Induction Therapy in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis with Renal Involvement: The Nephrologist’s Point of View

Abstract

Renal involvement with rapidly progressive glomerulonephritis is a common manifestation of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides characterised by end-stage renal disease and high mortality rates in untreated and late referral patients. Long-term renal survival has improved dramatically since the addition of cyclophosphamide and, more recently, rituximab in association with corticosteroids to remission induction therapeutic regimens. However, renal prognosis remains unfavourable for many patients and mortality is still significantly higher than in the general population. In this review, the open challenges to be addressed to optimise remission induction therapy, especially in patients with advanced kidney failure, are analysed. This concerns the first-line therapy (cyclophosphamide or rituximab) based on different parameters (estimated glomerular filtration rate at baseline, new or relapsed disease, ANCA specificity, tissue injury, and safety) and the role of plasma exchange. Furthermore, the paper discusses future perspectives on induction remission therapy by reporting recent advances in new targeted therapies, with particular reference to avacopan, an orally administered selective C5a receptor inhibitor.

Predictive utility of ANCA positivity and antigen specificity in the assessment of kidney disease in paediatric-onset small vessel vasculitis

“…12 13 In contrast, MPO-ANCA-positive AAV in adults typically presents with kidney-limited disease that is frequently more severe at presentation and more likely to progress to kidney failure 8 10 11 ; for these individuals, cyclophosphamide may be preferred for remissioninduction instead of rituximab. 14 The present study aimed to evaluate the potential clinical utility of ANCA positivity and specificity (for PR3 or MPO) as prognostic markers in paediatric-onset small vessel vasculitis, inclusive of AAV, and, of particular interest, whether our findings suggest similar, improved or limited utility relative to that reported in adult-onset AAV.…”

“… 12 13 In contrast, MPO-ANCA-positive AAV in adults typically presents with kidney-limited disease that is frequently more severe at presentation and more likely to progress to kidney failure 8 10 11 ; for these individuals, cyclophosphamide may be preferred for remission-induction instead of rituximab. 14 …”