Lupus Nephritis

Lupus nephritis (LN) is kidney inflammation caused by systemic lupus erythematosus (SLE) — one of the most common and serious complications of lupus. It occurs when autoantibodies and immune complexes deposit in the kidneys, triggering complement activation and inflammatory damage. Kidney biopsy with histologic classification remains essential for guiding treatment: the International Society of Nephrology/Renal Pathology Society (ISN/RPS) system classifies LN into Classes I–VI. Proliferative classes — Class III (focal) and Class IV (diffuse) — are the most severe and carry the highest risk of progression to chronic kidney disease and end-stage renal disease (ESRD). Class V (membranous) presents primarily with nephrotic-range proteinuria. The 2024 KDIGO Clinical Practice Guideline for Lupus Nephritis provides current evidence-based management recommendations.

• Foamy or frothy urine (proteinuria)
• Blood in the urine (hematuria), visible or microscopic
• Swelling (edema) in the legs, ankles, and feet
• Rising blood pressure or difficult-to-control hypertension
• Decreased urine output or changes in urination frequency
• Fatigue and generalized malaise
• Unexplained weight gain from fluid retention
• Symptoms may be subtle or absent early — lab abnormalities often precede symptoms

All SLE patients require routine kidney function monitoring. Standard monitoring includes urinalysis, urine protein-to-creatinine or albumin-to-creatinine ratio, serum creatinine and eGFR, and serologic markers of lupus activity (anti-dsDNA, complement C3/C4). Kidney biopsy is indicated when urine ACR exceeds 500 mg/g (or equivalent proteinuria), when active urinary sediment (RBC casts, dysmorphic red cells) is present, when eGFR is declining without explanation, or before initiating major immunosuppressive therapy. Biopsy histology guides induction regimen selection and is not replaceable by clinical or serologic data alone.

For active proliferative LN (Class III/IV), induction therapy with mycophenolate mofetil (MMF) plus low-dose corticosteroids is equivalent to cyclophosphamide and is preferred by most guidelines given its comparable efficacy and more favorable side-effect profile. Two newer agents are now incorporated into standard regimens: voclosporin (Lupkynis), a calcineurin inhibitor, added to MMF plus steroids demonstrated superior proteinuria reduction in the AURORA trial (FDA approved 2021); belimumab (Benlysta) added to standard of care reduced kidney-related events in the BLISS-LN trial (FDA approved for LN 2020). Maintenance therapy with MMF or azathioprine continues for at least 3 years after remission. For ESRD, kidney transplantation is the optimal treatment but Black patients face documented longer wait times and access barriers on transplant waitlists.