A pharmacologically-based approach to high dose methotrexate administration to investigate nephrotoxicity and acute kidney injury biomarkers in children and adolescents with newly diagnosed osteosarcoma

2021 ◽  
Author(s):  
Elizabeth Fox ◽  
Christine Busch ◽  
Alexander DeBernardo ◽  
Blair Segers ◽  
Joseph Gottschalk ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Children And Adolescents ◽  
Kidney Injury ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Newly Diagnosed ◽  
Dose Methotrexate

Identification of Risk Factors in High-Dose Methotrexate-Induced Acute Kidney Injury in Childhood Acute Lymphoblastic Leukemia

Chemotherapy ◽  
2018 ◽  
Vol 63 (2) ◽  
pp. 100-106 ◽  
Author(s):  
Dao-Hai Cheng ◽  
Hua Lu ◽  
Tao-Tao Liu ◽  
Xiao-Qin Zou ◽  
Hui-Mei Pang
Keyword(s):  
Risk Factors ◽  
Acute Kidney Injury ◽  
Logistic Regression ◽  
Lymphoblastic Leukemia ◽  
Kidney Injury ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Baseline Serum ◽  
Childhood All ◽  
Dose Methotrexate

Aims: Although high-dose methotrexate (HDMTX) is an effective means for the treatment of acute lymphoblastic leukemia (ALL), the development of renal dysfunction remains a significant management challenge. This study aimed to identify the key factors in HDMTX-induced acute kidney injury (AKI) in childhood ALL. Methods: We retrospectively analyzed the clinical data in 1,329 courses of HDMTX treatment in 336 Chinese ALL children at the First Affiliated Hospital of Guangxi Medical University from September 2012 to November 2016. The clinical data were compared between the groups of children with development of AKI and those without. Risk factors were identified by multiple logistic regression analysis, and the diagnostic performance of plasma MTX concentration was evaluated by receiver operating characteristic (ROC) curve analysis. Results: AKI was observed in 88 patients (26.2%) and 104 courses (7.8%). Binary logistic regression revealed that age (OR 1.349; p = 0.005), first HDMTX course (OR 1.767; p = 0.013), MTX dose per body surface area (BSA; OR 1.944; p = 0.015), and baseline serum total protein (OR 0.929; p = 0.021) significantly correlated with AKI. The area under the ROC for 48-h plasma MTX concentration was 0.890 (95% CI 0.850–0.930), and sensitivity and specificity values of the cut-off value were 78.8 and 90.4%, respectively. Conclusion: Increasing age, higher MTX dose per BSA, lower baseline serum protein, and first HDMTX course were significant risk factors for developing HDMTX-induced AKI in childhood ALL. The threshold of 48-h MTX plasma concentration is valuable for the prediction of HDMTX-induced AKI.

Risk factors for high‐dose methotrexate associated acute kidney injury in patients with hematological malignancies

2020 ◽  
Vol 38 (4) ◽  
pp. 584-588
Author(s):  
Irina Amitai ◽  
Uri Rozovski ◽  
Reem El‐Saleh ◽  
Shai Shimony ◽  
Daniel Shepshelovich ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Kidney Injury ◽  
Hematological Malignancies ◽  
Kidney Injury ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate

Toxicity of high-dose methotrexate administration at the Sidney Kimmel Cancer Center (SKCC): A retrospective review to guide establishment of an outpatient treatment program.

2020 ◽  
Vol 38 (29_suppl) ◽  
pp. 30-30
Author(s):  
Kelsey Sokol ◽  
Kelley Yuan ◽  
Katlin Fendler ◽  
Samantha Burdette ◽  
Patricia Galanis ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Treatment Group ◽  
B Cell ◽  
Retrospective Review ◽  
Kidney Injury ◽  
Cost Of Care ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Cns Prophylaxis ◽  
Dose Methotrexate

30 Background: High-dose methotrexate (HDMTX) is administered for the treatment of primary central nervous system (CNS) lymphoma (PCNSL), leptomeningeal metastases, and osteosarcoma, as well as CNS prophylaxis in patients with high-risk lymphoma and leukemia. Treatment is typically administered in an inpatient setting to enable aggressive hydration, urinary alkalinization, and frequent lab monitoring given the risk of acute kidney injury. Multiple pediatric centers have published experiences with outpatient administration of HDMTX. We aim to determine the toxicity rate in adult patients at SKCC receiving HDMTX to identify a population in which to pilot an outpatient HDMTX program. Methods: We performed a retrospective review of all patients receiving inpatient HDMTX at SKCC between January 1, 2018 and October 31, 2019. Results: Seventy-three patients (52% male) with median age of 60 years (range 22-81) received 255 cycles total of HDMTX. Diagnoses include PCNSL/vitreoretinal lymphoma (n=22), diffuse large B-cell lymphoma (n=17), B-cell acute lymphoblastic leukemia (n=16) and other diagnoses (n= 18). Thirty-one cycles were administered as CNS prophylaxis and 224 cycles as treatment, with a median prophylactic dose of 3.5 g/m2 (range 1-3.5) and median treatment dose of 3.5 g/m2 (range 0.25-12). The most common toxicity was acute kidney injury at a median day 3 of the cycle (range 1-7). See the table for details. Conclusions: Acute kidney injury occurred more often in the treatment group compared to prophylaxis group. Of all patients with AKI in the treatment group, 45% had a diagnosis of PCNSL. In the prophylactic group, only 21% of patients (3/14) experienced AKI of which all resolved. Of all AKI events, 90% were Grade 2 and 90% resolved. Based on these results, we plan to pilot an outpatient HDMTX program in patients receiving prophylactic HDMTX to determine its effect on patient quality of life and cost of care. [Table: see text]

Acute kidney injury associated with high dose methotrexate

2019 ◽  
Vol 4 (1-2) ◽  
pp. 64-65 ◽  
Author(s):  
Omar Mamlouk ◽  
Wut yi Hninn ◽  
Sreedhar Mandayam ◽  
Biruh Workeneh
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Injury ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate

scholarly journals Recovery of methotrexate-induced anuric acute kidney injury after glucarpidase therapy

2017 ◽  
Vol 5 ◽  
pp. 2050313X1770505 ◽  
Author(s):  
James Harms ◽  
Ayaz Khawaja ◽  
Maria Taylor ◽  
Xiaosi Han ◽  
Michal Mrug
Keyword(s):  
Acute Kidney Injury ◽  
Renal Function ◽  
Rescue Therapy ◽  
Kidney Injury ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
Renal Function Recovery ◽  
Function Recovery ◽  
Lethal Complications

Objectives: This case report describes two cases of high-dose methotrexate–induced nephrotoxicity: death in the case of conventional supportive care and successful renal function recovery in a patient treated with glucarpidase and continuous dialysis. Methods: High dose methotrexate is widely used for management of adult and pediatric malignancies. However, high-dose methotrexate–induced renal nephrotoxicity may cause severe, even lethal complications. Here we present examples of such outcomes. Results: We present one case of lethal high-dose methotrexate nephrotoxicity in a patient treated with conventional rescue therapy. We contrast this outcome with another patient with high-dose methotrexate–induced anuric acute kidney injury, who has recovered renal function following therapy with glucarpidase and continuous dialysis. Conclusions: This is only the second reported case of high-dose methotrexate–induced anuric acute kidney injury, and the only one with a reported clinical outcome. This first report of recovery from high-dose methotrexate–induced anuric acute kidney injury after glucarpidase administration supports available evidence pointing to the effectiveness of this therapy.

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