Remnant Cholesterol Linked to CKD Risk, Progression to End-Stage Renal Disease

Remnant cholesterol (RC) is associated with an increased risk of chronic kidney disease (CKD), according to findings from a recent systematic review and meta-analysis.1

In addition to being linked to CKD risk, RC was also associated with progression to end-stage renal disease (ESRD) in patients with type 2 diabetes-related kidney disease.1

“While type 2 diabetes and hypertension continue to be the primary drivers of incident CKD, numerous studies have demonstrated that dyslipidemia—closely associated with these entities—plays a crucial pathogenic role in the development and progression of CKD,” Paschalis Karakasis, MD, MSc, of Aristotle University of Thessaloniki in Greece, and colleagues wrote.1 “Although research to date has predominantly focused on traditional lipid parameters, there is a growing interest in alternative markers such as remnant cholesterol."

According to the US Centers for Disease Control and Prevention, more than 1 in 7 US adults—about 35.5 million people—are estimated to have CKD.2 Adequate lipid control has emerged as a key factor in the prevention and management of CKD, but less is known about RC’s role.1

To evaluate the association between RC and CKD, investigators conducted a systematic literature search across Medline, Cochrane Library, and Scopus databases from inception until September 2024 for randomized controlled trials or observational studies examining the relationship between RC levels and CKD in adult populations. No restrictions were applied based on date, language, publication status, or year.1

The primary endpoint for meta-analysis was the association between RC levels and the risk of CKD, defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m.1

Investigators identified 381 records and screened them based on titles and abstracts. Of these, 360 records were excluded. The remaining 21 records underwent a detailed full-text assessment, leading to the inclusion of 12 studies that met the eligibility criteria.1

A total of 9 studies including 4,109,777 individuals assessed the association between RC tertiles and CKD. Investigators noted participants with RC values in the highest quantile had significantly greater odds of CKD compared to those in the lowest quantile (Odds ratio [OR], 1.46; 95% confidence interval [CI], 1.26 to 1.68; P <.001; I2 = 90%; heterogeneity P <.01).1

In a sensitivity analysis confined to individuals with type 2 diabetes, those in the higher RC quantile also exhibited significantly increased odds of CKD compared to those in the lowest quantile (OR, 1.46; 95% CI, 1.20 to 1.78; P <.0001; I2 = 90%; heterogeneity P <.01).1

Investigators observed a significant inverse association between RC and eGFR. Specifically, eGFR declined by 1.43 mL/min/1.73 m2 for each 1 mmol/L increase in RC (mean difference, −1.43; 95% CI, −2.67 to −0.19; P <.001; I2 = 82%; heterogeneity P = .02).1

Further analysis revealed individuals with T2D-related CKD had a 24% increased risk of progression to end-stage renal disease for each 1 standard deviation increase in RC (Hazard Ratio [HR], 1.24; 95% CI, 1.04 to 1.47; P = .015; I2 = 34%; heterogeneity P = .22).1

“Considering the relatively limited treatment options currently available for preventing and effectively managing CKD, RC potentially emerges as a novel therapeutic target for this patient population,” investigators concluded.1 “However, the debate on the optimal RC levels and the potential additive benefit for patients who have already achieved the recommended LDL-C goals remains to be definitively addressed in future large-scale, rigorously designed RCTs.”

References

1. Karakasis P, Patoulias D, Rizzo M, et al. Association between remnant cholesterol and chronic kidney disease: Systematic review and meta-analysis. Diabetes Obes Metab. doi:10.1111/dom.16258

2. US Centers for Disease Control and Prevention. Chronic Kidney Disease in the United States, 2023. Accessed February 14, 2025. https://www.cdc.gov/kidney-disease/php/data-research/index.html