What treatment options are available for patients with Sjögren's (Systemic Lupus Erythematosus) syndrome and progressive Chronic Kidney Disease (CKD) who may have Sjögren's associated interstitial nephritis, even without active interstitial infiltrate?

Treatment Options for Sjögren's Associated Interstitial Nephritis Without Active Infiltrate

For patients with Sjögren's syndrome and progressive chronic kidney disease who have interstitial nephritis even without active interstitial infiltrate, immunosuppressive therapy with glucocorticoids and mycophenolate mofetil is recommended as first-line treatment to improve renal function and prevent progression to end-stage renal disease. 1

Understanding Sjögren's-Associated Renal Disease

• Renal involvement occurs in approximately 10% of patients with primary Sjögren's syndrome, with tubulointerstitial nephritis (TIN) being the most common manifestation 2
• Even without active interstitial infiltrate on biopsy, chronic tubulointerstitial changes can lead to progressive kidney dysfunction in Sjögren's patients 3
• Renal manifestations in Sjögren's syndrome include:
  • Tubulointerstitial nephritis (most common) 2
  • Renal tubular acidosis (distal or proximal) 1
  • Glomerulonephritis (less common, often membranoproliferative type) 3

Diagnostic Considerations

• Kidney biopsy remains the gold standard for diagnosis, even when active infiltrate may not be prominent 1
• CD4+ T-cell infiltrates are the predominant finding in Sjögren's-associated TIN, even when infiltration appears minimal 1
• Laboratory evaluation should include:
  • Urinalysis for hematuria, leukocyturia, and proteinuria (predictors of progressive renal dysfunction) 4
  • Serum creatinine and estimated GFR 3
  • Testing for tubular dysfunction (urinary acidification, electrolytes) 1
  • Complement levels and anti-dsDNA antibodies to monitor disease activity 5

Treatment Algorithm

First-Line Therapy

• Glucocorticoids plus Mycophenolate Mofetil (MMF)
  • Initial high-dose oral glucocorticoids (prednisone 0.5-1 mg/kg/day) with gradual taper over 3-6 months 5
  • MMF (starting at 500 mg twice daily, increasing to 1-2 g/day as tolerated) as steroid-sparing agent 1
  • This combination has shown significant improvement in renal function in patients with Sjögren's TIN 1

Alternative First-Line Options

• For patients with contraindications to glucocorticoids:
  • Consider rituximab (1000 mg IV on days 0 and 15) 5
  • Especially effective in patients with systemic manifestations beyond renal involvement 5

For Progressive or Refractory Disease

• Cyclophosphamide should be considered for rapidly progressive disease or when other therapies fail 5

  • Intravenous pulse therapy (0.5-0.75 g/m² every 2-4 weeks) is preferred over oral administration to reduce bladder toxicity 5
  • Pneumocystis jirovecii prophylaxis is mandatory with cyclophosphamide 5

• Rituximab (1 g IV given 2 weeks apart) may be effective in refractory cases 5

  • Particularly useful in patients with cryoglobulinemic glomerulonephritis associated with Sjögren's 3

Supportive Care

• Renin-angiotensin system (RAS) blockade with ACE inhibitors or ARBs for patients with proteinuria 5
• Hydroxychloroquine (200-400 mg daily) may be beneficial, particularly in patients with mild disease 5
• Electrolyte supplementation for patients with renal tubular acidosis or other electrolyte disturbances 1

Monitoring Response to Treatment

• Monitor serum creatinine and eGFR every 1-3 months during active treatment 1
• Assess urinary parameters (proteinuria, hematuria) regularly 4
• Follow complement levels and anti-dsDNA antibodies as markers of disease activity 5
• Consider repeat kidney biopsy in cases of treatment failure or unexpected deterioration 5

Prognosis and Special Considerations

• Without treatment, approximately 40% of patients with Sjögren's-associated TIN will develop chronic kidney disease 4
• Early treatment improves outcomes, with event-free (death or CKD) survival of approximately 89% at 5 years 4
• Patients with glomerular involvement (especially cryoglobulinemic) generally respond better to immunosuppressive therapy than those with pure TIN 3
• Patients with established chronic damage and eGFR <30 ml/min/1.73m² may have limited response to immunosuppression 5

Clinical Pearls and Pitfalls

• Even without active infiltrate on biopsy, progressive renal dysfunction can occur in Sjögren's patients, warranting treatment 3
• Baseline hematuria, leukocyturia, proteinuria, and thrombocytopenia are independent predictors of rising creatinine and should prompt more aggressive therapy 4
• Fatigue, polyarthritis, and vasculitis at baseline are predictors of nephritis development and may warrant closer renal monitoring 4
• Anti-Ro/SSA and anti-La/SSB antibodies are associated with higher risk of renal involvement 4