Recent advances in the application of Mendelian randomization to chronic kidney disease

Abstract

Objective

Chronic kidney disease (CKD) is a condition influenced by both genetic and environmental factors and has been a focus of extensive research. Utilizing Mendelian randomization, researchers have begun to untangle the complex causal relationships underlying CKD. This review delves into the advances and challenges in the application of MR in the field of nephrology, shifting from a mere summary of its principles and limitations to a more nuanced exploration of its contributions to our understanding of CKD.

Methods

Key findings from recent studies have been pivotal in reshaping our comprehension of CKD. Notably, evidence indicates that elevated testosterone levels may impair renal function, while higher sex hormone-binding globulin (SHBG) levels appear to be protective, predominantly in men. Surprisingly, variations in plasma glucose and glycated hemoglobin levels seem unaffected by genetically induced changes in the estimated glomerular filtration rate (eGFR), suggesting an independent pathway for renal function impairment.

Results

Furthermore, lifestyle factors such as physical activity and socioeconomic status emerge as significant influencers of CKD risk and kidney health. The relationship between sleep duration and CKD is nuanced; short sleep duration is linked to increased risk, while long sleep duration does not exhibit a clear causal effect. Additionally, lifestyle factors, including diet, exercise, and mental wellness activities, play a crucial role in kidney health. New insights also reveal a substantial causal connection between both central and general obesity and CKD onset, while no significant links were found between genetically modified LDL cholesterol or triglyceride levels and kidney function.

Conclusion

This review not only presents the recent achievements of MR in CKD research but also illuminates the path forwards, underscoring critical unanswered questions and proposing future research directions in this dynamic field.

Keywords:

• Chronic kidney disease
• Mendelian randomization
• systematic review
• metabolic disorder
• cardiovascular disease

Acknowledgments

Science and Technology Plan Project of Jilin Province (20210101440JC).

Authors contributions

Chaofan Wen1 was responsible for guiding the main writing of the article. Lanlan Chen2 refined and revised the manuscript. Dan Jia3 was responsible for proofreading the article. Ziqi Liu4 was responsible for the data collection section of the article. Yidan Lin5 was responsible for the drafting of the article. GuanLiu6: Upon reviewing and editing the manuscript, we identified sections with a high similarity index when compared against databases. To address this issue, we diligently revised these passages to reduce the level of duplication. ShuoZhang7: Upon reviewing and editing the manuscript, we identified sections with a high similarity index when compared against databases. To address this issue, we diligently revised these passages to reduce the level of duplication. This step was essential for ensuring the originality of our work and adhering to the standards of academic integrity. Baoshan Gao1*: Responsible for guiding the overall planning of the article.

Consent form

All contributing authors consent to the publication of this study.

Ethical approval

This was a systematic review and did not require ethical review.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by a grant from the Science and Technology Plan Project of Jilin Province (20210101440JC).