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Long-term dynamic effect of body mass index on adverse cardiovascular outcomes with targeted maximum likelihood estimation method: result from the KNOW-CKD study
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  • Published: 20 March 2026

Long-term dynamic effect of body mass index on adverse cardiovascular outcomes with targeted maximum likelihood estimation method: result from the KNOW-CKD study

  • Yun Jung Oh1,
  • Jayoun Kim2,
  • Suah Sung3,
  • Soo Wan Kim  ORCID: orcid.org/0000-0002-4675-94484,
  • Yeong Hoon Kim5,
  • Kook-Hwan Oh  ORCID: orcid.org/0000-0001-9525-21796,
  • Wookyung Chung  ORCID: orcid.org/0000-0001-7657-130X7,8,
  • Young Youl Hyun  ORCID: orcid.org/0000-0002-4204-99089 na1 &
  • …
  • Ji Yong Jung  ORCID: orcid.org/0000-0003-1271-80127,8 na1 

Scientific Reports , Article number:  (2026) Cite this article

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  • Medical research
  • Nephrology

Abstract

The relationship between body mass index (BMI) and cardiovascular outcomes in chronic kidney disease (CKD) remains controversial. While the obesity paradox has been observed in this population, the impact of longitudinal BMI patterns over time is not well established. In this study, we investigated the association between BMI trajectories and the risk of cardiovascular events (CVEs) using data from 1061 patients enrolled in the Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD). BMI was categorized as high (≥ 23 kg/m2) or low (< 23 kg/m2), and assessed at three time points over a 7-year period. We applied targeted maximum likelihood estimation (TMLE) and marginal structural models (MSMs) to adjust for time-varying covariates, including estimated glomerular filtration rate, blood pressure, hemoglobin, albumin, and C-reactive protein, as well as baseline demographic and clinical characteristics. Patients with persistently high BMI had a significantly reduced risk of CVEs (relative risk 0.279; 95% CI 0.143–0.546; P < 0.001) compared to those with consistently low BMI. Transient increases or decreases in BMI did not show the same benefit. Our findings suggest that sustained high BMI may be protective against cardiovascular events in patients with CKD, challenging current weight management recommendations and supporting individualized approaches based on long-term risk profiles.

Data availability

The data underlying this article cannot be publicly shared due to the privacy of the study participants. However, the data can be made available upon reasonable request to the corresponding author.

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Funding

This work was supported by the National Institutes of Health (NIH) research projects (2025E110100) and the Research Program funded by the Korea Disease Control and Prevention Agency (2011E3300300, 2012E3301100, 2013E3301600, 2013E3301601, 2013E3301602, 2016E3300200, 2016E3300201, 2016E3300202, 2019E320100, 2019E320101, 2019E320102, and 2022-11-007).

Author information

Author notes

  1. Young Youl Hyun and Ji Yong Jung contributed equally to this work.

Authors and Affiliations

  1. Department of Internal Medicine, H Plus Yangji Hospital, Seoul, Republic of Korea

    Yun Jung Oh

  2. Medical Research Collaborating Center, Seoul National University Hospital, Seoul, Republic of Korea

    Jayoun Kim

  3. Department of Internal Medicine, Eulji Medical Center, Eulji University, Seoul, Republic of Korea

    Suah Sung

  4. Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea

    Soo Wan Kim

  5. Department of Internal Medicine, Inje University Busan Paik Hospital, Busan, Republic of Korea

    Yeong Hoon Kim

  6. Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea

    Kook-Hwan Oh

  7. Division of Nephrology, Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University College of Medicine, 21, Namdong-daero 774 beon-gil, Namdong-gu, Incheon, 21565, Republic of Korea

    Wookyung Chung & Ji Yong Jung

  8. College of Medicine, Gachon University, Incheon, Republic of Korea

    Wookyung Chung & Ji Yong Jung

  9. Division of Nephrology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongnogu, Seoul, 03181, Republic of Korea

    Young Youl Hyun

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Contributions

Conceived and designed the experiments: J.Y.J.; data acquisition: Y.J.O., J.K., S.S., S.W.K., Y.H.K., K.O., W.C., Y.Y.H., and J.Y.J.; data analysis/interpretation: Y.J.O. and J.Y.J.; manuscript writing: Y.J.O. and J.Y.J.; counsel and advice: Y.Y.H. and J.K,; reviewing of the draft: Y.J.O, J.K., S.S., S.W.K., Y.H.K., K.O., W.C., Y.Y.H., and J.Y.J. Each author provided important intellectual content by presenting and solving questions about the accuracy or integrity of all parts of the work. All authors approved the final version of the manuscript.

Corresponding authors

Correspondence to Young Youl Hyun or Ji Yong Jung.

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Oh, Y.J., Kim, J., Sung, S. et al. Long-term dynamic effect of body mass index on adverse cardiovascular outcomes with targeted maximum likelihood estimation method: result from the KNOW-CKD study. Sci Rep (2026). https://doi.org/10.1038/s41598-026-45135-7

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  • Received: 19 May 2025

  • Accepted: 17 March 2026

  • Published: 20 March 2026

  • DOI: https://doi.org/10.1038/s41598-026-45135-7

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Keywords

  • Body mass index
  • Chronic kidney disease
  • Long-term dynamic effect
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