Beyond Rhabdomyolysis: C3 Glomerulopathy in 3,4-Methylenedioxymethamphetamine-Induced Multiorgan Dysfunction

A 40-year-old man developed life-threatening acute kidney injury after MDMA overdose, requiring dialysis. Kidney biopsy revealed two distinct causes: acute tubular necrosis from severe rhabdomyolysis and C3 glomerulopathy, a rare condition caused by dysregulation of the alternative complement pathway. Complement levels were low during the acute episode but normalized as kidney function recovered, and dialysis was discontinued at discharge. This case suggests that MDMA can trigger complement dysregulation leading to C3 glomerulopathy, which may resolve without specific complement-directed therapies. It underscores the need for broad diagnostic evaluation in drug-associated kidney injury.

Study at a glance

Abstract

Introduction: MDMA (3,4-methylenedioxymethamphetamine) toxicity can cause life-threatening complications, including hyperthermia, rhabdomyolysis, and acute kidney injury (AKI). While AKI from rhabdomyolysis is well known, C3 glomerulopathy (C3G) following MDMA use, to our knowledge, has not been reported. We present a case of oliguric AKI and biopsy-proven C3G after MDMA overdose. Case Description: A 40-year-old male with past medical history of psoriasis presented with altered mental status after suspected MDMA use. Examination showed hyperthermia and muscle rigidity. Labs revealed severe rhabdomyolysis (CK >200,000 U/L), metabolic acidosis, oliguric AKI, DIC, nephrotic-range proteinuria, hematuria, and low C3/C4. He required dialysis. Kidney biopsy showed acute tubular necrosis and a membranoproliferative glomerular pattern with dominant C3 staining, consistent with C3G. No infection or thrombotic microangiopathy was identified. Renal function recovered with supportive care alone, and dialysis was discontinued at the time of discharge. Complement levels had also normalized. Discussion: This case highlights C3G as a potential renal complication of MDMA use. C3G results from alternative complement pathway dysregulation, often triggered by a secondary insult. Case reports describing vessel injury and dissection in young, healthy MDMA users have been described. MDMA may consist of amphetamine subtypes that can drive adrenergic responses, which may result in endothelial injury. A comprehensive approach to our patient’s AKI revealed two diagnoses: rhabdomyolysis-induced tubular injury and C3GN. This case underscores the importance of broad diagnostic consideration in drug toxicity and renal injury. In our case, MDMA may have triggered complement dysregulation, which resolved spontaneously, without specific complement-directed therapies.