Lupus Nephritis
Kidney inflammation caused by systemic lupus erythematosus, leading to protein in the urine, high blood pressure, and potential kidney failure if not treated aggressively.
Emergency Management: Rapidly progressive renal failure or hypertensive emergency requires admission for urgent IV pulse steroids, potentially plasmapheresis, and urgent initiation of dialysis.
Lupus Nephritis (LN) is a severe, immune complex-mediated glomerulonephritis that occurs as a major complication of Systemic Lupus Erythematosus (SLE). It involves the deposition of autoantibodies in the glomeruli, leading to renal inflammation and potential end-stage kidney disease (ESKD).
Detailed Overview
LN affects up to 50% of patients with SLE. It presents clinically with proteinuria, hematuria, hypertension, and impaired renal function. The International Society of Nephrology/Renal Pathology Society (ISN/RPS) categorizes LN into six histological classes, with Class III (focal) and Class IV (diffuse) being the most severe and proliferative, requiring aggressive immunosuppressive therapy to prevent irreversible kidney failure.
Epidemiology & Demographics
Occurs in 40-50% of SLE patients, more frequently and severely in African American, Hispanic, and Asian populations. Affects women of childbearing age much more frequently than men.
Etiological Mechanism
An autoimmune process secondary to Systemic Lupus Erythematosus. Genetic susceptibility, environmental triggers (UV light, infections), and hormonal factors contribute to autoantibody production.
Primary Causes
Production of anti-double-stranded DNA (anti-dsDNA) antibodies and other nuclear autoantibodies that form immune complexes.
Circulating autoantibodies (primarily IgG anti-dsDNA) bind to intra-glomerular antigens or form circulating immune complexes that deposit in the mesangium, subendothelial, or subepithelial spaces of the glomerulus. These complexes activate the classical complement pathway, generating C3a and C5a, which attract neutrophils and macrophages. The ensuing intense inflammatory response causes endothelial damage, cellular proliferation, capillary necrosis, and eventually glomerulosclerosis and interstitial fibrosis.
Diagnostic Criteria & Guidelines
Renal biopsy is the gold standard and absolute requirement to diagnose the class of LN. Clinically suspected when an SLE patient has persistent proteinuria (>0.5 g/24hr), cellular casts, or an unexplained drop in GFR.
Induction Therapy for Class III/IV: Intravenous Cyclophosphamide (Eurolupus protocol: 500 mg IV every 2 weeks x 6 doses) OR Mycophenolate Mofetil (MMF) 2-3 g/day PO. PLUS High-dose Glucocorticoids (IV Methylprednisolone 500-1000 mg x 3 days, then oral Prednisone 1 mg/kg/day with rapid taper). All patients must be on Hydroxychloroquine 200-400 mg/day.
Second-Line & Adjunctive Therapy
Add-on therapy: Belimumab 10 mg/kg IV monthly, or Voclosporin 23.7 mg PO BID. For refractory disease: Rituximab 1000 mg IV on days 1 and 15.
Surgical & Procedural Management
Renal transplantation for patients who reach Class VI / ESKD (after SLE has been clinically inactive for 6 months).
Patient Counseling & Advice
Stress strict adherence to immunosuppressants to prevent kidney failure. Explain the high risk of infections due to therapy. Women of childbearing age need counseling on teratogenic drugs (MMF, Cyclophosphamide) and the need for effective contraception.
Follow-Up & Monitoring Schedule
Monthly check of BP, UPCR, urinalysis, serum creatinine, eGFR, anti-dsDNA, and C3/C4 levels until remission, then every 3 months.
Preventive Strategies
Adherence to background Hydroxychloroquine dramatically reduces the incidence of lupus nephritis in SLE patients.
With aggressive therapy, 50-80% achieve partial or complete remission. However, flares are common (up to 30%). 10-20% progress to ESKD requiring dialysis.