Lupus Nephritis
| Overview |
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- Nearly 80% of patients with Systemic Lupus Erythematosus (SLE) will develop inflammatory renal abnormalities, known as lupus nephritis, during the course of their disease. The most common manifestation of lupus nephritis is glomerular inflammation and is thought to be mediated by immune complex deposition within the glomerulus. Depending on the severity, a variety of morphologies of glomerulonephritis can develop. With mild disease patients may remain asymptomatic but with severe disease a picture of [nephritic syndrome]] tends to develop.
| Pathogenesis |
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- Lupus nephritis is largely thought to be a disease of pre-formed immune complex deposition within the glomerulus, especially within the mesangium and sub-endothelial space. Immune Complexes are likely composed of dsDNA in complex with anti-dsDNA Antibody and their deposition within the glomerulus leads to complement activation, immune infiltration, and attendant glomerular damage.
| Morphology and Clinical Consequences |
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- Overview
- A morphological classification system has been developed by the WHO for lupus nephritis and categorizes the disease into six morphological classes. Classes I-IV represent an increasing spectrum of inflammatory severity with increasingly aggressive nephritic symptoms including hematuria, secondary hypertension, azotemia, and oliguria. High titers of anti-dsDNA Antibody and hypocomplementemia often accompany the presentation. Class V disease is characterized by nephrotic range proteinuria and can occur on its own or in combination with the inflammatory classes III-IV. Class VI disease represents the healing phase of previous inflammation.
- In the absence of treatment, lupus nephritis will likely progress to acute renal failure. Treatment involves immunosupression typically with a pulse of high-dose corticosteroids; however, with advanced disease chronic renal failure is a common end-point.
- Class I: Minimal
- Normal morphology by light microscopy but presence of immune complexes by immunofluorescence. Patients are typically asymptomatic with almost no laboratory abnormalities.
- Class II: Mesangial
- Hypercellularity within the mesangium as well as mesangial matrix expansion. Presence of immune complexes by immunofluorescence. Patients are typically asymptomatic with evidence only of microscopic hematuria and proteinuria.
- Class III: Focal
- Less than 50% of glomeruli are affected and within a single glomerulus involvement is segmental, affecting only part of the structure. Proliferation of the mesangial cells and endothelial cells accompanied by neutrophilic infiltrate. Presence of immune complexes by immunofluorescence. Patients typically display hematuria, azotemia, and hypertension.
- Class IV: Diffuse
- Greater than 50% of glomeruli are affected and within a single glomerulus involvement may be segmental or global. Intense proliferation of the mesangial cells and endothelial cells accompanied by neutrophilic infiltrate are observed with the frequent crescent formation. Immune complex deposition may be so extensive that the capillary wall will appear diffusely thickened, reminiscent of "wire loops". Patients typically display the full-blown nephritic syndrome with hematuria, pyuria, secondary hypertension, azotemia, and oliguria.
- Class V: Membranous
- Diffuse deposition of sub-epithelial immune complexes on immunofluorescence accompanied by thickening of the glomerular basement membrane results in a clinical syndrome similar to membranous glomerulonephritis with associated nephrotic-range proteinuria. Class V disease may occur in isolation or may complicate CLass III-IV disease.
- Class VI: Sclerosing
- Diffuse and nearly uniform sclerosis of glomeruli in the absence of active glomerulonephritis, likely representing the healing of prior active glomerulonephritis. Patients typically display slowly progressive renal insufficiency ultimately ending in chronic renal failure.