What is the leading cause of mortality in Systemic Lupus Erythematosus (SLE)?

Leading Causes of Mortality in Systemic Lupus Erythematosus (SLE)

Infections, cardiovascular complications, and chronic kidney disease (especially kidney failure) are the major causes of death in SLE patients, with early deaths primarily related to infections or lupus activity, while cardiovascular complications, malignancies, and kidney failure account for late mortalities. 1

Temporal Pattern of Mortality in SLE

• Early mortality in SLE is predominantly caused by infections and active lupus disease 1
• Late mortality is primarily due to cardiovascular complications, malignancies, and kidney failure 1
• Patients with SLE show increased mortality rates compared to age- and sex-matched controls in the general population 1

Major Causes of Mortality

1. Infections

• Infections account for 25-50% of overall mortality in SLE patients 1
• Half of SLE patients may experience severe infection, with more than 20% of hospitalizations being due to infections 1
• Infections are a leading cause of early deaths, particularly in the first 3 months of dialysis for patients with end-stage lupus nephritis 2
• Risk factors for infection include disease-related immune dysregulation and immunosuppressive therapy 1

2. Cardiovascular Disease

• Cardiovascular disease is a major cause of late mortality in SLE patients 1
• SLE patients have both traditional risk factors (dyslipidemia, smoking, obesity) and non-traditional risk factors (proteinuria, inflammation) for cardiovascular disease 1
• Cardiovascular disease is the most common cause of death in both pediatric and adult patients with SLE who develop end-stage renal disease 3
• Risk attenuation strategies include dyslipidemia management, blood pressure control, and low-dose aspirin during pregnancy 1

3. Kidney Disease

• Kidney involvement in SLE has been associated with higher mortality, especially for patients progressing to kidney failure 1
• Lupus nephritis occurs in 20-60% of SLE patients and is a major determinant of overall morbidity and mortality 1, 4
• Lupus nephritis-related chronic kidney disease drives cardiovascular disease and secondary immunodeficiency 4
• Patients with ESRD secondary to SLE have a significantly increased risk of death compared to other ESRD patients (hazard ratio: 2.4 in pediatric patients, 1.7 in adult patients) 3

Special Considerations

Pediatric SLE

• Childhood-onset SLE is associated with a higher incidence of lupus nephritis and more severe disease than adult-onset SLE 1
• Pediatric patients with ESRD secondary to SLE have a 2-fold increased risk of death compared to other pediatric ESRD patients 3

Demographic Variations

• The incidence of lupus nephritis varies by race/ethnicity and age 1
• Higher index of suspicion should be maintained for patients of Asian, African/Caribbean, and Hispanic descent 1

Prevention Strategies

• Regular monitoring of SLE patients is essential as kidney involvement can remain silent or asymptomatic for significant periods 1
• Hydroxychloroquine treatment reduces flares and organ damage accrual 1
• Control of modifiable risk factors for CKD progression (obesity, hypertension, sodium-rich diet, smoking) 4
• Early use of renoprotective medications such as renin-angiotensin system inhibitors and sodium-glucose transporter-2 inhibitors 4
• Pneumococcal vaccination is recommended due to the high risk of pneumococcal infection in SLE patients 1
• Interdisciplinary care to minimize the risk of kidney failure, cardiovascular disease, and infections 4

Monitoring Recommendations

• Regular assessment of kidney function with serum creatinine, urinalysis, proteinuria, and blood pressure measurements 5
• Monitoring of anti-dsDNA antibody titers and complement levels as they may correlate with disease activity 5
• Vigilance for symptoms and signs suggestive of kidney involvement 1
• Regular screening for co-morbidities including infections, atherosclerosis, hypertension, dyslipidemia, diabetes, and osteoporosis 1