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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 -
Pediatrics in Review Nov 2017
Review
Topics: Acidosis, Renal Tubular; Diagnosis, Differential; Humans
PubMed: 29093127
DOI: 10.1542/pir.2016-0231 -
Annual Review of Physiology Feb 2022Nephrolithiasis is a worldwide problem with increasing prevalence, enormous costs, and significant morbidity. Calcium-containing kidney stones are by far the most common... (Review)
Review
Nephrolithiasis is a worldwide problem with increasing prevalence, enormous costs, and significant morbidity. Calcium-containing kidney stones are by far the most common kidney stones encountered in clinical practice, and thus, hypercalciuria is the greatest risk factor for kidney stone formation. Hypercalciuria can result from enhanced intestinal absorption, increased bone resorption, or altered renal tubular transport. Kidney stone formation is complex and driven by high concentrations of calcium-oxalate or calcium-phosphate in the urine. After discussing the mechanism mediating renal calcium salt precipitation, we review recent discoveries in renal tubular calcium transport from the proximal tubule, thick ascending limb, and distal convolution. Furthermore, we address how calcium is absorbed from the intestine and mobilized from bone. The effect of acidosis on bone calcium resorption and urinary calcium excretion is also considered. Although recent discoveries provide insight into these processes, much remains to be understood in order to provide improved therapies for hypercalciuria and prevent kidney stone formation.
Topics: Calcium; Calcium Oxalate; Calcium, Dietary; Humans; Hypercalciuria; Kidney Calculi
PubMed: 34699268
DOI: 10.1146/annurev-physiol-052521-121822 -
Bone Apr 2023Carbonic anhydrase II deficiency (OMIM # 259730), initially called "osteopetrosis with renal tubular acidosis and cerebral calcification syndrome", reveals an important...
Carbonic anhydrase II deficiency (OMIM # 259730), initially called "osteopetrosis with renal tubular acidosis and cerebral calcification syndrome", reveals an important role for the enzyme carbonic anhydrase II (CA II) in osteoclast and renal tubule function. Discovered in 1972 and subsequently given various names, CA II deficiency now describes >100 affected individuals encountered predominantly from the Middle East and Mediterranean region. In 1983, CA II deficiency emerged as the first osteopetrosis (OPT) understood metabolically, and in 1991 the first understood molecularly. CA II deficiency is the paradigm OPT featuring failure of osteoclasts to resorb bone due to inability to acidify their pericellular milieu. The disorder presents late in infancy or early in childhood with fracturing, developmental delay, weakness, short stature, and/or cranial nerve compression and palsy. Mental retardation is common. The skeletal findings may improve by adult life, and CA II deficiency can be associated with a normal life-span. Therefore, it has been considered an "intermediate" type of OPT. In CA II deficiency, OPT is uniquely accompanied by renal tubular acidosis (RTA) of proximal, distal, or combined type featuring hyperchloremic metabolic acidosis, rarely with hypokalemia and paralysis. Cerebral calcification uniquely appears in early childhood. The etiology is bi-allelic loss-of-function mutations of CA2 that encodes CA II. Prenatal diagnosis requires mutational analysis of CA2. Although this enzymopathy reveals how CA II is important for the skeleton and kidney tubule, the pathogenesis of the mental subnormality and cerebral calcification is less well understood. Several mouse models of CA II deficiency have shown growth hormone deficiency, yet currently there is no standard pharmacologic therapy for patients. Treatment of the systemic acidosis is often begun when growth is complete. Although CA II deficiency is an "osteoclast-rich" OPT, and therefore transplantation of healthy osteoclasts can improve the skeletal disease, the RTA and central nervous system difficulties persist.
Topics: Animals; Child, Preschool; Female; Humans; Mice; Pregnancy; Acidosis, Renal Tubular; Calcinosis; Carbonic Anhydrases; Intellectual Disability; Osteopetrosis; Urea Cycle Disorders, Inborn; Carbonic Anhydrase II
PubMed: 36709914
DOI: 10.1016/j.bone.2023.116684 -
Seminars in Nephrology Jul 2019Acid-base balance is critical for normal life. Acute and chronic disturbances impact cellular energy metabolism, endocrine signaling, ion channel activity, neuronal... (Review)
Review
Acid-base balance is critical for normal life. Acute and chronic disturbances impact cellular energy metabolism, endocrine signaling, ion channel activity, neuronal activity, and cardiovascular functions such as cardiac contractility and vascular blood flow. Maintenance and adaptation of acid-base homeostasis are mostly controlled by respiration and kidney. The kidney contributes to acid-base balance by reabsorbing filtered bicarbonate, regenerating bicarbonate through ammoniagenesis and generation of protons, and by excreting acid. This review focuses on acid-base disorders caused by renal processes, both inherited and acquired. Distinct rare inherited monogenic diseases affecting acid-base handling in the proximal tubule and collecting duct have been identified. In the proximal tubule, mutations of solute carrier 4A4 (SLC4A4) (electrogenic Na/HCO-cotransporter Na/bicarbonate cotransporter e1 [NBCe1]) and other genes such as CLCN5 (Cl/H-antiporter), SLC2A2 (GLUT2 glucose transporter), or EHHADH (enoyl-CoA, hydratase/3-hydroxyacyl CoA dehydrogenase) causing more generalized proximal tubule dysfunction can cause proximal renal tubular acidosis resulting from bicarbonate wasting and reduced ammoniagenesis. Mutations in adenosine triphosphate ATP6V1 (B1 H-ATPase subunit), ATPV0A4 (a4 H-ATPase subunit), SLC4A1 (anion exchanger 1), and FOXI1 (forkhead transcription factor) cause distal renal tubular acidosis type I. Carbonic anhydrase II mutations affect several nephron segments and give rise to a mixed proximal and distal phenotype. Finally, mutations in genes affecting aldosterone synthesis, signaling, or downstream targets can lead to hyperkalemic variants of renal tubular acidosis (type IV). More common forms of renal acidosis are found in patients with advanced stages of chronic kidney disease and are owing, at least in part, to a reduced capacity for ammoniagenesis.
Topics: Acid-Base Equilibrium; Acidosis, Renal Tubular; Ammonia; Animals; Bicarbonates; Homeostasis; Humans; Kidney
PubMed: 31300090
DOI: 10.1016/j.semnephrol.2019.04.004 -
Advances in Chronic Kidney Disease Jul 2018Hyperchloremic metabolic acidosis, particularly renal tubular acidosis, can pose diagnostic challenges. The laboratory phenotype of a low total carbon dioxide content,... (Review)
Review
Hyperchloremic metabolic acidosis, particularly renal tubular acidosis, can pose diagnostic challenges. The laboratory phenotype of a low total carbon dioxide content, normal anion gap, and hyperchloremia may be misconstrued as hypobicarbonatemia from renal tubular acidosis. Several disorders can mimic renal tubular acidosis, and these must be appropriately diagnosed to prevent inadvertent and inappropriate application of alkali therapy. Key physiologic principles and limitations in the assessment of renal acid handling that can pose diagnostic challenges are enumerated.
Topics: Acid-Base Equilibrium; Acidosis, Renal Tubular; Alkalosis, Respiratory; Bicarbonates; Diagnosis, Differential; Humans; Osmolar Concentration; Urinalysis; Urinary Diversion
PubMed: 30139462
DOI: 10.1053/j.ackd.2018.05.001 -
Advances in Chronic Kidney Disease Jul 2018Distal renal tubular acidosis (DRTA) is defined as hyperchloremic, non-anion gap metabolic acidosis with impaired urinary acid excretion in the presence of a normal or... (Review)
Review
Distal renal tubular acidosis (DRTA) is defined as hyperchloremic, non-anion gap metabolic acidosis with impaired urinary acid excretion in the presence of a normal or moderately reduced glomerular filtration rate. Failure in urinary acid excretion results from reduced H secretion by intercalated cells in the distal nephron. This results in decreased excretion of NH and other acids collectively referred as titratable acids while urine pH is typically above 5.5 in the face of systemic acidosis. The clinical phenotype in patients with DRTA is characterized by stunted growth with bone abnormalities in children as well as nephrocalcinosis and nephrolithiasis that develop as the consequence of hypercalciuria, hypocitraturia, and relatively alkaline urine. Hypokalemia is a striking finding that accounts for muscle weakness and requires continued treatment together with alkali-based therapies. This review will focus on the mechanisms responsible for impaired acid excretion and urinary potassium wastage, the clinical features, and diagnostic approaches of hypokalemic DRTA, both inherited and acquired.
Topics: Acidosis, Renal Tubular; Anion Exchange Protein 1, Erythrocyte; Biological Transport; Carbonic Anhydrase II; Glomerular Filtration Rate; Humans; Hypokalemia; Kidney Tubules, Distal; Mutation; Potassium; Vacuolar Proton-Translocating ATPases
PubMed: 30139458
DOI: 10.1053/j.ackd.2018.05.003 -
NeoReviews Feb 2024See Bonus NeoBriefs videos and downloadable teaching slides Metabolic acidosis can manifest in the neonatal period and cause significant morbidity and mortality in... (Review)
Review
See Bonus NeoBriefs videos and downloadable teaching slides Metabolic acidosis can manifest in the neonatal period and cause significant morbidity and mortality in neonates. Preterm infants are at an even higher risk of developing metabolic acidosis. If the acidosis results from a dysfunction of acid-base homeostasis by the renal system, the disorder is known as renal tubular acidosis (RTA). In this review, we will describe renal development and normal acid-base homeostasis by the renal system. We will also discuss the pathophysiology of the different types of RTA, laboratory findings to aid in diagnosis, and treatment considerations. Understanding RTA will help neonatal clinicians recognize and diagnose an infant affected by RTA and initiate treatment in a timely manner.
Topics: Infant; Humans; Infant, Newborn; Acidosis, Renal Tubular; Infant, Premature; Kidney; Homeostasis
PubMed: 38296789
DOI: 10.1542/neo.25-2-e99 -
Clinical Journal of the American... Feb 2018
Topics: Acid-Base Equilibrium; Acidosis, Renal Tubular; Ammonium Compounds; Humans; Kidney Diseases
PubMed: 29311217
DOI: 10.2215/CJN.13791217 -
Pediatric Nephrology (Berlin, Germany) Dec 2021
PubMed: 34251494
DOI: 10.1007/s00467-021-05185-7