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Vol. 28. Issue. 6.December 2008
Pages 572-666
Vol. 28. Issue. 6.December 2008
Pages 572-666
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Topiramate-induced renal tubular acidosis. A case report
Acidosis tubular renal inducida por topiramato. A propósito de un caso
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Seema Sujana, Alvaro Torres de Ruedaa, Remedios Toledoa, Silvia Rosa, Lorena Monterob, Guillermo Martín Reyesb
a Servicio de Nefrolog??a, Hospital Carlos Haya, M??laga, M??laga, Espa??a,
b Servicio de Medicina Interna, Hospital Axarqu??a, V??lez, M??laga, Espa??a,
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Sr Director: El Topiramato es un antiepiléptico, usado además en el trastorno bipolar, dolor neuropático y migrañas. Secundariamente puede producir, entre otros, acidosis metabólica por pérdida renal de bicarbonato y acúmulo de CO2 a nivel cerebral, por su efecto inhibidor de la anhidrasa carbónica (renal y la localizada en neuroglía, mielina y plexo coroideo).
To the editor: Topiramate is an antiepileptic drug also used to treat bipolar disorder, neuropathic pain and migraine. The potential side effects of the drug include metabolic acidosis due to renal bicarbonate loss and the accumulation of CO2 in the brain, as a result of its inhibitory action upon carbonic anhydrase (renal and located in the microglia, myelin and choroid plexus).
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To the editor: Topiramate is an antiepileptic drug also used to treat bipolar disorder, neuropathic pain and migraine.

The potential side effects of the drug include metabolic acidosis due to renal bicarbonate loss and the accumulation

of CO2 in the brain, as a result of its inhibitory action upon carbonic anhydrase (renal and located in the microglia,

myelin and choroid plexus).



We report the case of a 58-year-old male with a history of absence-type epilepsy subjected to treatment with topiramate (150 mg/day) for the past 10 years. He also presented chronic renal failure (CKF) not subjected to evaluation and with baseline serum creatinine 2 mg/dl, hypersomnolence under study, and pulmonary thromboembolism (PTE) secondary to deep venous thrombosis (DVT) in the right leg due to trauma, in 1981. The patient was admitted to the Service of Pneumology diagnosed with bilateral PTE associated to DVT. The Service of

Nephrology was consulted due to the sustained presence of acidosis.



The complementary explorations revealed the following:



The complete blood count and baseline coagulation parameters were normal. Urea 66 mg/dl, serum creatinine 2.3

mg/dl, creatinine clearance 35 ml/min., Na 145 mEq/l, K 4.8 mEq/l, Cl 109 mEq/l, PTH 92 pg/ml. The studies of hypercoagulability and autoimmunity proved negative. Twenty-four hour urine showed: pH 8, rest normal or negative, urine creatinine 38.1 mg/dl, proteins 0.5 g/d, urine Na 76 mEq/l, urine K 17.2 mEq/l, urine Cl 74 mEq/l. The urine sediment was normal. Abdominal ultrasound: a single left kidney measuring 12.6 cm in size, with loss of cortico-medullary differentiation. The echo-Doppler findings in the lower extremities were compatible with DVT, and computed tomographic angiography showed signs typical of bilateral PTE. Polysomnography revealed episodes of hypopnea and hypoventilation, without apnea. The observed pattern was not suggestive of obstructive sleep apnea syndrome (OSAS). The evolution of the blood gas parameters was as follows:



¿ Upon admission (arterial): pH 7.26, PCO2 32.4, PO2 68.4, HCO3 14.4, base excess 11.2

¿ After anticoagulation (venous): pH 7.11, PCO2 59.4, PO2 22.4, HCO3 21.9, base excess 6.1

¿ After start of treatment with BiPAP and bicarbonate: pH 7.27, PCO2 44.8, PO2 14.9, HCO3 17.9, base excess 3.9

¿ Following the start of bi-level positive airway pressure ventilation (BiPAP), bicarbonate treatment and the  withdrawal or topiramate: pH 7.33, PCO2 35.8, HCO3 19.3. The GAP anion was normal in all cases (between 11-14).



With anticoagulation, the PTE tended to resolve. A renal biopsy was discarded, and stage III CKF secondary to

diminished nephron mass and probable chronic interstitial nephropathy was diagnosed. BiPAP corrected the respiratory component of acidosis associated to central hypopnea, although GAP anion-normal hyperchloremic metabolic acidosis persisted. On administering bicarbonate, the tendency towards acidosis persisted, though to a lesser degree, and the pH was corrected upon suspending topiramate.



Topiramate, in the same way as acetazolamide, is a potent inhibitor of carbonic anhydrase (CA) isoenzymes II and VI ¿ this being the mechanism considered to involved in the development of metabolic acidosis when this drug is used. We recommend to the monitorization of serum bicarbonate during topiramate treatment, particularly in patients with respiratory problems or renal failure.

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