What are the symptoms of a lupus nephritis flare?

From the Guidelines

Lupus nephritis flare symptoms include increased protein in the urine, blood in the urine, rising creatinine levels, decreased kidney function, swelling, high blood pressure, and foamy urine, and patients may also experience systemic lupus symptoms such as joint pain, fatigue, fever, and skin rashes. These symptoms can be detected through regular monitoring of kidney function using blood tests (creatinine, BUN) and urine tests (protein-to-creatinine ratio, urinalysis) 1. If symptoms of a flare occur, patients should contact their healthcare provider immediately as prompt treatment is crucial to prevent permanent kidney damage. Treatment typically involves immunosuppressive medications such as high-dose corticosteroids (prednisone 1mg/kg/day), mycophenolate mofetil (2-3g/day), or cyclophosphosphate, depending on the severity of the flare, as recommended by the joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) 1. Maintaining medication adherence, regular follow-up appointments, and lifestyle modifications like a low-sodium diet and blood pressure control are important for managing lupus nephritis and preventing flares. Some key points to consider in managing lupus nephritis include:

• The use of the International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 classification system for pathological assessment of kidney biopsy 1
• The importance of achieving complete renal response with UPCR <50 mg/mol and normal or near-normal renal function, and partial renal response defined as ≥50% reduction in proteinuria to subnephrotic levels and normal or near-normal renal function 1
• The recommendation for initial treatment with mycophenolic acid (MPA) or low-dose intravenous cyclophosphosphate (CY) in combination with glucocorticoids for patients with class III A or III A/C (±V) and class IVA or IVA/C (±V) lupus nephritis 1
• The consideration of adjunct treatment with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers, cholesterol lowering with statins, hydroxychloroquine, and acetyl-salicylic acid in patients with anti-phospholipid antibodies 1. Lupus nephritis flares occur due to increased autoimmune activity causing inflammation and damage to the kidney's filtering units (glomeruli), which can lead to progressive kidney dysfunction if not promptly addressed, as highlighted by the American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis 1.

From the Research

Lupus Nephritis Flare Symptoms

• Lupus nephritis flares are common in patients with severe proliferative lupus nephritis, even in those with a complete response to therapy 2
• Renal flares are indicated by an increase in proteinuria and/or serum creatinine concentration, abnormal urine sediment, or a reduction in creatinine clearance rate as a result of active disease 3
• Symptoms of lupus nephritis flares may include:
  • Increased proteinuria
  • Increased serum creatinine concentration
  • Abnormal urine sediment
  • Reduction in creatinine clearance rate
• Nephritic flares are more common than proteinuric flares, and are associated with a higher risk of progression to end-stage renal disease (ESRD) 2

Risk Factors for Lupus Nephritis Flares

• Low C4 at the time of response and African American ethnicity are significant independent risk factors for renal flare 2
• Patients with a partial response to therapy are more likely to experience a flare, have a severe nephritic flare, or progress to ESRD compared to those with a complete response 2

Treatment and Prevention of Lupus Nephritis Flares

• Appropriate immunosuppressive maintenance therapy may lead to a decrease in the occurrence of renal and extrarenal flares in patients with SLE 3
• Monitoring for the early detection and treatment of renal flares could improve outcomes 3
• Mycophenolate mofetil (MMF) and azathioprine (AZA) are effective and safe maintenance therapies for proliferative lupus nephritis, and may reduce the risk of renal flares 4, 5, 6