Management of antineutrophil cytoplasmic antibody-associated vasculitis with glomerulonephritis as proposed by the ACR 2021, EULAR 2022 and KDIGO 2021 guidelines/recommendations

Abstract

Updated guidelines on the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) were released in 2021 by the American College of Rheumatology jointly with the Vasculitis Foundation and, subsequently, in 2022 by the European Alliance of Associations for Rheumatology. In addition, in 2021, the Kidney Disease: Improving Global Outcomes had released updated recommendations on the treatment of AAV with glomerulonephritis (AAV-GN). Kidney involvement is particularly relevant in microscopic polyangiitis and granulomatosis with polyangiitis, but is less frequent in eosinophilic granulomatosis with polyangiitis. The management of AAV-GN has been a focus for drug development and change over the past 10 years. Avoidance of progression to end-stage kidney disease (ESKD) or kidney failure is one of the main unmet needs in the management of AAV, with ESKD having a major impact on morbidity, health costs and mortality risk. Relevant changes in AAV-GN management are related to remission-induction treatment of patients with severe kidney disease, the use of glucocorticoids and avacopan, and remission-maintenance treatment. All the documents provide guidance in accordance with the evidence-based standard of care available at the time of their release. With our work we aim to (i) show the progress made and identify the differences between guidelines and recommendations, (ii) discuss the supporting rationale for those, and (iii) identify gaps in knowledge that could benefit from additional research and should be revised in subsequent updates.

Keywords: ANCA-associated vasculitis; glomerulonephritis; granulomatosis with polyangiitis; guidelines; microscopic polyangiitis.

Figure 1:

Comparison of the ACR/VF guidelines, the EULAR recommendations and KDIGO guideline on AAV management. (1) According to individual factors (Table 2). (2) No RCTs have assessed the benefit of RTX/CYC combination over RTX. However, the RTX/CYC combination has been shown to reduce cumulative CYC exposure in RITUXVAS and retrospective studies have indicated the possibility of GC minimization and improved responses that require investigation in an RCT (NCT03942887). (3) The ACR/VCRC guidelines recommend against the routine use of PLEX. However, it is added that PLEX may be considered for certain patients with active GN or those who are critically ill and whose disease is not responding to recommended remission induction therapies (i.e. plasma exchange as “salvage” or “rescue” therapy). Thus, there is no reference to the severity of kidney disease. (4) PLEX may be considered as part of therapy to induce remission in GPA or MPA for those with a SCr >300 µmol/L (>3.4 mg/dL) due to active GN. Routine use of plasma exchange to treat alveolar hemorrhage in GPA and MPA is not recommended. (5) IVIG or immunoglobulin G replacement therapy should be considered in the context of severe infection and hypogammaglobulinemia. IVIG, intravenous immunoglobulin; LFN, leflunomide; O/LT, organ-/life-threatening; RI, remission-induction; RM, remission-maintenance; TMP/SMX, trimethoprim/sulfamethoxazole.