What is the treatment for acute complications of lupus nephritis?

Treatment of Acute Complications of Lupus Nephritis

For acute complications of lupus nephritis, immediate recognition and aggressive treatment are critical, with thrombotic microangiopathy (TMA) requiring urgent plasma exchange and glucocorticoids for suspected TTP, anticoagulation for antiphospholipid syndrome nephropathy, and high-dose methylprednisolone pulses combined with immunosuppression for acute severe proliferative disease. 1

Thrombotic Microangiopathy (TMA) Complications

Thrombotic Thrombocytopenic Purpura (TTP)

Rapid diagnosis and prompt treatment are the keys to good outcomes in TMA complicating lupus nephritis. 1

• Use the PLASMIC score to risk-stratify suspected TTP cases when ADAMTS13 testing is not immediately available 1
• If intermediate-to-high risk for TTP in adults, immediately initiate plasma exchange and glucocorticoids while awaiting ADAMTS13 results 1
• In children, TTP is less common and plasma exchange carries considerable morbidity, so deferring plasma exchange for 24-48 hours until ADAMTS13 confirmation is acceptable 1

Confirmed TTP (ADAMTS13 activity ≤10%) requires:

• Plasma exchange 1
• High-dose glucocorticoids 1
• Rituximab 1
• Caplacizumab (von Willebrand factor inhibitor) 1

Antiphospholipid Syndrome (APS) Nephropathy

APS nephropathy should be treated with long-term anticoagulation using warfarin, not direct oral anticoagulants. 1

• Approximately 30% of SLE patients have antiphospholipid antibodies 1
• In retrospective data of 97 patients with kidney TMA, anticoagulated aPLA-positive patients showed higher complete response rates (59.5% vs. 30.8%) compared to those without anticoagulation 1
• Direct oral anticoagulants are inferior to warfarin for preventing thromboembolic events in this setting 1
• Combine anticoagulation with immunosuppressive treatment for optimal outcomes 1

Catastrophic Antiphospholipid Syndrome

This life-threatening complication requires immediate multi-modal therapy:

• High-dose glucocorticoids 1
• Plasma exchange (associated with improved survival in retrospective studies) 1
• Rituximab (emerging evidence supports use) 1
• Eculizumab (complement inhibitor with emerging efficacy data) 1

Co-management with an experienced hematologist is preferable when available. 1

Acute Severe Proliferative Lupus Nephritis

Patients with Adverse Prognostic Factors

For acute deterioration in renal function with substantial cellular crescents and/or fibrinoid necrosis:

• Initiate treatment with intravenous methylprednisolone pulses (500-750 mg for 3 consecutive days) 1
• Follow with oral prednisone 0.5 mg/kg/day for 4 weeks, then taper to ≤10 mg/day by 4-6 months 1
• Combine glucocorticoids with one of the following immunosuppressive regimens: 1
  • Mycophenolic acid analogs (target dose 3 g/day MMF for 6 months) 1
  • Low-dose intravenous cyclophosphamide (500 mg every 2 weeks for 6 doses) 1
  • Belimumab plus either MPAA or low-dose cyclophosphamide 1
  • MPAA plus calcineurin inhibitor (if eGFR >45 ml/min per 1.73 m²) 1

Reduced-Dose Glucocorticoid Approach

The KDIGO 2024 guidelines support reduced-dose glucocorticoid regimens when kidney and extrarenal manifestations show satisfactory improvement: 1

• Methylprednisolone IV pulses: 0.25-0.5 g/day up to 3 days 1
• Oral prednisone: 0.5-0.6 mg/kg/day (max 40 mg) for weeks 0-2 1
• Rapid taper to 15 mg by weeks 5-6, then 5 mg by weeks 11-12 1
• Target <2.5 mg/day by week 25 and beyond 1

This approach minimizes glucocorticoid toxicity while maintaining efficacy. 1

Acute Kidney Injury in Lupus Nephritis

Prevention and Management Strategies

Avoid nephrotoxic insults and optimize renoprotective measures: 1

• Avoid high-sodium diet 1
• Optimize blood pressure control 1
• Use RAAS blockade in stable patients without AKI 1
• Consider SGLT2 inhibitors in stable patients 1
• Screen for and treat infections aggressively (HBV, HCV, HIV) 1
• Provide Pneumocystis jirovecii prophylaxis during intensive immunosuppression 1

Infection Complications

Sepsis is a leading cause of death in lupus nephritis patients (accounting for 12 deaths in one long-term cohort). 2

Preventive measures include:

• Assessment of herpes zoster and tuberculosis history 1
• HBV vaccination for non-immune patients 1
• Individualized recombinant zoster vaccine consideration 1
• Pneumocystis prophylaxis during high-dose immunosuppression 1

Monitoring During Acute Complications

Visits should be scheduled every 2-4 weeks during acute flares or complications: 1

• Monitor body weight, blood pressure, estimated GFR, serum albumin 1
• Assess proteinuria (UPCR or 24-hour collection) 1
• Check urine red cell count/sediment and complete blood count 1
• Evaluate for thrombocytopenia, hemolysis, and schistocytes if TMA suspected 1

Critical Pitfalls to Avoid

• Never use direct oral anticoagulants instead of warfarin for APS nephropathy 1
• Do not delay plasma exchange in adults with intermediate-to-high PLASMIC scores for suspected TTP 1
• Avoid switching therapy prematurely in patients with nephrotic-range proteinuria, as they may require 12-18 months to achieve complete response 1
• Do not overlook antiphospholipid antibody testing in patients with TMA, as 62.9% may be aPLA-positive 1