ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005


The Latest on Twitter

Kidney Week

Abstract: PO2183

High-Dose Methotrexate (HDMTX) and Nephrotoxicity: Effect on Subsequent Dosing

Session Information

  • Onco-Nephrology - 1
    October 22, 2020 | Location: On-Demand
    Abstract Time: 10:00 AM - 12:00 PM

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 an important part of various chemotherapeutic protocols due to its central nervous system penetrance. A key complication of HDMTX is nephrotoxicity as this leads to delayed MTX excretion and further morbidity. Nephrotoxicity in a previous cycle of HMDTX leads to an increased risk of future toxicity. Our aim was to establish how nephrotoxicity affected clinical decision making with regards to future dosing


A retrospective review of the electronic medical record was perfoemd to identify patients who developed nephrotoxicity post HDMTX from 1/1/02 to 12/31/18. We stratified the effect of nephrotoxicity by grade of AKI, according to the acute kidney injury network criteria, on resumption of MTX. In those who received a subsequent dose, we assessed whether a dose reduction have an impact on rate of Nephrotoxicity. Analysis was performed in Minitab.


We identified 670 episodes of nephrotoxicity which equated to an overall incidence rate of 19% of total cycles. The majority were AKI grade 1 (79.7%). Higher grade AKI were significantly less likely to receive a future dose (p<0.001), with 71.3% of AKI N1, 59.2% of AKI N2, and 21.2% of AKI N3. Other factors associate with future dosing included elevated 48-hour MTX level (p<0.001), admission to ICU (p<0.001), and prolonged Hospital LOS (P=0.009). 449 patients received a future dose of Methotrexate with 152 (33.9%) receiving a reduced dose. The overall incidence of AKI with subsequent dosing was 33.85%. The incidence of AKI in subsequent dosing was 35.5% with no dose reduction compared to 30.3% with a dose reduction (p=0.29) (see table 1 for breakdown).


Nephrotoxicity had an important impact on subsequent dosing, especially with higher grade AKI. Previous AKI infers a higher rate of nephrotoxicity in future dosing with no significant reduction in incidence with reduction in MTX dose. Given the retrospective nature of the data and the many complexities to dosing calculation, this should be further explored with a prospective study.

Effect on dose reduction on subsequent AKI
No dose reduction
196 (64.5%)89 (29.3%)18 (5.9%)1 (0.3%)304
Dose reduction101 (69%)37 (25.5%)6 (4.1%)1 (0.7%)