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. 2021 Jul;114(1):79-84.
doi: 10.1007/s12185-021-03132-8. Epub 2021 Mar 20.

Risk factors for high-dose methotrexate-induced nephrotoxicity

Shinichiro Kawaguchi  1 , Shin-Ichiro Fujiwara  1   2 , Rui Murahashi  1 , Hirotomo Nakashima  1 , Sae Matsuoka  1 , Takashi Ikeda  1 , Yumiko Toda  1 , Shoko Ito  1 , Tetsuaki Ban  1 , Takashi Nagayama  1 , Kento Umino  1 , Daisuke Minakata  1 , Hirofumi Nakano  1 , Ryoko Yamasaki  1 , Masahiro Ashizawa  1 , Chihiro Yamamoto  1 , Kaoru Hatano  1 , Kazuya Sato  1 , Iekuni Oh  1 , Ken Ohmine  1 , Yoshinobu Kanda  3
Affiliations

Risk factors for high-dose methotrexate-induced nephrotoxicity

Shinichiro Kawaguchi et al. Int J Hematol. 2021 Jul.

Abstract

High-dose methotrexate (MTX) is widely used for the treatment of hematological malignancies. Despite the application of routine supportive care measures, such as intensive fluid hydration and urine alkalinization, nephrotoxicity is still a problem. The present study aimed to evaluate the risk factors for MTX-induced nephrotoxicity. We retrospectively reviewed 88 patients who received a regimen consisting of high-dose MTX (1000 mg/m2) and cytosine arabinoside between 2006 and 2018. Nephrotoxicity (≥ grade 2) was observed in 11 patients. Nephrotoxicity was observed only in patients with a high MTX concentration. Other than the MTX concentration, the serum uric acid level and urine pH at day 1 were associated with nephrotoxicity. A multivariate analysis revealed that urine pH was an independent risk factor for MTX-induced nephrotoxicity. Urine pH < 7.0 at day 1 was a significant risk factor for nephrotoxicity (odds ratio, 8.05; 95% confidence interval 1.95-33.3) and was also a predictor of delayed MTX elimination at 72 h after injection. Among pre-treatment factors, a low serum calcium level predicted urine pH < 7.0 at day 1. In conclusion, the present study suggests that low urine pH at day 1 is an independent risk factor for MTX-induced nephrotoxicity.

Keywords: Calcium; Methotrexate; Nephrotoxicity; Urine alkalization.

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