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Kidney Week

Abstract: TH-OR37

Risk Factors for Nephrotoxicity with High-Dose Methotrexate (HDMTX) in Haematological Malignancies

Session Information

Category: Onco-Nephrology

  • 1500 Onco-Nephrology


  • O'Donoghue, Darragh, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Truong, Huong L., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Finnes, Heidi Diann, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • McDonald, Jennifer, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Leung, Nelson, Mayo Clinic Minnesota, Rochester, Minnesota, United States

HDMTX is a key component for treatment of haematological malignancy. Nephrotoxicity remains a significant risk factor for HDMTX and therefore, hyper-hydration and urinary alkalinisation are employed to optimise excretion but despite these measures, nephrotoxicity remains 2-12%. Determination of risk factors is key in order to further stratify and ameliorate the risk of acute kidney injury.


A retrospective review of the electronic medical record was conducted to identify patients with leukaemia or lymphoma who received HDMTX from 1/1/2002 to 12/31/18. We characterised the incidence of AKI, using the acute kidney injury network criteria, and the time to AKI. We assessed key baseline demographics, underlying malignancy, delivered MTX dose, and previous nephrotoxicity. Significant factors on univariate analysis were further assessed on Multivariate analysis. Analysis was performed on Minitab.


We identified 3091 cycles of HDMTX with lymphoma accounting for 90.7% of cases. The incidence of AKI was 19.1% in the lymphoma cohort and 13.6% in the leukaemia cohort (p=0.023). The median time to AKI grade shortened with higher severity of AKI (p<0.001). In those with AKI N3, creatinine increased to this level in a median time of 1 day. All patients requiring dialysis (n=7) developed an AKI at day 1 post HDMTX. Univariate analysis revealed age (p=0.022), Gender (p<0.001), higher BSA (p<0.001), type of malignancy (p=0.023), nephrotoxicity on previous dose (p<0.001), cycle number (p<0.001), GFR by Cockcroft-Gault (p=0.016) and 48-hour MTX level (p<0.001). There was no association between AKI and MTX dose (p=0.225), or GFR by MDRD (p=0.497). Multivariate analysis revealed increased age (p<0.001), male Gender (p<0.001), Lymphoma (p=0.002), previous AKI (p<0.001), cycle number (p=0.032), and 48-hour MTX level (p<0.001) to be significant risk factors for nephrotoxicity.


Nephrotoxicity remains a significant complication with HDMTX despite current prevention measures. High grade AKI occurs early post HDMTX and therefore, risk stratification is vital. Our study identified key risk factors as older, male, AKI on previous dose, diagnosis of lymphoma, elevated 48-hour MTX level and earlier cycle.