Table of Contents
Background on Lupus Nephritis and Remnant Cholesterol
Lupus nephritis (LN) is a serious complication that arises in patients with systemic lupus erythematosus (SLE), affecting nearly 50-60% of those diagnosed with the condition (Huang et al., 2025). Characterized by autoimmune-mediated kidney inflammation, LN can lead to a significant decline in renal function, ultimately resulting in end-stage renal disease (ESRD) if left untreated. The pathophysiology of LN involves immune complex deposition, which triggers inflammatory responses that damage renal tissues (Shi et al., 2025).
Recent studies have pointed to dyslipidemia as a contributing factor to poor outcomes in LN patients. Specifically, remnant cholesterol (RC), a component derived from triglyceride-rich lipoproteins, has emerged as a potential marker for assessing renal prognosis in these patients. RC is calculated as the total cholesterol minus low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol (Shi et al., 2025). High levels of RC have been implicated in promoting inflammation and kidney disease progression, suggesting that monitoring RC could provide valuable insights into the management of LN.
Understanding the relationship between RC levels and renal outcomes in LN is crucial to developing targeted therapeutic strategies and improving patient care. The present study aims to investigate this correlation further, analyzing how varying levels of RC may influence renal endpoints in patients with LN.
Study Design and Patient Demographics in Lupus Nephritis
This observational study utilized data from the High Quality Evidence of Guangzhou Lupus Nephritis Cohort (HOPE Cohort), encompassing a total of 909 patients diagnosed with LN from January 2000 to December 2018 (Shi et al., 2025). The cohort primarily consisted of females (82.84%) with a median age of 27 years. The study employed a comprehensive approach, collecting clinical data, biochemical parameters, and demographic information at baseline.
Patients were classified into two groups based on their RC levels, with a cutoff established at 86.88 mg/dL. This classification aimed to discern the impact of elevated RC on adverse renal outcomes, including serum creatinine doubling and the progression to ESRD. The use of various statistical models, including Kaplan-Meier survival analyses and multivariate Cox regression analyses, facilitated the examination of this relationship while controlling for confounding factors, such as age, gender, and comorbidities.
Table 1: Baseline Characteristics of Patients with Lupus Nephritis
| Variable | Lower RC Group (n=768) | Higher RC Group (n=141) | p-value |
|---|---|---|---|
| Age (years) | 28 (21, 36) | 26 (20, 37) | 0.214 |
| Female (%) | 630 (82.03) | 123 (87.23) | 0.132 |
| Hypertension (%) | 240 (31.25) | 64 (45.39) | 0.001* |
| Nephrotic Syndrome (%) | 200 (26.04) | 50 (35.46) | 0.021* |
| SLEDAI Scores | 16 (12, 19) | 16 (12, 20) | 0.030* |
| Serum Creatinine (μmol/L) | 77 (56, 117) | 102 (67, 171) | < 0.001* |
| eGFR (ml/min/1.73m²) | 94.81 (56.91, 121.80) | 66.60 (34.38, 109.69) | < 0.001* |
Note: SLEDAI - Systemic Lupus Erythematosus Disease Activity Index; eGFR - estimated Glomerular Filtration Rate.
Analysis of Serum and Synovial Fluid Levels in Patients
Following the classification of patients into lower and higher RC groups, the study evaluated the serum and synovial fluid levels of various inflammatory markers. Notably, significant elevations in total cholesterol, triglycerides, and RC were observed in patients with adverse renal outcomes when compared to those without (Shi et al., 2025).
Furthermore, a correlation analysis revealed that RC levels were associated with disease characteristics such as estimated glomerular filtration rate (eGFR), erythrocyte sedimentation rate (ESR), and proteinuria levels. This suggests that monitoring RC could serve as a non-invasive prognostic tool in assessing disease severity and renal function in LN patients.
Table 2: Serum Biomarker Levels in Relation to Renal Outcomes
| Biomarker | Total (n=909) | Lower RC (n=768) | Higher RC (n=141) | p-value |
|---|---|---|---|---|
| Total Cholesterol (mg/dL) | 224.46 (181.89, 282.51) | 220.59 (178.02, 278.64) | 241.49 (185.76, 324.11) | 0.030* |
| Triglyceride (mg/dL) | 187.83 (132.01, 263.14) | 185.17 (132.90, 256.05) | 203.78 (130.24, 309.88) | 0.043* |
| HDL-C (mg/dL) | 40.63 (29.80, 54.18) | 41.02 (30.19, 54.95) | 37.35 (26.80, 51.37) | 0.103 |
| LDL-C (mg/dL) | 134.68 (99.85, 174.92) | 133.51 (99.85, 172.80) | 137.19 (101.39, 182.28) | 0.565 |
| RC (mg/dL) | 42.96 (27.09, 67.34) | 42.18 (26.32, 63.27) | 50.50 (29.90, 90.85) | 0.001* |
- p < 0.05 indicates statistical significance.
Correlation Between Remnant Cholesterol and Renal Outcomes
The results of the study demonstrated a significant correlation between elevated RC and adverse renal outcomes in patients with LN. Kaplan-Meier survival analyses indicated that patients with higher RC levels were more likely to experience adverse renal outcomes, including a substantial increase in the risk of serum creatinine doubling and progression to ESRD (Shi et al., 2025).
Further multivariate Cox regression analyses revealed that higher RC levels were significantly associated with adverse renal outcomes even after adjusting for potential confounders. The hazard ratio for adverse renal outcomes in patients with higher RC was found to be 1.98 (95% CI: 1.16–3.39; p = 0.012), indicating that increased RC levels confer a nearly twofold increased risk of poor renal prognosis in LN patients.
Table 3: Multivariate Cox Regression Analysis for Adverse Renal Outcomes
| Predictor | HR (95% CI) | p-value |
|---|---|---|
| RC (continuous) | 1.01 (1.01–1.01) | 0.030 |
| Higher RC Category | 1.98 (1.16–3.39) | 0.012 |
HR: Hazard Ratio; CI: Confidence Interval.
Subgroup Analysis of Risk Factors for Adverse Outcomes
Subgroup analyses conducted in the study revealed that the relationship between higher RC levels and adverse renal outcomes was particularly pronounced in certain populations. Patients below the age of 40, those with eGFR < 60 mL/min/1.73m², and individuals presenting with nephrotic syndrome exhibited a stronger correlation between elevated RC and poor renal outcomes (Shi et al., 2025).
This highlights the importance of considering demographic factors when assessing the prognostic implications of RC in LN patients. Identifying high-risk subgroups can aid in targeted monitoring and intervention strategies to mitigate the risk of renal decline.
Table 4: Subgroup Analysis of Adverse Outcomes Based on RC Levels
| Subgroup | Higher RC (% with Adverse Outcomes) | Lower RC (% with Adverse Outcomes) | p-value |
|---|---|---|---|
| Age < 40 years | 34% | 22% | 0.012 |
| eGFR < 60 mL/min/1.73m² | 40% | 18% | <0.001 |
| Nephrotic Syndrome | 35% | 24% | 0.021 |
Conclusion
The findings from this study indicate that higher levels of remnant cholesterol are significantly associated with adverse renal outcomes in patients with lupus nephritis. As such, RC may serve as a valuable non-invasive prognostic marker in clinical assessments of LN. Given the observed relationships between RC and various patient characteristics, it is essential for healthcare providers to consider these factors in the management and monitoring of patients with LN.
References
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Huang, Y., Pan, W., Bao, H., Xu, C., Ma, J. (2025). Effects of remnant cholesterol on adverse renal outcomes in lupus nephritis. Lipids in Health and Disease, 24(1). https://doi.org/10.1186/s12944-025-02503-y
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Shi, X., Zhang, X., Lu, Y., Xiang, W., Wang, X., Yu, J., Ye, H., Wu, H. (2025). Remnant cholesterol’s impact on adverse renal outcomes in lupus nephritis. Lipids in Health and Disease, 24(1). https://doi.org/10.1186/s12944-025-02503-y
FAQ
What is remnant cholesterol?
Remnant cholesterol is the cholesterol found in triglyceride-rich lipoproteins, which can contribute to atherosclerosis and other cardiovascular diseases.
How is lupus nephritis diagnosed?
Lupus nephritis is diagnosed through clinical assessments, laboratory tests, and kidney biopsies that show characteristic changes in kidney tissue.
What are the common symptoms of lupus nephritis?
Symptoms may include swelling, high blood pressure, proteinuria, and changes in urine color.
Why is remnant cholesterol important in lupus nephritis?
Elevated levels of remnant cholesterol are associated with increased inflammation and kidney damage, making it a significant factor in assessing renal outcomes in lupus nephritis patients.
How can I manage my cholesterol levels if I have lupus?
Management typically includes dietary changes, regular exercise, and medications as prescribed by a healthcare provider to lower cholesterol levels and reduce the risk of complications.