AKI in Cancer

An Oncologic Emergency

An estimated 2-12% of patients who receive high-dose methotrexate (HDMTX) chemotherapy will experience delayed clearance due to acute kidney injury (AKI), creating an oncologic emergency.1
Patients who survive an AKI episode have2:
  • Double the risk of death
  • Triple the risk of end-stage renal disease
  • Ten times the risk of developing incident or progressive chronic kidney disease
The rate of cardiovascular events in AKI patients is as high as 22%, and mortality related to cardiovascular events is 33% in patients with AKI.2

Inadequate Elimination of MTX Due to Impaired Renal Function Increases the Risk of Severe Toxicities3:

When renal dysfunction occurs and other toxicities are present, standard doses of leucovorin may no longer be an effective rescue intervention.4
Grade 3-4 toxicities post-HDMTX in 43 patients with delayed MTX clearance due to impaired renal function3
Toxicity Patients, n (%)
Hematological 26 (60%)
Mucositis 15 (35%)
Renal 8 (19%)
Liver 7 (16%)
CNS 6 (14%)
Skin 1 (2%)

Assessing the Risk of Acute Kidney Injury

There are many factors associated with MTX that can increase the risk of AKI, including1:
  • Dose and schedule of MTX
  • Preexisting renal insufficiency
  • Host factors including patient age and cancer type
Types of tumors* associated with higher risk of AKI5-8
Tumor types Incidence of AKI
Osteosarcoma (N=3887) 1.8%
Pediatric acute lymphoblastic leukemia (N=445) 3.3%
Adult acute lymphoblastic leukemia (n=31) 6.4%
Primary CNS lymphoma (n=154) 3%-7%
*Tumor types included acute lymphoblastic leukemia, lymphoma, CNS lymphoma germ cell tumor, and osteosarcoma.

Renal Toxicity Is Common in Patients With Lymphoma and Leukemia

The incidence of renal toxicity in lymphoma and leukemia patients remains underappreciated. A 2014 retrospective analysis of lymphoma patients found that9:
  • Nearly 10% of lymphoma patients treated with HDMTX experienced renal toxicity
  • 31.9% of lymphoma patients experienced delayed MTX elimination
  • Renal toxicity resulted in significantly longer hospital stays
Comparison of incidence of HDMTX-mediated renal toxicity and delayed MTX elimination in patients with lymphoma9
Bar chart comparing incidence of complications of lymphoma and sarcoma

Trust Voraxaze® for Rapid, Nonrenal Elimination of MTX4

It may not be possible to predict who will experience kidney injury or failure during HDMTX treatment. Only Voraxaze® reduced plasma MTX levels by >97% within 15 minutes.10

References

  1. Voraxaze® [prescribing information]. BTG International Inc; 2013.
  2. Howard SC, et al. Preventing and managing toxicities of high-dose methotrexate. The Oncologist 2016; 21:1-12.
  3. Widemann BC, Balis FM, Kim A, et al. Glucarpidase, leucovorin, and thymidine for high-dose methotrexate-induced renal dysfunction: clinical and pharmacologic factors affecting outcome. J Clin Oncol. 2010; 28:3979-3986.
  4. 2013 Annual Meeting of the North American Congress of Clinical Toxicology (NACCT), Clinical Toxicology 2013; 51(7):575-724. doi:10.3109/15563650.2013.817658.
  5. Ramsey L, Balis FM, O’Brien MM, et al. Consensus guidelines for use of glucarpidase in patients with high-dose methotrexate induced acute kidney injury and delayed methotrexate clearance. Durham, NC. The Oncologist. 2017 Oct 27. doi: 10.1634/theoncologist.2017-0243
  6. Widemann BC, Adamson PC. Understanding and managing methotrexate nephrotoxicity. Oncologist. 2006;11:694-703
  7. Schwartz S, Borner K,Müller K, et al. Glucarpidase (carboxypeptidase G2) intervention in adult and elderly cancer patients with renal dysfunction and delayed methotrexate elimination after high-dose methotrexate therapy. Oncologist. 2007;12:1299-1308.
  8. Widemann BC, Balis FM, Kempf-Bielack B, et al. High-dose methotrexate-induced nephrotoxicity in patients with osteosarcoma. Cancer. 2004;100:2222-2232
  9. Data on file. BTG International Inc. 2012.
  10. de Miguel D, García-Suárez J Martín Y, Gil-Fernández JJ, Burgaleta C. Severe acute renal failure following high-dose methotrexate therapy in adults with haematological malignancies: a significant number result from unrecognized co-administration of several drugs. Nephrol Dial Transplant. 2008;23:3762-3766.
  11. Jahnke K, Korfel A, Martus P, et al; on behalf of the German Primary Central Nervous System Lymphoma Study Group (G-PCNSL-SG). High-dose methotrexate toxicity in elderly patients with primary central nervous system lymphoma. Ann Oncol. 2005;16:445-449
  12. Flombaum C, Meyers P. High-dose leucovorin as sole therapy for methotrexate toxicity. Journal of Clinical Oncology 1999; 17(5): 1589-1594.
  13. Murashima M, et al. Methotrexate clearance by high-flux hemodialysis and peritoneal dialysis: a case report. Am J Kidney Dis 2009; 53:781-874.
  14. Wall S, Johansen M, et al. Effective clearance of methotrexate using high-flux hemodialysis membranes. Am J Kidney Dis 1996; 28(6):846-854.
  15. Dart RC, Goldfrank LR, Erstad BL, et al. Expert consensus guidelines for stocking of antidotes in hospitals that provide emergency care. Ann Emerg Med. 2018;71(3):314-325.
  16. Green JM. Glucarpidase to combat toxic levels of methotrexate in patients. Ther Clin Risk Manag. 2012;8:403-4
  17. Glucarpidase (Voraxaze®) National Drug Monograph and Considerations for Use. U.S. Department of Veterans Affairs website. 2014. http://www.pbm.va.gov/clinicalguidance/drugmonographs/Glucarpidase_ Drug_Monograph_and_Considerations_for_Use.doc. Published June 2014. Accessed November 04, 2016.
  18. Leucovorin [prescribing information]. Bedford Laboratories; 2011.