Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0392525 (nephrolithiasis)
 2,669 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Renal tubular acidosis are forms of metabolic acidosis characterized by an impairment of urinary acidification due to a lack of urine excretion of protons or loss of bicarbonates. Primary distal renal acidosis (dRTA) is characterized by hyperchloremic metabolic acidosis due to failure in proton excretion, variably severe nephrocalcinosis and/or nephrolithiasis associated with hypercalciuria and hypocitraturia. When the metabolic acidosis is compensated, dRTA can be diagnosed by the failure of urinary acidification after oral ammonium chloride or furosemide administration. dRTA is inherited as either an autosomal dominant or autosomal recessive trait. An autosomal dominant form results from a SLC4A1 gene mutation leading to dysfunction of the anionic exchanger type 1 (AE1). Otherwise, recessive forms are due to mutations of ATP6V1B1 gene encoding the B1-subunit of H+-ATPase expressed in the apical membrane of the alpha intercalated cells in collecting duct and in the cochlea. Those mutations lead to dRTA accompanied by sensorineural deafness. Also, mutations in ATP6V0A4 gene encode the accessory subunit a4 of the H+ATPase, leading to recessive forms of dRTA with preserved hearing or delayed signs of deafness. Molecular approach can identify mutations which are responsible for this pathology. The medical treatment is simple and involves an alkali load which allows curing the metabolic acidosis. Long-term outcome is usually good unless the patient's compliance is low or alkalizing treatment is insufficient.
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PMID:[Primary distal renal tubular acidosis]. 1929 87

Distal renal tubular acidosis (dRTA) is a tubular disorder with a primary defect of urinary acidification and acid excretion in the collecting duct system. Consequently, patients develop hyperchloremic metabolic acidosis with an inappropriately alkaline urine. Inherited forms of dRTA are due to mutations in at least three distinct genes: SLC4A1, ATP6V1B1, ATP6V0A4. Mutations in SLC4A1-(AE1) are inherited either in an autosomal dominant manner or in a recessive one. ATP6V1B and ATP6V0A4 mutations affect two different subunits of the vacuolar H+-ATPase proton-pump, the B1 and a4 subunits, and are inherited in an autosomal recessive manner. Clinical manifestations of inherited forms of dRTA usually occur during infancy or childhood. However, heterozygous carriers of ATP6V1B1 and ATP6V0A4 mutations may have a higher risk of developing nephrolithiasis and nephrocalcinosis in adulthood, respectively. In full forms of dRTA, patients may present with mild clinical symptoms, such as mild metabolic acidosis and incidental detection of kidney stones, as well as with more severe manifestations such as failure to thrive, severe metabolic acidosis, and nephrocalcinosis. Progressive sensorineural hearing loss develops in the majority of patients with recessive dRTA (ATP6V1B1 and ATP6V0A4 mutations). Some patients with recessive dRTA may also develop abnormal widening of the vestibular aqueduct. This review will discuss our current understanding of the pathophysiology of inherited forms of dRTA, diagnosis and prognosis of patients, and therapy.
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PMID:Pathophysiology, diagnosis and treatment of inherited distal renal tubular acidosis. 2899 37

Primary distal renal tubular acidosis (dRTA) is a rare genetic disorder caused by impaired distal acidification due to a failure of type A intercalated cells (A-ICs) in the collecting tubule. dRTA is characterized by persistent hyperchloremia, a normal plasma anion gap, and the inability to maximally lower urinary pH in the presence of systemic metabolic acidosis. Common clinical features of dRTA include vomiting, failure to thrive, polyuria, hypercalciuria, hypocitraturia, nephrocalcinosis, nephrolithiasis, growth delay, and rickets. Mutations in genes encoding three distinct transport proteins in A-ICs have been identified as causes of dRTA, including the B1/ATP6V1B1 and a4/ATP6V0A4 subunits of the vacuolar-type H+-ATPase (H+-ATPase) and the chloride-bicarbonate exchanger AE1/SLC4A1. Homozygous or compound heterozygous mutations in ATP6V1B1 and ATP6V0A4 lead to autosomal recessive (AR) dRTA. dRTA caused by SLC4A1 mutations can occur with either autosomal dominant or AR transmission. Red blood cell abnormalities have been associated with AR dRTA due to SLC4A1 mutations, including hereditary spherocytosis, Southeast Asia ovalocytosis, and others. Some patients with dRTA exhibit atypical clinical features, including transient and reversible proximal tubular dysfunction and hyperammonemia. Incomplete dRTA presents with inadequate urinary acidification, but without spontaneous metabolic acidosis and recurrent urinary stones. Heterozygous mutations in the AE1 or H+-ATPase genes have recently been reported in patients with incomplete dRTA. Early and sufficient doses of alkali treatment are needed for patients with dRTA. Normalized serum bicarbonate, urinary calcium excretion, urinary low-molecular-weight protein levels, and growth rate are good markers of adherence to and/or efficacy of treatment. The prognosis of dRTA is generally good in patients with appropriate treatment. However, recent studies showed an increased frequency of chronic kidney disease (CKD) in patients with dRTA during long-term follow-up. The precise pathogenic mechanisms of CKD in patients with dRTA are unknown.
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PMID:Improving outcomes for patients with distal renal tubular acidosis: recent advances and challenges ahead. 3058 51

Distal renal tubular acidosis (dRTA) is characterized by metabolic acidosis due to uric acid dysfunction. The aim of this study was to demonstrate the genetic diagnosis of Chinese children with dRTA by whole-exome sequencing. From Jan. 2010 to Sept. 2015, 16 children with dRTA were recruited to investigate the possibility of genetic diagnosis and to examine any genotype-phenotype relationships in these patients. Sanger sequencing was used to confirm mutations identified by whole-exome sequencing. Clinical and biological features in the patients included hyperchloremic metabolic acidosis, impaired growth, hypokalemia, nephrocalcinosis, nephrolithiasis, hypercalciuria, hypocitraturia, and rickets or osteomalacia. Seventeen mutations in the solute carrier family 4 member 1 (SLC4A1), ATPase H+ transporting V0 subunit a4 (ATP6V0A4), ATPase H+ transporting V1 subunit B1 (ATP6V1B1), WNK lysine deficient protein kinase 1 (WNK1) and the claudin 16 (CLDN16) were identified in 15 patients, and 14 of these mutations are novel. Only 1 patient was negative for any mutations. Our results demonstrate the existence of SLC4A1, ATP6V1B1, ATP6V0A4, WNK1 and CLDN16 mutations in Chinese children with dRTA and indicate that compound heterozygosity at 2 or more different but related genes can be responsible for its pathogenesis. This study also indicates that whole-exome sequencing is a labor and cost-effective means of analyzing dRTA-associated genes.
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PMID:Clinical features and genetic findings in Chinese children with distal renal tubular acidosis. 3194 30