www.kidney-international.

org KDIGO executive conclusions

Executive summary of the KDIGO 2024 Clinical

Practice Guideline for the Management of OPEN
ANCA–Associated Vasculitis
Jürgen Floege1, David R.W. Jayne2, Jan-Stephan F. Sanders3, Vladimı́r Tesar4, Ethan M. Balk5,
Craig E. Gordon6, Gaelen Adam5, Marcello A. Tonelli7, Michael Cheung8, Amy Earley8 and Brad H. Rovin9
1
Division of Nephrology, University Hospital, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, Aachen, Germany; 2Division
of Experimental Medicine & Immunotherapeutics, School of Clinical Medicine, University of Cambridge, Cambridge, UK; 3Division of
Nephrology, Department of Internal Medicine, University of Groningen, Groningen, The Netherlands; 4Department of Nephrology, 1st
Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic; 5Center for Evidence Synthesis in Health,
Brown University School of Public Health, Providence, Rhode Island, USA; 6Division of Nephrology, Tufts Medical Center, Boston,
Massachusetts, USA; 7Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; 8KDIGO,
Brussels, Belgium; and 9Department of Internal Medicine, The Ohio State University College of Medicine, Columbus, Ohio, USA

I
In 2021, the Kidney Disease: Improving Global Outcomes n 2021, a major revision of the Kidney Disease: Improving
(KDIGO) Guideline for the Management of Glomerular Global Outcomes (KDIGO) Clinical Practice Guideline for
Diseases was published. KDIGO is committed to providing the Management of Glomerular Diseases was published.1
the nephrology community with periodic updates, based Since publication, important data concerning anti-
on new developments for each disease. For patients with neutrophil cytoplasmic antibody (ANCA)–associated vascu-
anti-neutrophil cytoplasmic antibody (ANCA)–associated litis (AAV) have become available, prompting this guideline
vasculitis (AAV), avacopan received regulatory approval in update. Probably the most significant development has been
late 2021, leading to this KDIGO guideline update. In the approval of the C5a receptor inhibitor avacopan by the
addition, the evidence supporting a lower-dose United States Food and Drug Administration (FDA) and the
glucocorticoid induction regimen or even complete European Medicines Agency (EMA) as add-on therapy to
replacement of glucocorticoids has become stronger. standard-of-care for the treatment of AAV.2,3 This develop-
Herein, an executive summary of the most important ment directly relates to the second major emerging novel
guideline changes from the AAV chapter is provided as a approach to the treatment of AAV, namely, a reduction of
quick reference. systemic glucocorticoid exposure. Although the latter is
Kidney International (2024) 105, 447–449; https://doi.org/10.1016/ obviously desirable, given the short- and long-term compli-
j.kint.2023.10.009 cations of glucocorticoids, it is less clear which patients need
KEYWORDS: ANCA-associated vasculitis; glomerular diseases; glomerulone- avacopan in order to allow for lower glucocorticoid dosages.
phritis; guideline; KDIGO; systematic review At the same time, this new therapy adds significant cost to
Copyright ª 2023, Kidney Disease: Improving Global Outcomes (KDIGO). treatment, and long-term safety data are currently lacking.
Published by Elsevier Inc. on behalf of the International Society of
This Executive Summary provides a brief snapshot of the
Nephrology. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/). updated guideline, but readers are encouraged to view the full
chapter for detailed discussion and useful practice points
(Supplementary Table S1; https://kdigo.org/guidelines/gd/).
No major changes have been made in sections related to
diagnosis and assessment of prognosis of AAV (https://kdigo.
org/guidelines/gd/). The most important update in the ANCA
guideline relates to induction therapy. Recommendation
9.3.1.1, “We recommend that glucocorticoids in combina-
tion with cyclophosphamide or rituximab be used as initial
treatment of new-onset AAV (1B),” did not change, but the
Correspondence: Jürgen Floege, Division of Nephrology, RWTH Aachen discussion now places stronger emphasis on a more rapid
University Hospital, Pauwelsstrasse 30, Aachen 52074, Germany. E-mail:
jfl[email protected]
reduction of glucocorticoid dose, based on the recent Low-
Dose Glucocorticoid Vasculitis Induction Study (LoVAS),
The complete KDIGO 2024 Clinical Practice Guideline for the Management
of Antineutrophil Cytoplasmic Antibody (ANCA)–Associated Vasculitis is
among others.4 The study randomized patients with AAV to
published in Kidney International, volume 105, issue 3S, 2024, which is receive reduced-dose prednisolone (0.5 mg/kg/d) or high-
available online at www.kidney-international.org. dose prednisolone (1 mg/kg/d) plus 4 doses of 375 mg/m2/
Received 11 September 2023; revised 20 October 2023; accepted 20 wk rituximab. Reduced-dose glucocorticoids led to a similar
October 2023 remission rate, but the frequency of severe infections was

Kidney International (2024) 105, 447–449 447

KDIGO executive conclusions J Floege et al.: Executive summary of KDIGO 2024 AAV Guideline

Diagnosis of AAV

Disease assessment

Induction of remission

No organ-threatening Vital organ/life-threatening

involvement Serum creatinine >3.4 mg/dl (>300 µmol/l)

Rituximab + Cyclophosphamide + Rituximab + cyclophosphamide

(glucocorticoid taper (glucocorticoid taper OR
OR avacopan) OR avacopan) Cyclophosphamide +
(glucocorticoid taper OR avacopan)

Consider plasma exchange

Disease control
‘on drug’ remission

Maintenance

Continue Switch to azathioprine

rituximab Taper glucocorticoids

Stop Taper
rituximab azathioprine

Figure 1 | Practical treatment regimen for antineutrophil cytoplasmic antibody–associated vasculitis (AAV).

reduced. A limitation of the study is that it included only remission and severe adverse events was graded as moderate,
Japanese patients with predominantly myeloperoxidase but the certainty of evidence for infections and discontinua-
(MPO)-ANCA-associated vasculitis. Nonetheless, these data tion due to adverse events were graded as low. The Work
support the “reduced-glucocorticoid dose” as used in the Group considered the results of both randomized controlled
Plasma Exchange and Glucocorticoids for the Treatment of trials (RCTs) when deciding to make avacopan a practice
ANCA-Associated Vasculitis (PEXIVAS) trial.5 point rather than a recommendation. Patients with an
The most important change in AAV induction therapy is increased risk of glucocorticoid toxicity are likely to benefit
the availability of avacopan for AAV (Figure 1; Practice Point most from avacopan. Furthermore, a post hoc analysis of
9.3.1.1 and Practice Point 9.3.1.7 in guideline). Two patients with low glomerular filtration rate (GFR) (<30 ml/
placebo-controlled randomized controlled trials (RCTs) min per 1.73 m2) suggested greater GFR recovery with ava-
studied avacopan in AAV; one of the RCTs (A Phase 3 Clinical copan as compared to glucocorticoid therapy.8
Trial of CCX168 [Avacopan] in Patients with ANCA- Controversy still surrounds the value of plasma exchange in
Associated Vasculitis [ADVOCATE]) had no serious meth- AAV patients with a severe clinical course. From the Public
odological concerns,6 but the other RCT (Clinical ANCA Review, approval for Practice Point 9.3.1.9. was relatively low, at
Vasculitis Safety and Efficacy Study of Inhibitor of C5aR 75%: “Consider plasma exchange for patients with serum
[CLASSIC]) had a high dropout rate and changed the a priori creatinine (SCr) >3.4 mg/dl (>300 mmol/l), patients requiring
primary outcome.7 The certainty of the evidence for sustained dialysis or with rapidly increasing SCr, and patients with diffuse

448 Kidney International (2024) 105, 447–449

J Floege et al.: Executive summary of KDIGO 2024 AAV Guideline KDIGO executive conclusions

alveolar hemorrhage who have hypoxemia.” However, a 2022 JF reports receiving consultancy fees and/or speaker honoraria
meta-analysis concluded that there is a reduction of kidney from AstraZeneca, Bayer, Calliditas, Chinook, GlaxoSmithKline,
failure at 12 months with plasma exchange, with no evidence of Novartis, Omeros, Otsuka, Stadapharm, and Travere; and serving on
data safety monitoring boards for Novo Nordisk and Visterra. DRWJ
subgroup effects, but it comes at the cost of an increased risk of reports receiving consultancy fees from AstraZeneca,
serious infections.9 At present, the routine use of plasma ex- GlaxoSmithKline, Novartis, Takeda, and Vifor; grant/research support
change is not recommended for patients presenting with a from GlaxoSmithKline*, Roche*, and Vifor*; funding for lectures,
GFR <50 ml/min per 1.73 m2, but it can be considered in presentations, speakers’ bureaus, manuscript writing or educational
patients with more severe presentations (SCr >3.4 mg/dl [>300 events from Otsuka and Vifor; serving on a Data Safety Monitoring
mmol/l], especially if oliguric) or those with alveolar hemor- Board or Advisory Board for Chinook and GlaxoSmithKline; receiving
rhage and hypoxemia, in whom early mortality is high. Plasma funding support for a leadership or fiduciary role at Aurinia; and
receiving stock or stock options from Aurinia. VT reports receiving
exchange should be used in patients with concomitant anti- funding for a leadership or fiduciary role at Calliditas, Novartis,
glomerular basement membrane (GBM) disease. Conversely, Omeros, Otsuka, and Travere. CEG reports receiving consultancy fees
plasma exchange is not required for therapy of diffuse alveolar from Alexion; serving on the speaker bureau for Alexion; and
hemorrhage in the absence of hypoxemia. receiving funding for travel and/or accommodation from Alexion.
Maintenance therapy has not changed in the 2024 guide- MAT reports receiving payment for expert testimony from Gilead
line update, and Recommendation 9.3.2.1 still states “We Sciences (not related to the guideline topic). BHR reports receiving
recommend maintenance therapy with either rituximab, or consultancy fees from Alexion, AstraZeneca, Aurinia, Bristol Myers
Squibb, Exagen, Genentech, GlaxoSmithKline, Kezar Life Sciences,
azathioprine and low-dose glucocorticoids after induction Kyverna, Novartis, and Otsuka; and grant/research support from
of remission (1C).” For both azathioprine and rituximab, the Biogen*. All the other authors declared no competing interests.
updated guideline now mentions an optimal duration of *Monies paid to institution.
therapy of between 18 months and 4 years after the induction
of remission. As a maintenance drug, rituximab can be dosed
on a fixed schedule or upon reappearance of CD19þ B cells SUPPLEMENTARY MATERIAL
and/or ANCA, but dosing based on B cell counts led to fewer Supplementary File (PDF)
Supplementary Table S1. Comparison of the 2021 and 2024 KDIGO
infusions and thus lower cost.10,11
Clinical Practice Guideline for the Management of Antineutrophil
Even in patients on kidney replacement therapy, extrarenal Cytoplasmic Antibody (ANCA)–Associated Vasculitis.
AAV can and does relapse, and a remission should be
consolidated with maintenance therapy. In patients with kid-
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