Dataset Information

Consensus Guideline for Use of Glucarpidase in Patients with High-Dose Methotrexate Induced Acute Kidney Injury and Delayed Methotrexate Clearance.

ABSTRACT: Acute kidney injury due to high-dose methotrexate (HDMTX) is a serious, life-threatening toxicity that can occur in pediatric and adult patients. Glucarpidase is a treatment approved by the Food and Drug Administration for high methotrexate concentrations in the context of kidney dysfunction, but the guidelines for when to use it are unclear. An expert panel was convened to provide specific, expert consensus guidelines for the use of glucarpidase in patients who develop HDMTX-induced nephrotoxicity and delayed methotrexate excretion. The guideline provides recommendations to identify the population of patients who would benefit from glucarpidase rescue by more precisely defining the absolute methotrexate concentrations associated with risk for severe or life-threatening toxicity at several time points after the start of an HDMTX infusion. For an HDMTX infusion ≤24 hours, if the 36-hour concentration is above 30 µM, 42-hour concentration is above 10 µM, or 48-hour concentration is above 5 µM and the serum creatinine is significantly elevated relative to the baseline measurement (indicative of HDMTX-induced acute kidney injury), glucarpidase may be indicated. After a 36- to 42-hour HDMTX infusion, glucarpidase may be indicated when the 48-hour methotrexate concentration is above 5 µM. Administration of glucarpidase should optimally occur within 48-60 hours from the start of the HDMTX infusion, because life-threatening toxicities may not be preventable beyond this time point.

Implications for practice

Glucarpidase is a rarely used medication that is less effective when given after more than 60 hours of exposure to high-dose methotrexate, so predicting early which patients will need it is imperative. There are no currently available consensus guidelines for the use of this medication. The indication on the label does not give specific methotrexate concentrations above which it should be used. An international group of experts was convened to develop a consensus guideline that was specific and evidence-based to identify the population of patients who would benefit from glucarpidase.

SUBMITTER: Ramsey LB

PROVIDER: S-EPMC5759822 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Consensus Guideline for Use of Glucarpidase in Patients with High-Dose Methotrexate Induced Acute Kidney Injury and Delayed Methotrexate Clearance.

Ramsey Laura B LB Balis Frank M FM O'Brien Maureen M MM Schmiegelow Kjeld K Pauley Jennifer L JL Bleyer Archie A Widemann Brigitte C BC Askenazi David D Bergeron Sharon S Shirali Anushree A Schwartz Stefan S Vinks Alexander A AA Heldrup Jesper J

The oncologist 20171027 1

Acute kidney injury due to high-dose methotrexate (HDMTX) is a serious, life-threatening toxicity that can occur in pediatric and adult patients. Glucarpidase is a treatment approved by the Food and Drug Administration for high methotrexate concentrations in the context of kidney dysfunction, but the guidelines for when to use it are unclear. An expert panel was convened to provide specific, expert consensus guidelines for the use of glucarpidase in patients who develop HDMTX-induced nephrotoxic ...[more]

PMID: 29079637

Similar Datasets

Project description:BackgroundSurvivors of acute kidney injury (AKI) are at a high risk for cardiovascular complications. An underrecognition of this risk may contribute to the low utilization of relevant guideline-based therapies in this population.ObjectiveWe sought to assess accordance with guideline-based recommendations for survivors of AKI with diabetes, coronary artery disease (CAD), and preexisting chronic kidney disease (CKD) in a post-AKI clinic, and identify factors that may be associated with guideline accordance.DesignRetrospective cohort study.SettingPost-AKI clinics at 2 tertiary care centers in Ontario, Canada.PatientsWe included adult patients seen in both post-AKI clinics between 2013 and 2019 who had at least 2 clinic visits within 24 months of an index AKI hospitalization.MeasurementsWe assessed accordance to recommendations from the most recent North American and international guidelines available at the time of study completion for diabetes, CAD, and CKD.MethodsWe compared guideline accordance between visits using the Cochran Mantel Haenszel test. We used multivariable Poisson regression to identify prespecified factors associated with accordance.ResultsOf 213 eligible patients, 192 (90%) had Kidney Disease Improving Global Outcomes Stage 2-3 AKI, 91 (43%) had diabetes, 76 (36%) had CAD, and 88 (41%) had preexisting CKD. From the first clinic visit to the second, there was an increase in angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACE-I/ARB) use across all disease groups-from 33% to 46% (P = .028) in patients with diabetes, from 30% to 57% (P = .002) in patients with CAD, and from 16% to 35% (P < .001) in patients with preexisting CKD. Statin use increased in patients with preexisting CKD from 64% to 71% (P = .034). Every 25 μmol/L rise in the discharge serum creatinine was associated with a 19% (95% confidence interval [CI], 8%-28%) and 12% (95% CI, 2%-21%) lower likelihood of being on an ACE-I/ARB in patients with diabetes and preexisting CKD, respectively.LimitationsThe study lacked a comparison group that received usual care. The small sample and multiple comparisons make false positives possible.ConclusionThere is room to improve guideline-based cardiovascular risk factor management in survivors of AKI, particularly ACE-I/ARB use in patients with an elevated discharge serum creatinine.

Dataset Information

Consensus Guideline for Use of Glucarpidase in Patients with High-Dose Methotrexate Induced Acute Kidney Injury and Delayed Methotrexate Clearance.

Implications for practice

Publications

Consensus Guideline for Use of Glucarpidase in Patients with High-Dose Methotrexate Induced Acute Kidney Injury and Delayed Methotrexate Clearance.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets