What is the emergency management for an adult presenting with pulmonary‑renal syndrome characterized by hemoptysis, diffuse alveolar hemorrhage, and rapidly progressive glomerulonephritis?

Emergency Management of Pulmonary-Renal Syndrome

Initiate immediate triple therapy with high-dose corticosteroids, cyclophosphamide, and plasmapheresis as soon as pulmonary-renal syndrome is suspected—do not wait for biopsy confirmation or antibody results, especially in rapidly deteriorating patients. 1, 2

Immediate Diagnostic Steps

Urgent Serologic Testing

• Send ANCA (MPO and PR3), anti-GBM antibodies, ANA, and complement levels immediately upon presentation 2, 3
• Anti-GBM antibodies can be falsely negative in ~10% of cases, making tissue diagnosis critical when feasible 2
• Approximately 90% of patients with small-vessel vasculitis have detectable ANCA, though negativity does not exclude diagnosis 2, 3

Clinical Presentation Recognition

• Look for hemoptysis, dyspnea, hypoxemia (PO2 often <60 mmHg on room air), microscopic hematuria with dysmorphic RBCs, red cell casts, and rapidly rising creatinine over days to weeks 2, 4, 5
• Diffuse alveolar hemorrhage may be subtle—bronchoalveolar lavage can detect occult bleeding when clinical signs are minimal 6

Immediate Treatment Algorithm

Step 1: Start Empirical Therapy Immediately (Do Not Delay)

If positive anti-GBM antibodies or clinical suspicion for Goodpasture's disease:

• Pulse IV methylprednisolone (typically 500-1000 mg daily for 3 days) 1, 2
• Begin plasmapheresis immediately (daily exchanges until anti-GBM antibodies undetectable on 2 consecutive tests) 1, 2
• Use fresh frozen plasma for replacement if alveolar hemorrhage present or recent kidney biopsy performed; otherwise albumin is sufficient 1
• Add oral cyclophosphamide 2-3 mg/kg daily once infection excluded, dose-adjusted for reduced GFR or older age 1, 2

If positive ANCA or clinical suspicion for ANCA-associated vasculitis:

• High-dose glucocorticoids (oral prednisolone 1 mg/kg/day up to 60-80 mg, or pulse IV methylprednisolone if severe) 2
• Cyclophosphamide or rituximab as induction agent 3, 2
• Plasmapheresis for severe presentations: diffuse alveolar hemorrhage with hypoxemia, or serum creatinine >500 μmol/L (>5.7-5.8 mg/dL), especially if oliguric 2

Step 2: Critical Pre-Treatment Exclusion

• Rule out active infection before starting immunosuppression—check hepatitis B and C serologies, obtain cultures, consider chest imaging for occult infection 3, 2, 7

Step 3: Determine When NOT to Treat

Withhold immunosuppression only if ALL three criteria present: 1, 2

• Dialysis-dependent at presentation, AND
• 100% crescents (or >50% global glomerulosclerosis) on adequate biopsy, AND
• No pulmonary hemorrhage

Critical exception: Always treat pulmonary hemorrhage regardless of renal status or biopsy findings 1, 2

Disease-Specific Considerations

Anti-GBM Disease (Goodpasture's)

• Accounts for ~20% of pulmonary-renal syndrome cases 3, 6
• Plasmapheresis is mandatory (not optional) in anti-GBM disease—continue daily until antibodies undetectable 1, 2
• Complete glucocorticoid therapy by 6 months; oral prednisone taper after pulse steroids 1, 2
• No maintenance immunosuppression needed for isolated anti-GBM disease (relapse rate <5%) 1
• Exception: Double-positive patients (anti-GBM + ANCA) require maintenance therapy as for AAV, since relapse rates equivalent to ANCA-vasculitis 1

ANCA-Associated Vasculitis

• Accounts for ~60% of pulmonary-renal syndrome cases 3, 6
• Plasmapheresis role varies by guideline: KDIGO 2020 and EULAR/ERA-EDTA 2016 favor plasmapheresis for diffuse alveolar hemorrhage with hypoxemia 2
• Reduced-dose glucocorticoid regimens are as effective and safer than standard dosing (PEXIVAS trial data)—target 15 mg prednisolone by 12 weeks 2
• Maintenance therapy required after induction to prevent relapse 1

Prognostic Indicators

Favorable for Treatment Response

• Not requiring dialysis within 72 hours of presentation, even with creatinine >500 μmol/L 1, 2
• Presence of alveolar hemorrhage (indicates acute, potentially reversible disease) 1, 2
• Acute tubular injury, <50% glomerulosclerosis, <100% crescents on biopsy 2

Poor Prognosis

• Dialysis-dependent at presentation with 100% crescents: 35% mortality rate, >90% remain on dialysis at 1 year 1, 2
• Delayed treatment initiation: untreated mortality up to 96% in anti-GBM disease 2

Supportive Care

Respiratory Support

• Mechanical ventilation may be required for severe alveolar hemorrhage with respiratory failure 4, 7
• Monitor oxygen saturation closely—median PO2 at presentation often 5.8 kPa (~44 mmHg) 4

Renal Support

• Initiate hemodialysis for uremic complications or severe hyperkalemia 7, 2
• Dialysis requirement at presentation does NOT preclude immunosuppressive therapy if other favorable features present 1, 2

Prophylaxis During Treatment

• Trimethoprim-sulfamethoxazole for Pneumocystis prophylaxis until cyclophosphamide complete AND prednisone <20 mg daily 1

Common Pitfalls to Avoid

• Do not delay treatment waiting for biopsy confirmation—begin empirical therapy immediately when pulmonary-renal syndrome suspected 1, 2, 3
• Do not withhold treatment from patients with severe renal impairment (creatinine >500 μmol/L) if not yet dialysis-dependent 1
• Do not forget maintenance therapy in double-positive (anti-GBM + ANCA) patients—they behave like AAV, not isolated anti-GBM disease 1
• Do not use standard ANCA-vasculitis protocols for isolated anti-GBM disease—plasmapheresis is essential and maintenance therapy unnecessary 1, 2

Long-Term Considerations

• Defer kidney transplantation until anti-GBM antibodies undetectable for minimum 6 months 1
• Monitor for relapse in first 2 years, though anti-GBM disease is typically monophasic 2