LAUSR

Introduction: While rasburicase has shown efficacy to rapidly correct hyperuricemia compared with allopurinol, its overall impact in improving clinically significant outcomes in tumor lysis syndrome (TLS) is unknown. There are no studies demonstrating improvement of acute kidney injury (AKI) in patients with TLS and pre-existing renal dysfunction. In this study, we aim to address the comparative effectiveness of rasburicase versus allopurinol in cancer patients with hyperuricemia and AKI. Methods: In this retrospective cohort study, we included all hospitalized cancer patients with uric acid levels greater than 7.0 mg/dL and concurrent AKI who received either rasburicase or allopurinol from 2009 to 2015 at University of Washington affiliated hospitals. Inverse probability of treatment weighting (IPTW) using the propensity score was used to account for potential confounders and to estimate the causal effect associated with differential drug treatment. Balance after weighting was assessed by calculating standardized differences and variance ratios, where a standardized difference of less than 0.1 was considered adequate balance. Naïve linear and logistic regressions and weighted outcome regressions were performed after sampling weight assignment. The primary outcome of the study included renal function recovery defined by a final creatinine value return to less than 50% of baseline creatinine and not requiring dialysis at the time of discharge, death, or 30 days, whichever occurred first. Secondary outcomes included final creatinine, creatinine nadir and uric acid nadir within 7 days of drug administration. Results: Over the 6-year study period, a total of 150 patients met the inclusion criteria; 89 received rasburicase and 61 received allopurinol. After IPTW, 140 weighted patients were included in the final analysis with adequate balance of baseline characteristics (standardized difference <0.1 in age, sex, ICU admission, TLS risk, tumor type, chemotherapy type and timing, creatinine, LDH, potassium, phosphate, and calcium). In the weighted analysis, rasburicase was associated with a significantly lower mean uric acid nadir within 7 days compared to allopurinol (2.70 versus 5.82 mg/dL, p<0.01). However, the likelihood of renal function recovery (OR=0.90, p=0.79), the creatinine nadir within 7 days (1.80 versus 1.66 mg/dL, p=0.51), and the final creatinine value by 30 days (2.08 versus 2.07 mg/dL, p=0.98) were not significantly different for patients receiving rasburicase versus allopurinol (Table 1). The average time for final creatinine assessment was 12 days and overall survival did not significantly differ between the two cohorts. In subgroup analyses, the likelihood of renal recovery with rasburicase in patients at low-risk for TLS was associated with an odds ratio of 0.47 (p=0.12) compared to an odds ratio of 1.76 (p=0.34) for those at intermediate- and high-risk for TLS. Similarly, there was a trend towards benefit of rasburicase in improving renal function in patients with underlying high grade myeloid and very aggressive leukemia and lymphomas as opposed to those with more indolent malignancies, such as solid tumors and multiple myeloma (Figure 1). Conclusion: Among cancer patients with hyperuricemia and AKI, rasburicase administration was associated with a significant early reduction in uric acid but not associated with an improvement in the incidence of renal recovery or survival when compared to allopurinol. Though the benefit of rasburicase in higher grade malignancies remains inconclusive, this study emphasizes that uric acid correction alone may not be the most clinically effective strategy in treating AKI, particularly if renal dysfunction is unrelated to TLS. No relevant conflicts of interest to declare.