Rasburicase for Treatment of Hyperuricemia-Related Neonatal AKI

Introduction: Up to 10% of neonates with Trisomy 21 (T21) will develop Transient Myeloproliferative Disorder (TMD). Though tumor lysis syndrome (TLS) has been described with treatment of TMD, acute kidney injury (AKI) from hyperuricemia without TLS in this population has not been reported. We describe the case of a preterm neonate with T21, TMD-spectrum leukocytosis, and hyperuricemia-related AKI who was treated with recombinant uricase. Case Description: A 31 weeks’ gestation, low-birth weight neonate was born with T21 and severe leukocytosis (56,000 k/cumm) with blasts, along the spectrum of TMD. Hyperuricemia (8.6 mg/dL) followed, and with elevated lactate dehydrogenase (1516 U/L) was presumptively secondary to high cell turnover. Within the first 3 days of life, he developed stage 3 AKI, with rising urea (BUN) and creatinine (Cr) and decreased urine output, for which the nephrology team was consulted. Suspecting his rapidly progressive AKI may be secondary to hyperuricemia-related injury, and with the goal of avoiding renal replacement therapy (RRT) given the considerable risk associated with initiating RRT in an infant this size (1750 g), a single dose of rasburicase (0.2 mg/kg) was administered to treat the hyperuricemia. Following administration, BUN and Cr dropped precipitously (Figure 1), urine output increased by 67%, and he avoided RRT. Discussion: Given his T21 and TMD, this neonate was at increased risk for hyperuricemia, and his response to rasburicase suggests that he suffered from hyperuricemia-related AKI. Uric acid mediates AKI through both reduction in renal blood flow and proximal tubule (PT) toxicity, and he may have been particularly susceptible to this PT toxicity given his prematurity. This case demonstrates that hyperuricemia should be considered in the differential for AKI in neonates with T21 and TMD-spectrum disease, and that recombinant uricase is an effective treatment that may help to preserve kidney function and avoid RRT.Figure 1. Trend in kidney function tests (BUN and Cr) following rasburicase on day of life 4.