Rasburicase improves renal function and diuresis in hyperuricemic pulmonary arterial hypertension

This is a case of advanced pulmonary arterial hypertension (PAH) complicated by right heart failure and acute kidney injury (AKI). Due to diuretic-resistant volume overload and hyperuricemia, a trial of rasburicase was given for urate nephropathy, which led to a rapid decrease in uric acid (UA) levels and improvement in renal function. A 40-year-old female with idiopathic PAH on intravenous epoprostenol was admitted with increasing dyspnea and edema. She also complained of dizziness, chest discomfort, and palpitations. Prior to admission she was volume overloaded with hepatic congestion, but continued to have worsening symptoms despite use of 4 diuretics. Serum creatinine was significantly elevated compared to baseline. Vital signs demonstrated hypotension, tachycardia, and hypoxia. Physical exam showed anasarca, jugular venous distention and a loud P2 heart sound with a palpable right ventricular heave. Laboratory results were notable for a creatinine of 1.92 mg/dL and UA of 19.5 mg/dL. Intravenous diuretics were started, but ultimately a dopamine infusion was required to maintain adequate cardiac output. Despite moderate urine output, renal function did not improve. A renal biopsy was performed, which demonstrated urate nephropathy including a gouty tophus in the renal cortex. Subsequently, rasburicase 6 mg IV was given. UA decreased to 2.1 mg/dL over 48 hours. Diuresis and renal function improved steadily. The patient was discharged successfully. Hyperuricemia has been implicated as a contributor to various disease states, and also as a prognostic marker in patients with left-sided heart failure. PAH patients with hyperuricemia also have poor outcomes. Retrospective and observational analyses have shown that UA levels correlate with functional class, right atrial pressure, pulmonary vascular resistance, and mortality. Rasburicase treats hyperuricemia by converting existing UA into allantoin, which is more soluble. Rasburicase was developed for treatment of the tumor lysis syndrome, in which lysis of malignant cells leads to a rapid rise in UA. This can cause AKI in the form of urate nephropathy. Rasburicase has even been used successfully in the management of hyperuricemic AKI not related to malignancy. In our patient, rasburicase effectively lowered UA levels leading to a significant improvement in diuresis. To our knowledge, this is the first case describing urate nephropathy in the setting of hyperuricemic PAH as well as the first to describe the use of rasburicase for treatment of hyperuricemic AKI related to PAH. Early consideration and aggressive use of rasburicase may represent a new approach in the treatment of complicated PAH. (Table Presented).