Extended duration of prehydration does not prevent nephrotoxicity or delayed drug elimination in high-dose methotrexate infusions: A prospectively randomized cross-over study

Abstract

Extending prehydration beyond 4 hours does not reduce the risk of renal toxicity or delayed MTX clearance after infusions with HDMTX 5-8 g/m(2).

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

“…We demonstrated that children with higher MTX dosage are more likely to experience AKI, regardless of the risk group when adjusted with MTX dosage. In accordance with our study, Mikkelsen et al [15] reported that the occurrence rate of renal toxicity in patients treated with HDMTX 8 g/m 2 was significantly higher than that in 5 g/m 2 (40.0 vs. 18.5%). Lower serum protein and increasing age were also significant risk factors for MTX nephrotoxicity.…”

“…For example, renal functions in most courses of experienced AKI (70 out of 104) were not monitored within 48 h after the start of HDMTX infusion in this study. Since renal function usually decreases greatly within 36 h after the start of HDMTX infusion [15], it is meaningful to explore the 48-h plasma MTX concentration for prediction of AKI in these children. Our results showed that the occurrence of AKI was significantly related to an elevated plasma MTX concentration after starting the infusion, and revealed that a 48-h plasma MTX concentration > 1.20 μmol/L is a good indicator for the prediction of AKI in such patients.…”

Assessment of renal function during high‐dose methotrexate treatment in children with acute lymphoblastic leukemia

“…PCr was found to increase after 0.02% (28/1,164) of the MTX courses, which is in accordance with the present results. Mikkelsen et al showed a dose‐dependent increase in PCr in 47 children with ALL or non‐Hodgkin lymphoma after HD‐MTX. PCr was increased >50% in 18.5% of the patients after 5 g/m 2 HD‐MTX infusion and in 40.0% of the patients after 8 g/m 2 infusion.…”

Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy

“…Nearly all patients will subsequently tolerate full-dose HD-MTX without recurrent nephrotoxicity 127, 128 . Higher doses of folinic acid, adjusted by the plasma MTX levels, are essential to limit the risk of life-threatening myelosuppression and mucositis, but whether over-rescue could increase the risk of relapse remains an unsolved challenge 131– 133 . In cases with extremely delayed MTX clearance, glucarpidase may be helpful to degrade MTX by enzymatic cleavage to 2,4-diamino-N10-methyl-pteroic acid (DAMPA) and glutamate 127, 128 , but it does not promote restoration of renal function.…”