Hyperkalemia Following High-Dose Arginine Therapy in Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes: A Metabolic Consequence of Cationic Amino Acid Infusion

Introduction: Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a complex multisystem disorder. High-dose intravenous (IV) L-arginine is recommended for managing acute stroke-like episodes in MELAS due to its vasodilatory effects. Although hyperkalemia has been reported in patients with impaired kidney function, it remains underrecognized in those with preserved renal function. Case Description: A 25-year-old man with a five-year history of bilateral hearing loss and difficulty maintaining weight presented with headaches, aphasia, a left visual field deficit, and seizures. Brain MRI demonstrated parieto-occipital cortical ribboning, consistent with MELAS. Genetic testing confirmed a pathogenic variant, MT-TL1 m.3243A>G, at 50% heteroplasmy. The patient was started on IV L-arginine at a dose of 10 g daily (210 mg/kg body weight). Baseline labs: serum creatinine 0.8 mg/dL, bicarbonate 24 mEq/L, potassium (K+) 3.9 mEq/L, and arterial pH 7.40. Two weeks later, he developed hyperkalemia (K+ 6.2 mEq/L) with peaked T waves on EKG without QRS widening. The patient was normotensive, euvolemic, and was not on any hyperkalemia-inducing drugs or supplements. Urinalysis was bland; renal ultrasound excluded obstruction. Management included two doses of sodium zirconium cyclosilicate, IV furosemide, and sodium bicarbonate, which lowered K+ transiently to 5.3 mEq/L before rebounding to 5.8. Arginine was withheld, resulting in a drop in K+ to 4.3 mEq/L within 48 hours. Reintroduction of arginine at 7.5 g/day (150 mg/kg) in divided doses led to K+ normalization and continued neurologic improvement. Discussion: This case underscores a serious but underrecognized side effect of high-dose IV arginine, even in patients with normal kidney function. Cationic amino acids like arginine, ornithine, and lysine can displace intracellular potassium in muscle cells, leading to hyperkalemia—a mechanism independent of acidosis. In this patient, the timing of hyperkalemia onset, rapid potassium decline after stopping arginine, and successful reintroduction at a lower dose establish causality. While previously observed in uremic patients, our case suggests that even those with preserved renal function may be susceptible. Clinicians should monitor potassium levels closely during arginine therapy to prevent this serious complication.