Diabetes is a risk factor for high-dose methotrexate-associated AKI in lymphoma patients

The aim of the study was to investigate the incidence of acute kidney injury (AKI) occurring after high-dose methotrexate (HDMTX) administration and the role of type 2 diabetes (T2D) playing in the occurrence of AKI.

We assessed associations between T2D along with other confounding factors mainly including baseline estimated glomerular filtration rate (eGFR), methotrexate (MTX) elimination and urine pH, and AKI occurrence. Patients who were diagnosed as primary central nervous system lymphoma with treatment of HDMTX and with eGFR ≥60 mL/min/1.73 m² were enrolled in this study.

Of the 507 courses enrolled in this study, 132 courses have T2D. Lower baseline eGFR, delayed MTX elimination, lower urine pH, and higher incidence of AKI were observed in T2D group. Using univariate logistic regression, several confounding factors including baseline eGFR, hypertension, MTX elimination, and urine alkalinization statistically and clinically important were screened out. After adjusting for these factors, T2D remained an independent association with AKI occurrence. AKI outcome had no significant relationship with severe hematological toxicity or hepatotoxicity. AKI was associated with faster eGFR decline after a series of HDMTX treatment courses.

Patients with T2D have a higher sensitivity to AKI when administrated with HDMTX. This conclusion addresses safety concerns for making chemotherapy regimen for this population.