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Advances in Therapy Feb 2021Renal tubular acidosis (RTA) occurs when the kidneys are unable to maintain normal acid-base homeostasis because of tubular defects in acid excretion or bicarbonate ion... (Review)
Review
Renal tubular acidosis (RTA) occurs when the kidneys are unable to maintain normal acid-base homeostasis because of tubular defects in acid excretion or bicarbonate ion reabsorption. Using illustrative clinical cases, this review describes the main types of RTA observed in clinical practice and provides an overview of their diagnosis and treatment. The three major forms of RTA are distal RTA (type 1; characterized by impaired acid excretion), proximal RTA (type 2; caused by defects in reabsorption of filtered bicarbonate), and hyperkalemic RTA (type 4; caused by abnormal excretion of acid and potassium in the collecting duct). Type 3 RTA is a rare form of the disease with features of both distal and proximal RTA. Accurate diagnosis of RTA plays an important role in optimal patient management. The diagnosis of distal versus proximal RTA involves assessment of urinary acid and bicarbonate secretion, while in hyperkalemic RTA, selective aldosterone deficiency or resistance to its effects is confirmed after exclusion of other causes of hyperkalemia. Treatment options include alkali therapy in patients with distal or proximal RTA and lowering of serum potassium concentrations through dietary modification and potential new pharmacotherapies in patients with hyperkalemic RTA including newer potassium binders.
Topics: Acidosis, Renal Tubular; Bicarbonates; Humans; Hyperkalemia; Kidney; Potassium
PubMed: 33367987
DOI: 10.1007/s12325-020-01587-5 -
Pediatric Clinics of North America Feb 2019Renal tubular acidosis should be suspected in poorly thriving young children with hyperchloremic and hypokalemic normal anion gap metabolic acidosis, with/without... (Review)
Review
Renal tubular acidosis should be suspected in poorly thriving young children with hyperchloremic and hypokalemic normal anion gap metabolic acidosis, with/without syndromic features. Further workup is needed to determine the type of renal tubular acidosis and the presumed etiopathogenesis, which informs treatment choices and prognosis. The risk of nephrolithiasis and calcinosis is linked to the presence (proximal renal tubular acidosis, negligible stone risk) or absence (distal renal tubular acidosis, high stone risk) of urine citrate excretion. New formulations of slow-release alkali and potassium combination supplements are being tested that are expected to simplify treatment and lead to sustained acidosis correction.
Topics: Acidosis, Renal Tubular; Child; Diagnosis, Differential; Humans; Risk Factors
PubMed: 30454739
DOI: 10.1016/j.pcl.2018.08.011 -
Indian Journal of Pediatrics Sep 2020Renal tubular acidosis (RTA) comprises a group of disorders characterized by low capacity for net acid excretion and persistent hyperchloremic metabolic acidosis,... (Review)
Review
Renal tubular acidosis (RTA) comprises a group of disorders characterized by low capacity for net acid excretion and persistent hyperchloremic metabolic acidosis, despite preserved glomerular filtration rate. RTA are classified into chiefly three types (1, 2 and 4) based on pathophysiology and clinical and laboratory characteristics. Most patients have primary RTA that presents in infancy with polyuria, growth retardation, rickets and/or hypotonia. Diagnosis requires careful evaluation, including exclusion of other entities that can cause acidosis. A variety of tests, administered stepwise, are useful for the diagnosis and characterization of RTA. A genetic or acquired basis can be determined in majority of patients through focused evaluation. Management involves correction of acidosis and dyselectrolytemia; patients with proximal RTA with Fanconi syndrome and rickets require additional supplements of phosphate and vitamin D.
Topics: Acidosis; Acidosis, Renal Tubular; Fanconi Syndrome; Glomerular Filtration Rate; Humans; Phosphates
PubMed: 32591997
DOI: 10.1007/s12098-020-03318-8 -
Nature Reviews. Nephrology Jun 2023The kidneys have a central role in the control of acid-base homeostasis owing to bicarbonate reabsorption and production of ammonia and ammonium in the proximal tubule... (Review)
Review
The kidneys have a central role in the control of acid-base homeostasis owing to bicarbonate reabsorption and production of ammonia and ammonium in the proximal tubule and active acid secretion along the collecting duct. Impaired acid excretion by the collecting duct system causes distal renal tubular acidosis (dRTA), which is characterized by the failure to acidify urine below pH 5.5. This defect originates from reduced function of acid-secretory type A intercalated cells. Inherited forms of dRTA are caused by variants in SLC4A1, ATP6V1B1, ATP6V0A4, FOXI1, WDR72 and probably in other genes that are yet to be discovered. Inheritance of dRTA follows autosomal-dominant and -recessive patterns. Acquired forms of dRTA are caused by various types of autoimmune diseases or adverse effects of some drugs. Incomplete dRTA is frequently found in patients with and without kidney stone disease. These patients fail to appropriately acidify their urine when challenged, suggesting that incomplete dRTA may represent an intermediate state in the spectrum of the ability to excrete acids. Unrecognized or insufficiently treated dRTA can cause rickets and failure to thrive in children, osteomalacia in adults, nephrolithiasis and nephrocalcinosis. Electrolyte disorders are also often present and poorly controlled dRTA can increase the risk of developing chronic kidney disease.
Topics: Adult; Child; Humans; Acidosis, Renal Tubular; Kidney Calculi; Kidney Tubules, Proximal; Forkhead Transcription Factors; Vacuolar Proton-Translocating ATPases
PubMed: 37016093
DOI: 10.1038/s41581-023-00699-9 -
Journal of Nephrology Dec 2021Renal tubular acidosis (RTA) comprises a group of disorders in which excretion of hydrogen ions or reabsorption of filtered HCO is impaired, leading to chronic metabolic... (Review)
Review
Renal tubular acidosis (RTA) comprises a group of disorders in which excretion of hydrogen ions or reabsorption of filtered HCO is impaired, leading to chronic metabolic acidosis with normal anion gap. In the current review, the focus is placed on the most common type of RTA, Type 1 RTA or Distal RTA (dRTA), which is a rare chronic genetic disorder characterized by an inability of the distal nephron to secrete hydrogen ions in the presence of metabolic acidosis. Over the years, knowledge of the molecular mechanisms behind acid secretion has improved, thereby greatly helping the diagnosis of dRTA. The primary or inherited form of dRTA is mostly diagnosed in infancy, childhood, or young adulthood, while the acquired secondary form, as a consequence of other disorders or medications, can happen at any age, although it is more commonly seen in adults. dRTA is not as "benign" as previously assumed, and can have several, highly variable long-term consequences. The present review indeed reports and summarizes both clinical symptoms and diagnosis, long-term outcomes, genetic inheritance, epidemiology and current treatment options, with the aim of shedding more light onto this rare disorder. Being a chronic condition, dRTA also deserves attention in the transition between pediatric and adult nephrology care, and as a rare disease it has a place in the European and Italian rare nephrological diseases network.
Topics: Acid-Base Equilibrium; Acidosis, Renal Tubular; Adult; Biological Transport; Child; Humans; Young Adult
PubMed: 33770395
DOI: 10.1007/s40620-021-01032-y -
Acta Medica Indonesiana 2007Acute metabolic acidosis is frequently encountered in critically ill patients. Metabolic acidosis can occur as a result of either the accumulation of endogenous acids... (Review)
Review
Acute metabolic acidosis is frequently encountered in critically ill patients. Metabolic acidosis can occur as a result of either the accumulation of endogenous acids that consumes bicarbonate (high anion gap metabolic acidosis) or loss of bicarbonate from the gastrointestinal tract or the kidney (hyperchloremic or normal anion gap metabolic acidosis). The cause of high anion gap metabolic acidosis includes lactic acidosis, ketoacidosis, renal failure and intoxication with ethylene glycol, methanol, salicylate and less commonly with pyroglutamic acid (5-oxoproline), propylene glycole or djenkol bean (gjenkolism). The most common causes of hyperchloremic metabolic acidosis are gastrointestinal bicarbonate loss, renal tubular acidosis, drugs-induced hyperkalemia, early renal failure and administration of acids. The appropriate treatment of acute metabolic acidosis, in particular organic form of acidosis such as lactic acidosis, has been very controversial. The only effective treatment for organic acidosis is cessation of acid production via improvement of tissue oxygenation. Treatment of acute organic acidosis with sodium bicarbonate failed to reduce the morbidity and mortality despite improvement in acid-base parameters. Further studies are required to determine the optimal treatment strategies for acute metabolic acidosis.
Topics: Acidosis; Acidosis, Lactic; Acidosis, Renal Tubular; Acute Disease; Bicarbonates; Diabetic Ketoacidosis; Humans; Risk Factors; Sodium Bicarbonate
PubMed: 17936961
DOI: No ID Found -
Pediatrics in Review Nov 2017
Review
Topics: Acidosis, Renal Tubular; Diagnosis, Differential; Humans
PubMed: 29093127
DOI: 10.1542/pir.2016-0231 -
Current Opinion in Pediatrics Apr 2017To facilitate the understanding and knowledge of renal tubular acidosis by providing a summarized information on the known clinical and biochemical characteristics of... (Review)
Review
PURPOSE OF REVIEW
To facilitate the understanding and knowledge of renal tubular acidosis by providing a summarized information on the known clinical and biochemical characteristics of this group of diseases, by updating the genetic and molecular bases of the primary forms renal tubular acidosis and by examining some issues regarding the diagnosis of distal renal tubular acidosis (RTA) in the daily clinical practice.
RECENT FINDINGS
The manuscript presents recent findings on the potential of next-generation sequencing to disclose new pathogenic variants in patients with a clinical diagnosis of primary RTA and negative Sanger sequencing of known genes. The current review emphasizes the importance of measuring urinary ammonium for a correct clinical approach to the patients with metabolic acidosis and discusses the diagnosis of incomplete distal RTA.
SUMMARY
We briefly update the current information on RTA, put forward the need of additional studies in children to validate urinary indexes used in the diagnosis of RTA and offer a perspective on diagnostic genetic tests.
Topics: Acidosis, Renal Tubular; Ammonium Compounds; Child; Child, Preschool; Disease Progression; Female; Humans; Kidney; Male; Prognosis; Risk Assessment
PubMed: 28092281
DOI: 10.1097/MOP.0000000000000460 -
Journal of Nephrology 2006Renal tubular acidosis (RTA) is a form of metabolic acidosis due to abnormal alkali (bicarbonate) loss by the kidneys or their failure to excrete net acid. While the... (Review)
Review
Renal tubular acidosis (RTA) is a form of metabolic acidosis due to abnormal alkali (bicarbonate) loss by the kidneys or their failure to excrete net acid. While the latter does occur in chronic renal failure, the term RTA is usually applied only when the glomerular filtration rate is normal or near normal. As well as a cause of metabolic acidosis, RTA often presents as renal stone disease with nephrocalcinosis, rickets/osteomalacia, and growth retardation in children. In this brief review, we have summarized the classification, clinical features and the underlying cell and molecular pathophysiology of RTA. However, despite significant advances in our understanding of the mechanisms of RTA, its treatment is still empirical and based largely on alkali replacement therapy; but its wider significance in renal stone and bone disease is becoming increasingly recognized.
Topics: Acidosis, Renal Tubular; Acids; Bicarbonates; Humans; Kidney Tubules
PubMed: 16736441
DOI: No ID Found -
Acta Biochimica Polonica 2012Renal tubular acidosis (RTA) is a hyperchloremic metabolic acidosis characterized by a normal anion gap and normal (or near normal) glomerular filtration rate in the... (Review)
Review
Renal tubular acidosis (RTA) is a hyperchloremic metabolic acidosis characterized by a normal anion gap and normal (or near normal) glomerular filtration rate in the absence of diarrhoea. Inherited isolated forms of renal tubular acidosis are not common. However, they can also be a part of a more generalized tubule defect, like in Fanconi syndrome. In recent years more and more gene mutations have been found which are associated with RTA (mutations in the gene SLC4A4, encoding a Na(+)-HCO(3)(-) cotransporter (NBC-1); in the gene SLC4A1, encoding Cl(-)/HCO3(-) exchanger (AE1); in the gene ATP6B1, encoding B1 subunit of H(+)-ATPase; in the gene CA2 encoding carbonic anhydrase II; and others) and allow better understanding of underlying processes of bicarbonate and H(+) transport. Isolated renal tubular acidosis can be frequently acquired due to use of certain drug groups, autoimmune disease or kidney transplantation. As the prevalence of acquired forms of RTA is common, new therapeutic options for the currently used supplementation of oral alkali, are awaited.
Topics: Acidosis, Renal Tubular; Animals; Humans; Kidney Transplantation; Kidney Tubules, Proximal
PubMed: 22693689
DOI: No ID Found