[Renal toxicity of high-dose methotrexate].

Abstract

INTRODUCTION:

High-dose methotrexate (at least 1g/m2) is used to treat haematologic malignancies and osteosarcomas. Acute kidney injury is a well-known adverse-event after high-dose methotrexate and may lead to delayed drug elimination. Besides usual therapeutics (hyperhydration, urine alkalinisation, leucovorin rescue, renal replacement therapy), a costly specific enzymatic treatment (glucarpidase) is now available but its clinical impact remains elusive.

PATIENTS AND METHODS:

We analysed high-dose methotrexate prescription charts in 11 clinical centres during the last 15 years to identify and describe adult patients who developed acute kidney injury (according to KDIGO classification). Glucarpidase use was recorded (French temporary regulatory approval criteria: methotrexate at least 10μmol/L at 48h or at least 3μmol/L at 48h associated with acute kidney injury).

RESULTS:

Seventy-six acute kidney injury cases have been studied. Mean peak creatinine was 206μmol/L after a mean delay of 5.6 days, with 19 cases of stage 1 acute kidney injury (25%), 29 cases of stage 2 (38%) and 27 cases of stage 3 (36%). Anuria (one case) and need for renal replacement therapy (four cases) were unusual whereas fluid overload was often observed (29%). Three months after high-dose methotrexate treatment, mortality-rate was 17%, and 12% of surviving patients developed renal sequelae.

CONCLUSION:

Sixty-one percent of patients received a glucarpidase perfusion during acute kidney injury. Despite a dramatic decrease of methotrexate serum levels, glucarpidase as compared with conservative treatment did not modify acute kidney injury stage, recovery delay, need for renal replacement therapy or the incidence of extrarenal toxicities. Net clinical benefit was not observed even after stratification according to eligibility criteria for glucarpidase use. Glucarpidase has probably no or little effects on methotrexate localized into tubular lumen or proximal tubular cells and that may account for the absence of nephroprotective effect for enzymatic treatment.

• Authors: Hugo Garcia, Véronique Leblond, François Goldwasser, Didier Bouscary, Emmanuel Raffoux, Nicolas Boissel, Sophie Broutin, Dominique Joly
• Journal: Nephrologie & therapeutique (Nephrol Ther) Vol. 14 Suppl 1 Pg. S103-S113 (Apr 2018) ISSN: 1872-9177 [Electronic] France
• Vernacular Title: Toxicité rénale du méthotrexate à haute dose.
• PMID: 29606256 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Association Société de néphrologie. Published by Elsevier Masson SAS. All rights reserved.

Chemical References

• Antimetabolites, Antineoplastic
• gamma-Glutamyl Hydrolase
• Methotrexate

Topics

• Acute Kidney Injury (chemically induced, mortality, therapy)
• Adult
• Antimetabolites, Antineoplastic (adverse effects)
• Female
• Humans
• Male
• Methotrexate (adverse effects)
• Middle Aged
• Renal Replacement Therapy (methods)
• Retrospective Studies
• Survival Rate
• gamma-Glutamyl Hydrolase (therapeutic use)