II. Epidemiology

  1. Renal disease or Lupus Nephritis is ultimately present in 50 to 60% of SLE cases

III. Grading

  1. Class 1: Minimal Mesangial (earliest and most mild form)
    1. Minimal Proteinuria
    2. Normal Serum Creatinine
    3. Histology with immune complex deposition on immunofluorescence, but otherwise normal glomeruli
  2. Class 2: Mesangial Proliferative
    1. Microscopic Hematuria with or without Proteinuria
    2. Histology with mesangial matrix expansion and immune complex deposition
  3. Class 3: Focal Lupus Nephritis
    1. Microscopic Hematuria
    2. Proteinuria (Nephrotic Syndrome may be present)
    3. Hypertension
    4. eGFR decreased
    5. Histology with Glomerulonephritis (focal, segmental or global) affecting <50% of glomeruli
  4. Class 4: Diffuse Lupus Nephritis (most common)
    1. Includes Class 3 features
    2. Complement C3 low
    3. Anti-Double Stranded DNA Antibody (dsDNA) elevated
    4. Histology with Glomerulonephritis affecting >50% of glomeruli and subendothelial diffuse immune deposits
      1. Diffuse Segmental Subtype (4S): Segmental lesions affecting >50% of glomeruli
      2. Diffuse Global Subtype (4G): Global lesions affecting >50% of glomeruli
      3. Subtypes may be further characterized: Active, Active and chronic, and Inactive with glomerular scar
  5. Class 5: Membranous Nephropathy
    1. Nephrotic Syndrome
    2. Microscopic Hematuria
    3. Hypertension
    4. Serum Creatinine normal
    5. Membranous Nephropathy may be the only SLE manifestation, and may occur combined with Class 3 ot 4
    6. Histology with subepithelial immune deposits (global or segmental)
  6. Class 6: Advanced Sclerosing Lupus
    1. Slowly progressive Chronic Kidney Disease to end-stage Renal Failure
    2. Proteinuria with otherwise negative Urine Microscopic Exam
    3. Histology with global sclerosis affecting >90% of glomeruli

IV. Labs

  1. Screening in Systemic Lupus Erythematosus patients (without diagnosed renal disease)
    1. Screen Urinalysis and Serum Creatinine every 3-6 months
    2. Reflex abnormal findings to Urine Protein to Creatinine Ratio
  2. Renal biopsy indications
    1. Proteinuria >=1 g per 24 hours OR
    2. Hematuria > 0.5 g per 24 hours OR
    3. Cellular Casts

V. Management

  1. General
    1. See Prevention of Kidney Disease Progression
    2. Consult nephrology and Rheumatology
  2. Class 1 and 2
    1. Renin-Angiotensin System agents (e.g. ACE Inhibitors or Angiotensin Receptor Blockers)
  3. Class 3, 4 and 5
    1. Induction Phase
      1. Pulse IV Corticosteroids AND
      2. Cyclophosphamide IV for 6 doses (over 3-6 months) OR Mycophenolate daily for 6 months
        1. Cyclosporine or Tacrolimus may be used as alternative in Class 5 disease
    2. Maintenance Phase
      1. Wean Corticosteroids to lowest effective dose
      2. Longterm Mycophenolate or Aziothioprine
  4. Class 6
    1. Renin-Angiotensin System agents (e.g. ACE Inhibitors or Angiotensin Receptor Blockers)
    2. Prepare for renal replacment therapy (e.g. Hemodialysis, Renal Transplant)

VI. Resources

  1. Lupus Nephritis (StatPearls)
    1. https://www.ncbi.nlm.nih.gov/books/NBK499817/

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