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Journal of Veterinary Emergency and... May 2022To describe renal tubular acidosis (RTA) and secondary acquired hyperaldosteronism in a cat as an adverse effect of topiramate therapy.
OBJECTIVE
To describe renal tubular acidosis (RTA) and secondary acquired hyperaldosteronism in a cat as an adverse effect of topiramate therapy.
CASE SUMMARY
An 8-year-old neutered female cat on chronic oral topiramate therapy at a recommended dose (11.9 mg/kg q 8 h) for seizure control was presented with severe metabolic acidosis and hypokalemia. Plasma electrolyte and acid-base analysis identified a severe metabolic acidosis (pH 7.153, reference interval: 7.31-7.46), hypokalemia (2.08 mmol/L [2.08 mEq/L], reference interval: 3.5-4.8 mmol/L [3.5-4.8 mEq/L]), and ionized hypercalcemia (1.85 mmol/L [1.85 mEq/L], reference range: 1.1-1.4 mmol/L [1.1-1.4 mEq/L]). Urinalysis revealed a urine specific gravity of 1.021 and a pH of 7.0. Diagnostic workup suggested distal RTA as a cause of the cat's acid-base and electrolyte disturbances. Aldosterone concentration was moderately increased, suggestive of secondary hyperaldosteronism. The metabolic abnormalities resolved with supportive care and discontinuation of topiramate.
NEW OR UNIQUE INFORMATION PROVIDED
Topiramate is suggested to have led to the development severe RTA in a cat.
Topics: Acidosis, Renal Tubular; Animals; Cat Diseases; Cats; Electrolytes; Female; Hyperaldosteronism; Hypokalemia; Male; Topiramate
PubMed: 35142423
DOI: 10.1111/vec.13168 -
Journal of the American Society of... Jun 2019The gene encodes electrogenic sodium bicarbonate cotransporter 1 (NBCe1). Inheritance of recessive mutations in causes proximal renal tubular acidosis (pRTA), a... (Comparative Study)
Comparative Study
BACKGROUND
The gene encodes electrogenic sodium bicarbonate cotransporter 1 (NBCe1). Inheritance of recessive mutations in causes proximal renal tubular acidosis (pRTA), a disease characterized by metabolic acidosis, growth retardation, ocular abnormalities, and often dental abnormalities. Mouse models of pRTA exhibit acidemia, corneal edema, weak dental enamel, impacted colons, nutritional defects, and a general failure to thrive, rarely surviving beyond weaning. Alkali therapy remains the preferred treatment for pRTA, but it is unclear which nonrenal signs are secondary to acidemia and which are a direct consequence of NBCe1 loss from nonrenal sites (such as the eye and enamel organ) and therefore require separate therapy. encodes three major NBCe1 variants: NBCe1-A, NBCe1-B, and NBCe1-C. NBCe1-A is expressed in proximal tubule epithelia; its dysfunction causes the plasma bicarbonate insufficiency that underlies acidemia. NBCe1-B and NBCe1-C exhibit a broad extra-proximal-tubular distribution.
METHODS
To explore the consequences of Nbce1b/c loss in the absence of acidemia, we engineered a novel strain of Nbce1b/c-null mice and assessed them for signs of pRTA.
RESULTS
Nbce1b/c-null mice have normal blood pH, but exhibit increased mortality, growth retardation, corneal edema, and tooth enamel defects.
CONCLUSIONS
The correction of pRTA-related acidemia should not be considered a panacea for all signs of pRTA. The phenotype of Nbce1b/c-null mice highlights the physiologic importance of NBCe1 variants expressed beyond the proximal tubular epithelia and potential limitations of pH correction by alkali therapy in pRTA. It also suggests a novel genetic locus for corneal dystrophy and enamel hypomineralization without acidemia.
Topics: Acidosis; Acidosis, Renal Tubular; Acidosis, Respiratory; Analysis of Variance; Animals; Bicarbonates; Blood Gas Analysis; Disease Models, Animal; Gene Expression Regulation; Mice; Mice, Knockout; Mutation, Missense; Phenotype; Sodium-Bicarbonate Symporters
PubMed: 31040187
DOI: 10.1681/ASN.2018050545 -
Kidney International Jul 2002Familial distal renal tubular acidosis (dRTA) and Southeast Asian ovalocytosis (SAO) may coexist in the same patient. Both can originate in mutations of the... (Review)
Review
Familial distal renal tubular acidosis (dRTA) and Southeast Asian ovalocytosis (SAO) may coexist in the same patient. Both can originate in mutations of the anion-exchanger 1 gene (AE1), which codes for band 3, the bicarbonate/chloride exchanger in both the red cell membrane and the basolateral membrane of the collecting tubule alpha-intercalated cell. Dominant dRTA is usually due to a mutation of the AE1 gene, which does not alter red cell morphology. SAO is caused by an AE1 mutation that leads to a nine amino acid deletion of red cell band 3, but by itself does not cause dRTA. Recent gene studies have shown that AE1 mutations are responsible for autosomal recessive dRTA in several countries in Southeast Asia; these patients may be homozygous for the mutation or be compound heterozygotes of two different AE1 mutations, one of which is usually the SAO mutation.
Topics: Acidosis, Renal Tubular; Amino Acid Sequence; Anion Exchange Protein 1, Erythrocyte; Asia, Southeastern; Elliptocytosis, Hereditary; Humans; Kidney Tubules, Collecting; Molecular Sequence Data; Mutation
PubMed: 12081559
DOI: 10.1046/j.1523-1755.2002.00417.x -
Current Opinion in Nephrology and... Sep 2013There has been significant progress in our understanding of the structural and functional properties and regulation of the electrogenic sodium bicarbonate cotansporter... (Review)
Review
PURPOSE OF REVIEW
There has been significant progress in our understanding of the structural and functional properties and regulation of the electrogenic sodium bicarbonate cotansporter NBCe1, a membrane transporter that plays a key role in renal acid-base physiology. The NBCe1 variant NBCe1-A mediates basolateral electrogenic sodium-base transport in the proximal tubule and is critically required for transepithelial bicarbonate absorption. Mutations in NBCe1 cause autosomal recessive proximal renal tubular acidosis (pRTA). The review summarizes recent advances in this area.
RECENT FINDINGS
A topological model of NBCe1 has been established that provides a foundation for future structure-functional studies of the transporter. Critical residues and regions have been identified in NBCe1 that play key roles in its structure, function (substrate transport, electrogenicity) and regulation. The mechanisms of how NBCe1 mutations cause pRTA have also recently been elucidated.
SUMMARY
Given the important role of proximal tubule transepithelial bicarbonate absorption in systemic acid-base balance, a clear understanding of the structure-functional properties of NBCe1 is a prerequisite for elucidating the mechanisms of defective transepithelial bicarbonate transport in pRTA.
Topics: Acidosis, Renal Tubular; Animals; Cell Membrane; Cytoplasm; Fanconi Syndrome; Genes, Recessive; Humans; Mutation; Sodium-Bicarbonate Symporters
PubMed: 23917030
DOI: 10.1097/MNH.0b013e328363ff43 -
American Journal of Kidney Diseases :... Sep 2016
Topics: Acid-Base Equilibrium; Acidosis, Renal Tubular; Ammonia; Bicarbonates; Curriculum; Homeostasis; Humans; Kidney Tubules, Proximal; Nephrons; Protons
PubMed: 27188519
DOI: 10.1053/j.ajkd.2016.03.422 -
Pediatric Nephrology (Berlin, Germany) Feb 2006Renal tubular acidosis (RTA) comprises a group of disorders characterized by a low capacity for net acid excretion and persistent hyperchloremic, metabolic acidosis. To...
Renal tubular acidosis (RTA) comprises a group of disorders characterized by a low capacity for net acid excretion and persistent hyperchloremic, metabolic acidosis. To investigate the role of chloride, we performed hypotonic (0.45%) saline-loading experiments in 12 children with alkali-treated distal RTA (dRTA) and compared the results with data obtained from 17 healthy control subjects. In patients, but not in controls, saline loading induced both hyperchloremia and metabolic acidosis. Hyperchloremia was associated with high total and high distal fractional reabsorption of chloride [C(H20)/(C(H20)+C(Cl))]. The increase in plasma chloride varied inversely with the fractional excretion of chloride (C(Cl)) and correlated with the decrease in blood pH. However, the urinary excretion of bicarbonate did not correlate with either changes in blood pH or plasma bicarbonate concentration. Our findings suggest that the mechanism of hyperchloremia was enhanced Cl(-)/HCO(3) (-) exchange by the distal tubule. The resulting metabolic acidosis is better explained by changes in the strong ion difference (the Stewart theory) than by changes in the urine bicarbonate excretion (the traditional theory).
Topics: Acid-Base Imbalance; Acidosis, Renal Tubular; Child; Child, Preschool; Chlorides; Female; Humans; Hypotonic Solutions; Infant; Male; Sodium Chloride
PubMed: 16362393
DOI: 10.1007/s00467-005-2081-8 -
Proceedings of the Royal Society of... Nov 1972
Topics: Acidosis, Renal Tubular; Bicarbonates; Female; Humans; Infant; Infant, Newborn
PubMed: 4642035
DOI: No ID Found -
South African Medical Journal =... Oct 1967
Review
Topics: Acidosis, Renal Tubular; Humans; Pedigree; Radiography
PubMed: 4866153
DOI: No ID Found -
Biochemia Medica Jun 2023Renal tubular acidosis (RTA) is a rare disorder that can be inherited or acquired, and results in an inability of the kidneys to maintain normal acid-base balance. We...
Renal tubular acidosis (RTA) is a rare disorder that can be inherited or acquired, and results in an inability of the kidneys to maintain normal acid-base balance. We present a case of recurrent, severe hypokalaemia and rhabdomyolysis in a young woman who had an associated normal anion gap metabolic acidosis and was subsequently diagnosed with distal RTA associated with Hashimoto's thyroiditis. Distal RTA associated with Hashimoto's thyroiditis is rare and probably develops because of autoimmune-mediated mechanisms, causing an inability of the H-ATPase pump in alpha-intercalated cells of the cortical collecting duct to secrete H, with subsequent failure of urinary acidification. In this case, this hypothesis was supported by the exclusion of common genetic mutations associated with distal RTA. We illustrate that utilizing a systematic, physiology-based approach for challenging electrolyte and acid-base disorders enables identification of the root cause and underlying disease mechanisms.
Topics: Female; Humans; Acidosis, Renal Tubular; Acidosis; Hypokalemia; Mutation; Thyroiditis
PubMed: 37324116
DOI: 10.11613/BM.2023.020802 -
The Veterinary Clinics of North... Mar 1986Distal RTA is characterized by decreased distal renal tubular hydrogen ion secretion, decreased ability to acidify urine, hypercalciuria, hyperphosphaturia,...
Distal RTA is characterized by decreased distal renal tubular hydrogen ion secretion, decreased ability to acidify urine, hypercalciuria, hyperphosphaturia, hypocitraturia, and metabolic acidosis. Because of the resulting alterations in urine composition and pH, patients with distal RTA are predisposed to urolithiasis and renal calcification. Diagnosis of distal RTA is important because it is a potentially reversible disorder that, left untreated, may cause nephrocalcinosis, recurrent urolith formation, moderate to severe metabolic acidosis, and renal failure.
Topics: Acidosis, Renal Tubular; Animals; Calcium Phosphates; Dog Diseases; Dogs; Magnesium; Magnesium Compounds; Phosphates; Struvite; Urinary Calculi
PubMed: 3486513
DOI: 10.1016/s0195-5616(86)50028-0