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Nefrologia : Publicacion Oficial de La... 2013Distal renal tubular acidosis (dRTA) or RTA type I is characterised by reduced H+ hydrogen ions and ammonium urinary excretion. In children affected by dRTA there... (Review)
Review
Distal renal tubular acidosis (dRTA) or RTA type I is characterised by reduced H+ hydrogen ions and ammonium urinary excretion. In children affected by dRTA there is stunted growth, vomiting, constipation, loss of appetite, polydipsia and polyuria, nephrocalcinosis, weakness and muscle paralysis due to hypokalaemia. This work summarises progress made in dRTA genetic studies in populations studied so far. DRTA is heterogeneous and as such, transporters and ion channels are analysed which have been identified in alpha-intercalated cells of the collecting duct, which could explain cases of dRTA not associated with the hitherto studied genes. DRTA can be autosomal dominant or autosomal recessive. Autosomal recessive dRTA appears in the first months of life and progresses with nephrocalcinosis and early or late hearing loss. Autosomal dominant dRTA is less severe and appears during adolescence or adulthood and may or may not develop nephrocalcinosis. In alpha-intercalated cells of the collecting duct, the acid load is deposited into the urine as titratable acids (phosphates) and ammonium. Autosomal recessive dRTA is associated with mutations in genes ATP6V1B1, ATP6V0A4 and SLC4A1, which encode subunits a4 and B1 of V-ATPase and the AE1 bicarbonate/chloride exchanger respectively. By contrast, autosomal dominant dRTA is only related to mutations in AE1.
Topics: Acidosis, Renal Tubular; Humans
PubMed: 23640117
DOI: 10.3265/Nefrologia.pre2012.Oct.11592 -
Pediatric Nephrology (Berlin, Germany) Dec 2015In the absence of a gastrointestinal origin, a maintained hyperchloremic metabolic acidosis must raise the diagnostic suspicion of renal tubular acidosis (RTA). Unlike... (Review)
Review
In the absence of a gastrointestinal origin, a maintained hyperchloremic metabolic acidosis must raise the diagnostic suspicion of renal tubular acidosis (RTA). Unlike adults, in whom RTA is usually secondary to acquired causes, children most often have primary forms of RTA resulting from an inherited genetic defect in the tubular proteins involved in the renal regulation of acid-base homeostasis. According to their pathophysiological basis, four types of RTA are distinguished. Distal type 1 RTA, proximal type 2 RTA, mixed-type 3 RTA, and type 4 RTA can be differentiated based on the family history, the presenting manifestations, the biochemical profile, and the radiological findings. Functional tests to explore the proximal wasting of bicarbonate and the urinary acidification capacity are also useful diagnostic tools. Although currently the molecular basis of the disease can frequently be discovered by gene analysis, patients with RTA must undergo a detailed clinical study and laboratory work-up in order to understand the pathophysiology of the disease and to warrant a correct and accurate diagnosis.
Topics: Acidosis, Renal Tubular; Child; Child, Preschool; Humans; Kidney
PubMed: 25823989
DOI: 10.1007/s00467-015-3083-9 -
Annales de Biologie Clinique 2009Renal 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... (Review)
Review
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.
Topics: Acidosis, Renal Tubular; Adult; Ammonium Chloride; Child; Furosemide; Genes, Dominant; Genes, Recessive; Humans; Infant, Newborn; Sodium Bicarbonate; Urinary Calculi
PubMed: 19297287
DOI: 10.1684/abc.2009.0307 -
Nephrology, Dialysis, Transplantation :... Dec 2012Proximal renal tubular acidosis (RTA) (Type II RTA) is characterized by a defect in the ability to reabsorb HCO(3) in the proximal tubule. This is usually manifested as... (Review)
Review
Proximal renal tubular acidosis (RTA) (Type II RTA) is characterized by a defect in the ability to reabsorb HCO(3) in the proximal tubule. This is usually manifested as bicarbonate wastage in the urine reflecting that the defect in proximal tubular transport is severe enough that the capacity for bicarbonate reabsorption in the thick ascending limb of Henle's loop and more distal nephron segments is overwhelmed. More subtle defects in proximal bicarbonate transport likely go clinically unrecognized owing to compensatory reabsorption of bicarbonate distally. Inherited proximal RTA is more commonly autosomal recessive and has been associated with mutations in the basolateral sodium-bicarbonate cotransporter (NBCe1). Mutations in this transporter lead to reduced activity and/or trafficking, thus disrupting the normal bicarbonate reabsorption process of the proximal tubules. As an isolated defect for bicarbonate transport, proximal RTA is rare and is more often associated with the Fanconi syndrome characterized by urinary wastage of solutes like phosphate, uric acid, glucose, amino acids, low-molecular-weight proteins as well as bicarbonate. A vast array of rare tubular disorders may cause proximal RTA but most commonly it is induced by drugs. With the exception of carbonic anhydrase inhibitors which cause isolated proximal RTA, drug-induced proximal RTA is associated with Fanconi syndrome. Drugs that have been recently recognized to cause severe proximal RTA with Fanconi syndrome include ifosfamide, valproic acid and various antiretrovirals such as Tenofovir particularly when given to human immunodeficiency virus patients receiving concomitantly protease inhibitors such as ritonavir or reverse transcriptase inhibitors such as didanosine.
Topics: Acidosis, Renal Tubular; Animals; Humans; Mutation
PubMed: 23235953
DOI: 10.1093/ndt/gfs493 -
International Journal of Clinical... Mar 2011Renal tubular acidosis (RTA) is a group of disorders observed in patients with normal anion gap metabolic acidosis. There are three major forms of RTA: A proximal (type... (Review)
Review
Renal tubular acidosis (RTA) is a group of disorders observed in patients with normal anion gap metabolic acidosis. There are three major forms of RTA: A proximal (type II) RTA and two types of distal RTAs (type I and type IV). Proximal (type II) RTA originates from the inability to reabsorb bicarbonate normally in the proximal tubule. Type I RTA is associated with inability to excrete the daily acid load and may present with hyperkalaemia or hypokalaemia. The most prominent abnormality in type IV RTA is hyperkalaemia caused by hypoaldosteronism. This article extensively reviews the mechanism of hydrogen ion generation from metabolism of normal diet and various forms of RTA leading to disruptions of normal acid-base handling by the kidneys.
Topics: Acid-Base Equilibrium; Acidosis, Renal Tubular; Acids; Adult; Carbon Dioxide; Carbonic Acid; Glomerular Filtration Rate; Humans; Hydrogen-Ion Concentration; Hyperkalemia; Hypokalemia; Kidney Tubules; Mineralocorticoids; Protons; Sodium Potassium Chloride Symporter Inhibitors
PubMed: 21314872
DOI: 10.1111/j.1742-1241.2009.02311.x -
Internal Medicine Journal Dec 2013Renal tubular acidosis is a common cause of normal anion gap metabolic acidosis but these disorders can be easily missed or misdiagnosed. We highlight the approach to... (Review)
Review
Renal tubular acidosis is a common cause of normal anion gap metabolic acidosis but these disorders can be easily missed or misdiagnosed. We highlight the approach to assessing renal tubular acidosis by discussing a case study with a temporal data set collected over more than 5 weeks. We highlight the principles and the necessary information required for a diagnosis of classic distal renal tubular acidosis. We also briefly review several aspects of type 1 renal tubular acidosis related to autoimmune disease, drugs and thyroid disorders.
Topics: Acidosis, Renal Tubular; Aged; Biomarkers; Female; Humans; Sjogren's Syndrome
PubMed: 24330363
DOI: 10.1111/imj.12300 -
Seminars in Nephrology Jul 2009The multiple and complex functions of the renal tubule in regulating water, electrolyte, and mineral homeostasis make it prone to numerous genetic abnormalities... (Review)
Review
The multiple and complex functions of the renal tubule in regulating water, electrolyte, and mineral homeostasis make it prone to numerous genetic abnormalities resulting in malfunction. The phenotypic expression depends on the mode of interference with the normal physiology of the segment affected, and whether the abnormality is caused by loss of function or, less commonly, gain of function. In this review we address the current knowledge about the association between the genetics and clinical manifestations and treatment of representative disorders affecting the length of the nephron.
Topics: Acidosis, Renal Tubular; Bartter Syndrome; Diabetes Insipidus, Nephrogenic; Fanconi Syndrome; Gitelman Syndrome; Humans; Kidney Diseases; Kidney Tubules; Kidney Tubules, Collecting; Loop of Henle; Models, Biological; Pseudohypoaldosteronism
PubMed: 19615561
DOI: 10.1016/j.semnephrol.2009.03.013 -
Zhonghua Minguo Xiao Er Ke Yi Xue Hui... 1990Nineteen children with clinical diagnoses of renal tubular acidosis were followed for periods ranging from 3 months to 20 years. Twelve patients had Type 1 renal tubular...
Nineteen children with clinical diagnoses of renal tubular acidosis were followed for periods ranging from 3 months to 20 years. Twelve patients had Type 1 renal tubular acidosis, five had Type 2, and two had Type 4. No sex predilection was found for any one of the types. Most patients had been diagnosed before 18 months of age, with failure to thrive the most common presentation. Tachypnea, polydipsia, polyuria, and vomiting were frequent symptoms. Some of these children had associated renal hypoplasia, vesicoureteral reflux, unilateral renal agenesis, glomerulocystic disease, adult polycystic kidney disease, and cyanotic congenital heart disease. Urinary anion gap may be useful for differential diagnosis of altered distal urinary acidification from other hyperchloremic metabolic acidosis. Furosemide test may need further investigation. Inability to raise urine to blood pCO2 gradient is helpful for diagnosis of Type 1 renal tubular acidosis. Hypokalemia, hypocalcemia, hypophosphatemia, decreased tubular reabsorption of phosphate, and hypercalciuria occurred in some patients. Complications included rickets in two, nephrocalcinosis in one, and episodic hematuria in one. There was relative bicarbonate wasting in children with Type 1 renal tubular acidosis, with a mean therapeutic bicarbonate requirement of 4.4 +/- 2.6 meq/kg/day. The mean bicarbonate dose for patients with Type 2 renal tubular acidosis was 8.3 +/- 2.6 meq/kg/day. Most children had good response to treatment with complete catch-up linear growth in 13, improved growth in 4, and continuing poor growth in 2. Two patients died during follow-up. Two other patients maintained normal growth without medication.
Topics: Acidosis, Renal Tubular; Child; Child, Preschool; Electrolytes; Female; Growth; Humans; Infant; Infant, Newborn; Male
PubMed: 2264480
DOI: No ID Found -
Annals of the Academy of Medicine,... Jan 1986The clinical features and biochemical profile of 10 patients with Renal Tubular Acidosis (RTA) were described. The commonest mode of presentation was muscular weakness...
The clinical features and biochemical profile of 10 patients with Renal Tubular Acidosis (RTA) were described. The commonest mode of presentation was muscular weakness due to severe hypokalaemia in 5 patients while the other 5 presented with renal colic, haematuria or passage of gravel. Nine patients had nephrocalcinosis on X-rays and one had rickets. All the patients had Type I RTA, 2 of whom presenting initially with Incomplete Type I RTA which progressed to Complete Type I RTA. Two other patients had associated features of proximal tubular involvement evidenced by hypophosphatemia, hypouricemia, hyperphosphaturia, aminoaciduria and glycosuria. Six of the 10 patients had secondary RTA: 2 associated with medullary sponge kidneys, 2 with gout, 1 with idiopathic hypercalciuria and hyperuricosuria and the remaining patient with systemic lupus erythematosus.
Topics: Acidosis, Renal Tubular; Adolescent; Adult; Ammonium Chloride; Female; Gout; Humans; Hypokalemia; Lupus Erythematosus, Systemic; Male; Muscles; Nephrocalcinosis; Osmolar Concentration; Radiography; Rickets
PubMed: 3707033
DOI: No ID Found -
La Revue Du Praticien Oct 1990Normal adults with normal protein intakes have a urinary NH4 excretion of 40 to 50 mmol/24 hours and a variable urinary pH. In cases of metabolic acidosis a urinary pH...
Normal adults with normal protein intakes have a urinary NH4 excretion of 40 to 50 mmol/24 hours and a variable urinary pH. In cases of metabolic acidosis a urinary pH less than 5.5 suggests an extra-renal origin whilst a urinary pH greater than 5.5 is in favour of renal acidosis, but there are many exceptions to this rule. On the other hand, urinary NH4 excretion is always greater than 70 mmol/24 hours in the first case and less than 40-50 mmol/24 hours in the second; and the use of the urinary anionic gap (Na + K - Cl), negative in the first case and positive in the second, enables the two situations to be distinguished. The acidosis of nephron reduction is easily recognised in cases of severe renal failure with an increase in unmeasured plasma anions whilst tubular acidoses are accompanied by a hyperchloremia. Measurement of fractional HCO3 excretion after an oral loading dose of NaHCO3, preferably by TmCHO3 with respect to GFR, distinguishes proximal tubular acidosis (low TmHCO3) from distal tubular acidosis (normal or high TmHCO3). In the latter case, the presence of hypokalemia suggests a distal tubular acidosis either due to deficiency of the H(+)-ATPase pumps (absence of increased urinary pCO2 after oral loading dose of NaHCO3) or to the inability of the kidney to maintain a normal H+ gradient (normal increase of urinary pCO2. The presence of hyperkalemia suggests diseases associated with hypoaldosteronism (low or inappropriate serum aldosterone concentrations), abnormal transepithelial voltages or with a pseudo-hypoaldosteronism syndrome (high plasma aldosterone concentration). The prevalence of distal tubular acidosis with hyperkalemia is on the increase whilst tubular acidosis with hypokalemia remains rare.
Topics: Acid-Base Equilibrium; Acidosis, Renal Tubular; Adult; Humans; Hyperkalemia; Hypokalemia
PubMed: 2237203
DOI: No ID Found