“…About 25% of patients on long-term low-dose oral methotrexate develop some degree of toxicity that limits treatment (111-113), including myelosuppression (1%-10%) (112-120), elevated liver enzymes (10%-25%) (112,113,117, 120-123), and mucositis (5%-20%) (112,113,118). No AKI/CKD 5-15 (13,23,31-37,170,180,183,188,194,195,197,200,203,205-207, 209,210,212-216,221-224,227,230,232,235,237,245,250,268 Preexisting CKD (113,115,124,125), kidney failure (even after a single dose of 2.5 mg) (32, [126][127][128][129][130][131][132][133][134][135], or AKI during maintenance methotrexate therapy (113,(136)(137)(138) are major risk factors for developing toxicity. Other risk factors include length of exposure, weekly dosing, cumulative dose (111,115,137,139,140), and lack of folate supplementation (141).…”