Clinical associations of renal involvement in ANCA-associated vasculitis

doi:10.1016/j.autrev.2020.102495

Autoimmunity Reviews

Volume 19, Issue 4, April 2020, 102495

https://doi.org/10.1016/j.autrev.2020.102495 Get rights and content

Abstract

Objective

Renal involvement in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis is associated with significant morbidity and higher mortality rates. This study examined clinical manifestations associated with renal involvement in ANCA-associated vasculitis within a large, international cross-sectional cohort.

Methods

Univariate and multivariate analyses were performed to identify clinical factors associated with renal disease, which was defined as i) a serum-creatinine >30% above normal and a fall in creatinine-clearance >25%; or ii) haematuria attributable to active vasculitis.

Results

The study cohort include 1230 patients from 31 countries; 723 (58.8%) presented with renal involvement: microscopic polyangiitis (82.2%), granulomatosis with polyangiitis (58.6%), and eosinophilic granulomatosis with polyangiitis (26.4%). The following clinical and laboratory factors were more common among patients with renal disease: age (OR 1.01, 95% CI 1.01–1.02), fever (OR 1.97, 95% CI 1.35–2.88), fatigue (OR 1.55, 95% CI 1.14–2.10), weight loss (OR 1.62, 95% CI 1.23–2.12), polyarthritis (OR 1.39, 95% CI 1.02–1.89), petechiae/purpura (OR 1.47, 95% CI 1.06–2.05), pulmonary haemorrhage (OR 5.23, 95% CI 1.39–19.63), gastrointestinal symptoms (OR 2.19, 95% CI 1.34–3.58), seizures (OR 3.42, 95% CI 1.26–9.30), lower serum albumin (OR 2.42, 95% CI 1.64–3.57), higher CRP (OR 2.06, 95% CI 1.04–4.06), low serum C3 at baseline (OR 3.86, 95% CI 1.30–11.53), myeloperoxidase- (OR 7.97, 95% CI 2.74–23.20) and proteinase 3-ANCA (OR 3.40, 95% CI 1.22–9.50). The following clinical factors were less common among patients with renal disease: mononeuritis multiplex (OR 0.63, 95% CI 0.41–0.98), proptosis/exophthalmos (OR 0.19, 95% CI 0.06–0.59), nasal polyps (OR 0.32, 95% CI 0.19–0.55), septal defect/perforation (OR 0.29, 95% CI 0.14–0.60), respiratory distress/pulmonary fibrosis/asthma (OR 0.08, 95% CI 0.04–0.19), and wheeze/obstructive airway disease (OR 0.29, 95% CI 0.16–0.52).

Conclusion

In this large international study, several clinical and laboratory factors were identified as associated with renal involvement in ANCA-associated vasculitis.

Introduction

The group of anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitides encompasses three entities: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA) [1]. ANCA-associated vasculitides are characterised by inflammatory processes, executed by diverse stimuli including neutrophil activation, the complement system, extracellular vesicles and neutrophil extracellular traps [2]. The availability of ANCA as a biomarker facilitates initial diagnosis [3]. A cytoplasmic pattern (c-ANCA) and antibodies to the target autoantigen proteinase 3 (PR3) are predominantly present in GPA (40–50% in localised GPA, 70–95% in generalised cases), while the perinuclear pattern (p-ANCA) and presence of antibodies against myeloperoxidase (MPO) are observed in most cases of MPA (70–95%) and to a lesser extent in EGPA (around 40%) [[4], [5], [6], [7]]. Consistent with previous investigations, the Diagnostic and Classification Criteria in Vasculitis (DCVAS) study observed MPO-ANCA positivity predominantly in Japanese, Chinese, and Southern European populations, while PR3-ANCA positivity was more frequent in other geographic locations [8]. Renal vasculitis is observed in the majority of patients with MPA (90–100%) and GPA (50–80%), while the frequency of kidney involvement is highly associated with ANCA-positivity in EGPA (31–51% in ANCA-positive cases and 4–16% in ANCA-negative patients, respectively) [4]. Despite an overall improvement in the management and survival of ANCA-associated vasculitis [9], the presence of renal involvement in ANCA-associated vasculitis portends higher morbidity and mortality rates [10,11]. Initial and follow-up screening for kidney involvement to detect overt renal abnormalities should include assessment of proteinuria, urine microscopy to detect red blood cell casts and serial serum creatinine and estimated glomerular filtration rate (eGFR) determination [12], with renal biopsy necessary for confirming a diagnosis of glomerulonephritis in ANCA-associated vasculitis.

DCVAS was an international observational study conducted to develop new classification criteria for ANCA-associated vasculitis [13]. The dataset is comprised of data on clinical manifestations and laboratory findings of newly diagnosed patients. The aim of the current study was to evaluate the frequency of renal involvement in patients with underlying ANCA-associated vasculitis and determine what other clinical factors are associated with the development of renal involvement.

Section snippets

Study population

The methodology for the DCVAS study has been previously described in detail [13]. Patients with a suspected diagnosis of ANCA-associated vasculitis were recruited into the study between January 2011 and March 2016. Ethical approval for the DCVAS study was obtained at all participating sites. All participants gave their written consent to the study and to access their medical records. The procedures followed were in accordance with the ethical standards of the local responsible committee on

Results

For this study the DCVAS database as of March 22, 2016 was used. Among a total of 1276 patients with ANCA-associated vasculitis, no urine sample was obtained at study inclusion in 35 patients and urinalysis was not performed in a further 11 patients. Thus, a total of 1230 patients were included for this analysis. Six-hundred, seventy-four patients had a diagnosis of GPA (54.8%), 325 had MPA (26.4%), and 231 had EGPA (18.8%). Renal involvement was observed in 723 patients (58.8%) in the entire

Discussion

This study analysed clinical and laboratory associations of renal involvement in ANCA-associated vasculitis in a large international cohort comprising 1230 patients. Most prior studies focused on severity and impact of renal disease in ANCA-associated vasculitis. It is well established that patients with renal involvement are at increased risk of death during follow-up [10]. This study observed renal manifestations in 723 patients (58.8%) of the total cohort. This is in line with previous

Declaration of Competing Interest

Dr. Kronbichler received consulting fees from Vifor Pharma and speaking fees from Novartis, TerumoBCT and Miltenyi Biotech. Dr. Luqmani received research support from Roche, Vifor Pharma and InflaRx and speaking fees from Roche. Dr. Merkel received research support from AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Celgene, ChemoCentryx, Genentech/Roche, Genzyme/Sanofi, GlaxoSmithKline, Kypha and TerumoBCT, consulting fees from Abbvie, AstraZeneca, Biogen, Boehringer-Ingelheim,

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Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis consists of two main diseases, granulomatosis with polyangiitis and microscopic polyangiitis, and remains among the most devastating and potentially lethal forms of autoimmune inflammatory disease. Granulomatosis with polyangiitis and microscopic polyangiitis are characterised by a necrotising vasculitis that can involve almost any organ, and have generally been studied together. The diseases commonly affect the kidneys, lungs, upper respiratory tract, skin, eyes, and peripheral nerves. Granulomatous inflammation and multinucleated giant cells are key pathological hallmarks of granulomatosis with polyangiitis, but are absent in microscopic polyangiitis. Many immune system events are essential to disease aetiopathogenesis, such as activation of the alternative complement pathway, neutrophil activation via complement receptors, and the influx of inflammatory cells, including monocytes and macrophages. These cells perpetuate inflammation and lead to organ damage. During the 21st century, the management of ANCA-associated vasculitis has moved away from reliance on cytotoxic medications and towards targeted biological medications for both the induction and maintenance of disease remission. Earlier diagnosis, partly the result of more reliable ANCA testing, has led to improved patient outcomes and better survival. Reductions in acute disease-related mortality have now shifted focus to long-term morbidities related to ANCA-associated vasculitis and their treatments, such as chronic kidney disease and cardiovascular disease. Therapeutic approaches in both clinical trials and clinical practice still remain too reliant on glucocorticoids, and continued efforts to reduce toxicity from glucocorticoids remain a priority in the development of new treatment strategies.
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¹: These authors contributed equally to this work.

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Clinical associations of renal involvement in ANCA-associated vasculitis

Abstract

Objective

Methods

Results

Conclusion

Introduction

Section snippets

Study population

Results

Discussion

Declaration of Competing Interest

Autoimmun Rev

Autoimmun Rev

Autoimmun Rev

Autoimmun Rev

Autoimmun Rev

Autoimmun Rev

Autoimmun Rev

Autoimmun Rev

Am J Kidney Dis

Autoimmun Rev

Autoimmun Rev

Autoimmun Rev

Autoimmun Rev

Autoimmun Rev

Antineutrophil cytoplasmic antibody-associated vasculitides: is it time to split up the group?

Ann Rheum Dis

Global ethnic and geographic differences in the clinical presentations of anti-neutrophil cytoplasm antibody-associated vasculitis

Rheumatology (Oxford)

Clinical characteristics and outcome of Spanish patients with ANCA-associated vasculitides: impact of the vasculitis type, ANCA specificity, and treatment on mortality and morbidity

Medicine (Baltimore)