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

Best Next Step in Management

Perform a renal biopsy to confirm the diagnosis, assess disease activity and chronicity, and guide appropriate immunosuppressive therapy for lupus nephritis. 1

Rationale for Renal Biopsy as the Priority

While this patient clearly has active SLE with evidence of lupus nephritis (positive anti-dsDNA, proteinuria/hematuria), the renal biopsy is the critical next step because it determines the specific histologic class of nephritis, degree of active inflammation versus chronic damage, and thereby dictates the intensity and type of immunosuppressive therapy required. 1

Why Biopsy Takes Precedence

• Renal biopsy confirms the diagnosis, evaluates disease activity versus chronicity/damage, and determines prognosis and appropriate therapy in suspected lupus nephritis. 1
• The histologic classification (proliferative Class III/IV versus membranous Class V versus mixed patterns) fundamentally changes treatment decisions - proliferative disease requires aggressive induction with cyclophosphamide or mycophenolate mofetil plus high-dose corticosteroids, while membranous disease may be managed less aggressively. 1
• The chronicity index on biopsy (interstitial fibrosis, tubular atrophy, glomerular sclerosis) predicts response to immunosuppression - patients with high chronicity scores are less likely to benefit from aggressive immunosuppression and may need focus on blood pressure control instead. 2

Why Other Options Are Insufficient as the "Next Step"

Blood Pressure Control (Option C) - Important But Not First

• Hypertension control is absolutely essential in lupus nephritis and persistent hypertension after treatment is a major predictor of end-stage renal disease (P < 0.0001) and persistent proteinuria (P = 0.0001). 2
• However, blood pressure management is an adjunctive therapy that should be initiated concurrently with, not instead of, definitive diagnosis and immunosuppressive treatment. 3
• The blood pressure of 155/90 mmHg, while elevated, is not a hypertensive emergency requiring immediate intervention before establishing the diagnosis. 1

Corticosteroid Therapy (Option B) - Premature Without Biopsy

• Starting corticosteroids before biopsy is problematic because the histologic findings guide the intensity and duration of immunosuppression. 1
• Proliferative lupus nephritis (Class III/IV) requires combination therapy with corticosteroids PLUS cyclophosphamide, mycophenolate mofetil, or calcineurin inhibitors - corticosteroids alone are insufficient. 1, 4
• The 2024 KDIGO guidelines and 2024 APLAR consensus recommend combination immunosuppression as first-line therapy, not corticosteroids alone. 1, 4
• Starting empiric corticosteroids may partially treat the disease but delays definitive diagnosis and risks under-treatment if proliferative disease is present. 1

Reassurance (Option A) - Dangerous and Inappropriate

• This patient has active, potentially severe lupus nephritis requiring immediate evaluation and treatment. 1
• Lupus nephritis leads to end-stage renal disease in 10% of cases at 10 years, making early aggressive treatment essential to preserve renal function. 1, 5

The Algorithmic Approach After Biopsy

Once biopsy results are available, management proceeds as follows:

For Proliferative Lupus Nephritis (Class III/IV)

• Induction therapy: Glucocorticoids (methylprednisolone pulses followed by oral prednisone) PLUS either cyclophosphamide, mycophenolate mofetil, or calcineurin inhibitors. 1, 4
• Triple immunosuppression with belimumab or voclosporin added to standard therapy shows superior efficacy in recent high-quality trials. 1
• Maintenance therapy should continue for at least 36 months with mycophenolate mofetil or azathioprine to reduce renal flares. 1, 4

For Membranous Lupus Nephritis (Class V)

• Less aggressive immunosuppression may be appropriate depending on degree of proteinuria and renal function. 1

Concurrent Management Regardless of Histology

• Aggressive blood pressure control targeting <130/80 mmHg with ACE inhibitors or ARBs as first-line agents. 3, 2
• Hydroxychloroquine should be initiated in all SLE patients unless contraindicated, as it reduces mortality and disease activity. 6, 5
• Monitor for response at 6-12 months: complete response is proteinuria <0.5 g/g with stable/improved renal function; partial response is ≥50% reduction in proteinuria to <3 g/g. 1

Critical Pitfalls to Avoid

• Do not delay biopsy due to concerns about bleeding risk - the diagnostic and prognostic information is essential and outweighs the procedural risk in most cases. 1
• Do not start immunosuppression empirically without histologic confirmation - the specific regimen depends on the biopsy findings. 1
• Do not neglect blood pressure control while pursuing immunosuppression - persistent hypertension is the strongest predictor of poor renal outcome and should be addressed immediately alongside definitive therapy. 2
• Patients with persistent anti-dsDNA antibodies and hypocomplementemia after treatment are at high risk for renal relapse and may require continuation of immunosuppressive therapy. 2