What are the diagnostic criteria for lupus nephritis in a patient with Systemic Lupus Erythematosus (SLE)?

Diagnostic Criteria for Lupus Nephritis

Lupus nephritis is diagnosed when a patient with SLE presents with persistent proteinuria >0.5 g/day (or spot urine protein/creatinine ratio >0.5) and/or active urinary sediment (>5 RBC/hpf, >5 WBC/hpf without infection, or cellular casts), with definitive diagnosis requiring renal biopsy showing immune complex-mediated glomerulonephritis classified by ISN/RPS criteria. 1, 2

Clinical Screening Criteria

The diagnostic approach begins with identifying urinary abnormalities in patients with established or suspected SLE:

Proteinuria Thresholds:

• Dipstick protein ≥2+ warrants quantification 1
• Persistent proteinuria >0.5 g/24 hours is the primary screening threshold 1, 2
• Spot urine protein/creatinine ratio >0.5 can substitute for 24-hour collection 1, 2

Active Urinary Sediment:

• 5 RBC/hpf or >5 WBC/hpf (in absence of infection) 1, 2

• Presence of cellular casts (RBC casts, WBC casts, hemoglobin, granular, or tubular casts) 1, 2
• Acanthocytes ≥5% 1

Renal Function Changes:

• Abnormal or decreasing eGFR below expected level for age with no attributable cause other than SLE 1

Renal Biopsy: The Definitive Diagnostic Standard

All patients with clinical evidence of active lupus nephritis should undergo renal biopsy unless strongly contraindicated. 1, 2 The biopsy serves multiple critical functions beyond diagnosis:

Absolute Indications for Biopsy:

• Proteinuria ≥1.0 g/24 hours alone 2
• Proteinuria ≥0.5 g/24 hours plus hematuria or cellular casts 1, 2
• Increasing serum creatinine without compelling alternative causes 2
• Even with eGFR <30 ml/min if kidney size is normal and there is evidence of active disease 2

Critical Timing Consideration: The biopsy should be performed within the first month after disease onset, preferably before initiating immunosuppressive treatment. 2 This timing is essential because clinical findings do not correlate reliably with histologic severity—proteinuria can appear "insignificant" even in severe active nephritis. 1

Adequate Biopsy Requirements

Minimum Technical Standards:

• At least 10 glomeruli for light microscopy evaluation 1, 2
• Light microscopy with H&E, PAS, Masson's trichrome, and silver stain 2
• Immunofluorescence for IgG, C3, IgA, IgM, C1q, κ and λ light chains 2
• Electron microscopy for ultrastructural evaluation (where available) 1

The biopsy must be read by an experienced renal pathologist and classified according to ISN/RPS criteria. 1, 2 This classification into Classes I-VI directly determines treatment strategy, as different classes require vastly different immunosuppressive regimens. 1, 2

ISN/RPS Classification and Clinical Implications

Class I (Minimal Mesangial): Immune deposits without hypercellularity—no immunosuppression required 2

Class II (Mesangial Proliferative): Mesangial hypercellularity (≥4 nuclei fully surrounded by matrix)—generally no immunosuppression needed 2

Class III (Focal Proliferative): <50% of glomeruli involved—requires aggressive therapy with glucocorticoids and immunosuppressive agents 2

Class IV (Diffuse Proliferative): ≥50% of glomeruli involved—requires aggressive therapy with glucocorticoids and cytotoxic agents 2

Class V (Membranous): When combined with III or IV, treat as III or IV; pure membranous may be approached differently 2

Class VI (Advanced Sclerosis): ≥90% glomerular sclerosis—prepare for renal replacement therapy rather than immunosuppression 2

Critical Diagnostic Pitfalls to Avoid

Do not rely solely on clinical parameters. Clinical, serological, or laboratory tests cannot accurately predict histological findings, and the threshold for biopsy should be low. 2 A holistic assessment including repeated investigations over time is essential, as proteinuria severity varies considerably even in severe active nephritis. 1

Do not delay biopsy for advanced GFR decline. Even with eGFR <30 ml/min, biopsy should be performed if kidney size is normal and there is evidence of active disease. 2

Recognize ANA-negative lupus nephritis exists. While rare, some patients present with biopsy-proven lupus nephritis despite negative ANA and other SLE serologies, requiring high clinical suspicion and close monitoring. 3

The diagnosis can be considered valid based on rheumatologist or nephrologist opinion when biopsy is contraindicated, but this represents a less optimal diagnostic pathway. 1