What is the best next step in managing 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?

Best Next Step: Perform a Renal Biopsy

The best next step in management is to perform a renal biopsy (Option D) while simultaneously initiating blood pressure control. Although this patient has clear evidence of lupus nephritis based on clinical and serological findings, the histologic classification obtained from biopsy is essential to guide the intensity and specific regimen of immunosuppressive therapy, which directly impacts long-term renal outcomes and patient survival 1.

Why Renal Biopsy Takes Priority

Biopsy provides independent predictive value for clinical outcomes that cannot be obtained from serologic markers alone. While positive anti-dsDNA antibodies and clinical evidence suggest active nephritis, these markers 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 combination therapy, while membranous disease may be managed differently 1.

• The KDIGO 2024 guidelines emphasize that biopsy classification determines whether patients require aggressive induction therapy (glucocorticoids plus mycophenolic acid analogs, cyclophosphamide, or combination regimens) or less intensive approaches 2.
• The American College of Rheumatology recommends performing renal biopsy to definitively classify lupus nephritis before initiating class-specific immunosuppressive therapy 1, 3.
• Delaying biopsy based on positive anti-dsDNA alone can lead to undertreatment and irreversible kidney damage 4.

Concurrent Blood Pressure Management

While arranging urgent biopsy, blood pressure control must be initiated immediately. The patient's BP of 155/90 mmHg requires intervention, as hypertension is both a complication of lupus nephritis and an independent risk factor for progressive renal damage 1.

• KDIGO 2024 guidelines recommend optimizing blood pressure and using renoprotective medications such as RAAS blockade (ACE inhibitors or ARBs) in stable patients without acute kidney injury 2.
• EULAR guidelines recommend antihypertensive therapy including ACE inhibitors as adjunctive management, providing dual benefits of blood pressure reduction and antiproteinuric effects that may slow nephritis progression 2, 1.
• Blood pressure control should be initiated using renin-angiotensin system blockade while awaiting biopsy results 1.

Why Other Options Are Inadequate

Reassurance (Option A) is inappropriate given the presence of active lupus nephritis with hypertension, which carries significant risk for progressive renal damage and poor outcomes if left untreated 1.

Starting corticosteroid therapy alone (Option B) without biopsy confirmation is suboptimal. While glucocorticoids are part of the treatment regimen, the KDIGO 2024 guidelines recommend combination therapy with glucocorticoids PLUS an additional immunosuppressive agent (mycophenolic acid analogs, cyclophosphamide, belimumab, or calcineurin inhibitors) based on the specific histologic class 2. Starting steroids without knowing the class risks either undertreatment or overtreatment and delays definitive therapy 1.

Blood pressure control alone (Option C) is necessary but insufficient. While hypertension management is critical, it does not address the underlying active immune-mediated glomerular injury that requires prompt immunosuppressive therapy guided by biopsy findings 1.

Optimal Management Algorithm

1. Arrange urgent renal biopsy to determine ISN/RPS histologic class and assess disease activity versus chronicity 1, 4.

2. Simultaneously initiate ACE inhibitor or ARB for blood pressure control and renoprotection 2, 1.

3. Ensure hydroxychloroquine is prescribed if not already taking it, as KDIGO recommends this for all SLE patients including those with lupus nephritis unless contraindicated 2.

4. Based on biopsy results showing Class III/IV nephritis, initiate combination induction therapy with glucocorticoids (pulse methylprednisolone followed by oral prednisone taper) plus one of the following: mycophenolic acid analogs, low-dose IV cyclophosphamide, belimumab with MPAA or cyclophosphamide, or MPAA with calcineurin inhibitor if eGFR >45 mL/min/1.73m² 2.

5. Target at least partial remission within 6-12 months with monitoring every 2-4 weeks initially 4, 5.

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. Rare cases of lupus nephritis with negative anti-dsDNA have been reported, further emphasizing that biopsy is the gold standard 6, 7.

Avoid prolonged high-dose glucocorticoid monotherapy, which increases infection risk and cardiovascular complications without addressing the need for class-specific combination immunosuppression 1.

Do not ignore hypertension management, as uncontrolled blood pressure accelerates renal damage and worsens long-term outcomes 1.

Recognize that patients require holistic SLE management including photoprotection (broad-spectrum sunscreen), cardiovascular risk assessment, infection prophylaxis, and bone health monitoring as outlined in KDIGO's risk attenuation strategies 2.