topiramate and Acidosis--Renal-Tubular

To describe renal tubular acidosis (RTA) and secondary acquired hyperaldosteronism in a cat as an adverse effect of topiramate therapy.. 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.. 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

Topics: Acidosis, Renal Tubular; Anticonvulsants; Female; Humans; Hypokalemia; Incidental Findings; Middle Aged; Topiramate

The Nephrology Quiz and Questionnaire remains an extremely popular session for attendees of the Annual Kidney Week Meeting of the American Society of Nephrology. Once again, in 2014 the conference hall was overflowing with audience members and eager quiz participants. Topics covered by the expert discussants included electrolyte and acid-base disorders, glomerular disease, ESRD/dialysis, and transplantation. Complex cases from each of these categories along with single-best-answer questions were prepared and submitted by the panel of experts. Before the meeting, program directors of United States nephrology training programs and nephrology fellows answered the questions using an Internet-based questionnaire. During the live session, members of the audience tested their knowledge and judgment on a series of case-oriented questions prepared and discussed by the experts. They compared their answers in real time using audience response devices with the answers of the nephrology fellows and training program directors. The correct and incorrect answers were then discussed after the audience responses and the results of the questionnaire were displayed. As always, the audience, lecturers, and moderators enjoyed this educational session. This article recapitulates the acid-base and electrolyte disorders portion of the session and reproduces its educational value for the readers of the Clinical Journal of the American Society of Nephrology. Enjoy the clinical cases and expert discussions.

Topics: Acid-Base Equilibrium; Acid-Base Imbalance; Acidosis, Renal Tubular; Adult; Drug Interactions; Educational Measurement; Female; Fructose; Headache; Humans; Male; Middle Aged; Nephrology; Neuroprotective Agents; Renal Insufficiency, Chronic; Sjogren's Syndrome; Surveys and Questionnaires; Topiramate

A 42-year old woman was referred for a metabolic evaluation after two episodes of kidney stones. Her laboratory results revealed a normal anion-gap metabolic acidosis, a marked hypocitraturia (0,6 mmol/24h; norm 1,6-4,5) and a urinary pH of 7,0 confirming renal tubular acidosis (RTA). We identified topiramate, our patient's medication for migraine, as the cause of the RTA. Topiramate, a carboanhydrase inhibitor leads to RTA of a mixed (proximal and distal) type and thus significantly increases the risk for kidney stones.

Topics: Acidosis; Acidosis, Renal Tubular; Adult; Anticonvulsants; Citric Acid; Diagnosis, Differential; Female; Fructose; Humans; Kidney Calculi; Migraine Disorders; Renal Colic; Topiramate

Topics: Acidosis; Acidosis, Renal Tubular; Aged; Anticonvulsants; Cerebral Hemorrhage, Traumatic; Comorbidity; Drug Substitution; Epilepsies, Partial; Fructose; Humans; Male; Phenytoin; Polypharmacy; Schizophrenia, Paranoid; Topiramate

Carbonic anhydrase (CA) inhibitors topiramate and zonisamide can induce metabolic acidosis in some patients. Our aims were to assess the prevalence and severity of this acidosis and to determine its predictors.. For 70 patients established on treatment with topiramate (n=55) or zonisamide (n=14) or both (n=1), we measured electrolytes, and genotyped single nucleotide polymorphisms (SNPs) in the main renal CA isoenzymes (II, IV and XII).. Twenty-six percent of patients had a metabolic acidosis (serum bicarbonate <20 mmol/l). The mean serum bicarbonate of patients taking topiramate was significantly lower than those taking zonisamide (P=0.002). We found no association between serum bicarbonate and the dose of drug or the duration of treatment. Serum bicarbonate levels were associated with the CA type XII SNPs rs2306719 (P=0.006 by one-way analysis of variance) and rs4984241 (P=0.015), but this association was not strong enough to survive correction for multiple testing.. The development of acidosis with topiramate and zonisamide is not determined by drug dose or by treatment duration, but may be influenced by polymorphisms in the gene for CA type XII. The aforementioned SNPs lie 9.8 kb apart in intron 1 of the CA type XII gene, and deserve further study in a larger cohort of patients.

Topics: Acid-Base Equilibrium; Acidosis, Renal Tubular; Adult; Aged; Carbonic Anhydrase Inhibitors; Carbonic Anhydrases; Epilepsy; Female; Fructose; Genome-Wide Association Study; Humans; Isoxazoles; Male; Middle Aged; Polymorphism, Single Nucleotide; Prevalence; Severity of Illness Index; Topiramate; Young Adult; Zonisamide

Topiramate is licensed for the treatment of epilepsy and for migraine prophylaxis, but is also used off-licence for a wide range of indications. With the increasing use of topiramate, reports have emerged that topiramate can cause metabolic acidosis in some patients. It does this by impairing both the normal reabsorption of filtered HCO(3)(-) by the proximal renal tubule and the excretion of H(+) by the distal renal tubule. This combination of defects is termed mixed renal tubular acidosis (RTA). The mechanism involves the inhibition of the enzyme carbonic anhydrase, which is consistent with the fact that genetic deficiency of carbonic anhydrase is associated with mixed RTA. Topiramate-induced RTA can make patients acutely ill, and chronically, can lead to nephrolithiasis, osteoporosis and, in children, growth retardation. There is no proven method for predicting or preventing the effect of topiramate on acid-base balance, but patients with a history of renal calculi or known RTA should not receive topiramate. The utility of regular monitoring of HCO(3)(-) levels has not been proven and is not routine practice currently. For patients with persistent RTA, topiramate should usually be discontinued as alternative agents are available.

Topics: Acid-Base Equilibrium; Acidosis, Renal Tubular; Adult; Anticonvulsants; Carbonic Anhydrase II; Child; Epilepsy; Fructose; Genetic Predisposition to Disease; Humans; Kidney Tubules, Distal; Middle Aged; Topiramate; Young Adult

Topics: Acidosis, Renal Tubular; Anticonvulsants; Fructose; Humans; Male; Middle Aged; Topiramate

Topics: Acidosis, Renal Tubular; Anticonvulsants; Carbonic Anhydrases; Female; Fructose; Humans; Kidney; Middle Aged; Migraine Disorders; Models, Biological; Topiramate

Topiramate infrequently induces anion gap metabolic acidosis through carbonic anhydrase inhibition on the distal tubule of the nephron--a type 2 renal tubular acidosis. We report on a 40 years old woman previously healthy that developed significant asymptomatic metabolic acidosis during topiramate therapy at a dosage of 100 mg/day for three months. Stopping medication was followed by normalization of the acid-base status within five weeks. This infrequent side effect appears unpredictable and should be given careful attention.

Topics: Acidosis, Renal Tubular; Carbonic Anhydrase Inhibitors; Female; Fructose; Humans; Middle Aged; Topiramate

Topics: Acidosis, Renal Tubular; Adult; Anticonvulsants; Female; Fructose; Humans; Seizures; Topiramate