What is the initial approach to assessing and managing a patient with Systemic Lupus Erythematosus (SLE) with suspected renal involvement?

Initial Assessment and Management of SLE with Suspected Renal Involvement

The initial approach to a patient with SLE and suspected renal involvement should include screening for proteinuria, hematuria, and kidney function assessment, followed by kidney biopsy when indicated to guide appropriate immunosuppressive therapy. 1

Diagnostic Approach

Initial Screening

• Urinalysis: Look for:
  • Proteinuria (dipstick ≥2+)
  • Active urinary sediment (acanthocytes ≥5%, RBC casts, WBC casts)
• Quantification of proteinuria:
  • Urine protein-to-creatinine ratio (UPCR) in morning first void urine
  • 24-hour urine protein collection
• Kidney function assessment:
  • Serum creatinine
  • eGFR calculation
  • Look for unexplained decrease in GFR or abnormal eGFR below expected level for age

Laboratory Workup

• Anti-dsDNA antibodies (marker of disease activity)
• Complement levels (C3 and C4) - low levels suggest active disease
• Anti-C1q antibodies (when available)
• Antiphospholipid antibodies (important to identify concurrent thrombotic microangiopathy)
• Serum albumin (low levels suggest nephrotic syndrome)

Kidney Biopsy Indications

Kidney biopsy should be performed when there is evidence of kidney involvement, particularly:

• Persistent proteinuria ≥0.5 g/24 hours (or UPCR ≥500 mg/g)
• Unexplained decrease in GFR 1

Biopsy remains indispensable as clinical findings do not always correlate with the extent or severity of kidney involvement. The diagnostic and prognostic value cannot be substituted by other clinical or laboratory variables. 1

Classification and Assessment

The International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification system should be used to categorize lupus nephritis:

• Class I: Minimal mesangial LN
• Class II: Mesangial proliferative LN
• Class III: Focal LN (<50% of glomeruli affected)
• Class IV: Diffuse LN (≥50% of glomeruli affected)
• Class V: Membranous LN
• Class VI: Advanced sclerosing LN

Additional assessment should include:

• Activity and chronicity indices
• Thrombotic and vascular lesions associated with antiphospholipid syndrome
• Tubulointerstitial lesions (fibrosis and tubular atrophy) 1

Management Approach

Initial Treatment Based on LN Class

1. Class III or IV LN (with or without Class V):

   • Immunosuppressive agents combined with glucocorticoids
   • Options include:
     • Mycophenolate mofetil (MMF) 2-3 g/day + glucocorticoids
     • Low-dose IV cyclophosphamide (500 mg × 6 biweekly doses) + glucocorticoids
     • For nephrotic-range proteinuria with adverse prognostic factors: consider MMF/calcineurin inhibitor combination or high-dose cyclophosphamide 1

2. Pure Class V LN:

   • For nephrotic-range proteinuria or proteinuria >1 g/24 hours despite RAAS blockers:
     • MMF + glucocorticoids is preferred 1

3. Class II LN:

   • Usually does not require specific immunosuppressive therapy
   • Monitor closely as it may progress to more severe classes 1

Hydroxychloroquine

• All patients with SLE, including those with lupus nephritis, should receive hydroxychloroquine unless contraindicated
• Regular ophthalmological monitoring is required 1

Glucocorticoid Regimen

• Initial: IV methylprednisolone pulses, followed by oral prednisone 0.3-0.5 mg/kg/day
• Aim to taper to low-dose (<7.5 mg/day) or discontinue during maintenance phase 1

Monitoring Disease Activity

Regular monitoring is essential as kidney involvement can remain silent or asymptomatic:

• Urinalysis and UPCR at each visit
• Serum creatinine and eGFR
• Anti-dsDNA antibodies and complement levels
• Blood pressure control

Treatment Targets

• Complete response: proteinuria <0.5-0.7 g/24 hours with (near-) normal GFR by 12 months
• This target may be extended in patients with baseline nephrotic-range proteinuria 1

Special Considerations

High-Risk Populations

Maintain higher vigilance for patients with:

• Asian, African/Caribbean, or Hispanic descent
• Childhood-onset SLE (associated with higher incidence of LN and more severe disease) 1

Pregnancy Considerations

• Active LN patients should avoid pregnancy until disease is inactive for ≥6 months
• Continue hydroxychloroquine during pregnancy
• Start low-dose aspirin before 16 weeks gestation
• Safe immunosuppressants during pregnancy: glucocorticoids, hydroxychloroquine, azathioprine, tacrolimus, and cyclosporine 1

Pitfalls to Avoid

1. Delaying kidney biopsy: Clinical findings do not always correlate with histological severity. Biopsy provides crucial information for treatment decisions and prognosis.

2. Underestimating mild proteinuria: The severity of proteinuria can vary considerably in active nephritis and may appear relatively "insignificant" at times.

3. Inadequate monitoring: SLE patients should be actively and regularly monitored for kidney involvement, even when asymptomatic.

4. Overlooking antiphospholipid syndrome: Test for antiphospholipid antibodies in all SLE patients with suspected kidney involvement, as thrombotic microangiopathy carries prognostic implications.

5. Discontinuing hydroxychloroquine: This medication should be continued in all patients unless contraindicated, as it reduces flare rates and improves outcomes.