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Comparative effectiveness of rasburicase versus allopurinol for cancer patients with renal dysfunction and hyperuricemia.
Leuk Res 2020; 89:106298LR

Abstract

While rasburicase has shown efficacy to rapidly correct hyperuricemia compared with allopurinol, its overall impact in improving clinically significant outcomes, such as acute kidney injury (AKI), in tumor lysis syndrome (TLS) is unknown. In this retrospective cohort study, we included all hospitalized cancer patients with hyperuricemia and AKI who received rasburicase +/- allopurinol or allopurinol alone from 2009 to 2015. Inverse probability of treatment weighting using propensity score was used to account for potential confounders and to estimate the causal effect associated with differential drug treatment. 150 patients met inclusion criteria; 89 received rasburicase +/- allopurinol and 61 received allopurinol alone. Weighted outcome regression analysis demonstrated that rasburicase was associated with significantly lower mean uric acid nadir at 7 days compared to allopurinol (2.70 versus 5.82 mg/dL, p < 0.01). However, likelihood of renal function recovery (OR = 0.90, p = 0.79), creatinine nadir by 7 days (1.80 versus 1.66 mg/dL, p = 0.51), and final creatinine by 30 days (2.08 versus 2.07 mg/dL, p = 0.98) did not significantly differ. In conclusion, the clinical benefit of rasburicase in promoting renal function recovery in cancer patietns with concurrent hyperuricemia and renal failure remains inconclusive. Our results suggest that correction of hyperuricemia as a surrogate endpoint may not be associated with significant renal function improvement, particularly if renal dysfunction is unrelated to TLS.

Authors+Show Affiliations

Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.Case Western Reserve University School of Medicine, Cleveland, OH, USA.Pharmacy Services, University of Washington Medical Center, Seattle, WA, USA.Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.Pharmacy Services, University of Washington Medical Center, Seattle, WA, USA.Division of Hematology, University of Washington School of Medicine, Seattle, WA, USA.Division of Hematology, University of Washington School of Medicine, Seattle, WA, USA.Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA; Division of Nephrology, Seattle Children's Hospital, Seattle, WA, USA.Division of Hematology, University of Washington School of Medicine, Seattle, WA, USA. Electronic address: ali2015@uw.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31945598

Citation

Martens, Kylee L., et al. "Comparative Effectiveness of Rasburicase Versus Allopurinol for Cancer Patients With Renal Dysfunction and Hyperuricemia." Leukemia Research, vol. 89, 2020, p. 106298.
Martens KL, Khalighi PR, Li S, et al. Comparative effectiveness of rasburicase versus allopurinol for cancer patients with renal dysfunction and hyperuricemia. Leuk Res. 2020;89:106298.
Martens, K. L., Khalighi, P. R., Li, S., White, A. A., Silgard, E., Frieze, D., ... Li, A. (2020). Comparative effectiveness of rasburicase versus allopurinol for cancer patients with renal dysfunction and hyperuricemia. Leukemia Research, 89, p. 106298. doi:10.1016/j.leukres.2020.106298.
Martens KL, et al. Comparative Effectiveness of Rasburicase Versus Allopurinol for Cancer Patients With Renal Dysfunction and Hyperuricemia. Leuk Res. 2020 Jan 7;89:106298. PubMed PMID: 31945598.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparative effectiveness of rasburicase versus allopurinol for cancer patients with renal dysfunction and hyperuricemia. AU - Martens,Kylee L, AU - Khalighi,Parisa R, AU - Li,Shan, AU - White,Andrew A, AU - Silgard,Emily, AU - Frieze,Deborah, AU - Estey,Eli, AU - Garcia,David A, AU - Hingorani,Sangeeta, AU - Li,Ang, Y1 - 2020/01/07/ PY - 2019/10/31/received PY - 2020/01/02/revised PY - 2020/01/06/accepted PY - 2020/1/17/pubmed PY - 2020/1/17/medline PY - 2020/1/17/entrez KW - Acute kidney injury KW - Comparative effectiveness KW - Hematologic disease KW - Propensity score KW - Tumor lysis syndrome SP - 106298 EP - 106298 JF - Leukemia research JO - Leuk. Res. VL - 89 N2 - While rasburicase has shown efficacy to rapidly correct hyperuricemia compared with allopurinol, its overall impact in improving clinically significant outcomes, such as acute kidney injury (AKI), in tumor lysis syndrome (TLS) is unknown. In this retrospective cohort study, we included all hospitalized cancer patients with hyperuricemia and AKI who received rasburicase +/- allopurinol or allopurinol alone from 2009 to 2015. Inverse probability of treatment weighting using propensity score was used to account for potential confounders and to estimate the causal effect associated with differential drug treatment. 150 patients met inclusion criteria; 89 received rasburicase +/- allopurinol and 61 received allopurinol alone. Weighted outcome regression analysis demonstrated that rasburicase was associated with significantly lower mean uric acid nadir at 7 days compared to allopurinol (2.70 versus 5.82 mg/dL, p < 0.01). However, likelihood of renal function recovery (OR = 0.90, p = 0.79), creatinine nadir by 7 days (1.80 versus 1.66 mg/dL, p = 0.51), and final creatinine by 30 days (2.08 versus 2.07 mg/dL, p = 0.98) did not significantly differ. In conclusion, the clinical benefit of rasburicase in promoting renal function recovery in cancer patietns with concurrent hyperuricemia and renal failure remains inconclusive. Our results suggest that correction of hyperuricemia as a surrogate endpoint may not be associated with significant renal function improvement, particularly if renal dysfunction is unrelated to TLS. SN - 1873-5835 UR - https://www.unboundmedicine.com/medline/citation/31945598/Comparative_effectiveness_of_rasburicase_versus_allopurinol_for_cancer_patients_with_renal_dysfunction_and_hyperuricemia L2 - https://linkinghub.elsevier.com/retrieve/pii/S0145-2126(20)30003-5 DB - PRIME DP - Unbound Medicine ER -