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For further information, see CMDT Part 22-15: Nephritic Spectrum Glomerular Diseases

Key Features

  • Renal involvement is common in systemic lupus erythematosus (SLE), occurring in 35–90% of SLE patients

Clinical Findings

  • History and physical examination consistent with SLE

  • Urinalysis: hematuria and proteinuria


  • Kidney biopsy shows one of six histologic patterns

    • Class I: minimal mesangial nephritis

    • Class II: mesangial proliferative

    • Class III: focal (< 50% of glomeruli affected with capillary involvement) proliferative

    • Class IV: diffuse (> 50% of glomeruli affected with capillary involvement) proliferative

    • Class V: membranous nephropathy

    • Class VI: advanced sclerosis without residual disease activity

  • Class III and IV, the most severe forms of proliferative lupus nephritis, are further classified as active or chronic, and global or segmental, which confers additional prognostic value


  • No treatment required for classes I and II

  • Hydroxychloroquine should be considered for all patients with lupus nephritis, regardless of histologic class

  • Corticosteroids should be considered for those with class II lesions with nephrotic-range proteinuria

  • Aggressive immunosuppressive therapy for extensive class III lesions and all class IV lesions

  • Immunosuppressive therapy for class V lupus nephritis is indicated if superimposed proliferative lesions exist

  • Class VI lesions should not be treated

  • Corticosteroids: methylprednisolone, 1 g once daily for 3 days intravenously, followed by prednisone, 1 mg/kg once daily orally with subsequent taper for 6–12 months

  • Cyclophosphamide induction regimens

    • Vary, but usually involve monthly intravenous pulse doses (500–1000 mg/m2) for 6 months

    • Induction is followed by daily oral mycophenolate mofetil or azathioprine maintenance therapy

  • Cyclosporine or tacrolimus may be considered, but relapse is high upon discontinuation

  • Mycophenolate mofetil

    • Used to treat class V disease with or without rituximab

    • Typically given at 2–3 g/day orally, then tapered to 1–2 g/day for maintenance

    • Has a more favorable side-effect profile than does cyclophosphamide

    • Should be favored when preservation of fertility is a consideration

  • Rituximab

    • Was used in addition to corticosteroids and mycophenolate mofetil for class III/IV LN induction therapy in a recent clinical trial but did not show significant renal improvement over placebo at 1 year

    • Remission rates with induction vary from 80% for partial remission to 50–60% for full remission

    • Relapse is common and rates of disease flare are higher in those who do not experience complete remission

  • The use of add-on B-cell targeted therapy with rituximab or belimumab for class III, IV, and/or V disease may be considered

  • Monitoring dsDNA antibodies; C3, C4, and CH50; urinary protein; and urine sediment activity can be useful during treatment

  • Patients with SLE undergoing kidney transplants can have recurrent kidney disease, although rates are relatively low

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