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Effect of Low-Dose Methotrexate on eGFR and Kidney Adverse Events: A Randomized Clinical Trial.

Publication ,  Journal Article
Sparks, JA; Vanni, KMM; Sparks, MA; Xu, C; Santacroce, LM; Glynn, RJ; Ridker, PM; Solomon, DH
Published in: J Am Soc Nephrol
December 1, 2021

BACKGROUND: Low-dose methotrexate (LD-MTX) is contraindicated in advanced CKD, but kidney safety in normal kidney function or mild-to-moderate CKD is less clear. METHODS: We performed a secondary analysis for eGFR and kidney AEs using the randomized double-blind, placebo-controlled Cardiovascular Inflammation Reduction Trial. Adults with cardiovascular disease and diabetes and/or metabolic syndrome were randomly allocated to oral LD-MTX (target dose 15-20 mg/week) or placebo. All participants took folic acid 1 mg 6 days/week. Exclusion criteria included systemic rheumatic disease and creatinine clearance <40 ml/min. The least-squares mean Δ eGFR from baseline was calculated at each study visit; the difference in eGFR between LD-MTX and placebo was compared. We used Cox proportional hazard models to compare rates of kidney AEs for LD-MTX versus placebo. RESULTS: A total of 2391 participants were randomized to LD-MTX and 2395 to placebo. At baseline, the mean age was 66 years, 19% were female, and mean eGFR was 80.0 ml/min per 1.73 m 2 (54% had Stage 2 CKD and 18% had Stage 3 CKD). Median follow-up was 23 months. The LD-MTX group had less decline in eGFR than placebo (difference in least-squares mean ΔeGFR from baseline to on-treatment visits: 0.93 ml/min per 1.73 m 2 , 95% confidence interval [95% CI], 0.45 to 1.40, P <0.001). There were 138 (incidence rate [IR], 2.97 per 100 person-years) kidney AEs in the LD-MTX group and 184 (IR, 3.99 per 100 person-years) among placebo (hazard ratio [HR] 0.73, 95% confidence interval [95% CI], 0.59 to 0.91) during safety laboratory monitoring. CONCLUSIONS: These results demonstrate the kidney safety of LD-MTX among patients with normal kidney function or mild-to-moderate CKD at baseline.

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Published In

J Am Soc Nephrol

DOI

EISSN

1533-3450

Publication Date

December 1, 2021

Volume

32

Issue

12

Start / End Page

3197 / 3207

Location

United States

Related Subject Headings

  • Urology & Nephrology
  • Renal Insufficiency, Chronic
  • Methotrexate
  • Male
  • Kidney
  • Humans
  • Glomerular Filtration Rate
  • Folic Acid
  • Female
  • Double-Blind Method
 

Citation

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Sparks, J. A., Vanni, K. M. M., Sparks, M. A., Xu, C., Santacroce, L. M., Glynn, R. J., … Solomon, D. H. (2021). Effect of Low-Dose Methotrexate on eGFR and Kidney Adverse Events: A Randomized Clinical Trial. J Am Soc Nephrol, 32(12), 3197–3207. https://doi.org/10.1681/ASN.2021050598
Sparks, Jeffrey A., Kathleen M. M. Vanni, Matthew A. Sparks, Chang Xu, Leah M. Santacroce, Robert J. Glynn, Paul M. Ridker, and Daniel H. Solomon. “Effect of Low-Dose Methotrexate on eGFR and Kidney Adverse Events: A Randomized Clinical Trial.J Am Soc Nephrol 32, no. 12 (December 1, 2021): 3197–3207. https://doi.org/10.1681/ASN.2021050598.
Sparks JA, Vanni KMM, Sparks MA, Xu C, Santacroce LM, Glynn RJ, et al. Effect of Low-Dose Methotrexate on eGFR and Kidney Adverse Events: A Randomized Clinical Trial. J Am Soc Nephrol. 2021 Dec 1;32(12):3197–207.
Sparks, Jeffrey A., et al. “Effect of Low-Dose Methotrexate on eGFR and Kidney Adverse Events: A Randomized Clinical Trial.J Am Soc Nephrol, vol. 32, no. 12, Dec. 2021, pp. 3197–207. Pubmed, doi:10.1681/ASN.2021050598.
Sparks JA, Vanni KMM, Sparks MA, Xu C, Santacroce LM, Glynn RJ, Ridker PM, Solomon DH. Effect of Low-Dose Methotrexate on eGFR and Kidney Adverse Events: A Randomized Clinical Trial. J Am Soc Nephrol. 2021 Dec 1;32(12):3197–3207.

Published In

J Am Soc Nephrol

DOI

EISSN

1533-3450

Publication Date

December 1, 2021

Volume

32

Issue

12

Start / End Page

3197 / 3207

Location

United States

Related Subject Headings

  • Urology & Nephrology
  • Renal Insufficiency, Chronic
  • Methotrexate
  • Male
  • Kidney
  • Humans
  • Glomerular Filtration Rate
  • Folic Acid
  • Female
  • Double-Blind Method