Randomized Trial of Plasma Exchange or High-Dosage Methylprednisolone as Adjunctive Therapy for Severe Renal Vasculitis

Abstract

Systemic vasculitis associated with autoantibodies to neutrophil cytoplasmic antigens (ANCA) is the most frequent cause of rapidly progressive glomerulonephritis. Renal failure at presentation carries an increased risk for ESRD and death despite immunosuppressive therapy. This study investigated whether the addition of plasma exchange was more effective than intravenous methylprednisolone in the achievement of renal recovery in those who presented with a serum creatinine Ͼ500 mol/L (5.8 mg/dl). A total of 137 patients with a new diagnosis of ANCA-associated systemic vasculitis confirmed by renal biopsy and serum creatinine Ͼ500 mol/L (5.8 mg/dl) were randomly assigned to receive seven plasma exchanges (n ϭ 70) or 3000 mg of intravenous methylprednisolone (n ϭ 67). Both groups received oral cyclophosphamide and oral prednisolone. The primary end point was dialysis independence at 3 mo. Secondary end points included renal and patient survival at 1 yr and severe adverse event rates. At 3 mo, 33 (49%) of 67 after intravenous methylprednisolone compared with 48 (69%) or 70 after plasma exchange were alive and independent of dialysis (95% confidence interval for the difference 18 to 35%; P ϭ 0.02). As compared with intravenous methylprednisolone, plasma exchange was associated with a reduction in risk for progression to ESRD of 24% (95% confidence interval 6.1 to 41%), from 43 to 19%, at 12 mo. Patient survival and severe adverse event rates at 1 yr were 51 (76%) of 67 and 32 of 67 (48%) in the intravenous methylprednisolone group and 51 (73%) of 70 and 35 of (50%) 70 in the plasma exchange group, respectively. Plasma exchange increased the rate of renal recovery in ANCA-associated systemic vasculitis that presented with renal failure when compared with intravenous methylprednisolone. Patient survival and severe adverse event rates were similar in both groups.

An Unusual Case of Hematuria

“…Plasma exchange has been shown to be beneficial in patients with segmental necrotizing glomerulonephritis and severe renal disease (36,37). The randomized MEPEX trial enrolled 137 patients with a new diagnosis of pauci-immune glomerulonephritis and the results supported the findings that plasma exchange was more effective than methylprednisolone pulses in renal function recovery (33). Therefore, plasma exchange is currently the best complementary treatment to immunomodulation in advanced renal disease (29 -31).…”

“…Oral and pulse CYC has been shown to be equivalent in terms of clinical response (32). In a randomized controlled trial comparing the efficacy of oral CYC (2 mg/kg/day) with intravenous pulse CYC (15 mg/kg every 2 weeks for the first 3 pulses, then every 3 weeks) with the same corticosteroid regimen in both arms (CYCLOPS trial [randomized trial of daily oral versus pulse CYC as therapy for ANCAassociated systemic vasculitis]) (32), CYC pulses were found to be associated with fewer episodes of leukopenia and the cumulative dose of the drug was inferior to that found in patients treated with oral CYC, but there was a tendency toward more frequent relapses in the patients treated with pulse CYC (32)(33)(34). Our patient was placed on daily oral CYC along with corticosteroids, since she had an increased risk of relapse due to her age and rapidly worsening kidney function, as well as the presence of the sclerosis pattern in the tissue specimen.…”

S1 guidelines Diagnostics and treatment of ANCA-associated vasculitis

“…Höher dosierte GC-Pulse (bis zu 1000 mg Methylprednisolon/Tag) wurden in einigen Studienprotokollen ver-wendet, jedoch wurde deren Nutzen bisher nicht systematisch untersucht [106]. Sie können initial bei besonders schwerwiegenden Verläufen erwogen werden.…”

“…Für GPA-und MPA-Patienten mit einer schweren Nierenfunktionseinschränkung (Kreatinin >500 μmol/l bzw. >5,8 mg/dl) durch eine aktive rapid progrediente Glomerulonephritis (RPGN) konnte in einer randomisiert kontrollierten Studie gezeigt werden, dass eine zu oraler CYC-Medikation zusätzliche Plasmaseparation gegenüber 3 Methylprednisolonpulsen initial zu einer höhe-ren Rate an Dialysefreiheit ohne Vorteile im Gesamtüberleben führt [106]. Im Langzeit-Follow-up ließen sich keine signifikanten Vorteile der Plasmaseparation mehr nachweisen, möglicherweise als Folge der hohen Gesamtmortalität der Kohorte bei kleiner Fallzahl [253].…”

Intravenous Immunoglobulin as an Immunomodulating Agent in Antineutrophil Cytoplasmic Antibody–Associated Vasculitides: A French Nationwide Study of Ninety‐Two Patients

“…To minimize adverse events, caution should be taken, and since advanced age is the major risk factor for venous thromboembolism (38,39), the risk/benefit ratio should be carefully evaluated in this population. IVIG should probably be avoided if the estimated glomerular filtration rate is ,30 ml/minute/1.73 meter 2 , with plasma exchanges being a likely beneficial alternative if an adjunctive therapy is needed (40).…”