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

Abstract

ObjectivesThe objective of this study is to evaluate whether anti-neutrophil cytoplasmic antibody (ANCA) seropositivity and antigen specificity at diagnosis have predictive utility in paediatric-onset small vessel vasculitis.MethodsChildren and adolescents with small vessel vasculitis (n=406) stratified according to the absence (n=41) or presence of ANCA for myeloperoxidase (MPO) (n=129) and proteinase-3 (PR3) (n=236) were compared for overall and kidney-specific disease activity at diagnosis and outcomes between 1 and 2 years using retrospective clinical data from the ARChiVe/Paediatric Vasculitis Initiative registry to fit generalised linear models.ResultsOverall disease activity at diagnosis was higher in PR3-ANCA and MPO-ANCA-seropositive individuals compared with ANCA-negative vasculitis. By 1 year, there were no significant differences, based on ANCA positivity or specificity, in the likelihood of achieving inactive disease (~68%), experiencing improvement (≥87%) or acquiring damage (~58%). Similarly, and in contrast to adult-onset ANCA-associated vasculitis, there were no significant differences in the likelihood of having a relapse (~11%) between 1 and 2 years after diagnosis. Relative to PR3-ANCA, MPO-ANCA seropositivity was associated with a higher likelihood of kidney involvement (OR 2.4, 95% CI 1.3 to 4.7, p=0.008) and severe kidney dysfunction (Kidney Disease Improving Global Outcomes (KDIGO) stages 4–5; OR 6.04, 95% CI 2.77 to 13.57, p<0.001) at onset. Nonetheless, MPO-ANCA seropositive individuals were more likely to demonstrate improvement in kidney function (improved KDIGO category) within 1 year of diagnosis than PR3-ANCA seropositive individuals with similarly severe kidney disease at onset (p<0.001).ConclusionsThe results of this study suggest important paediatric-specific differences in the predictive value of ANCA compared with adult patients that should be considered when making treatment decisions in this population.

Course of paediatric ANCA-associated glomerulonephritis: advocating for an age-inclusive approach

“…Moreover, even in the adult population, ANCA-GN was a common direct or indirect (lack of allowance of intravenous therapies or higher doses of glucocorticoids) exclusion criterion in the landmark trials performed for these agents. 14 The current analysis by Mann et al 5 is limited by the relatively short-term follow-up and therefore the effects of the ANCA serotype, for instance, on the risk of disease relapse might have been missed. Other common complications, such as cardiovascular disease or side effects of higher cumulative glucocorticoid exposure, are seen during an observational period that expands beyond what has been reported in the current study.…”

“…Those with MPO-ANCA+ vasculitis more commonly presented with severely and moderately impaired kidney function at baseline, defined as estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m 2 (15.9% vs 6.0%) and eGFR between 15 and 49 mL/min/1.73 m 2 (19.8% vs 8.2%). 5 In other words, 35.7% and 14.2% presented with an eGFR below 50 mL/min/1.73 m 2 , and thus kidney function in children is less severely impacted at the time of diagnosis. In the UK National Registry of Rare Kidney Diseases (RaDaR), the median age at diagnosis was >60 years for females and males with AAV, and the average eGFR at the time of initial presentation was 29.5 and 31.4 mL/min/1.73 m 2 , 6 indicating that presentation between children and adults differs.…”

“…This is in contrast to adults, who only experience a modest increase in eGFR of 8 mL/min/1.73 m 2 and 10 mL/min/1.73 m 2 in the focal and mixed classes, a greater increase of 19 mL/min/1.73 m 2 in the crescentic class and a decline of −1 mL/min/1.73 m 2 in the sclerotic class over a 5-year observational period. 9 In the paper by Mann et al , 5 14 children with PR3-ANCA and 20 with MPO-ANCA vasculitis presented with an eGFR <15 mL/min/1.73 m 2 at baseline. The eGFR in the PR3-ANCA+ patients increased from 11.8 at baseline to 20.5 mL/min/1.73 m 2 (+8.7 mL/min/1.73 m 2 ) at 12 months, while there was an increase from 13 to 44.6 mL/min/1.73 m 2 (+31.6 mL/min/1.73 m 2 ) in the MPO-ANCA+ patients.…”

“…The 10-year kidney survival in RaDaR was approximately 80%, and given the median age at presentation, most patients did not progress to kidney failure. 6 The median age in the paediatric population reported from the ARChiVE/PedVas registry was 14 years, 5 thus, children with ANCA-GN are likely to progress through the stages of chronic kidney disease (CKD) over their life course. Preserving kidney function is therefore important in this population.…”

“…Many scientific questions remain unanswered in the childhood population. One of the major limitations of the large investigation by Mann et al 5 is that the role of currently used histopathological classification or prediction tools has not been investigated. Additionally, potential differences in treatment regimens have not been reported.…”