Malignancies in lupus nephritis: a retrospective cohort study on epidemiology and risk factors

Objectives This study aimed to evaluate the epidemiology and predisposing factors for malignancy in lupus nephritis (LN). Methods This retrospective cohort study included 290 patients diagnosed with LN from 1969 to 2023. Demographic and clinical variables were analysed using the Mann-Whitney U test and Fisher's test. To identify predictors of cancer development, univariate logistic regression analysis was conducted. Results Over a median follow-up period of 15 years (IQR 6-25), 27 malignancies were diagnosed (prevalence 9.3%, incidence 6.08 per 1000 person-years), 22.2% affecting the urinary tract and 33.3% the skin. Cancer diagnoses were evenly distributed across the decades of observation and 85.2% occurred during a quiescent phase of LN. Mortality was significantly higher in patients with malignancies compared with those without (25.9% vs 6.9%, p=0.012). Patients with malignancies were significantly older at LN diagnosis (31.6 vs 28.7 years, p=0.035) and at the end of follow-up (58.1 years vs 45.2 years, p<0.001), were more frequently smokers (84.6% vs 37.7%, p=0.001) and exposed to higher cumulative doses of glucocorticoids (37.0 g vs 23.7 g, p=0.031). Univariate analysis identified smoking (OR 9.081, 95% CI 1.921 to 42.937; p<0.001), older age (OR 1.058, 95% CI 1.028 to 1.089; p<0.001) and higher proteinuria at LN onset (OR 1.126, 95% CI:1.024 to 1.237; p=0.016) as significant risk factors for malignancy. Conclusion In patients with LN, the considerable risk of malignancy and its associated increase in mortality necessitate long-term monitoring, regardless of activity phase and disease duration. Smoking remains a major risk factor in this population, and its cessation should be actively promoted as part of patient care.