High-flux hemodialysis versus glucarpidase for methotrexate-associated acute kidney injury: What’s best?

Abstract

Kidney-related adverse drug effects from chemotherapeutic agents can cause acute kidney injury that may influence cancer treatment and patient outcomes. Many current chemotherapy drugs are associated with acute kidney injury, including methotrexate which causes dose-dependent tubular injury. In this review, we will focus on the manifestations of kidney disease secondary to methotrexate and discuss management strategies. In particular, we will review the use of high-flux hemodialysis versus glucarpidase for reducing toxic serum levels of methotrexate.

Keywords

Acute kidney injury acute tubular necrosis methotrexate leucovorin glucarpidase hemodialysis

Get full access to this article

View all access options for this article.

References

Farber

Diamond

LK.

Temporary remissions in acute leukemia in children produced by folic acid antagonist, 4-aminopteroyl-glutamic acid. N Engl J Med 1948; 238(23): 787–793.

Farber

Some observations on the effect of folic acid antagonists on acute leukemia and other forms of incurable cancer. Blood 1949; 4(2): 160–167.

Malaviya

AN.

Landmark papers on the discovery of methotrexate for the treatment of rheumatoid arthritis and other systemic inflammatory rheumatic diseases: a fascinating story. Int J Rheum Dis 2016; 19(9): 844–851.

Bertino

. Karnofsky memorial lecture. Ode to Methotrexate. J Clin Oncol 1993; 11: 5–14.

Berkowitz

Goldstein

Bernstein

MR.

Ten year’s experience with methotrexate and folinic acid as primary therapy for gestational trophoblastic disease. Gynecol Oncol 1986; 23: 111–118.

Maesta

Nitecki

Horowitz

et al . Effectiveness and toxicity of first-line methotrexate chemotherapy in low-risk postmolar gestational trophoblastic neoplasia: the New England Trophoblastic Disease Center experience. Gynecol Oncol 2018; 148: 161–167.

Barrera

Laan

van Riel

et al . Methotrexate-related pulmonary complications in rheumatoid arthritis. Ann Rheum Dis 1994; 53: 434–439.

Conway

Low

Coughlan

et al . Methotrexate use and risk of lung disease in psoriasis, psoriatic arthritis, and inflammatory bowel disease: systematic literature review and meta-analysis of randomised controlled trials. BMJ 2015; 350: h1269.

Fukuhara

Ikawa

Morikawa

et al . Population pharmacokinetics of high-dose methotrexate in Japanese adult patients with malignancies: a concurrent analysis of the serum and urine concentration data. J Clin Pharm Ther 2008; 33: 677–684.

10.

Mikkelsen

Thorn

Yang

et al . PharmGKB summary: methotrexate pathway. Pharmacogenet Genom 2011; 21: 679–686.

11.

Widemann

Adamson

PC.

Understanding and managing methotrexate nephrotoxicity. Oncologist 2006; 11: 694–703.

12.

Widemann

Sung

Anderson

et al . Pharmacokinetics and metabolism of the methotrexate metabolite 2, 4-diamino-N(10)-methylpteroic acid. J Pharmacol Exp Ther 2000; 294: 894–901.

13.

Wall

Johansen

Molony

et al . Effective clearance of methotrexate using high-flux hemodialysis membranes. Am J Kidney Dis 1996; 28: 846–854.

14.

Ramsey

Balis

O’Brien

et al . Consensus guideline for use of glucarpidase in patients with high-dose methotrexate induced acute kidney injury and delayed methotrexate clearance. Oncologist 2018; 23(1): 52–61.

15.

Kawase

Yamamoto

Egashira

et al . Stereoselective inhibition of methotrexate excretion by glucuronides of nonsteroidal anti-inflammatory drugs via multidrug resistance proteins 2 and 4. J Pharmacol Exp Ther 2016; 356(2): 366–374.

16.

Mir

Ropert

Babinet

et al . Hyper-alkalinization without hyper-hydration for the prevention of high-dose methotrexate acute nephrotoxicity in patients with osteosarcoma. Cancer Chemother Pharmacol 2010; 66(6): 1059–1063.

17.

Jacobs

Stoller

Chabner

et al . 7-Hydroxymethotrexate as a urinary metabolite in human subjects and rhesus monkeys receiving high dose methotrexate. J Clin Invest 1976; 57: 534–538.

18.

Howard

McCormick

Pui

et al . Preventing and managing toxicities of high-dose methotrexate. Oncologist 2016; 21(12): 1471–1482.

19.

Seideman

Muller-Suur

Renal effects of aspirin and low dose methotrexate in rheumatoid arthritis. Ann Rheum Dis 1993; 52(8): 613–615.

20.

Hoekstra

Haagsma

Neef

et al . Bioavailability of higher dose methotrexate comparing oral and subcutaneous administration in patients with rheumatoid arthritis. J Rheumatol 2004; 31(4): 645–648.

21.

Widemann

Balis

Kim

et al . Glucarpidase, leucovorin, and thymidine for high-dose methotrexate-induced renal dysfunction: clinical and pharmacologic factors affecting outcome. J Clin Oncol 2010; 28(25): 3979–3986.

22.

Widemann

Balis

Kempf-Bielack

et al . High-dose methotrexate-induced nephrotoxicity in patients with osteosarcoma. Cancer 2004; 100(10): 2222–2232.

23.

Schwartz

Borner

Muller

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(11): 1299–1308.

24.

Kintzel

Dorr

RT.

Anticancer drug renal toxicity and elimination: dosing guidelines for altered renal function. Cancer Treat Rev 1995; 21(1): 33–64.

25.

Wilmanns

Sauer

Schalhorn

Biochemical control of high-dose methotrexate/leucovorin rescue therapy. Recent Results Cancer Res 1980; 74: 42–49.

26.

Ahmad

Shen

Bleyer

WA.

Methotrexate-induced renal failure and ineffectiveness of peritoneal dialysis. Arch Intern Med 1978; 138(7): 1146–1147.

27.

Diskin

Stokes

Dansby

et al . Removal of methotrexate by peritoneal dialysis and hemodialysis in a single patient with end-stage renal disease. Am J Med Sci 2006; 332(3): 156–158.

28.

Murashima

Adamski

Milone

et al . Methotrexate clearance by high-flux hemodialysis and peritoneal dialysis: a case report. Am J Kidney Dis 2009; 53(5): 871–874.

29.

Fujikura

Akiu

Miyauchi

et al . Blood purification therapies in methotrexate-induced acute kidney injury: four case reports. Renal Replacement Therapy 2017; 3: 6.

30.

Saland

Leavey

Bash

et al . Effective removal of methotrexate by high-flux hemodialysis. Pediatr Nephrol 2002; 17(10): 825–829.

31.

Widemann

Balis

Murphy

et al . Carboxypeptidase-G2, thymidine, and leucovorin rescue in cancer patients with methotrexate-induced renal dysfunction. J Clin Oncol 1997; 15(5): 2125–2134.

32.

Bleyer

WA.

Methotrexate: clinical pharmacology, current status and therapeutic guidelines. Cancer Treat Rev 1977; 4(2): 87–101.

33.

Buchen

Ngampolo

Melton

et al . Carboxypeptidase G2 rescue in patients with methotrexate intoxication and renal failure. Br J Cancer 2005; 92(3): 480–487.

34.

Widemann

Schwartz

Jayaprakash

et al . Efficacy of glucarpidase (carboxypeptidase g2) in patients with acute kidney injury after high-dose methotrexate therapy. Pharmacotherapy 2014; 34(5): 427–439.

35.

DeAngelis

Tong

Lin

et al . Carboxypeptidase G2 rescue after high-dose methotrexate. J Clin Oncol 1996; 14(7): 2145–2149.

36.

Hempel

Lingg

Boos

Interactions of carboxypeptidase G2 with 6S-leucovorin and 6R-leucovorin in vitro: implications for the application in case of methotrexate intoxications. Cancer Chemother Pharmacol 2005; 55: 347–353.

37.

Albertioni

Rask

Eksborg

et al . Evaluation of clinical assays for measuring high-dose methotrexate in plasma. Clin Chem 1996; 42: 39–44.

38.

BTG International, Inc. Voroxaze (package insert). Brent-wood, Tennessee: BTG International Inc., 2012.

39.

Christensen

Pauley

Molinelli

et al . Resumption of high-dose methotrexate after acute kidney injury and glucarpidase use in pediatric oncology patients. Cancer 2012; 118: 4321–4330.

40.

Krause

Weihrauch

Bode

et al . Carboxypeptidase-G2 rescue in cancer patients with delayed methotrexate elimination after high-dose methotrexate therapy. Leuk Lymphoma 2002; 43(11): 2139–2143.

41.

BTG International Inc. Voraxaze (Glucarpidase). Personal Correspondence ed. 2018, https://btgplc.com/en-US/Investors-Media/Press-Releases/View?press=Voraxaze%C2%AE-(glucarpidase)-Launched-in-the-US (accessed 19 February 2019).

42.

Scott

Zhou

Cheng

et al . Comparable efficacy with varying dosages of glucarpidase in pediatric oncology patients. Pediatr Blood Cancer 2015; 62(9): 1518–1522.

43.

Canadian Pharmaceutical Distribution Network. Personal Correspondence ed. 2018, https://cpdn.ca/ (accessed 19 February 2019).

44.

Flombaum

Liu

Yan

et al . Management of patients with acute methotrexate nephrotoxicity with high-dose leucovorin. Pharmacotherapy. Epub ahead of print 4 June 2018. DOI: 10.1002/phar.2145.

45.

Garcia

Leblond

Goldwasser

et al . [Renal toxicity of high-dose methotrexate]. Nephrol Ther 2018; 14(Suppl. 1): S103–S113.

46.

Wright

Panetta

Onar-Thomas

et al . Delayed methotrexate excretion in infants and young children with primary central nervous system tumors and postoperative fluid collections. Cancer Chemother Pharmacol 2015; 75: 27–35.

47.

Gwilt

The effect of malignant effusions on methotrexate disposition. Cancer Chemother Pharmacol 2002; 50(5): 373–382.

48.

Pauley

Panetta

Schmidt

et al . Late-onset delayed excretion of methotrexate. Cancer Chemother Pharmacol 2004; 54(2): 146–152.

49.

Evans

Pratt

CB.

Effect of pleural effusion on high-dose methotrexate kinetics. Clin Pharmacol Ther 1978; 23: 68–72.

50.

Fermiano

Bergsbaken

Kolesar

JM.

Glucarpidase for the management of elevated methotrexate levels in patients with impaired renal function. Am J Health Syst Pharm 2014; 71: 793–798.