O’Donoghue D, Truong HL, Finnes HD, et al.
Risk Factors for Nephrotoxicity with High-Dose Methotrexate (HDMTX) in
Haematological Malignancies
ASN Annual Meeting 2020 -- Digital Meeting
J Am Soc Nephrol
(Oct) 31:11A 2020

BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSION
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.

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