Hypokalemic paralysis due to distal renal tubular acidosistype 1 in patient of mucormycosison amphotericin B: a case report

A 42-year-old male patient who is a known case of DM and mucormycosison treatment presented with sudden onset difficulty in moving all 4 limbs followed by decreased depth of respiration for 4 hours. The patient was known case of DM for 10 years and was on OHA for the same, he had history of biopsy diagnosed rhino mucormycosis 4 months ago and was on treatment for the same. On initial examination the tone was hypotonic in all4 limbs along with power of 3+, respiration was shallow and patient was bedridden unable to stand on his own, he was ambulatory 6 days before presentingto hospital. Potassium-1.7 mEq/l, ABGA pH-7.18, HCO3-10 Meq/l, urine osmolality 220 mOsm/l, urine pH-7.0, potassium-to-creatinine rstio (K/Cr)-3.9 mEq/ml, urine K-22 mEq/ml. Distal RTA (dRTA) is the classical form of RTA, being the first described. DistalRTA is characterized by a failure of H+ secretion into lumen of nephron by the alpha intercalatedcellsof themedullary collecting ductof thedistalnephron.This failure of acid secretion may be due to a number of causes, and it leads to an inability to acidify the urine to apHof less than 5.3.This case study enumerates the potentially dangerous side effects of amphotericin B in patients which canprecipitate RTA type 1 leading to severe hypokalaemia and acidosis, thus all patients receiving amphotericin B should be cautiously warned regarding side effect of hypokalaemia and prophylactic potassium syrup supplementation may be given in predisposed patients.

Primary Autosomal Recessive Distal Renal Tubular Acidosis Caused by a Common Homozygous SLC4A1 Mutation in Two Lao Families

Primary distal renal tubular acidosis (dRTA) caused by mutations of the SLC4A1 gene, which encodes for erythroid and kidney isoforms of anion exchanger, shows marked difference in inheritance patterns and clinical features in different parts of the world. While the disease shows autosomal dominant inheritance without any red cell morphological abnormalities in the temperate countries, it is almost invariably recessive, and often accompanies red cell morphological abnormalities or hemolytic anemia in the tropics, especially in Southeast Asia. Here, we report three patients with autosomal recessive (AR) dRTA, presenting with typical findings of failure to thrive and rickets, from two unrelated Lao families. The mutational analyses revealed that all three patients harbored the same homozygous SLC4A1 mutation, p.Gly701Asp. Adequate supplementation of alkali and potassium resulted in remarkable improvement of growth retardation and skeletal deformities of the patients. This is the first case report of Lao patients with AR dRTA caused by SLC4A1 mutations.

The distal renal tubular acidosis caused by ATP6V1B1 gene mutation:a case report / 临床儿科杂志

Objective To explore the clinical features and gene diagnosis of the distal renal tubular acidosis (dRTA). Methods The clinical data and gene detection results of one child with dRTA were retrospectively analyzed. The related literatures were reviewed. Results Four-month-old female was admitted with frequent vomiting and hearing impairment. The laboratory examination showed refractory hypokalemia and it was difficult to correct metabolic acidosis. Gene detection found a new mutation on ATP6V1B1 gene. The diagnosis of dRTA was confirmed. Conclusions dRTA is a rare disease, ATP6V1B1 gene is the causative gene of the dRTA with sensorineural deafness.

Sequenciamento total do exoma como ferramenta de diagnóstico de acidose tubular renal distal / Whole-exome sequencing as a diagnostic tool for distal renal tubular acidosis

Resumo Objetivo A acidose tubular renal distal (ATRd) é caracterizada por acidose metabólica devido à excreção renal de ácido prejudicada. O objetivo deste artigo é apresentar o diagnóstico genético de quatro crianças com ATRd com uso do sequenciamento total do exoma. Métodos Selecionamos duas famílias não relacionadas, quatro crianças com ATRd e seus pais, para fazer o sequenciamento total do exoma. A audição foi preservada em ambas as crianças da família um, porém em nenhuma criança da família dois, na qual um par de gêmeas teve perda auditiva severa. Fizemos o sequenciamento total do exoma em dois conjuntos de amostras e confirmamos os achados com o método de sequenciamento de Sanger. Resultados Duas mutações foram identificadas nos genes ATP6V0A4 e ATP6V1B1. Na família um, detectamos uma nova mutação no éxon 13 do gene ATP6V0A4 com uma alteração em um nucleotídeo único GAC → TAC (c.1232G>T) que causou substituição de ácido aspártico por tirosina na posição 411. Na família dois, detectamos uma mutação recorrente do homozigoto com inserção de um par de bases (c.1149_1155insC) no éxon 12 do gene ATP6V1B1. Conclusão Nossos resultados confirmam o valor do sequenciamento total do exoma para o estudo de nefropatias genéticas complexas e permitem a identificação de mutações novas e recorrentes. Adicionalmente, demonstramos claramente pela primeira vez a aplicação desse método molecular em doenças tubulares renais.

Abstract Objective Distal renal tubular acidosis (dRTA) is characterized by metabolic acidosis due to impaired renal acid excretion. The aim of this study was to demonstrate the genetic diagnosis of four children with dRTA through use of whole-exome sequencing. Methods Two unrelated families were selected; a total of four children with dRTA and their parents, in order to perform whole-exome sequencing. Hearing was preserved in both children from the first family, but not in the second, wherein a twin pair had severe deafness. Whole-exome sequencing was performed in two pooled samples and findings were confirmed with Sanger sequencing method. Results Two mutations were identified in the ATP6V0A4 and ATP6V1B1 genes. In the first family, a novel mutation in the exon 13 of the ATP6V0A4 gene with a single nucleotide change GAC → TAC (c.1232G>T) was found, which caused a substitution of aspartic acid to tyrosine in position 411. In the second family, a homozygous recurrent mutation with one base-pair insertion (c.1149_1155insC) in exon 12 of the ATP6V1B1 gene was detected. Conclusion These results confirm the value of whole-exome sequencing for the study of rare and complex genetic nephropathies, allowing the identification of novel and recurrent mutations. Furthermore, for the first time the application of this molecular method in renal tubular diseases has been clearly demonstrated.

HIV Infection Itself may be a Cause of Hypokalemic Distal Renal Tubular Acidosis without Hypergammaglobulinemia.

Distal renal tubular acidosis (dRTA) is seen in the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) population in the setting of hypergammaglobulinemia and antiretroviral agents, whereas isolated HIV infection is rarely reported to be associated with dRTA. We report a case of a young woman with a history of untreated HIV/AIDS who presented with profound generalized weakness and refractory hypokalemia along with non-anion gap metabolic acidosis and inappropriately high urine pH. Her serum gamma-globulin level was not significantly elevated and she was not on highly active antiretroviral therapy (HAART). No other cause of dRTA was evident. Subsequently, a diagnosis of dRTA secondary to isolated HIV/AIDS was made. Distal RTA can be acquired or inherited and is caused by defects in proton pumps or pH pressure gradients. In dRTA, the potassium level can be low, normal, or even high depending upon the pathophysiologic abnormality. Early recognition and prompt treatment is imperative to avoid the serious consequences of severe electrolyte and metabolic disturbances. Our case report is a reminder to clinicians to be mindful of this rare condition when evaluating unexplained dRTA and to include HIV/AIDS as part of the differential diagnosis of dRTA even in the absence of significant hypergammaglobulinemic (IgG level was slightly elevated) state or antiretroviral agents. We believe this is the second such case to be documented.

A Case of Distal Renal Tubular Acidosis with Sjögren's Syndrome Presenting as Hypokalemic Paralysis / 계명의대학술지

Distal renal tubular acidosis (RTA) caused by autoimmune nephritis occurs in up to 25% of patients with Sjögren's syndrome. However, patients with hypokalemic paralysis are sometimes overlooked, because most symptoms of autoimmune nephritis in Sjögren's syndrome are mild. We present a case of hypokalemic paralysis in a 54-year-old female who also had dry eyes and mouth, and Raynaud's phenomenon. Further evaluation, including autoantibody tests, revealed distal RTA with Sjögren's syndrome as the cause of hypokalemia. Distal RTA diagnosis was made based on normal anion gap hyperchloremic metabolic acidosis, alkaline urine with positive urine anion gap, high transtubular potassium concentration gradient (TTKG), positive anti-La antibody, and symptoms of sicca complex. The patient's symptoms resolved following treatment with intravenous and oral potassium, immunosuppressants, and steroids. This case illustrates that distal RTA and Sjögren's syndrome should be considered in cases of hypokalemic paralysis.

Síndrome de Sjögren y acidosis tubular renal distal reversible: una mirada a sus manifestaciones renales / Sjögren's syndrome and reversible distal renal tubular acidosis: Renal manifestations

Resumen Presentamos el caso de un paciente masculino con síndrome de Sjögren cuya manifestación clínica inicial fue extraglandular, teniendo el riñón como principal órgano afectado bajo la forma de acidosis tubular renal distal, que lo llevó a nefrocalcinosis como complicación en su evolución natural. Su hallazgo permitió el diagnóstico de esta exocrinopatía autoinmune, lográndose la remisión clínica y estabilización de la función renal con el uso de esteroides.

Abstract We describe a male patient with Sjögren's syndrome, whose initial clinical manifestation was extraglandular. The kidney was the main organ affected in the form of distal renal tubular acidosis that led to nephrocalcinosis as a complication during its natural progression. These findings led to the diagnosis of autoimmune exocrinopathy, with clinical remission and stabilization of renal function being achieved with the use of steroids.

Abordaje del niño con hipercalcemia: reporte de 3 casos / Approach to the child with hypercalcemia: report of 3 cases

La hipercalcemia en niños es un trastorno electrolítico raro. Su presentación clínica es variable, al igual que su etiología. En esta publicación se abordan los casos de tres niños con hipercalcemia. Primeramente, un neonato de 24 días con irritabilidad, pobre succión y nefrocalcinosis. El segundo caso es de un niño de 1 año de edad con estenosis pulmonar, falla para progresar, retraso en el desarrollo psicomotor, fascies de duende y nefrocalcinosis. Por último, se presenta una niña de 11 años, con cuadro de dolor abdominal, polidipsia, náuseas, vómitos, lesiones líticas en huesos largos y anemia. Las causas determinadas para cada caso fueron, respectivamente: acidosis tubular distal, síndrome de Williams y leucemia linfocítica aguda. Para el abordaje del niño con hipercalcemia se muestran dos esquemas de diagnóstico realizados con fundamento en los hallazgos clínicos, laboratorios y gabinete. La terapeútica en estos niños debe basarse en el aumento de la excreción renal de calcio (hidratación, diuréticos), reducción de la absorción a nivel intestinal(restricción nutricional de calcio y vitamina D, glucocorticoides), inhibición de la resorción ósea (bifosfonatos, glucocorticoides), redistribución del calcio y, sobre todo, la prontitud con la que se instaure una terapia eficaz, ya que esta tendrá un impacto a largo plazo sobre su salud y calidad de vida...

Distal Renal Tubular Acidosis with Hereditary Spherocytosis.

Hereditary spherocytosis (HS) and distal renal tubular acidosis (dRTA), although distinct entities, share the same protein i.e. the anion exchanger1 (AE1) protein. Despite this, their coexistence has been rarely reported. We hereby describe the largest family to date with coexistence of dRTA and HS and discuss the molecular basis for the co-inheritance of these conditions.

Acidosis tubular renal distal, a propósito de un caso / Distal renal tubular acidosis, a case report

Describimos las características clínicas y de laboratorio de una escolar con los diagnósticos de acidosis tubular renal distal y raquitismo secundario. Se aprovecha el caso para hacer una revisión de la literatura.

We described the clinical and laboratory findings of a child with distal renal tubular acidosis associated to severe rickets and review the literature.

Refractory rickets caused by mild distal renal tubular acidosis

Type I (distal) renal tubular acidosis (RTA) is a disorder associated with the failure to excrete hydrogen ions from the distal renal tubule. It is characterized by hyperchloremic metabolic acidosis, an abnormal increase in urine pH, reduced urinary excretion of ammonium and bicarbonate ions, and mild deterioration in renal function. Hypercalciuria is common in distal RTA because of bone resorption, which increases as a buffer against metabolic acidosis. This can result in intractable rickets. We describe a case of distal RTA with nephrocalcinosis during follow-up of rickets in a patient who presented with clinical manifestations of short stature, failure to thrive, recurrent vomiting, dehydration, and irritability.

Distal Renal Tubular Acidosis with Nephrocalcinosis in a Patient with Primary Sjogren's Syndrome

Renal involvement is not uncommon in primary Sjogren's syndrome; however, it is clinically insignificant in most cases. Distal renal tubular acidosis accounts particularly for the majority. While the underlying distal renal tubular acidosis is an important cause of nephrocalcinosis and urolithiasis, nephrocalcinosis is rarely a presenting feature of primary Sjogren's syndrome. We report a 65-year-old woman who was diagnosed with distal renal tubular acidosis accompanied by primary Sjogren's syndrome, according to nephrocalcinosis, which was incidentally identified by an abdominal ultrasonography during a medical examination.

Distúrbios ácido-base na leishmaniose visceral / Acid-base disorders in visceral leishmaniasis

Defeitos na capacidade de acidificação e concentração urinárias têm sido descritos em pacientes portadores de leishmaniose visceral. Foram avaliados os distúrbios do equilíbrio ácido-base presentes nos pacientes com calazar, bem como os fatores relacionados. Metodologia: Foram estudados 59 pacientes com formas crônicas de calazar e comparados a um grupo controle. A gasometria arterial foi colhida em jejum; o pH urinário, a acidez titulável e a amônia urinária foram determinadas em urinas colhidas sob óleo mineral. A amônia foi dosada pela técnica de Berthelot e a acidez titulável, pela técnica de Palmer. Resultados: Todos os pacientes tinham hipoalbuminemia, hipergamaglobulimenia e hiponatremia. O grupo I compreendeu 75,5% dos pacientes, que apresentaram quadro misto de alcalose respiratória e alcalose metabólica. Hipocloremia ocorreu em 37,6%; hipocalemia associada a um potássio urinário elevado foi observada em 24,8% dos casos. Hipomagnesemia com perda renal de magnésio e potássio foi detectada em 44% dos casos. O grupo II, constituído por 24,5% dos pacientes, apresentou quadro de acidose metabólica. A excreção urinária de H+, a acidez titulável e a amônia foram semelhantes nos dois grupos. Um elevado pH urinário e uma carga elétrica urinária positiva confirmaram no grupo II a presença de acidose tubular renal distal. O equilíbrio ácido-base, pelo modelo stewart-Figge, mostra diminuição da diferença de íons fortes (SIDa), elevação do SIG e diminuição da concentração de ácidos fracos. Conclusões: Alcalose respiratória crônica e alcalose metabólica associada 9grupo I) foram observadas em 75.5% dos casos e relacionaram-se com o quadro de pneumonite intersticial, anemia, febre e disfunção hepática. Hipomagnesemia com depleção de potássio e magnésio estava presente.

Defects in the ability of urinary acidification and concentration have been described in patients with visceral leishmaniasis. We assessed disorders present acid-base balance in patients with kala-azar, as well as the related factors. Methodology: We studied 59 patients with chronic forms of leishmaniasis and compared to a control group. The arterial blood gas was collected in fasting, urinary pH, titratable acidity and urinary ammonium were determined in urine collected under mineral oil. Ammonia was measured by the Berthelot technique and acidity, the technique of Palmer. Results: All patients had hypoalbuminemia, and hyponatremia hipergamaglobulimenia. Group I comprised 75.5% of patients, who had mixed picture of respiratory alkalosis and metabolic alkalosis. Hypochloremia occurred in 37.6%, hypokalemia associated with a high urinary potassium was observed in 24.8% of cases. Hypomagnesemia with renal loss of magnesium and potassium was detected in 44% of cases. Group II, consisting of 24.5% of patients presented with metabolic acidosis. The urinary excretion of H +, acidity and ammonia were similar in both groups. A high urinary pH and urinary a positive electric charge in the group II confirmed the presence of distal renal tubular acidosis. The acid-base balance by Stewart-Figge model shows decrease in strong ion difference (AIDS), an increase of GIS and decreased concentration of weak acids. Conclusions: Chronic respiratory alkalosis and metabolic alkalosis associated 9grupo I) were observed in 75.5% of cases and were related to the picture of interstitial pneumonitis, anemia, fever and liver dysfunction. Hypomagnesemia with depletion of potassium and magnesium was present. Metabolic acidosis (group II) was observed in 24.5% of patients presenting with.

A Case of Distal Renal Tubular Acidosis by Damage of H+-ATPase Pump after Paraquat Intoxication / 대한신장학회잡지

Distal Renal tubular acidosis is characterized by tubular dysfunction with a decrease in net H+-secretion in the collecting tubules regardless of normal glomerular filtration rate. It classified into primary and secondary form. The causes of secondary form could be many drugs such as amphotericin B, toluene, lithium carbonate, ifosfamide, but paraquat has not been reported. The mechanism of renal damage by paraquat has not be fully comprehensive but it is thought that paraquat causes damage to renal proximal tubules and clinically induces acute tubular necrosis. Our case demonstrated that immunohistochemical staining of renal biopsy specimen with anti H+-ATPase antibody showed absence of proton pump in collecting duct. Thus a case of distal renal tubular acidosis in association with paraquat intoxication is reported with a review of literatures.

Distal Renal Tubular Acidosis Complicated with Periodic Hypokalemic Paralysis

A 5-year-old girl was admitted because of an acute onset of weakness in her extremities. She had experienced a similar episode before but had recovered spontaneously. She had previously been diagnosed with distal renal tubular acidosis(RTA) at the age of 2 months. During the period of acute paralysis, her serum potassium level was 1.8 mmol/L and the muscle enzymes were markedly raised suggesting massive rhabdomyolysis. Although hypokalemia is common in renal tubular acidosis, acute paralytic presentation is uncommon and is rarely described in children. We report a case of distal RTA complicated with hypokalemic paralysis with a brief review of related literatures.

H+ -ATPase Pump Defects of Distal Renal Tubular Acidosis as Initial Manifestation of Systemic Lupus Erythematosus / 대한신장학회잡지

Systemic lupus erythematosus (SLE) is a multisystem disease with marked variability in its manifestation. Tubulointerstitial involvement is well recognized in SLE. But usually the tubular dysfunction is latent and usually presents after diagnosis of SLE. We report a 20 years old female whose initial symptom of SLE was distal renal tubular acidosis (RTA). She presented with severe muscle weakness at emergency room with laboratory fingding consistent with distal RTA. After several months she developed fever, arthritis, serologic fingding which was compatible to diagnose SLE. We report a case whose initial symptom of SLE had been distal RTA.

A Case of Distal Renal Tubular Acidosis Associated with Medullary Sponge Kidney

Renal tubular acidosis is a clinical state of systemic hyperchloremic acidosis resulting from impaired urine acidification. Medullary sponge kidney is a renal parenchymal malformation characterized by cystic dilatation of the collecting ducts. Although medullary sponge kidney is a congenital disease, it is rarely identified in childhood and is usually discovered in adulthood. Medullary sponge kidney patients may have defects in urinary acidification and concentration mechanism. We experienced a case of distal renal tubular acidosis associated with medullary sponge kidney. So, we report a case of distal renal tubular acidosis associated with medullary sponge kidney with a brief review of the related literature.

Defect of Acid-base Transporters in Distal Renal Tubular Acidosis / 대한신장학회잡지

The purpose of this study was to elucidate whether the molecular defect of acid-base transporters in renal tubules is related to the functional defect of urinary acidification in distal renal tubular acidosis(RTA). We performed NH4Cl, furosemide, or bicarbonate loading test to evaluate renal acidification function, and immunohistochemistry using antibodies to H+- ATPase, Cl-/HCO3- exchanger(band-3 protein), and Na+/K+-ATPase in kidney tissue in 6 patients with RTA and renal cell carcinoma patients as normal controls. Kidney tissue was obtained either by percutaneous needle biopsy(RTA) or nephrectomy(NC). The results were as follows; 1) In all six RTA patients, proton secretory defect of distal acidification was shown by a failure to lower the urine pH after NH4Cl loading or furosemide test or abnormally low urine-blood pCO2 difference during bicarbonate loading. In two patients with RTA, proximal acidification defect was combined, which was demonstrated by increased fractional excretion of bicarbonate. 2) In normal control, intense H+-ATPase and band-3 protein staining was observed in collecting ducts. 3) In distal RTA patients, H+-ATPase and band- 3 protein staining was not demonstrable or markedly decreased in the intercalated cells of distal nephron. 4) In two patients who had both proximal and distal RTA, H+-ATPase staining was markedly decreased in the brush border of proximal tubules as well as the distal nephron. In conclusion, the defect of acid-base transporters in renal tubule was related with the functional defect of urinary acidification in distal RTA.

A Case of Sj gren's Syndrome Presented as Hypokalemic Periodic Paralysis due to Distal Renal Tubular Acidosis / 대한류마티스학회지

Distal renal tubular acidosis (dRTA) can be associated with some autoimmune disease such as systemic lupus erytheuatosus, Sj gren's syndrome, and rheumatoid arthritis. Although hypokalemia in Sj gren's syndrome is a frequent complication, severe symptomatic hypokalemia has been reported only in few cases. Recently we experienced a case of Sj gren's syndrome diagnosed after the discovery of distal renal tubular acidosis with severe hypokalemia manifestating periodic weakness, myalgia in lower extremities, nausea, vomiting, and flaccid paralysis. She complained continuous sensation of dryness of her eyes and mouth. After the Schirmer's test, salivary scan, serologic tests, and lip biopsy, Sj gren's syndrome was confirmed. Intravenous and oral potassium replacement was started immediately, oral sodium bicarbonate later. Marked improvement in periodic paralysis was noted within a few hours and she was fully regained her muscle strength within 48 hours. She discharged with oral sodium bicarbonate and artificial tears. With this treatment blood pH and potassium were kept in the normal range during follow up visits.

A Case of Distal Renal Tubular Acidosis with Systemic Lupus Erythematosus (SLE)

Distal renal tubular acidosis (RTA) is well-recognized complication of immunologically mediated condition such as Sj ogren's syndrome, SLE, idiopathic hypergammaglobulinemia, autoimmune liver disease, autoimmune thyroid disease, multiple myeloma, and renal tranplant rejection. Tubulointerstitial involvement frequently occurrs in SLE. A sepctrum of abnormalities including impaired uriary concentration or acidification, increased fractional excretion of low molecular weight protein, hyporeinaemic hypoaldosteroniam and impaired tubular potassium excretion can occur in SLE. But complete distal RTA associated wih SLE is rare. We report a 13 year-old female with SLE and distal RTA which was diagnosed by NaHCO3 loading test. She had nephrotic syndrome, hypokalemia, hyperchloremic metabolic acidosis with alkali urine. She had fatiquebility, general weakness, intermittent fever and chest pain for at least 12months. And then, the butterfly-shaped malar rash was developed, so pediatrician suspected SLE and she was refer to us. At hospitalization. She had malar rash, percardial effusion, persistent proteinuria greater than 3+, hemolytic anemia, lymphopenia, leukopenia, positive LE cell, Anti-DNA Ab and posotive ANA. So her clinical data are satisfied ARA criteria for SLE. Her renal biopsy showed diffuse proliferative SLE nephpritis and marked focal tubular atrophy with localized heavy mononuclear cell infiltration and fibrosis. We performed NaHCO3 loading test to confirm distal RTA. During the test, we detected the inability to achieve a high urinary PCO2. This result is the most sensitive index of impaired distal acidification, so we can diagnose distal RTA. She had a good response to the therapy with prednisolone NaHCO3 and oral KCL supplement.