Abstract Introduction Metformin, a first line agent for type 2 diabetes, is generally safe, but rarely can lead to metformin-associated lactic acidosis (MALA), a life threatening complication. Though uncommon, occurring in fewer than 10 cases per 100,000 patient-years, MALA carries significant morbidity and mortality of up to 30%. Early initiation of renal replacement therapy (RRT) improves outcomes. This case highlights the importance of maintaining a high index of suspicion for MALA in patients with compatible clinical features. Case description A 55-year-old man with metastatic lung adenocarcinoma on immunotherapy, atrial fibrillation and type 2 diabetes on metformin was admitted with persistent vomiting, diarrhea and dehydration. He continued medications despite poor oral intake. He was enrolled in a blinded immunotherapy trial (pembrolizumab vs. ivonescimab), with his last cycle administered two weeks prior. On arrival, he was hypoxic and hypotensive requiring vasopressors and ICU admission for shock and profound acidosis. Laboratory tests revealed severe hyperkalemia 7.6 mmol/L, anion gap metabolic acidosis (HAGMA) with pH 6.73, anion gap 36 mmol/L, bicarbonate 3 mmol/L, and lactate 15 mmol/L. He developed oliguric acute kidney injury (AKI) with creatinine 8.0 mg/dL (baseline 1.0 mg/dL). Refractory acidosis and hyperkalemia prompted emergent hemodialysis. Initially, his presentation was attributed to immunotherapy related adverse events; however, neither agent is known to cause such complications, prompting consideration of alternative etiologies. The clinical picture and rapid metabolic improvement following dialysis supported a diagnosis of MALA, after ruling out infectious and cardiogenic etiologies. Despite supportive care, he remained oliguric. Later, renal biopsy revealed acute tubular necrosis without evidence of immune-mediated injury. He remained on dialysis for four months before renal recovery. Discussion While immune check point inhibitor toxicities are well recognized, diagnostic closure on this etiology can delay recognition of other causes such as metformin toxicity. This case illustrates how anticancer therapy-induced gastrointestinal losses can precipitate severe AKI, triggering life-threatening MALA. In chronic metformin users, MALA typically arises from an underlying illness rather than recent dosing, and neither plasma metformin nor lactate levels correlate with mortality. RRT is essential, with intermittent hemodialysis typically eliminating over 80% metformin in the first session. Due to tissue redistribution and severe acidosis, extended or continuous RRT may be needed. Early initiation, ideally within six hours, significantly improves renal recovery and survival. This abstract is funded by: None
Ashraf et al. (Fri,) studied this question.