PMC10288105_01
Efficacy of ANCA autoantibody clearance by high-dose IVIGs prior to PEX treatment. (A) Timeline of the reported case with clinical symptoms, diagnostic workup and treatment regimens. (B) Chest CT scans of the lungs showed bilateral ground-glass opacities and severe DAH compatible with pulmonary vasculitis. (C) A representative kidney section stained with periodic acid-Schiff confirmed mixed class pauci-immune, necrotizing, and crescentic ANCA-associated glomerulonephritis (scale bar: 50 mum). (D) Measurements of MPO-ANCAs are aligned to the left axis, bar graphs of percentual MPO-ANCA reduction without and with high-dose application of IVIGs (1 g/kg body weight) two hours prior to PEX treatment to the right axis. (E) Measurements of serum MPO-ANCA autoantibody levels before/after the first application of high-dose IVIGs. (F) Measurements of percentual serum MPO-ANCA reduction directly assessed before/after PEX treatment are aligned to the left axis, percentual MPO-ANCAs measured in the exchange fluid relative to serum levels to the right axis.
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At admission, she presented with lung failure requiring non-invasive mechanical ventilation (PaO2/FiO2 ratio 153 mmHg), acute kidney injury (serum creatinine of 1.43 mg/dL, reference range: 0.5-1 mg/dL; eGFR 36 mL/min/1.73 m2, reference range: >60 mL/min/1.73 m2), and albuminuria (953 mg/g creatinine, reference range: <30 mg/g), and hematuria ( Figure 1A  and  Table 1 ). Computed tomography (CT) scans showed bilateral ground-glass opacities and severe DAH compatible with pulmonary vasculitis ( Figure 1B ), a kidney biopsy showed pauci-immune crescentic ANCA-associated glomerulonephritis ( Figure 1C ), and laboratory testing confirmed presence of myeloperoxidase (MPO)-ANCA autoantibodies (>134 IU/mL, reference range: <3.5 IU/mL,  Table 1 ). Direct assessment of MPO-ANCAs before the sixth PEX treatment and two days thereafter showed limited efficacy of circulating MPO-ANCA autoantibody elimination (647 IU/mL to 575 IU/mL, 11% reduction,  Figure 1D ). After high-dose application of IVIGs (1 g/kg body weight, 70 g in total, Kiovig 10g/100mL, Takeda Manufacturing Austria AG, Vienna, Austria) two hours prior to the next PEX treatment, efficacy of MPO-ANCA autoantibody elimination was almost doubled (575 IU/mL to 452 IU/mL, 21% reduction,  Figure 1D ). Based on these observations, IVIGs were administered prior to additional two PEX treatments and resulted in rapid clearance of MPO-ANCA autoantibodies ( Figure 1D ). Figure 1F ). Pulmonary hemorrhage rapidly ceased and mechanical ventilation was no longer required, while high-dose IVIGs were well tolerated not exacerbating kidney injury ( Figure 2A ). Furthermore, white blood cell (WBC) counts (reference range: 4,000-11,000/microL), and fibrinogen levels (reference range: 200-393 mg/dL) were stable by using FFP substitution ( Figure 2B ).
High-dose IVIGs did not exacerbate kidney injury. (A) Measurements of serum creatinine are aligned to the left axis, bar graphs of albuminuria to the right axis. Respective arrowheads indicate PEX without and with high-dose application of IVIGs (1 g/kg body weight) two hours prior to treatment. (B) Measurements of WBC counts are aligned to the left axis, bar graphs of fibrinogen levels to the right axis. Respective arrowheads indicate PEX without and with high-dose application of IVIGs (1 g/kg body weight) two hours prior to treatment.
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Figure 1F ). Pulmonary hemorrhage rapidly ceased and mechanical ventilation was no longer required, while high-dose IVIGs were well tolerated not exacerbating kidney injury ( Figure 2A ). Furthermore, white blood cell (WBC) counts (reference range: 4,000-11,000/microL), and fibrinogen levels (reference range: 200-393 mg/dL) were stable by using FFP substitution ( Figure 2B ).