title: Effect of single agent high-dose methotrexate-related acute kidney injury on length of hospitalization and relative dose intensity in adult patients with central nervous system lymphoma.
abstract: Purpose Grade ≥3 adverse effects prolong hospitalization and reduce chemotherapy dose intensity. The purpose of this study was to evaluate the rate and severity of high-dose methotrexate-related acute kidney injury and analyze its effect on hospital length of stay and relative chemotherapy dose intensity. Methods This was a retrospective cohort analysis. Patients receiving ≥1 dose of high-dose methotrexate were analyzed for acute kidney injury and length of stay. Patients receiving ≥6 cycles of induction therapy were included in the analysis of relative chemotherapy dose intensity. Chi squared analysis was used to determine the differences between dichotomous data; Student's t-test for parametric data and Mann-Whitney U test for non-parametric data for continuous variables. Statistical analyses were performed with IBM SPSS Statistics (version 21). Results Twenty-six patients and 194 treatment encounters were identified. Thirteen patients were evaluated for relative chemotherapy dose intensity. Grade ≥3 acute kidney injury occurred in four patients (15% of patients; 2% of encounters). There were no grade 5 adverse events. Mean length of stay for encounters with grade ≥3 acute kidney injury was almost three times longer than for those with ≤ grade 2 acute kidney injury (p = 0.041). Mean relative chemotherapy dose intensity was reduced approximately in half for patients experiencing grade ≥3 acute kidney injury (p < 0.01). The most common adverse events were hypokalemia and nausea. Proton pump inhibitors were the most frequently co-administered medications with the potential to affect high-dose methotrexate pharmacokinetics. Conclusion At our cancer program, the rate of grade ≥3 acute kidney injury with high-dose methotrexate is similar to that reported by others. Grade ≥3 acute kidney injury following high-dose methotrexate administration significantly prolonged length of stay and reduced relative chemotherapy dose intensity.
authors.affiliation: 1 Department of Pharmacy, Northwestern Memorial Hospital, Chicago, IL, USA.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Steward
authors.affiliation: 2 Department of Pharmacy, The University of Chicago Medical Center, Chicago, IL, USA.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Bullard
authors.affiliation: 3 Medical Oncology, Cancer and Hematology Centers of West Michigan, Grand Rapids, MI, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: O'Rourke
authors.affiliation: 3 Medical Oncology, Cancer and Hematology Centers of West Michigan, Grand Rapids, MI, USA.
authors.forename: Alan D
authors.initials: AD
authors.lastname: Campbell
authors.affiliation: 3 Medical Oncology, Cancer and Hematology Centers of West Michigan, Grand Rapids, MI, USA.
authors.forename: Brett T
authors.initials: BT
authors.lastname: Brinker
authors.affiliation: 3 Medical Oncology, Cancer and Hematology Centers of West Michigan, Grand Rapids, MI, USA.
authors.forename: Kathleen J
authors.initials: KJ
authors.lastname: Yost
authors.affiliation: 3 Medical Oncology, Cancer and Hematology Centers of West Michigan, Grand Rapids, MI, USA.
authors.forename: Amy C
authors.initials: AC
authors.lastname: Vanderwoude
authors.affiliation: 3 Medical Oncology, Cancer and Hematology Centers of West Michigan, Grand Rapids, MI, USA.
authors.forename: William L
authors.initials: WL
authors.lastname: Scott
authors.affiliation: 4 Department of Pharmacy, Spectrum Health Hospitals, Grand Rapids, MI, USA.
authors.forename: Polly E
authors.initials: PE
authors.lastname: Kintzel
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced*; D000368:Aged; D015331:Cohort Studies; D005260:Female; D006760:Hospitalization; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D008727:Methotrexate
keywords: Acute kidney injury; dose intensity; length of stay; methotrexate; nephrotoxicity