What is the best next step in management for a patient with systemic lupus erythematosus (SLE) presenting with photosensitivity, malar rash, arthritis, positive Anti-double stranded Deoxyribonucleic acid (Anti-dsDNA) antibodies, evidence of lupus nephritis, and hypertension?

Management of SLE with Lupus Nephritis and Hypertension

The best next step is to perform a renal biopsy (Option D) to definitively classify the lupus nephritis and guide appropriate immunosuppressive therapy, while simultaneously initiating blood pressure control. 1

Rationale for Renal Biopsy as Priority

Renal biopsy is essential before initiating immunosuppressive therapy for lupus nephritis because the histologic class (proliferative vs. membranous) fundamentally determines treatment intensity and regimen. 1 The KDIGO 2024 guidelines emphasize that biopsy classification directly informs whether patients require aggressive induction with cyclophosphamide or mycophenolate mofetil versus less intensive approaches. 1

• Biopsy provides independent predictive value for clinical outcomes that cannot be obtained from serologic markers alone. 1, 2 While positive anti-dsDNA and low complement suggest active nephritis, they have limited ability to predict treatment response or guide therapy selection. 1

• The distinction between Class III/IV (proliferative) versus Class V (membranous) lupus nephritis is critical, as proliferative forms require immediate intensive immunosuppression with glucocorticoids plus either mycophenolate mofetil (2-3 g/day) or cyclophosphamide, while membranous disease may be managed differently. 1

Concurrent Blood Pressure Management

While awaiting biopsy, blood pressure control should be initiated immediately using renin-angiotensin system (RAS) blockade (ACE inhibitors or ARBs). 1 This patient's BP of 155/90 mmHg requires intervention because:

• Hypertension is both a complication of lupus nephritis and an independent risk factor for progressive renal damage. 1

• RAS blockade provides dual benefits: blood pressure reduction and antiproteinuric effects that may slow nephritis progression. 1

• The EULAR guidelines specifically recommend antihypertensive therapy (including ACE inhibitors) as adjunctive management in SLE patients with renal involvement. 1

Why Other Options Are Inadequate

Reassurance (Option A) is inappropriate because this patient has active lupus nephritis with hypertension—both require immediate intervention to prevent irreversible renal damage and reduce mortality risk. 1

Starting corticosteroids alone (Option B) without biopsy confirmation is suboptimal because:

• Modern guidelines emphasize minimizing glucocorticoid exposure, with target maintenance doses <7.5 mg/day prednisone equivalent. 1, 3
• Proliferative lupus nephritis requires combination therapy (glucocorticoids PLUS immunosuppressive agents like mycophenolate mofetil or cyclophosphamide), not steroids alone. 1
• Starting empiric high-dose steroids without histologic confirmation exposes patients to unnecessary toxicity if the nephritis class doesn't warrant such aggressive therapy. 1

Blood pressure control alone (Option C) addresses only one component of this multiorgan disease and delays definitive diagnosis and treatment of potentially rapidly progressive glomerulonephritis. 1

Optimal Management Algorithm

1. Perform renal biopsy urgently to classify lupus nephritis histologically. 1

2. Simultaneously initiate:

   • ACE inhibitor or ARB for blood pressure control and renoprotection. 1
   • Hydroxychloroquine (≤5 mg/kg real body weight) if not already prescribed, as this reduces flares and organ damage in all SLE patients. 2, 3, 4

3. Based on biopsy results, initiate class-specific induction therapy:

   • For Class III/IV (proliferative): Glucocorticoids (methylprednisolone pulse followed by oral prednisone tapered to <7.5 mg/day by 3 months) PLUS mycophenolate mofetil (2-3 g/day for 6 months) OR cyclophosphamide (500 mg IV every 2 weeks × 6 doses). 1
   • For Class V (membranous): Consider less intensive regimens based on proteinuria severity and renal function. 1

4. Target at least partial remission (≥50% reduction in proteinuria to subnephrotic levels with creatinine within 10% of baseline) within 6-12 months. 1, 2

Critical Pitfalls to Avoid

• Do not delay biopsy based on positive anti-dsDNA alone, as serologic markers cannot reliably distinguish nephritis class or guide treatment intensity. 1

• Avoid prolonged high-dose glucocorticoid monotherapy, which increases infection risk, cardiovascular complications, and osteoporosis without addressing the underlying immune-mediated injury adequately. 1

• Do not ignore hypertension management, as uncontrolled BP accelerates renal damage through non-immune mechanisms even with appropriate immunosuppression. 1

• Recognize that this patient requires holistic SLE management including photoprotection for cutaneous manifestations, cardiovascular risk assessment, infection prophylaxis considerations, and bone health monitoring given anticipated glucocorticoid exposure. 1