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

Steward, Jennifer; Bullard, Heather; O’Rourke, Timothy J.; Campbell, Alan D.; Brinker, Brett T.; Yost, Kathleen J.; VanderWoude, Amy; Scott, William L.; Kintzel, Polly E

doi:10.1177/1078155216665244

Cited by 8 publications

(9 citation statements)

References 17 publications

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“…We found that AKI significantly increased LOS from 4 days with no AKI to 13 days with AKI grade 3 ( P < .001). These replicate the findings by Steward et al, 21 who reported an almost three-fold increase in LOS comparing AKI grade 3 versus lower grades of AKI, with the mean LOS rising from 5 days to 14 days. May et al 5 reported similar results with a mean LOS of 5.6 days with no renal toxicity compared with 8.9 days with grade ≥ 2.…”

Section: Discussionsupporting

confidence: 89%

High-Dose Methotrexate in Patients With Lymphoma: Predictors of a Complicated Course

O'Donoghue

Truong

Finnes

et al. 2022

JCO Oncology Practice

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PURPOSE: High-dose methotrexate (HDMTX; > 500 mg/m2) is an important component of lymphoma therapy. Serum MTX monitoring at 48 hours is the standard approach to identify those at increased risk of developing MTX toxicity. Our aim was to characterize the incidence of complications and their association with MTX levels. METHODS: A retrospective review of our institutional electronic medical record was conducted to identify patients with lymphoma who received HDMTX between January 1, 2002, and December 31, 2018. We characterized the incidence of acute kidney injury (AKI), intensive care unit (ICU) admission, length of hospital stay (LOS), and 30-day mortality across 48-hour MTX levels. To establish an association between 48-hour MTX levels and the complications listed, we performed chi-square analysis for dichotomous variables and Kruskal-Wallis for nonparametric data. Receiver operator characteristic curve analysis was performed to identify the MTX level where AKI grade ≥ 2 was more likely. Multivariate logistic regression analysis was performed to identify risk factors for this MTX level. RESULTS: We identified 642 patients with 2,804 cycles of HDMTX. The incidence of AKI was 19.1% with AKI grade ≥ 2 making up 21% of cases. Rates of AKI, ICU admission, and 30-day mortality are associated with elevated 48-hour MTX levels. There was a significant increase in median LOS with elevated MTX levels ( P < .001). Receiver operator characteristic curve analysis for AKI grade ≥ 2 demonstrated a 48-hour MTX level threshold of 1.28 μmol/L. Multivariate logistic regression analysis revealed age, male sex, elevated body surface area, higher MTX dose, monotherapy, and first cycle as independent factors. CONCLUSION: Elevated MTX levels are associated with a significant increased rate of AKI, ICU admission, prolonged LOS, and 30-day mortality. Elevated 48-hour MTX levels, particularly > 1.28 μmol/L, should alert clinicians for complications and to initiate measures to reduce MTX levels.

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Section: Discussionsupporting

confidence: 89%

High-Dose Methotrexate in Patients With Lymphoma: Predictors of a Complicated Course

O'Donoghue

Truong

Finnes

et al. 2022

JCO Oncology Practice

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“…Methotrexate (MTX) is a folate antagonist and cytotoxic chemotherapeutic drug commonly used in the management of malignancies specifically lymphoblastic leukemia, osteosarcoma, and tumors of the head and neck. 1,2 Unfortunately, the efficacy and usefulness of most chemotherapeutic drugs are associated with side effects due to their detrimental effects on both cancerous and normal cells. Specifically, the clinical use of MTX reportedly elicits hematological disorder, myelosuppression, hepatotoxicity, [3][4][5][6] and nephrotoxicity.…”

Section: Introductionmentioning

confidence: 99%

Hepatorenal protective effects of protocatechuic acid in rats administered with anticancer drug methotrexate

2019

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The efficacy of methotrexate (MTX) as an anticancer drug is limited by some adverse effects including hepatic and renal toxicities. The present study investigated the possible protective effect of protocatechuic acid (PCA), a phenolic phytochemical widely present in several edible vegetables and fruits, on hepatorenal toxicity associated with MTX treatment in rats. Male Wistar rats were randomly assigned to five groups ( n = 10), namely control, MTX alone (20 mg/kg), PCA alone (50 mg/kg), and rats that were coadministered MTX and PCA at 25 and 50 mg/kg. The MTX was administered as a single intraperitoneal dose on the first day, whereas PCA treatment lasted 7 days. Results indicated that PCA significantly ( p < 0.05) abrogated MTX-mediated elevation in indices of hepatorenal toxicity. Furthermore, PCA protected against MTX-induced decreases in glutathione level and antioxidant enzyme activities as well as the increase in reactive oxygen and nitrogen species and lipid peroxidation in the liver and kidney of the treated rats. Administration of PCA markedly abated MTX-induced increases in interleukin-1β, tumor necrosis factor alpha, and caspase 3 activity in the rats. The biochemical data on the hepatorenal protective effects of PCA were well supported by the histological data. Collectively, PCA protected against MTX-induced hepatorenal toxicity via antioxidant, anti-inflammatory, and antiapoptotic mechanisms.

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“…Incidence of AKI was higher pre-protocol compared to reported rates in the literature. 3–6 Post-protocol implementation, the rate of AKI decreased to better reflect literature findings. Results were presented to providers who communicated their support and satisfaction.…”

Section: Discussionmentioning

confidence: 70%

“…3 AKI has been reported in 2–12% of oncology indications. 3–6 AKI delays methotrexate clearance resulting in complications including cytopenia, hepatotoxicity, mucositis, neurotoxicity, and pulmonary toxicity. 7 Before implementing supportive care measures, life-threatening methotrexate-induced toxicity was around 10% with 4.6–6% mortality rate.…”

Section: Introductionmentioning

confidence: 99%

A single-center qualitative study evaluating the safety and efficacy of a pharmacist-driven protocol for high-dose methotrexate management

Matta

Gieselman

Mancini

2020

J Oncol Pharm Pract

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Introduction Delayed methotrexate clearance in several patients admitted to the oncology unit at a regional medical center necessitated the development of a pharmacist-driven protocol for supportive therapy with high-dose methotrexate. This performance improvement project evaluated the impact of the protocol on inpatient length of stay, patient safety, and clinical outcomes. Methods Retrospective data were collected over 14 months pre-implementation and prospective data were collected over 19 months post-implementation. Primary outcomes included mean length of stay and incidence of kidney injury. Secondary outcomes included myelosuppression, treatment delays, mucositis, protocol adherence, and pharmacist interventions. Chi-squared and unpaired two sample t-test were used for data analysis. Intervention A literature review of consensus recommendations for supportive care post high-dose methotrexate administration was conducted to develop the protocol. Education on implementation was provided to involved disciplines. Results One-hundred ten high-dose methotrexate admissions for 23 patients were analyzed: 24 pre-protocol and 86 post-protocol. Mean length of stay was 5.17 nights pre-protocol and 3.91 nights post-protocol ( p = 0.026). Incidence of kidney injury significantly decreased (16.7% pre-protocol versus 3.5% post-protocol; p = 0.0394). Lower incidences of all-grade anemia (83.3% versus 58.1%), neutropenia (62.5% versus 29.1%), and thrombocytopenia (58.3% versus 33.7%) as well as treatment delays (29.2% versus 11.6%; p = 0.036) were reported post protocol. No statistically significant difference in mucositis was detected. Pharmacist adherence to protocol was ≥80% resulting in 348 interventions with 99.4% provider acceptance. Conclusion The implementation of a pharmacist-driven high-dose methotrexate management protocol resulted in a statistically significant decrease in inpatient length of stay and kidney injury. Further studies are needed to assess the impact on additional outcomes.

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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

Cited by 8 publications

References 17 publications

High-Dose Methotrexate in Patients With Lymphoma: Predictors of a Complicated Course

High-Dose Methotrexate in Patients With Lymphoma: Predictors of a Complicated Course

Hepatorenal protective effects of protocatechuic acid in rats administered with anticancer drug methotrexate

A single-center qualitative study evaluating the safety and efficacy of a pharmacist-driven protocol for high-dose methotrexate management

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