Autosomal dominant distal renal tubular acidosis in two pediatric patients with mutations in the SLC4A1 gene. Can the maximum urinary pCO2 test be normal?

Primary distal renal tubular acidosis (dRTA) is a rare tubulopathy characterised by the presence of hyperchloremic metabolic acidosis. It is caused by the existence of a defect in the function of the H+ -ATPase located on the luminal side of the α-intercalated cells or the Cl - HCO3- (AE1) anion exchanger located on the basolateral side. Patients do not acidify the urine after acid overload (NH4Cl) or after stimulating H+ secretion by obtaining a high intratubular concentration of an anion such as chlorine (pH is measured) or HCO3- (urinary pCO2 is measured). We present a family with autosomal dominant dRTA produced by a heterozygous mutation in the SLC4A1 gene in which the two paediatric members showed a test of normal maximum urinary pCO2. Our hypothesis is that since the H + -ATPase is intact, at least initially, the stimulation induced by intratubular electronegativity to secrete H + could be effective, which would allow the maximum urinary pCO2 to be paradoxically normal, which could explain the onset, moderate presentation of symptoms and late diagnosis in patients with this mutation. This is the first documented case of a dominant dRTA in Mexico.

Acidosis tubular renal distal autosómica dominante en dos pacientes pediátricos con mutaciones en el gen SLC4A1. ¿La prueba de la pCO2 urinaria máxima puede ser normal? / Autosomal dominant distal renal tubular acidosis in two pediatric patients with mutations in the SLC4A1 gene. Can the maximum urinary pCO2 test be normal?

La acidosis tubular renal distal (ATRd) primaria es una tubulopatía poco frecuente caracterizada por la presencia de acidosis metabólica hiperclorémica. Está generada por la existencia de un defecto en la función de la H+-ATPasa situada en el lado luminal de las células α-intercaladas o del intercambiador de aniones Cl−-HCO3− (AE1) ubicado en el lado basolateral. Los pacientes no acidifican la orina tras una sobrecarga ácida (NH4Cl) o tras estimular la secreción de H+ mediante la obtención de una elevada concentración intratubular de un anión como cloro (se mide el pH) o HCO3− (se mide la pCO2 urinaria). Se presenta una familia con ATRd autosómica dominante producida por una mutación heterocigota en el gen SLC4A1 en la que los 2 miembros en edad pediátrica mostraron una prueba de la pCO2 urinaria máxima normal. Nuestra hipótesis es que al estar intacta, al menos inicialmente, la H+-ATPasa, podría ser efectivo el estímulo inducido por la electronegatividad intratubular para secretar H+ lo que permitiría que la pCO2 urinaria máxima fuera paradójicamente normal, lo que pudiera explicar el inicio tardío, la presentación moderada de los síntomas y el diagnóstico en edades más avanzadas, en los pacientes con dicha mutación. Este es el primer caso documentado de una ATRd dominante en México. (AU)

Primary distal renal tubular acidosis (dRTA) is a rare tubulopathy characterized by the presence of hyperchloremic metabolic acidosis. It is caused by the existence of a defect in the function of the H+-ATPase located on the luminal side of the α-intercalated cells or the Cl− HCO3− (AE1) anion exchanger located on the basolateral side. Patients do not acidify the urine after acid overload (NH4Cl) or after stimulating H+ secretion by obtaining a high intratubular concentration of an anion such as chlorine (pH is measured) or HCO3− (urinary pCO2 is measured). We present a family with autosomal dominant dRTA produced by a heterozygous mutation in the SLC4A1 gene in which the two pediatric members showed a test of normal maximum urinary pCO2. Our hypothesis is that since the H+-ATPase is intact, at least initially, the stimulation induced by intratubular electronegativity to secrete H+ could be effective, which would allow the maximum urinary pCO2 to be paradoxically normal, which could explain the onset, moderate presentation of symptoms and late diagnosis in patients with this mutation. This is the first documented case of a dominant dRTA in Mexico. (AU)

Acidosis tubular renal distal en dos niñas diagnosticadas de hipotiroidismo adquirido / Distal renal tubular acidosis in two children with acquired hypothyroidism

Se presentan dos casos en edad pediátrica diagnosticados de acidosis tubular renal (ATR) asociada a hipotiroidismo de causa autoinmune. El caso 1 desarrolló un íleo intestinal a los 5 años de edad en el seno de un problema respiratorio. En los exámenes realizados se constató acidosis metabólica, hipercloremia, hipopotasemia y nefrocalcinosis. El caso 2 fue diagnosticado de hipotiroidismo a los 11 años de edad y 2 años después, de ATR. En ambos pacientes, se comprobó el diagnóstico de ATR al observarse una pCO2 urinaria máxima reducida. En el caso 2 se constató, además, una fuga proximal de bicarbonato (ATR tipo 3), que constituye el primer caso publicado sobre el tema. Se revisan las causas de ATR en pacientes con hipotiroidismo. El efecto deletéreo sobre el riñón puede ser debido a la propia ausencia de hormona tiroidea y/o a los autoanticuerpos en los casos de hipotiroidismo autoinmune

Two cases of children diagnosed with renal tubular acidosis (RTA) associated with autoimmune hypothyroidism are presented. Case 1 developed an intestinal ileus at the age of five in the context of a respiratory problem. The tests performed confirmed metabolic acidosis, hyperchloraemia, hypokalaemia and nephrocalcinosis. Case 2 was diagnosed with hypothyroidism at the age of 11, and with RTA two years later. In both patients, the diagnosis of RTA was verified when decreased maximum urinary pCO2 was found. In case 2, a proximal bicarbonate leak (type 3 RTA) was also confirmed. This was the first case to be published on the topic. The causes of RTA in patients with hypothyroidism are reviewed. The deleterious effect on the kidneys may be due to the absence of thyroid hormone and/or autoantibodies in the cases of autoimmune hypothyroidism

Distal renal tubular acidosis in two children with acquired hypothyroidism. / Acidosis tubular renal distal en dos niñas diagnosticadas de hipotiroidismo adquirido.

Two cases of children diagnosed with renal tubular acidosis (RTA) associated with autoimmune hypothyroidism are presented. Case 1 developed an intestinal ileus at the age of five in the context of a respiratory problem. The tests performed confirmed metabolic acidosis, hyperchloraemia, hypokalaemia and nephrocalcinosis. Case 2 was diagnosed with hypothyroidism at the age of 11, and with RTA two years later. In both patients, the diagnosis of RTA was verified when decreased maximum urinary pCO2 was found. In case 2, a proximal bicarbonate leak (type 3 RTA) was also confirmed. This was the first case to be published on the topic. The causes of RTA in patients with hypothyroidism are reviewed. The deleterious effect on the kidneys may be due to the absence of thyroid hormone and/or autoantibodies in the cases of autoimmune hypothyroidism.

Distal Renal Tubular Acidosis Screening by Urinary Acidification Testing in Mexican Children.

BACKGROUND: Primary distal renal tubular acidosis is a clinical disorder characterized by hyperchloremic metabolic acidosis, hypercalciuria, hypocitraturia, urinary acidification impairment, hypokalemia, metabolic bone disease, and nephrocalcinosis. Urinary acidification ability may be evaluated by an acidification test or maximum urinary pCO2 assessment with alkaline urine. The maximum urinary pCO2 test using acetazolamide and sodium bicarbonate is an easy test to confirm the lack of urine acidification in distal renal tubular acidosis in children. OBJECTIVE: To determine the urinary acidification ability using the maximum urinary pCO2 assessment in a group of children with a distal renal tubular acidosis diagnosis. MATERIAL AND METHODS: Thirty children were evaluated (13 males and 17 females); 23 children had been diagnosed with distal renal tubular acidosis by other physicians and were under alkali treatment with potassium and sodium citrates (21) and bicarbonate (2), and five children were not under alkali treatment. Two children had been diagnosed with primary distal renal tubular acidosis by our medical group. The maximum urinary pCO2 was determined by the oral intake of acetazolamide and sodium bicarbonate. RESULTS: Two cases with primary distal renal tubular acidosis were found, and they had a history of dehydration episodes during infancy and showed hyperchloremic metabolic acidosis with hypokalemia. They also exhibited urine acidification impairment with furosemide and reduced urinary pCO2 (< 60 mmHg), and the urine-blood pCO2 gradient was reduced in both cases (< 30 mmHg). One of them developed bilateral sensorineural deafness, while the other showed severe hypocitraturia. One case of proximal or type 2 renal tubular acidosis with hyperaminoaciduria was identified. Twenty-eight children displayed normal urinary acidification and did not show signs of distal renal tubular acidosis. CONCLUSIONS: The urinary acidification test with furosemide and urinary pCO2 assessment are reliable tests to identify the renal excretion of hydrogen ions (H+) and allow confirmation of the lack of urine acidification in distal renal tubular acidosis.

Válvulas de uretra posterior y ausencia de reflujo vesicoureteral bilateral: Seguimiento de la función renal / Posterior urethral valves and lack of bilateral vesicoureteral reflux: Renal function follow-up background

Introducción. Las válvulas de uretra posterior congénitas son repliegues de mucosa que se originan únicamente en varones. Constituyen la causa más común de obstrucción de la vía urinaria en el período neonatal. Debido a la alta presión que se genera en la vejiga urinaria, con frecuencia se acompañan de reflujo vesicoureteral (RVU) bilateral. En ocasiones, el reflujo es unilateral, asociado a displasia renal homolateral (síndrome VURD). Se ha comunicado que en estos casos el pronóstico a largo plazo es mejor, no obstante, existe muy poca experiencia sobre éste en el subtipo constituido por los niños en los que no existe reflujo. Métodos. Se estudiaron a 4 pacientes con válvulas de uretra posterior y ausencia de RVU, en seguimiento por un tiempo comprendido entre 3 y 6 años. Se describe su evolución desde el diagnóstico, la cirugía realizada, los marcadores de función renal, estudios de imagen y evolución. Así como los valores de los cocientes calculados entre las concentraciones urinarias de N-acetil-glucosaminidasa (NAG) y de microalbúmina con respecto a la creatinina urinaria. Resultados. La función glomerular renal fue normal en los 4 casos. Únicamente un paciente tenía un discreto defecto de la capacidad de concentración y un ligero incremento en la eliminación urinaria de NAG. Conclusiones. El manejo médico y quirúrgico de las válvulas de uretra posterior ha mejorado la supervivencia de los niños con este diagnóstico. La ausencia de RVU, la presencia de ascitis urinaria o urinoma en el período neonatal y la asociación con un gran divertículo vesical proveen un mecanismo de "escape", lo que resulta en una preservación de la función renal.

Introduction. The posterior urethral congenital valves are mucosal folds in the posterior urethra that occur only in male patients. They are the most common cause of urinary tract obstruction in the neonatal period. Due to hyper pressure that begins in the urinary bladder, it is highly frequent for these to come together with bilateral vesico-ureteral reflux. In some cases, this reflux is unilateral and is associated with posterior urethral valve and renal dysplasia (VURD syndrome). A better long-term renal outcome in these cases has been reported. Nevertheless, there is very little experience regarding prognosis of the remaining group of children without reflux. Methods. We studied 4 children with posterior urethral valves and lack of vesico-ureteral reflux with controlled follow-up during 3 and 6 years. We described disease presentation and clinical course from diagnosis, surgical intervention, renal function, radiologic features, N-acetylglucosaminidase (NAG), and microalbuminuria during follow-up. Results. Renal glomerular function is normal in all 4 cases. Only one patient had a mild default in urinary concentration capacity and a slight increase in urinary elimination of N-acetylglucosaminidase. Conclusion. Medical and surgical management of the posterior urethral valves has improved long-term renal outcome in the sepatients. Lack of vesico-ureteral reflux, urinary ascites, urinary extravasation, and large congenital bladder diverticula can serve as a pop-off mechanism to buffer hyperpressure in the urinary tract, leading to the preservation of improved renal function in boys with posterior urethral valves.