What is the epidemiology and brief pathophysiology of Systemic Lupus Erythematosus (SLE) and Lupus Nephritis (LN)?

From the Guidelines

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease with a prevalence of 20-150 cases per 100,000 individuals, characterized by a complex interplay of genetic, environmental, and hormonal factors leading to immune dysregulation and tissue damage. The epidemiology of SLE is notable for its higher prevalence and severity among certain racial and ethnic populations, including Black, Hispanic, and Asian populations 1. The pathophysiology of SLE involves the production of autoantibodies, particularly antinuclear antibodies (ANA), impaired clearance of apoptotic cells, and complement activation, resulting in tissue inflammation and damage.

Epidemiology of Lupus Nephritis

Lupus nephritis, a common complication of SLE, affects approximately 20-60% of SLE patients, with a reported lifetime incidence of 20%–60% depending on the demographics of the population studied 1. The risk factors for lupus nephritis include younger age at SLE diagnosis, male sex, and certain racial/ethnic backgrounds. Early detection through regular urinalysis and kidney function tests is essential, as lupus nephritis significantly impacts SLE prognosis and is a major cause of morbidity and mortality in these patients.

Pathophysiology of Lupus Nephritis

The pathophysiology of lupus nephritis involves autoantibody binding to nuclear antigens, forming immune complexes that deposit in the glomerular basement membrane, activating complement and recruiting inflammatory cells. This process leads to various histological patterns classified into six classes (I-VI) by the International Society of Nephrology/Renal Pathology Society, ranging from minimal mesangial involvement to advanced sclerosing nephritis. Kidney involvement in SLE has been associated with higher mortality, especially for patients progressing to kidney failure, and the ultimate goal of treating lupus nephritis is to preserve kidney function and reduce the morbidity and mortality associated with chronic kidney disease (CKD) and kidney failure, while minimizing medication-associated toxicities 1.

Some key points to consider in the management of lupus nephritis include:

• The use of the International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 classification system to assess kidney biopsy findings 1
• The importance of regular monitoring of patients with lupus nephritis, including measurements of serum creatinine, proteinuria, and anti-dsDNA antibody levels 1
• The consideration of adjunct treatments, such as angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers, cholesterol-lowering medications, and hydroxychloroquine, to improve outcomes and reduce treatment-related comorbidities 1

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Epidemiology of SLE

• Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by inflammation and immune-mediated injury to multiple organ systems, including the mucocutaneous, musculoskeletal, hematologic, and kidney systems 2
• Approximately 3.4 million people worldwide have received a diagnosis of SLE, with approximately 90% of people with SLE being female 2
• The 2019 European Alliance of Associations for Rheumatology (formerly the European League Against Rheumatism)/American College of Rheumatology classification criteria developed for scientific study are an estimated 96.1% sensitive and 93.4% specific for SLE 2

Pathophysiology of SLE

• SLE is characterized by the presence of autoantibodies towards nuclear antigens, immune complex deposition, and chronic inflammation at classic target organs such as skin, joints, and kidneys 3
• The autoantibodies, especially anti-dsDNA and anti-Sm autoantibodies, are highly specific to SLE and participate in the immune complex formation and inflammatory damage on multiple end-organs such as kidney, skin, and central nervous system (CNS) 4
• Single cell analysis of autoreactive B cells and monoclonal antibody screening from patients with active SLE has improved our understanding on the origin of autoreactive B cells and the antigen targets of the pathogenic autoantibodies 4

Epidemiology and Pathophysiology of Lupus Nephritis

• Lupus nephritis (LN) is one of the most common manifestations of SLE, affecting approximately 40% of patients with lupus 5
• LN represents a major risk factor for morbidity and mortality, and 10% of patients with LN will develop end-stage kidney disease (ESKD) 5, 2
• The primary goal of treatment for LN is to achieve disease remission or quiescence, defined by minimal symptoms, low levels of autoimmune inflammatory markers, and minimal systemic glucocorticoid requirement while the patient is treated with maintenance doses of immunomodulatory or immunosuppressive medications 2
• Treatments for LN include hydroxychloroquine, immunosuppressive agents, such as azathioprine, mycophenolate mofetil, and cyclophosphamide, as well as biologic therapies, such as belimumab and voclosporin 6, 2