scholarly journals Renal failure after high-dose methotrexate in a child homozygous for MTHFR C677T polymorphism

2008 ◽  
Vol 50 (1) ◽  
pp. 154-156 ◽  
Author(s):  
Rita Turello ◽  
Katharina Rentsch ◽  
Ermindo Di Paolo ◽  
Maja Beck Popovic
Keyword(s):  
Renal Failure ◽  
Mthfr C677t ◽  
High Dose ◽  
High Dose Methotrexate ◽  
C677t Polymorphism ◽  
Mthfr C677t Polymorphism ◽  
Dose Methotrexate

Associations of Methylene Tetrahydrofolate Reductase Polymorphism and Methotrexate-Related Toxicities in Korean Treated for Malignant Lymphoma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1607-1607
Author(s):  
Hyangmin Park ◽  
Dok Hyun Yoon ◽  
Youngcheon Song ◽  
Heese Kim ◽  
Youngseol Huh ◽  
...  
Keyword(s):  
Mthfr C677t ◽  
P Value ◽  
High Dose ◽  
Close Monitoring ◽  
High Dose Methotrexate ◽  
C677t Polymorphism ◽  
Mutant Genotype ◽  
Methylene Tetrahydrofolate Reductase ◽  
Dose Methotrexate ◽  
Methylene Tetrahydrofolate

Abstract Abstract 1607 Methotrexate is an antifolate agent commonly used for the treatment of lymphoma. The most common adverse effects include mucositis, myelosuppression, hepatic dysfunction and renal toxicities. It inhibits DNA replication by blocking the conversion of 5,10-methylene tetrahydrofolate to 5-methylene tetrahydrofolate by methylene tetrahydrofolate reductase (MTHFR). MTHFR is a key enzyme in folate metabolism and C677T is one of principal polymorphisms implicated in the metabolism of methotrexate. We aimed to investigate the relationship of the C677T polymorphism with methotrexate concentration in serum as well as methotrexate-associated toxicities. The study cohort included 169 cases treated with regimens containing high dose methotrexate (higher than 1 g/m2) between January 2010 and May 2011. Median age of the patients was 56 years (range, 24–78 years). Concentration of methotrexate was measured daily beginning 48 hours after infusion until the concentration reaches below 0.05 μmol/L. Forty four cases (26.0%) had a wild genotype of CC, 78 (46.2%) a heterozygous genotype of CT, and 47 (27.8%) a homozygous mutant genotype of TT. Mutant cases of TT had significantly higher MTX serum levels when compared with the other genotypes (Table 1) and required significantly longer time for elimination of methotrexate (p=0.011, Table 2). While hematologic toxicities, hepatotoxicities or number of febrile neutropenic episodes did not differ according to the genopypes, TT genotypes had significantly higher MTX levels and higher incidence of nephrotoxicity. Among them, two required therapeutic plasma exchange for prolonged exposure to high levels of methotrexate. Table 1. Concentration of methotrexate at different time points 48 h 72 h 96 h 120 h Wild-type (CC) 0.38 ± 0.47 0.15 ± 0.20 0.08 ± 0.12 0.09 ± 0.10 Heterozygous type (CT) 0.32 ± 0.46 0.12 ± 0.20 0.08 ± 0.11 0.07 ± 0.10 Mutant type (TT) 1.93 ± 5.84 0.92 ± 2.39 0.67 ± 1.25 0.59 ± 0.83 p-value 0.020 0.011 0.002 0.006 * Data expressed as mean ± SEM Table 2. Duration (days) to serum concentration of methotrexate < 0.05 μmol/L MTHFR C677T CC CT TT p-value Duration until methotrexate level < 0.05 μmol/L (days) 4.89 ± 2.95 4.35 ± 2.05 7.66 ± 9.00 0.011 * Data expressed as mean ± SEM Table 3. MTHFR polymorphisms vs. grade 3/4 toxicities Grades 3/4 toxicity MTHFR C677T CC (%) CT (%) TT (%) p-value Hb 27.3 17.9 34.0 0.431 WBC 52.3 61.5 53.2 0.950 PLT 45.5 51.3 53.2 0.465 AST 2.3 10.3 8.5 0.277 ALT 11.4 11.5 10.6 0.911 Total bilirubin 6.8 1.3 4.3 0.532 Creatinine* 0 1.3 10.6 0.006 ANC 47.7 62.8 68.1 0.050 FN episodes** 31.8 37.2 42.6 0.291 Mucositis 15.9 14.1 17.0 0.650 * grade 2 toxicity ** Adverse event positive Our data shows that cases with TT genotype for the MTHFR C677T polymorphism are associated with methotrexate-related renal toxicities. When high dose methotrexate is administered to the patients with TT genoptype, close monitoring for the nephrotoxicity seems to be required. Disclosures: No relevant conflicts of interest to declare.

Successful rescue with leucovorin and thymidine in a patient with high-dose methotrexate induced acute renal failure

2001 ◽  
Vol 47 (6) ◽  
pp. 537-540 ◽  
Author(s):  
Desirée van den Bongard ◽  
Ron Mathôt ◽  
Willem Boogerd ◽  
Jan Schornagel ◽  
Marcel Soesan ◽  
...  
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate

Significant interaction between high-dose methotrexate and high-dose piperacillin-tazobactam causing reversible neurotoxicity and renal failure in an osteosarcoma patient

2020 ◽  
pp. 107815522095387 ◽  
Author(s):  
Irene Krämer ◽  
Jelena Rosentreter ◽  
Marius Fried ◽  
Michael Kühn
Keyword(s):  
Renal Failure ◽  
Significant Interaction ◽  
Rescue Therapy ◽  
Pharmacokinetic Interaction ◽  
Serum Levels ◽  
Calcium Folinate ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Medicinal Products ◽  
Dose Methotrexate

Introduction Pharmacokinetic interaction of high-dose methotrexate (MTX) and other concomitantly administered renally secreted medicinal products may lead to insufficient methotrexate serum level decrease and significant MTX toxicity. Case report We report the case of an 18-year-old male patient treated with high-dose MTX for an osteosarcoma and with high-dose piperacillin-tazobactam at the same time. MTX serum levels were severely elevated 24 hours after the MTX infusion and did not decrease in accordance with the specific calcium folinate rescue protocol. The patient experienced renal failure accompanied by neurological symptoms, most consistent with MTX-related renal and CNS toxicity. Management and outcome: After discontinuation of piperacillin-tazobactam, intensified calcium folinate rescue therapy, and IV hydration, the MTX serum levels decreased appropriately, and toxicity symptoms resolved. Discussion Severe MTX-related toxicity, caused by drug-drug interaction, suggests that the concomitant use of high-dose MTX and high-dose piperacillin-tazobactam should be avoided generally.

scholarly journals Acute Renal Failure after High-Dose Methotrexate Therapy

Nephron ◽  
1989 ◽  
Vol 51 (3) ◽  
pp. 416-417 ◽  
Author(s):  
F.X. Thierry ◽  
I. Vernier ◽  
J.M. Dueymes ◽  
H. Roche ◽  
P. Canal ◽  
...  
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Methotrexate Therapy ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate
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