Obesity Linked to Acute Kidney Injury After HDMTX for Hematologic Cancer

Some patients with hematologic cancer and obesity are at higher risk of acute kidney injury (AKI) after receiving high-dose methotrexate (HDMTX) in the outpatient setting, suggesting a differential drug clearance and the need for guidelines specific to obese patients. These results were published in Hematology, Transfusion and Cell Therapy

HDMTX (500 mg/m² or higher) is a key part of chemotherapy regimens for the treatment of hematologic cancers; however, AKI is a major drug-induced toxicity that can result in critical organ damage and death when not detected early and treated. 

Therefore, HDMTX is administered in the hospital allowing for postadministration monitoring. But in resource-poor areas, it is administered in the outpatient clinic without drug monitoring. 

This retrospective study of 302 patients was conducted to review the toxicity data after outpatient administration of HDMTX without drug monitoring. Data were from patients aged 16 years and older with a hematologic cancer who had received at least 1 infusion of HDMTX without drug-level monitoring during a 10-year period. A total of 840 infusions were administered, with a median 2 infusions per patient. 

Hospitalization was reported in 8.6% of the patients, and 25 patients experienced AKI after HDMTX administration, which correlated to 3% of the infusions and 8.3% of the patients. The most common diagnoses in the patients with AKI was HIV-associated Burkitt lymphoma (28%) and diffuse large B-cell lymphoma (28%).

Baseline factors related to AKI after administration of HDMTX included age (older than 44 years), body surface area 1.76 m² and greater, and body mass index (BMI) 23.8 kg/m² and higher, as well as estimated glomerular filtration rate (eGFR) and thrombocytopenia (more than 150×10⁹/L). 

Additionally, only 9 of the 25 patients with AKI had their methotrexate serum level measured at the event. This demonstrates low clinician awareness of this complication, explained the researchers. They also noted that thrombocytopenia, neutropenia, and hyperbilirubinemia grade 3 or higher were found in 36%, 64% and 36% of patients, respectively, and 22 of the 25 patients required hospitalization. 

The findings indicated that age, BMI, eGFR, and baseline thrombocytopenia were statistically significant for AKI, but the strongest correlation was with BMI. The researchers wrote that this highlights the need for more studies on methotrexate pharmacokinetics, especially in overweight patients. 

“Our data showed a similar rate of AKI after HDMTX to that reported in the literature, even without drug monitoring,” the researchers wrote in conclusion. “However, patients who developed AKI in our cohort fared worse than expected, with more hospitalizations and deaths. A higher BMI was associated with [methotrexate]-induced AKI in our cohort suggesting a differential drug clearance and the need for specific guidelines for obese patients. Careful selection for this procedure is warranted.”