Intravenous Cyclophosphamide and Plasmapheresis in Dialysis-Dependent ANCA-Associated Vasculitis

Abstract

Study (EUVAS) investigators SummaryBackground and objectives Induction therapy with oral cyclophosphamide (CYP) has been a mainstay of treatment in patients with severe renal failure secondary to ANCA-associated vasculitis (AAV). Recent evidence proposes using pulsed intravenous CYP in less severe disease to minimize adverse events. It is unclear if this can be translated to those with dialysis-dependent renal insufficiency.Design, setting, participants, & methods All AAV patients presenting between 2005 and 2010 requiring dialysis at presentation were retrospectively analyzed. Patients were treated with plasma exchange, corticosteroids, and intravenous CYP. Rate of dialysis independence at 3 and 12 months and adverse effects were assessed and compared with the outcome of the plasmapheresis, prednisolone, and oral CYP arm of the randomized MEPEX (methylprednisolone versus plasma exchange) trial.Results Forty-one patients were included. At 3 months, 3 (7.3%) patients had died on dialysis, 12 (29.3%) remained dialysis dependent, and 26 (63.4%) were dialysis independent (creatinine, 2.5 mg/dl; GFR, 26 ml/min per 1.73 m 2 ). Four patients subsequently reached ESRD at a median time of 83 days. Thirty-seven (90%) patients reached 1 year follow-up, 13 (35%) remained dialysis dependent, and 24 (65%) had independent renal function. Eleven patients (27%) had episodes of leukopenia (white cell count ,4310 9 /L) during CYP therapy and 17 (41%) experienced infectious complications. This compares favorably with the dialysis-dependent cohort treated with plasmapheresis in the MEPEX study in which 51% were alive with independent renal function at 1 year.Conclusions Intravenous CYP used with corticosteroids and plasmapheresis may be an effective alternative to oral CYP in patients with dialysis-dependent AAV.

Outcomes of Elderly Patients with Anti-Neutrophil Cytoplasmic Autoantibody-Associated Vasculitis Treated with Immunosuppressive Therapy

“…Numbers of patients in each of the treatment groups were small and only 46 patients were treated with oral cyclophosphamide (7 patients received no treatment), compared with a total of 110 patients aged >65 years in our cohort [13]. In multivariate analysis, increasing age was a significant predictor of survival as seen in our cohort; however, dialysis-dependence was not, in contrast to our findings and other studies [1,4,7,13]. The follow-up time in the study was relatively short (2 years) and the wide-ranging effects of immunosuppressive treatment in the elderly such as risk of infections, leukopenia and relapse were not assessed, which as we have shown, contribute to significant morbidity and mortality in this population.…”

“…Despite a greater total immunosuppression burden in younger patients, they were more likely to relapse than older patients (p = 0.004). This may relate to PR3-positivity, which is a major prognostic factor for relapse in AAV as well as renal survival in long-term follow-up [3,7,19,20,21,22]. PR3-positivity and age appear to be independent predictors of a poorer outcome in AAV [8,19].…”

“…AAV in the elderly population is associated with a poor prognosis with higher rates of death and progression to end-stage renal disease (ESRD) compared to the younger AAV population [3,4,6]. Furthermore, the elderly population are more susceptible to experiencing hazards of immunosuppression such as infection and malignancy [4,6,7]. …”

Management of Elderly Patients with Rapidly Progressive Glomerulonephritis

“…Thus, pulsed CYC has become increasingly used in the induction treatment in generalized AAV [27]. Later, Pepper et al [28] have shown that intravenous CYC (in combination with plasma exchange) may be successfully used even in the treatment of dialysis-dependent patients, who were excluded from the CYCLOPS Trial.…”

Modern Opportunities in Uveitis Treatment

“…Благодаря этому плазмаферез активно применяется при аутоиммунных заболеваниях, таких как системная красная волчанка, ревматоидный артрит, псориаз и др. [42,[44][45][46][47].…”