Topiramate causing type II renal tubular acidosis: A case and review of the mechanism

Abstract

Topiramate has a wide array of pharmacologic effects, including proximal renal tubular acidosis (RTA). Clinicians must be wary of the possibility for development of somnolence due to compensatory hyperventilation and cardiac dysrhythmias.

A review of renal tubular acidosis

“…82,84 Secondary proximal (type 2) RTA Secondary or acquired pRTA has been reported in association with several disease conditions and drugs/toxins, with some overlap with causes of acquired dRTA. 5,147 These include gammopathies, 148,149 amyloidosis, 150 vitamin D deficiency, 151 heavy metals, 152,153 ifosfamide, 154 carbonic anhydrase inhibitors (CAIs), 155 antiretrovirals, 156 oxaliplatin 157 and cisplatin, 158 outdated tetracycline, 159 iron chelation therapy with deferasirox, 160 psoriasis/psoriatic arthritis therapy with apremilast, 161 toxic effect of phenols after a Lysol burn, 162 antiepileptic drugs including valproic acid 163 and topiramate, 164 aminoglycosides, 165 IV bisphosphonates, 166,167 and the inherited disorder, lysinuric protein intolerance. 168 Mechanisms implicated in pRTA in disease conditions include tubular injury secondary to deposition of immunoglobulin light chains in proximal tubular cells 148,149,169 (monoclonal gammopathies including light-chain gammopathy 148,149 and multiple myeloma) 148,170 ; amyloid deposits in tubules 171 (amyloidosis) 150 ; and inhibition of Na + -for-H + exchange by parathyroid hormone 172 (vitamin D deficiency).…”

“…to cause Fanconi syndrome. 162 Proximal tubulopathy involving antiepileptic drugs is thought to be associated with mitochondrial cytopathy due to lipid peroxidation 187 (valproic acid 163 ) and CA inhibition 188 (topiramate 164 ). Aminoglycosides such as gentamicin cause pRTA due to intracellular accumulation of the drug in proximal tubular cells, impairing transport mechanisms.…”