Age and baseline creatinine as risk factors for methotrexate
nephrotoxicity in children with acute lymphoblastic leukemia in
resource-limited countries
Abstract
Introduction. The search for risk factors for high-dose methotrexate
(MTX)–induced nephrotoxicity in children with acute lymphoblastic
leukemia (ALL) has been complex in the context of resource-limited
countries where serum levels of MTX are not always available. Objective.
To analyze the demographic, clinical, and biochemical factors associated
with MTX-induced nephrotoxicity in children with ALL. Methodology.
Case-control study in children with ALL from a General Hospital in
Mexico over a four-year period (2016-2020). Kidney damage was defined
with KDIGO criteria and the following variables were analyzed: sex, age,
weight, height, creatinine, urea, transaminases, hematic cytometry,
vomiting, mucositis, dermatitis, and number of MTX applications.
Results: One hundred and eight children were studied, 22 females (38%)
and 36 males (62%), ages 1 to14 years. The incidence of nephrotoxicity
was 5.8% in 238 events of MTX administration. The children in the group
with nephrotoxicity were older (average age 9.5 vs 5, p = 0.036), had
higher baseline creatinine (0.5 mg/dL vs 0.4 mg/dL p = 0.006), and had
lower baseline hemoglobin (10.1 g/dL vs 11.3 g/dL, p = 0.034). Mucositis
was associated with nephrotoxicity with OR 13 95% CI 4-42, p
<0.001. A cut-off value for creatinine of 0.44 mg/dL (AUC of
68%) and an age of 8 years (AUC of 64%) were identified for risk of
nephrotoxicity. Conclusions: The incidence of MTX nephrotoxicity in
children with ALL was 5.8%, with a high association with mucositis. The
risk is greater for children older than 8 years and baseline creatinine
higher than 0.44 mg/dL.