What is the best test to diagnose lupus nephritis?

Diagnosing Lupus Nephritis: Best Testing Approach

Renal biopsy is the gold standard and optimal test for diagnosing lupus nephritis, allowing classification of disease type and guiding treatment decisions. 1

Initial Diagnostic Approach

• Lupus nephritis should be suspected in SLE patients with clinical and laboratory manifestations that meet ACR criteria: persistent proteinuria >0.5g/day or >3+ by dipstick, and/or cellular casts (red cell, hemoglobin, granular, tubular or mixed) 1
• A spot urine protein/creatinine ratio >0.5 can substitute for the 24-hour protein measurement 1
• Active urinary sediment (>5 RBC/hpf, >5 WBC/hpf without infection, or RBC/WBC casts) can substitute for cellular casts 1

Renal Biopsy: The Definitive Test

• All patients with clinical evidence of active lupus nephritis should undergo renal biopsy unless strongly contraindicated 1
• Biopsy allows classification according to the International Society of Nephrology/Renal Pathology Society (ISN/RPS) criteria, which guides treatment decisions 1
• Biopsy is particularly recommended in patients with:
  • Increasing serum creatinine without compelling alternative causes 1
  • Confirmed proteinuria ≥1.0 g/24 hours 1
  • Proteinuria ≥0.5 g/24 hours plus hematuria or cellular casts 1
  • Even patients with lower levels of proteinuria (<1000 mg/24h) may have significant renal disease requiring biopsy 2

Biopsy Processing and Evaluation

• Renal tissue should be processed for:
  • Light microscopy (LM) 1, 3
  • Immunofluorescence (IF) 1, 3
  • Electron microscopy (EM) 1, 3
• A minimum of 10 glomeruli is generally appropriate for evaluation 1
• Biopsy allows classification into six classes (I-VI) according to ISN/RPS criteria 1

Classification and Scoring Systems

• ISN/RPS classification divides lupus nephritis into classes I-VI based on glomerular involvement 1
• Activity Index (AI) and Chronicity Index (CI) should be assessed to evaluate:
  • AI: presence of fresh inflammatory and potentially reversible lesions 3
  • CI: presence of irreversible glomerular lesions (sclerosis, tubular atrophy, interstitial fibrosis) 3
• High AI with low CI suggests potential benefit from aggressive treatment 3
• High CI with low AI indicates irreversible damage where aggressive immunosuppression may not be beneficial 3

Clinical Implications of Biopsy Findings

• Class I (minimal mesangial) and Class II (mesangial hypercellularity) generally do not require immunosuppressive treatment 1
• Class III (focal proliferative, <50% of glomeruli) and Class IV (diffuse proliferative, ≥50% of glomeruli) require aggressive therapy with glucocorticoids and immunosuppressive agents 1
• Class V (membranous) when combined with III or IV should be treated like III or IV; pure membranous may be approached differently 1
• Class VI (advanced sclerosis in ≥90% of glomeruli) generally requires preparation for renal replacement therapy rather than immunosuppression 1

Repeat Biopsies

• Protocol repeat biopsies may be valuable to:
  • Detect histological class transformation (occurs in approximately 25% of cases) 4
  • Identify progression to greater chronicity 4
  • Guide treatment modifications in cases of treatment resistance or relapse 5

Pitfalls to Avoid

• Do not rely solely on clinical parameters without biopsy, as histopathological lesions may precede symptoms and clinical manifestations 3
• Do not exclude biopsy in patients with low-level proteinuria (<1000 mg/24h), as significant renal disease (Class III, IV, or V) can still be present 2
• Avoid delaying biopsy in patients with suspected lupus nephritis, as early diagnosis and treatment improves outcomes 5
• Remember that non-lupus renal diseases can coexist in SLE patients, making biopsy essential for accurate diagnosis 5, 2