Estimated small dense low-density lipoprotein-cholesterol and the risk of kidney and cardiovascular outcomes in diabetic kidney disease

Abstract

Aims

This study aimed to investigate the correlations between estimated small dense low-density lipoprotein-cholesterol (esd-LDL-c) and the development of end-stage kidney disease (ESKD), cardiovascular mortality, and all-cause mortality in individuals with diabetic kidney disease (DKD) or diabetes mellitus (DM) concomitant chronic kidney disease (CKD).

Methods

We analyzed the data from a biopsy-proven DKD cohort conducted at West China Hospital of Sichuan University between 2009 and 2021 (the DKD cohort) and participants with DM and CKD in the National Health and Nutrition Examination Survey (NHANES) 2011–2014 (the NHANES DM-CKD cohort). Cox regression analysis was also used to estimate associations between esd-LDL-c and the incidence of ESKD, cardiovascular mortality, and all-cause mortality.

Results

There were 175 ESKD events among 338 participants in the DKD cohort. Patients were divided into three groups based on esd-LDL-c tertiles (T1 < 33.7 mg/dL, T2 ≥ 33.7 mg/dL to <45.9 mg/dL, T3 ≥ 45.9 mg/dL). The highest tertile of esd-LDL-c was associated with ESKD (adjusted HR 2.016, 95% CI 1.144–3.554, p = .015). Furthermore, there were 99 deaths (39 cardiovascular) among 293 participants in the NHANES DM-CKD cohort. Participants were classified into three groups in line with the tertile values of esd-LDL-c in the DKD cohort. The highest tertile of esd-LDL-c was associated with cardiovascular mortality (adjusted HR 3.95, 95% CI 1.3–12, p = .016) and all-cause mortality (adjusted HR 2.37, 95% CI 1.06–5.32, p = .036).

Conclusions

Higher esd-LDL-c was associated with increased risk of ESKD in people with biopsy-proven DKD, and higher cardiovascular and all-cause mortality risk among those with DM-CKD.

Keywords:

• Type 2 diabetes mellitus
• diabetic kidney disease
• risk factor
• small dense low-density lipoprotein-cholesterol
• cohort study

Acknowledgements

We thank the NHANES personnel for allowing us access to high-quality data for our clinical study. We also thank AiMi Academic Services (www.aimieditor.com) for English language editing and review services.

Author contributions

F.L. and Q.Y. designed the study. Q.Y., Y.Z., Y.L., J.Y., Y.W., X.X., C.Q., and Y.Z. contributed to patient follow-up and data collection. Q.Y. and Y.Z. participated in the data analysis. Q.Y. drafted the manuscript. F.L. supervised and advised the entire procedure and was in charge of the manuscript review and editing. All authors have read and agreed to the final manuscript.

Ethical approval

For the DKD cohort from West China Hospital, the study design received approval from the ethics committee of West China Hospital, Sichuan University (Ethical number 20231143).

Consent form

All individuals provided written informed consent. For NHANES, the protocol was approved by the National Center for Health Statistics Ethics Review Board, and written informed consent was obtained from all participants.

Disclosure statement

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

Additional information

Funding

This study was supported by the Health Commission of Sichuan Province Program (No. 21ZD001).