Nephritis, Lupus

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

Diagnosis

• 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

Treatment

• No treatment required for classes I and II

• 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

  • Typically given at 2–3 g orally daily, 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

• 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