lupus nephritis

Classification

of renal disease

• class 1: normal
• class 2:
  • mild mesangial change
  • no clinical findings of renal disease in 50% of patients
  • mild proteinuria
  • microscopic hematuria
• class 3:
  • focal & segmental proliferative glomerulonephritis
  • 20% nephritic with or without nephrotic syndrome
    • < 50% of glomeruli involved
  • hypertension may be present
  • progresses to class 4 in 20% of patients
• class 4:
  • diffuse proliferative glomerulonephritis
  • 70% nephritic with or without nephrotic syndrome
    • > 50% of glomeruli involved
  • necrotizing lesions with large amounts of subendothelial deposits
  • active SLE serology
  • active urine sediment
  • treatable with glucocorticoids with or without cytotoxic agents
• class 5:
  • membranous glomerulonephritis
  • nephrotic syndrome without active sediment
  • usually not treatable with immunosupressive agents
• class 6
  • advanced sclerosing glomerulonephritis
  • > 90% glomerulosclerosis
  • no treatment prevents renal failure

Etiology

• systemic lupus erythematosus (SLE)
• drug induced lupus seldom involves the kidney
• common in women with active SLE during pregnancy

Epidemiology

• 50% of lupus patients present with renal disease
• 90% of lupus patients have renal disease at some time during their disease
• poor outcomes in African Americans & Hispanics compared to Caucasians

Pathology

• acute & chronic tubulointerstitial nephritis
• vasculitis
• chronic changes (not responsive to therapy)
  • glomerular scarring
  • tubular atrophy
  • interstitial fibrosis
• thrombotic microangiopathy (hypercoagulable states due to antiphospholipid antibodies & anticardiolipin antibodies)
• renal vein thrombosis

Clinical manifestations

• new onset hypertension or edema
• often begins concurrently with or shortly after the onset of SLE
  • features of SLE generally present
    • polyarthritis, oral ulcers ...

Laboratory

• anti-nuclear antibody in serum present
• dsDNA antibodies in serum present with high titer
• CH50: hypocomplementemia
  • low complement C3 in serum & complement C4 in serum
• urinalysis:
  • proteinuria (> 500 mg/24 hours)
  • hematuria
  • erythrocyte casts, granular casts
• laboratory features of SLE may be present

Diagnostic procedures

• renal biopsy for suspected lupus nephritis
  • required for diagnosis
  • defines histologic subtype, degree of disease activity & chronicity for treatment planning
  • begin high dose glucocorticoid prior to biopsy

Management

• ACE inhibitor or ARB for class 1 or 2 lupus nephritis
• therapy for proliferative glomerulonephritis (class 3 or 4)
  • high-dose glucocorticoids for 6-8 weeks
  • cyclophosphamide
    • 0.5-1.0 g/m2 IV every 4-6 weeks
    • may be given in combination with azathioprine
    • 6 monthly doses may be most effective regimen
    • continue every 3 months for up to 2 years
  • mycophenolate may be better than cyclophosphamide or azathioprine for induction & for maintenance of remission (up to 48 months)
  • combination prednisone/mycophenolate recommended for flare of lupus nephritis (class IV)
• class 5 membranous lupus nephritis
  • glucocorticoids + cyclophosphamide similar to class 4
    • cyclosporine, tacrolimus* or mycophenolate less toxic than cyclophosphamide
• supportive therapy for membranous glomerulonephritis
• anticoagulation for thrombotic events
• hydroxychloroquine for all patients with lupus nephritis, unless contraindicated; not mentioned in (MKSAP)
• lupus 'burns out' with end-stage renal disease & generally does not recur in renal transplant recipients
• renal transplantation lowers ESRD-associated mortality ~50%

* or other calcineurin inhibitor

More general terms

• glomerulonephritis (GN, nephritic syndrome)
• systemic lupus erythematosus

Additional terms

• nephrotic syndrome

Patient information

lupus nephritis patient information