Lupus nephritis is the most severe complication of systemic lupus erythematosus (SLE), characterized by a complex pathogenesis involving immune imbalance leading to the generation of a large number of autoantibodies, intense activation of the complement system, dysregulation of inflammatory signaling pathways, and excessive production of cytokines(24, 25). Clinical manifestations and treatment response vary greatly among individuals, with a high risk of mortality(26, 27). Therefore, early recognition, diagnosis, and immunomodulatory therapy are crucial for improving the survival rate and quality of life of LN patients (24). Over the years, scientists have been working to explore indicators that can predict the occurrence and adverse progression of LN kidney damage. In the past 50 years, the appearance of rashes, low serum complement C3 and C4 levels have been used to indicate lupus disease activity, which may be risk factors for LN kidney damage and adverse progression, but the specific relationship is still under investigation. By studying the progression of SLE to LN and the further progression of LN, we discuss their relationship, which guides the understanding of the disease and helps in timely adjustment of treatment plans.
In the occurrence section of LN, we divided all patients into SLE group and LN group. In this study section, the incidence of skin rash and level of complement C3 in the LN group were significantly lower than in the SLE group. Correlation analysis revealed a significant association between skin rash, complement C3, and LN occurrence, all showing a negative correlation.A study based on systemic lupus erythematosus in South Africa, utilizing retrospective data analysis, indicated that malar rash presentation is associated with renal damage (odds ratio of 2.8 (1.6–4.7)), while discoid rash is linked to arthritis (odds ratio of 2.02 (1.24–3.29)), with minimal involvement in renal injury. This conclusion has also been mentioned in similar studies(14, 28, 29).Zhou Wen, Wu Hong, and others have also found that patients with skin rashes may be more likely to experience damage to other systems(13).However, in our study, the absence of skin rashes has a significant implication for the occurrence of lupus nephritis (LN). The results of the multifactor analysis show that skin rashes (OR: 0.231, P < 0.001) and complement C3 (OR: 0.080, P < 0.001) are both influencing factors for the development of lupus nephritis, which is consistent with the results of differential analysis and correlation analysis.Multiple studies have described that patients presenting with a rash are mostly in the active phase of the disease, and the appearance of the rash is a risk factor for the occurrence of lupus nephritis (LN)(30–32).We analyzed the correlation between SLEDAI scores (Systemic Lupus Erythematosus Disease Activity Index) and the occurrence of Lupus Nephritis (LN), but found no significant relationship. This may be due to the effects of treatment.Further utilize ROC curve analysis to evaluate the predictive ability of absence of rash and low complement level C3 for the occurrence of LN, The results indicate that the absence of rash or low complement C3 levels have limited diagnostic value for lupus nephritis (LN). However, when these two indicators are combined, they exhibit a good diagnostic value (AUC (95% CI) = 0.71 (0.64–0.78), P < 0.001), with a diagnostic sensitivity of 0.83 and specificity of 0.51.Therefore, we recommend paying attention in clinical practice to patients who do not present with rash or have mild rash that is not obvious, and whose complement C3 levels remain low after treatment. It is important to monitor renal function promptly, recheck urine indicators, and take early intervention measures to prevent the occurrence of lupus nephritis (LN).
In the development of lupus nephritis (LN), some studies have shown that low levels of C3 in the early stages of the disease or persistent isolated low C3 levels are predictive risk factors for end-stage renal disease (ESRD). Furthermore, a decrease in complement C4 levels is an important indicator of disease recurrence in ESRD patients(33, 34).We divided LN patients into high eGFR group and low eGFR group for research analysis. In our data, the incidence of rash in the low eGFR group was much lower than in the high eGFR group. However, complement C3 and C4 levels were significantly higher in the high eGFR group, and these differences were statistically significant (P < 0.05).There is a significant correlation between the absence of rash, high levels of complement C3 and C4, and the progression of renal involvement in LN, while there is no significant correlation with SLEDAI score. In the regression analysis, the absence of rash (OR: 0.093, P < 0.001) remains associated with the progression of renal involvement in LN, while complement C3 and C4 are not statistically significant (P > 0.05), and SLEDAI score is also not statistically significant (P > 0.05). These data indicate that although the disease is not active, the condition has still progressed. In clinical practice, attention should also be paid to other exacerbating factors leading to worsening kidney damage, which contradicts the findings of Sjöwall C etal(35).However, our viewpoint has also been corroborated by some literature. Duong MD and colleagues have proposed that total cortical interstitial inflammation is a risk factor for the adverse progression of renal function in lupus nephritis(36).The existing data indicate that DENV (dengue virus) and COVID-19 (coronavirus-19) can induce and exacerbate lupus nephritis(37).In conclusion, our research findings suggest that activity is not the sole factor determining the poor progression of lupus nephritis. Attention should also be paid to drug adverse effects, non-glomerular renal diseases, infections, endocrine abnormalities, nursing factors, and other influences.
The current study has some limitations. Firstly, the data are obtained through a retrospective method, with all patient medical history data coming from our internal electronic medical record system. There may be inaccuracies in data collection and recording, leading to potential information bias. Secondly, due to limitations in the clinical sample size at our hospital, although the statistical methods used in the study have provided conclusions with good accuracy, the reliability still needs further investigation. Future plans include expanding the sample size and conducting further clinical validation to enhance the accuracy of the study findings. Finally, predicting the occurrence and progression of lupus nephritis (LN) and renal function deterioration, and timely intervention strategies are of significant importance in improving patient quality of life. There may be other influencing factors that were not further explored in the study, indicating the need for more in-depth investigations in the future.
In conclusion, the absence of skin rash and low complement C3 levels are risk factors for the progression of systemic lupus erythematosus (SLE) to lupus nephritis (LN). Clinically, it is important to monitor the renal function of patients who do not develop skin rashes or have subtle rashes and persistently low complement C3 levels even after treatment. Furthermore, disease activity in LN is not the sole factor contributing to renal deterioration in LN patients, so it is crucial to identify other relevant factors that may contribute to disease progression.