What antifibrotic therapy is recommended for a patient with fibrotic Non-Specific Interstitial Pneumonia (NSIP) and Chronic Kidney Disease (CKD)?

Antifibrotic Therapy for Fibrotic NSIP in CKD Patients

Nintedanib is the preferred antifibrotic agent for progressive fibrotic NSIP in patients with CKD, as it can be used after failure of standard immunosuppressive management and has demonstrated efficacy in progressive pulmonary fibrosis regardless of underlying ILD subtype. 1

Treatment Algorithm

First-Line Approach

• Initiate nintedanib for progressive fibrotic NSIP after standard management (typically immunosuppressive therapy) has failed to stabilize disease 1, 2
• Nintedanib is conditionally recommended for progressive pulmonary fibrosis in non-IPF interstitial lung diseases, including fibrotic NSIP 1
• The INBUILD trial demonstrated that nintedanib reduced FVC decline in 663 patients with progressive pulmonary fibrosis, including those with NSIP 1

Alternative Option

• Pirfenidone may be considered as an alternative, though evidence is weaker with only conditional recommendation (62% committee support vs 38% abstaining due to insufficient evidence) 1
• The RELIEF trial included NSIP patients but was terminated early for futility, limiting confidence in pirfenidone's efficacy specifically for fibrotic NSIP 1

CKD-Specific Considerations

Drug Safety in CKD

• Pirfenidone use in CKD is limited - only 24.6% of IPF patients with CKD received pirfenidone, with 89.5% of those not requiring renal replacement therapy 3
• Nintedanib is hepatically metabolized, making it theoretically safer in CKD patients, though dose adjustments should be discussed with nephrology 1
• Mortality in IPF patients with comorbid CKD did not increase regardless of antifibrotic use, suggesting safety of these agents when appropriately selected 3

Monitoring Requirements

• Assess FVC and DLCO every 3-6 months to monitor treatment response and disease progression 2
• Monitor liver function tests monthly for the first 6 months, then every 3 months thereafter 2
• Coordinate with nephrology for medication dosing adjustments based on renal function 1

Managing Adverse Effects

Nintedanib-Specific

• Gastrointestinal effects are most common: diarrhea (2.8× increased risk), nausea (3.1×), vomiting (3.6×), abdominal pain (4.2×) 1
• Hepatotoxicity: elevated AST (3.2×) and ALT (3.6×) 1
• Management strategy: dose reduction (7.9× more likely needed) or temporary treatment interruption 1, 2
• Treatment discontinuation occurs in 1.9× more patients compared to placebo 1

Pirfenidone-Specific (if used)

• Common effects: nausea, rash, photosensitivity, fatigue, diarrhea, elevated liver enzymes 2
• Management: gradual dose titration, take with food, strict sun avoidance 2

Critical Caveats

What to Avoid

• Do NOT use triple therapy (prednisone + azathioprine + N-acetylcysteine) as it increases mortality 2
• Avoid corticosteroid monotherapy except for incapacitating cough or acute exacerbations 2
• Nephrotoxic antibiotics (aminoglycosides, tetracyclines) must be avoided in CKD patients 1

Standard Management Before Antifibrotics

• Standard management for fibrotic NSIP typically includes immunosuppressive therapy (corticosteroids with azathioprine, mycophenolate, or rituximab) 1
• Antifibrotics should only be initiated after documented progression despite immunosuppression 1
• Progression is defined by: FVC decline ≥10% predicted, FVC decline 5-10% with worsening symptoms/imaging, or worsening radiographic fibrosis 1

Supportive Measures

• Annual influenza and pneumococcal vaccinations are strongly recommended 2
• Long-term oxygen therapy for severe hypoxemia at rest 2
• Consider lung transplantation for patients <65 years with severe or worsening disease 2