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Long-term visit-to-visit variability in low-density lipoprotein cholesterol is associated with poor cardiovascular and kidney outcomes in patients with primary nephrotic syndrome

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Abstract

Purpose

It is unclear whether long-term variability in low-density lipoprotein cholesterol (LDL-C) is associated with clinical outcomes in patients with nephrotic syndrome (NS).

Methods

A large cohort of 1100 patients with primary NS underwent treatment and regular follow-up. Long-term variability in LDL-C was assessed by calculating its weighted standard deviation (w-SD). The primary endpoints of this study were the occurrence of arteriosclerotic cardiovascular disease (ASCVD) or kidney dysfunction. Factors associated with the w-SD of LDL-C were evaluated by linear regression. Associations of the w-SD of LDL-C with clinical outcomes were evaluated by Cox proportional hazards regression.

Results

Over a median follow-up of 44.8 (interquartile range, 26.8, 70.1) months, 198 patients developed ASCVD (45.9 cases per 1,000 patient-years), and 84 patients developed kidney dysfunction (17.6 cases per 1,000 patient-years). The incidence rates of the primary outcomes increased across the quartiles of the w-SD of LDL-C (log-rank, P < 0.001). Multivariate Cox regression analysis showed that higher LDL-C variability was associated with an increased risk of ASCVD [hazard ratio (HR), 2.236; 95% confidence interval (CI), 1.684–2.969, P < 0.001] and an increased risk of kidney dysfunction (HR, 3.047; 95% CI 2.240–4.144, P < 0.001). The results were similar after adjusting the w-SD of LDL-C by its related parameters (baseline and mean LDL-C as well as mean total cholesterol), although the mean LDL-C was also an independent risk factor for ASCVD and kidney dysfunction.

Conclusion

Long-term variability in LDL-C was independently associated with the risk of ASCVD and kidney dysfunction in NS patients.

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Data availability

The data underlying this article are available in the article and in its online supplementary material.

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Acknowledgements

We thank Jin-ying Wang for providing technical support.

Funding

This work was supported by grants from the Natural Science Foundation of China (81870486, 82070732, and 82090021).

Author information

Authors and Affiliations

  1. Renal Division, Institute of Nephrology, Key Laboratory of Renal Disease, Key Laboratory of CKD Prevention and Treatment, Peking University First Hospital, Peking University, Ministry of Health of China, Ministry of Education of China, Beijing, China

    Xuan Lai, Zhao Cui, Yi-Miao Zhang, Fang Wang, Xin Wang, Li-Qiang Meng, Xu-Yang Cheng, Gang Liu & Ming-Hui Zhao

  2. Geriatrics Department, Peking University Third Hospital, Beijing, China

    Xuan Lai

  3. Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, China

    Hua Zhang

  4. Peking–Tsinghua Center for Life Sciences, Beijing, China

    Ming-Hui Zhao

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  1. Xuan Lai
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  2. Zhao Cui
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Correspondence to Zhao Cui.

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All procedures involving human participants were approved by the Ethics Committee of Peking University First Hospital and complied with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

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Lai, X., Cui, Z., Zhang, H. et al. Long-term visit-to-visit variability in low-density lipoprotein cholesterol is associated with poor cardiovascular and kidney outcomes in patients with primary nephrotic syndrome. Int Urol Nephrol 55, 1565–1574 (2023). https://doi.org/10.1007/s11255-023-03467-7

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