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CC BY-NC-ND 4.0 · Thromb Haemost
DOI: 10.1055/a-2439-5200
Stroke, Systemic or Venous Thromboembolism

Estimated Glomerular Filtration Rate Decline is Causally Associated with Acute Pulmonary Embolism: A Nested Case–Control and Mendelian Randomization Study

Yanshuang Lyu   *
1   State Key Laboratory of Respiratory Health and Multimorbidity, Department of Physiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China
2   National Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
3   Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
,
Haobo Li   *
2   National Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
3   Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
4   Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China
,
Xin Liu   *
5   Department of Nephrology, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, China
,
Xiaomeng Zhang   *
2   National Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
4   Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China
6   Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China
,
Yinong Chen   *
2   National Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
4   Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China
6   Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China
,
Guohui Fan
2   National Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
7   Data and Project Management Unit, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China
,
Hong Zhang
1   State Key Laboratory of Respiratory Health and Multimorbidity, Department of Physiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China
2   National Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
,
Zhifa Han
2   National Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
4   Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China
,
Zhuangjie Guo
1   State Key Laboratory of Respiratory Health and Multimorbidity, Department of Physiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China
2   National Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
3   Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
,
Haoyi Weng
8   Shenzhen WeGene Clinical Laboratory, Shenzhen, China
9   Wegene Shenzhen Zaozhidao Technology Co., Ltd, Shenzhen, China
10   Hunan Provincial Key Lab on Bioinformatics, School of Computer Science and ngineering, Central South University, Changsha, China
,
Huiyuan Hu
11   First Clinical College, Xi'an Jiaotong University, Xi'an, ShaanXi, China
,
Xincheng Li
12   Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Harbin Medical University, Harbin, China
,
Zhu Zhang
2   National Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
4   Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China
,
Yu Zhang
2   National Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
4   Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China
13   China China-Japan Friendship Hospital, Capital Medical University, Beijing, China
,
Feiya Xu
2   National Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
3   Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
4   Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China
,
Chen Wang
1   State Key Laboratory of Respiratory Health and Multimorbidity, Department of Physiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China
2   National Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
3   Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
4   Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China
6   Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China
7   Data and Project Management Unit, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China
11   First Clinical College, Xi'an Jiaotong University, Xi'an, ShaanXi, China
12   Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Harbin Medical University, Harbin, China
13   China China-Japan Friendship Hospital, Capital Medical University, Beijing, China
,
Dingyi Wang   **
2   National Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
7   Data and Project Management Unit, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China
,
Peiran Yang   **
1   State Key Laboratory of Respiratory Health and Multimorbidity, Department of Physiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China
2   National Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
,
Zhenguo Zhai   **
1   State Key Laboratory of Respiratory Health and Multimorbidity, Department of Physiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China
2   National Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
3   Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
4   Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China
6   Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China
7   Data and Project Management Unit, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China
11   First Clinical College, Xi'an Jiaotong University, Xi'an, ShaanXi, China
12   Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Harbin Medical University, Harbin, China
13   China China-Japan Friendship Hospital, Capital Medical University, Beijing, China
› Author Affiliations Funding This study is supported by the National High Level Hospital Clinical Research Funding 2024-NHLHCRF-JBGS-WZ- 09; The National Key Research and Development Program of China (2023YFC2507200); Beijing Hospital Clinical Research 121 Project (BJ-2019-197); National High Level Hospital Clinical Research Funding, Elite Medical Professionals, Project of China-Japan Friendship Hospital (ZRJY2023- QM20); Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2021-I2M-1-061, 2021-I2M-1-001, 2023-I2M-2-001); CAMS Institute of Respiratory Medicine Grant for Young Scholars (2023-ZF-8), Non-Profit Central Research Institute Fund of the Chinese Academy of Medical Sciences (2021-RC310-016), National Natural Science Foundation of China (Excellent Youth Scholars Program), National Natural Science Foundation of China (82270062, 31920103011, 31770829, 32171443), State Key Laboratory Special Fund 2060204(2060204), Beijing Municipal Natural Science Foundation (7242096), Beijing Hospital Clinical Research 121 Project (BJ-2019-197), the National Laboratory of Biomacromolecules, and the CAS Center of Excellence in Biomacromolecules.
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Abstract

Background

Renal dysfunction is highly prevalent among patients with pulmonary embolism (PE). This study combined population-based study and Mendelian randomization (MR) to observe the relationship between renal function and PE.

Methods

A nested case–control study were performed using data of PE patients and controls were from two nationwide cohorts, the China pUlmonary thromboembolism REgistry Study (CURES) and China Health and Retirement Longitudinal Survey (CHARLS). Baseline characteristics were balanced using propensity score matching and inverse probability of treatment weighting. Restricted cubic spline models were applied for the relationship between estimated glomerular filtration rate (eGFR) decline and the risk of PE. Bidirectional two-sample MR analyses were performed using genome-wide association study summary statistics for eGFR involving 1,201,909 individuals and for PE from the FinnGen consortium.

Results

The nested case–control study including 17,547 participants (6,322 PE patients) found that eGFR distribution was significantly different between PE patients and controls (p < 0.001), PE patients had a higher proportion of eGFR < 60 mL/min/1.73 m2. eGFR below 88 mL/min/1.73 m2 was associated with a steep elevation in PE risk. MR analyses indicated a potential causal effect of eGFR decline on PE (odds ratio = 4·26, 95% confidence interval: 2·07–8·79), with no evidence of horizontal pleiotropy and reverse causality.

Conclusion

Our findings support the hypothesis that renal function decline contributes to an elevated PE risk. Together with the high prevalence of chronic kidney diseases globally, there arises the necessity for monitoring and modulation of renal function in effective PE prevention.

Keywords

pulmonary embolism - glomerular filtration rate - risk factors - causal inference - nested case–control study - Mendelian randomization analysis

* These authors contributed equally to the article.


** These authors contributed equally to this work as corresponding authors.


Authors' Contribution

D.W., P.Y., Z.Zhai conceived and designed the study. Y.L., H.L., X.Z., Y.C. collected data. Y.L., H.L., G.F., H.Z., Z.H., H.W., H.H., X.L. analyzed and interpreted data. Y.L. and H.L. replicated the results of this article back-to-back. Y.L., H.L., D.W. and X.L. drafted the manuscript. Y.Z., F.X. contributed to the design and building of the CURES. X.L. provided profession of nephrology. X.L., P.Y., Z.Zhai, C.W. revised the manuscript. D.W. were the lead corresponding authors. All authors participated in the proofreading of the manuscript and provided final approval of the version to be published.


Supplementary Material



Publication History

Received: 12 May 2024

Accepted: 09 October 2024

Accepted Manuscript online:
14 October 2024

Article published online:
28 March 2025

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