1 group was more than UUO2 group.Conclusion In obstructive nephropathy,renal tubular acidosis can up-regulate expression of ILK and FN sedimentation,then lead to interstitial fibrosis promotion.

Diagnóstico de anomalías dentarias en pacientes pediátricos con acidosis tubular distal mediante radiografía panorámica / Diagnóstico de anomalias dentárias em pacientes pediátricos com acidose tubular distal por meio de radiografia panorâmica

Objetivo: Determinar a presença de anomalias dentaria em crianças com acidose tubular distal. Métodos: Estudo transversal, sendo a amostra composta por 50 radiografias panorâmicas de crianças com idades entre 4 e 13 anos (29 meninos e 21 meninas) com diagnóstico de acidose tubular distal atendidas no Serviço de Nefrologia Pediátrica do Hospital "Dr. Enrique Tejera" de Valencia, Estado Carabobo, Venezuela. Adotou-se como critérios de exclusão: presença de síndromes dimórficas, alterações endócrinas, displasias ósseas, cromossomopatias e antecedentes traumáticos nos maxilares. As radiografias foram analisadas por um radiologista e um odontopediatra calibrados. Foram identificadas as anomalias de tamanho, número, forma e posição, sendo determinados quais dentes foram os mais afetados, sua localização e distribuição por gênero. As informações foram registradas em ficha específica e os dados analisados com o software SPSS versão 17, por meio da estatística descritiva (distribuições absolutas e percentuais). Resultados: A ocorrência de anomalias foi de 62%, sendo mais prevalentes a giroversão (40%), o taurodontismo (8%) e a microdontia (6%). Não se verificou diferença entre o sexo e o tipo de anomalia. Conclusão: Neste grupo de pacientes infantis com acidose tubular distal as anomalias dentárias mais frequentes foram a giroversão e o taurodontismo, sendo a prevalência observada semelhante a encontrada em pacientes sem alterações sistêmicas.

Objetivo: Determinar la presencia de anomalías dentarias en un grupo de niños con acidosis tubular distal. Métodos: Estudio transversal, la muestra, probabilísta intencional, consta de 50 radiografías panorámicas en niños entre 4 y 13 años de edad, (29 niños y 21 niñas) con diagnóstico de acidosis tubular distal tratados en el Hospital de Servicio de Nefrología Pediátrica "Dr. Enrique Tejera" en Valencia, estado Carabobo, Venezuela. Adoptado como criterios de exclusión: presencia de síndromes dimórfico, alteraciones endocrinas, displasias óseas, cromosómicas y antecedentes traumáticos en la mandíbula. Las radiografías fueron analizadas por un radiólogo y un dentista pediátrico calibrado. Se han identificado deficiencias en el tamaño, número, forma y posición e cuales dientes fueron afectados, su localización y distribución por edad y géneroy. La información fueron registrada en los archivos específicos e os datos fueron analizados con el programa SPSS versión 17, por medio de estadística descriptiva (distribuciones absolutas y porcentuales). Resultados: La ocurrencia de anomalías fue del 62%, y más giroversion prevalente (40%), el taurodontismo (8%) y microdoncia (6%). No hubo diferencia entre el sexo y el tipo de anomalía. Conclusión: En este grupo de pacientes pediátricos con acidosis tubular distal, las anomalías dentales más comunes fueron giroversion y taurodontismo, la prevalencia se observó similar a la encontrada en los pacientes sin cambios sistémicos.

Systemic Lupus Erythematosus Preceded by Distal Renal Tubular Acidosis / 대한내과학회지

Distal renal tubular acidosis (RTA) is characterized by a decreased net H+ secretion in the collecting tubules, which results in a failure of urine acidification and results in metabolic acidosis, hypokalemia, and nephrocalcinosis. The acquired form of distal RTA is associated with tubulointerstitial involvement of immune-mediated disorders such as Sjogren's syndrome and systemic lupus erythematosus (SLE). Only a few case reports have indicated that distal RTA precedes SLE by months to years. We present a 39-year-old woman who had manifestations of distal RTA for 21 years before the development of overt symptoms of SLE.

Molecular Approach for Distal Renal Tubular Acidosis Associated AE1 Mutations

The molecular approaches to distal renal tubular acidosis (dRTA) associated AE1 mutations lead us to understand the genetic and pathophysiological aspects of the acidification defects. An unanticipated high value of the urine-blood (U-B) PCO2 after NaHCO3 loading observed in a case of dRTA and southeast Asian ovalocytosis (SAO) might be from a mistarget of the AE1 to the luminal membrane of type A intercalated cells. The mutations of the AE1 gene resulted in SAO and also affected renal acidification function. Notwithstanding, after the NH4Cl loading in 20 individuals with SAO, the acidification in the distal nephron was normal. The presence of both SAO and G701D mutations of AE1 gene would explain the abnormal urinary acidification in the patients with the compound heterozogosity. In terms of the effect of the mutations on trafficking of AE1, truncated kidney isoform (kAE1) of wild-type showed a 'dominant-positive effect' in rescuing the recessive mutant kAE1 (S773P or G701D) trafficking to the plasma membrane, in contrast with the dominant mutant kAE1 (R589H) resulting in a 'dominant-negative effect' when heterodimerized with the wild-type kAE1. It is notable that the dominant mutants kAE1 (R901X or G609R) expression in MDCK cells clearly results in aberrant surface expression with some mutant protein appearing at the apical membrane. These might result in net bicarbonate secretion and increasing U-B PCO2 in the distal nephron. The molecular physiological and genetic approaches have permitted identification of the molecular defects, predominantly in transporter proteins, and should in turn prompt development of novel therapeutic strategies.

Role of Pendrin in Acid: base Balance

Pendrin (SLC26A4) is a Na+-independent Cl-/HCO3- exchanger which is expressed in the apical membranes of type B and non-A, non-B intercalated cells within the distal convoluted tubule, the connecting tubule, and the cortical collecting duct. In those segments it mediates HCO3- secretion and chloride (Cl-) absorption. In mice, no renal abnormalities are observed under basal conditions, and individuals with genetic disruption of the pendrin (SLC26A4) gene (Pendred syndrome) have normal acid-base balance. In contrast, there are definite differences under conditions wherein the transporter is stimulated. In animal studies, pendrin (SLC26A4) is upregulated with aldosterone analogues, Cl- restriction, and metabolic alkalosis, and is down-regulated with Cl loading and metabolic acidosis, independently. However, the exact role of pendrin in humans has not been established to date, and further examinations are necessary.

Sj gren's syndrome associated with voltage defect distal renal tubular acidosis and nephrogenic diabetes insipidus / 대한내과학회지

Distal renal tubular acidosis is a condition characterized by an inability of the distal nephron to acidify urine, causing hyperchloremic metabolic acidosis. Distal renal tubular acidosis is classified as proton secretory defect, permeability defect and voltage defect based on its pathophysiology. In the former two, serum level of potassium decreases due to increased excretion of potassium. But in the latter (voltage defect), hyperkalemia is characteristic by impaired the generation of an optimal electrical gradient for hydrogen ion and potassium secretion. We experienced a case of Sj gren's syndrome associated with both voltage defect distal renal tubular acidosis and nephrogenic diabetes insipidus. The patient was a 58- year-old woman who complained of general weakness, nausea and xerostomia. Laboratory analysis showed metabolic acidosis with alkaline urine and hyperkalemia. Anti-nuclear antibody and anti-ds DNA antibody were positive. She presented with polyuria, low urine osmolarity and inadequate response to DDAVP. The response to Shirmer test was decreased. Salivary scintigraphy showed decrease of uptake in the parotid and submandibular salivary glands. We believe this is the first case report in which Sj gren's syndrome is associated with both voltage defect distal renal tubular acidosis and nephrogenic diabetes insipidus.

Sj gren's syndrome associated with voltage defect distal renal tubular acidosis and nephrogenic diabetes insipidus / 대한내과학회지

Distal renal tubular acidosis is a condition characterized by an inability of the distal nephron to acidify urine, causing hyperchloremic metabolic acidosis. Distal renal tubular acidosis is classified as proton secretory defect, permeability defect and voltage defect based on its pathophysiology. In the former two, serum level of potassium decreases due to increased excretion of potassium. But in the latter (voltage defect), hyperkalemia is characteristic by impaired the generation of an optimal electrical gradient for hydrogen ion and potassium secretion. We experienced a case of Sj gren's syndrome associated with both voltage defect distal renal tubular acidosis and nephrogenic diabetes insipidus. The patient was a 58- year-old woman who complained of general weakness, nausea and xerostomia. Laboratory analysis showed metabolic acidosis with alkaline urine and hyperkalemia. Anti-nuclear antibody and anti-ds DNA antibody were positive. She presented with polyuria, low urine osmolarity and inadequate response to DDAVP. The response to Shirmer test was decreased. Salivary scintigraphy showed decrease of uptake in the parotid and submandibular salivary glands. We believe this is the first case report in which Sj gren's syndrome is associated with both voltage defect distal renal tubular acidosis and nephrogenic diabetes insipidus.