Severe Anemia and Acute Kidney Injury After Pegloticase in a Patient With Glucose-6-Phosphate Dehydrogenase Deficiency

Pegloticase is an effective therapy for refractory gout but carries a risk of oxidative hemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Reported cases of hemolytic complications remain limited, particularly those with delayed presentation, where traditional markers such as haptoglobin and bilirubin may have normalized, making diagnosis challenging. We describe a 61-year-old female with known G6PD deficiency who presented with near syncope, nausea, vomiting, and volume depletion four days after receiving her first dose of intravenous pegloticase and recently starting mycophenolate. Initial evaluation revealed severe anemia (hemoglobin 5.1 g/dL) and acute kidney injury (creatinine 9.23 mg/dL). Hemolysis markers were not overtly diagnostic, with normal haptoglobin and bilirubin; however, urinalysis revealed heme-positive urine with no red blood cells, a finding highly suggestive of hemoglobinuria from recent intravascular hemolysis rather than true hematuria. An extensive workup for anemia and acute kidney injury was otherwise unrevealing. Given the temporal association with pegloticase exposure and underlying G6PD deficiency, oxidative hemolysis with concomitant prerenal acute kidney injury was suspected. The patient improved with discontinuation of the offending agents, blood transfusion, and supportive care, with stabilization of hemoglobin and gradual recovery of renal function. This case highlights the importance of recognizing delayed or atypical presentations of drug-induced hemolysis, in which traditional markers may be normal at the time of evaluation. Clinicians should maintain a high index of suspicion for hemolysis after pegloticase administration in G6PD-deficient patients and ensure appropriate screening prior to therapy.