HDCN Abstract:  ASN Annual Meeting 2020 -- Digital Meeting  

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


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.

c Copyright 2020 -2021 American Society of Nephrology. Reproduced with permission.
All ASN abstracts from the 2020 Annual Meeting are available at this link and also are archived in .pdf form at ASN-Online.org

Disclaimer: Abstracts often have errors, both typographical and otherwise. This posting is an electronic translation of submitted abstracts which has not been verified against the original submitted abstract nor with the authors for accuracy. As a result, there may be errors, especially with regard to drug doses, but not limited to these. Abstracts undergo only limited review, and data often are changed as a result of the peer review process, so their reliability is less than manuscripts published in peer-reviewed journals. In using these summaries, you are agreeing that you are aware of these limitations.

The materials are provided on an as-is basis without any warranty of any kind, either express or implied. In addition to errors, the information presented may be incomplete or outdated. The information contained is not intended nor recommended as a substitute for professional medical advice. You are advised to check the appropriate medical literature and the product information currently provided by the manufacturer of each device to be used or drug to be administered to verify the dosage, the method and duration of administration, or contraindications. It is the responsibility of the treating physician or other health care professional, relying on independent experience and knowledge of the patient, to determine drug, disease, and the best treatment for the patient.

To the fullest extent permitted by law, HDCN, ASN and their affiliates and suppliers disclaim all warranties, express or implied, including, but not limited to, any warranty of merchantability, non- infringement or fitness for a particular purpose.

In no event shall HDCN, ASN, or their affiliates or suppliers be liable for any damages whatsoever (including, but not limited to, direct, indirect, incidental, consequential, punitive or exemplary damages, or any damages for loss of profits, use, data, goodwill or other intangibles) arising from or in any way relating to these terms, the materials, or any information, goods or services obtained from or referred to in the materials, whether based on warranty, contract, tort (including, but not limited to, negligence), or any other legal theory, and whether or not any or all of the limited entities is advised of the possibility of such damages.