Synergistic Nephrotoxicity: AKI Following Combined Intrapleural Alteplase-DNase and Vancomycin: A Case Report

Introduction: The nephrotoxic potential of vancomycin is well-established, but the renal safety profile of intrapleural fibrinolytic therapy remains poorly understood. We present a clinically significant case of acute kidney injury developing during concurrent treatment with intrapleural alteplase-DNase and intravenous vancomycin for loculated empyema complicating chronic osteomyelitis. This case highlights a potentially underrecognized drug interaction and proposes mechanisms for this novel nephrotoxic synergy. Case Description: A 53-year-old male with chronic left shoulder osteomyelitis presented with loculated empyema requiring chest tube drainage. Treatment was initiated with intrapleural alteplase 10mg/DNase 5mg daily and intravenous vancomycin (target trough 15-20μg/mL). Within 72 hours, serum creatinine rose from baseline 1.04 mg/dL to 1.69 mg/dL, coinciding with supratherapeutic vancomycin trough levels (22.7 μg/mL). Renal ultrasound showed normal kidney size and parenchyma without hydronephrosis. The AKI resolved following vancomycin discontinuation and intravenous hydration (creatinine decreased to 1.39 mg/dL), suggesting reversible acute tubular injury. Notably, the temporal association with fibrinolytic therapy initiation raised concerns about potential contribution to nephrotoxicity. Discussion: This case represents the first well-documented instance of AKI potentially attributable to the combination of intrapleural fibrinolytics and vancomycin. Two key observations merit emphasis: the temporal relationship between fibrinolytic initiation and renal function decline and the exaggerated vancomycin toxicity at typically tolerated levels suggesting altered pharmacokinetics. Potential mechanisms include systemic absorption of fibrinolytic agents causing glomerular microthrombi or synergistic tubular toxicity. These findings challenge current assumptions about intrapleural therapy safety and suggest the need for enhanced renal monitoring protocols and further pharmacokinetic studies of this interaction.