ABSTRACT
INTRODUCTION: Epithelial-to-mesenchymal transition (EMT) is a key event in renal fibrosis. The aims of the study were to evaluate acidosis induced EMT, transforming-growth-factor (TGF) β1 role and citrate effect on it. METHODS: HK2 cells (ATCC 2290) were cultured in DMEM/HAM F12 medium, pH 7.4. At 80% confluence, after 24 hr under serum free conditions, cells were distributed in three groups (24 hours): A) Control: pH 7.4, B) Acidosis: pH 7.0 and C) Calcium citrate (0.2 mmol/L) + pH 7.0. Change (Δ) of intracellular calcium concentration, basal and after Angiotensin II (10-6M) exposition, were measured to evaluate cellular performance. EMT was evaluated by the expression of α-smooth muscle actin (α-SMA) and E-cadherin by immunocytochemistry and/or Western blot. TGF-β1 secretion was determined by ELISA in cell supernatant. RESULTS: At pH 7.0 HK2 cells significantly reduced E-cadherin and increased α-SMA expression (EMT). Supernatant TGF-β1 levels were higher than in control group. Calcium citrate decreased acidosis induced EMT and improved cells performance, without reduction of TGF-β production. CONCLUSIONS: Acidosis induces EMT and secretion of TGF-β1 in tubular proximal cells in culture and citrate improves cellular performance and ameliorates acidosis induced EMT.
INTRODUÇÃO: A transição epitélio-mesenquimal (TEM) é um evento chave na fibrose renal. Os objetivos do estudo foram avaliar se o citrato seria capaz de reverter a TEM induzida por acidose, e qual seria o papel do fator de crescimento transformador (TGF) β1 neste evento. MÉTODOS: Células de túbulo proximal (HK2) foram cultivadas em meio DMEM-F12, pH 7,4. Após confluência, as células foram distribuídas em três grupos A) controle: pH 7,4, B) Acidose: pH 7,0 e C) Acidose: pH 7,0 + citrato de cálcio (0,2 mmol/L). A variação na concentração de cálcio intracelular, antes e após a adição de angiotensina II (10-6M) foi medida para avaliar o desempenho celular. TEM foi avaliada pela expressão de α-actina de músculo liso (α-SMA) e E-caderina por imunocitoquímica e/ou de Western blot. A secreção de TGF-β1 foi determinada por ELISA no sobrenadante. RESULTADOS: Em pH 7,0, houve redução significante na expressão de E-caderina e aumento de α-SMA indicando a presença de TEM e a concentração de TGF-β1 foi maior do que no grupo controle. O citrato de cálcio melhorou TEM induzida pela acidose e a resposta das células à angiotensina II, sem redução do TGF-β. CONCLUSÕES: Acidose induz TEM e secreção de TGF-β1 em células tubulares proximais em cultura e o citrato melhora o desempenho celular e a TEM induzida por acidose.
Subject(s)
Humans , Acidosis, Renal Tubular/drug therapy , Acidosis, Renal Tubular/pathology , Calcium Citrate/pharmacology , Calcium Citrate/therapeutic use , Epithelial-Mesenchymal Transition/drug effects , Kidney Tubules, Proximal/cytology , Kidney Tubules, Proximal/drug effects , Cells, CulturedABSTRACT
No abstract available.
Subject(s)
Adult , Female , Humans , Acidosis/complications , Acidosis, Renal Tubular/drug therapy , Aquaporin 2/analysis , Biomarkers/analysis , Biopsy , Immunohistochemistry , Kidney Tubules/chemistry , Nephrocalcinosis/etiology , Proton-Translocating ATPases/analysis , Sodium Bicarbonate/therapeutic use , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
We report a 28-year-old woman who presented with quadriparesis and respiratory failure, and had severe hypokalaemia and distal renal tubular acidosis. She recovered completely on potassium and alkali supplementation. Biopsy and scintigraphy of the minor salivary glands confirmed the presence of Sjogren syndrome. A 6-month course of prednisolone did not correct the distal renal tubular acidosis.
Subject(s)
Acidosis, Renal Tubular/drug therapy , Adult , Biopsy , Female , Humans , Hypokalemia/complications , Radionuclide Imaging , Respiratory Paralysis/etiology , Salivary Glands/pathology , Sjogren's Syndrome/complicationsABSTRACT
BACKGROUND: Distal renal tubular acidosis (RTA) is a common cause of intractable calcium nephrolithiasis. In adults, the use of potassium citrate (PC) in distal RTA effectively decreases metabolic acidosis and the risk of calcium oxalate stone but it cannot decrease the risk of calcium phosphate stone. However, there is no report for the optimal dose of PC and the risk of calcium stone in distal RTA in children. OBJECTIVE: To evaluate the optimal dose of PC that minimizes the risk of calcium nephrolithiasis in children with distal RTA. METHOD: Prospective study PATIENTS: Children who have distal RTA and were followed-up for 4 months. Patients were studied in a control phase, 1 month of PC 2 mEq/kg/day, 2 months of PC 3 mEq/kg/day and 1 month of PC 4 mEq/kg/day. The urine specimens of 41 normal children were measured for the reference value of the parameters determining the risk of calcium stone. RESULTS: Eight children (mean age of 10 +/- 3.7 years, female : male = 6: 2) with distal RTA were studied during the control phase and after receiving PC 2 mEq/kg/day for I month. Treatment with PC 2 mEq/kg/day was not able to normalize serum bicarbonate and caused no significant change in the urine citrate/creatinine ratio, and activity production of calcium phosphate stone but it caused a significant decrease in the urine calcium/citrate ratio. Although PC 3 mEq/kg/day for I month normalized plasma bicarbonate, only this dose given for 2 months caused a significant increase in the urine citrate/creatinine ratio and urine calcium/ citrate ratio to values that were not different from normal children, while the activity production of calcium phosphate stone did not decrease to normal level. The effect of PC 4 mEq/kg/day was similar to that of 3 mEq/kg/day. CONCLUSION: Potassium citrate 3 mEq/kg/day for 2 months effectively normalized serum bicarbonate and decreased the risk of calcium oxalate stone but this treatment was theoretically unable to reduce the risk of calcium phosphate stone in children with distal RTA.
Subject(s)
Acidosis, Renal Tubular/drug therapy , Adolescent , Child , Child, Preschool , Diuretics/administration & dosage , Dose-Response Relationship, Drug , Female , Humans , Male , Potassium Citrate/administration & dosageABSTRACT
Los transtornos de acidificación renal se manifiestan por síntomas y signos poco específicos, por lo que el pediatra debe sospechar el diagnóstico frente a un niño con dificultad en el progreso ponderal, anorexia, poliuria y que en los exámenes presenta acidosis metabólica hiperclómerica. Con estos antecedentes es importante la derivación oportuna al nefrólogo para la determinación del tipo de acidosis tubular renal y el tratamiento adecuado que repercutirá en el pronóstico vital del niño
Subject(s)
Humans , Child , Acidosis, Renal Tubular/diagnosis , Bicarbonates , Hyperkalemia/etiology , Acidosis, Renal Tubular/drug therapy , Acidosis, Renal Tubular/etiology , Hyperkalemia/drug therapy , Potassium , Potassium/blood , Prognosis , Signs and Symptoms , Sodium Bicarbonate/metabolism , Vitamin K/therapeutic useABSTRACT
A nefrolitíase é uma das mais antigas doenças que afligem o homem, estando presente, provavelmente, durante toda a sua história. O conhecimento das características físico-químicas necessárias para a formaçäo de cálculos, bem como a identificaçäo dos distúrbios metabólicos primários relacionados com a calculose, têm permitido uma melhor abordagem terapêutica, observando-seas agressÆes às vias urinárias e ao parênquima renal. Ainda que o uso de tratamento medicamentoso deva ser restrito aos pacientes que apresentam elevada recorrência, medidas gerais de adaptaçäo da dieta e ingesta hídrica adequada devem ser preconizadas para que todos que apresentem algum risco de doença calculosa
Subject(s)
Humans , Male , Female , Urinary Calculi/diagnosis , Urinary Calculi/etiology , Urinary Calculi , Urinary Calculi/therapy , Acidosis, Renal Tubular/drug therapy , Calcium/administration & dosage , Citrates , Diet , Hyperoxaluria , Ultrasonics , Uric Acid , UrineABSTRACT
A hipocalemia severa é causa incomum de rabdomiólise. Descreve-se ocaso de uma paciente de 28 anos com acidose tubular renal distal, que desenvolveu hipocalemia severa com consequente rabdomiólise. O estudo histológico do músculo evidenciou áreas focais de necrose muscular predominando em fibras do tipo II, com discreta reaçäo macrofágica. A melhota clínica e laboratorial apresentada pela paciente ocorreu após a normalizaçäo do potássio sérico, tendo sido fundamental, neste caso, a correçäo da acidose metabólica
Subject(s)
Humans , Female , Adult , Acidosis, Renal Tubular/complications , Hypokalemia/etiology , Rhabdomyolysis/etiology , Acidosis, Renal Tubular/drug therapy , Acidosis, Renal Tubular/pathology , Potassium Chloride/therapeutic use , Diagnosis, Differential , Hypokalemia/drug therapy , Hypokalemia/pathology , Rhabdomyolysis/pathology , Rhabdomyolysis/drug therapy , Sodium Bicarbonate/therapeutic useABSTRACT
Doenças tireoidianas autoimunes (DTA) tem sido associadas esporadicamente à acidose tubular renal tipo 1 (ART-1). Apresentamos o segundo caso descrito na literatura, de nosso conhecimento, de doenças de Basedow-Graves associada à ATR e à paralisia periódica tiretóxica (PPT). Os níveis de pH sanguíneo e de eletrólitos nao se normalizaram com a correçao da disfunçao tireodiana. A paralisia revertou com a administraçao de grandes quantidades de potássio (300-445 mEq/dia) e a acidose com ingestao de bicarbonato (15g/24h). Nefrocalcinose bilateral estava presente com hipercalciúria (310-603 mg/24 h) e diabetes insípidus nefrogênico (Osmolaridade urinárias= 347 mOsm após DDAVP). Aventa-se um mecanismo autoimune na gênese da ATR-1à semelhança do que ocorre na doença tireodiana associada. (Arq Bras Endocrinol Metab 1994; 38/1:35-38).