Diagnosis of Lupus Nephritis
Lupus nephritis should be diagnosed through a combination of clinical criteria, laboratory testing, and most importantly, a renal biopsy to determine the specific histological class, which is essential for guiding appropriate treatment decisions. 1
Clinical and Laboratory Diagnosis
Initial Screening
Urinalysis findings that suggest lupus nephritis:
Laboratory abnormalities:
When to Suspect Lupus Nephritis
- Higher suspicion should be maintained for patients of Asian, African/Caribbean, and Hispanic descent 1
- Childhood-onset SLE is associated with higher incidence and more severe nephritis 1
- Regular monitoring is crucial as kidney involvement may be asymptomatic 1
Renal Biopsy: The Gold Standard
Indications for Renal Biopsy
- All patients with clinical evidence of active lupus nephritis should undergo renal biopsy unless strongly contraindicated 1
- Particularly recommended in patients with:
- Increasing serum creatinine without explanation
- Confirmed proteinuria ≥0.5 g/day (or equivalent spot protein/creatinine ratio)
- Combinations of proteinuria (≥0.5 g/day), active urinary sediment, and hypertension 1
Why Biopsy is Essential
- Clinical and laboratory parameters alone cannot accurately predict the histological class of lupus nephritis 3
- Studies show poor correlation between clinical staging based on laboratory findings and actual histological staging 3
- Biopsy allows assessment of both activity and chronicity indices, which guide treatment decisions 1
- Can identify alternative or additional causes of renal disease 1
Histological Classification
Renal biopsy specimens should be classified according to the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification 1, 4:
| Class | Description | Treatment Implications |
|---|---|---|
| I | Minimal mesangial immune deposits | Generally no immunosuppression needed |
| II | Mesangial hypercellularity/matrix expansion | Generally no immunosuppression needed |
| III | Focal proliferative (<50% of glomeruli) | Requires aggressive immunosuppression |
| IV | Diffuse proliferative (≥50% of glomeruli) | Requires aggressive immunosuppression |
| V | Membranous | Requires specific treatment approach |
| VI | Advanced sclerosis (≥90% of glomeruli) | Preparation for renal replacement |
Pathological Assessment
- Light microscopy, immunofluorescence, and electron microscopy (where available) 1
- Assessment should include:
- Active lesions (potentially reversible with treatment)
- Chronic damage (not reversible with immunosuppression)
- Tubular and vascular changes 1
Diagnostic Pitfalls to Avoid
Relying solely on clinical parameters: Laboratory findings alone cannot accurately predict histological class 3
Dismissing mild proteinuria: Even "insignificant" levels of proteinuria can be present in severe active nephritis 1
Delaying biopsy: Early diagnosis and treatment significantly impact long-term renal outcomes 5
Inadequate biopsy assessment: Ensure biopsies are read by experienced renal pathologists and classified according to ISN/RPS criteria 1
Missing concomitant pathologies: Biopsy can identify additional causes of renal disease beyond lupus nephritis 1
Monitoring After Diagnosis
- Regular assessment of renal function, proteinuria, and urinary sediment 4
- Monitor serum C3/C4 and anti-dsDNA antibody levels 4, 2
- Consider repeat renal biopsy in cases of:
- Treatment failure
- Relapse
- Unexplained worsening of GFR 4
By following this diagnostic approach, clinicians can accurately diagnose lupus nephritis, determine its specific histological class, and guide appropriate treatment decisions to improve patient outcomes and reduce morbidity and mortality.