Authors’ Reply
Authors: Idris Boudhabhay, Guillaume Coutance, Alexandre Karras, Jean Paul Duong Van Huyen
Journal: Journal of the American Society of Nephrology (2022)

We thank Aendekerk et al. for their comments and original data that reinforce our results by confirming in an independent cohort of 318 patients most of our findings concerning the incidence, the phenotype, and the severity of a specific subtype of ANCA-associated vasculitis (AAV) with arteritis of small renal arteries (AAV_A+).1 Aendekerk et al. reported an increased risk of all-cause mortality of patients who were AAV_A+. In our cohort, patients who were AAV_A+ had a decreased overall survival in Kaplan–Meier analysis. Additional multivariable analysis showed that patients who were AAV_A+ were at increased risk of all-cause mortality compared with patients who were AAV_A- (hazard ratio, 5.23; 95% confidence interval, 2.13 to 12.83), even after adjustment for age, extrarenal involvement, C-reactive protein, sex, and dialysis at diagnosis. However, this association between pathologic findings and all-cause mortality should be taken cautiously. Further studies are warranted to determine the causes of increased mortality in patients who were AAV_A+, such as organ-specific involvement, that is, cardiac, central nervous system, or intestinal injuries. In contrast, Aendekerk et al. did not find any association between arteritis and a renal survival, whereas the arteritis status was independently associated with renal survival in our cohort. The short follow-up of their study (median follow-up, 1.2 years; interquartile range, 0.4–6.1) compared with our study (3.5 years, interquartile range, 1–7.4) may explain this important difference, together with differences in ANCA specificity (PR3 was more frequent in their series, whereas MPO predominated in our cohort). In our study, we validated the prognostic value of the histopathologic classification proposed by Berden et al.2 and the ANCA renal risk score.3 We therefore completely agree with authors on the importance of the assessment of glomerular and tubulointerstitial lesions to predict ESKD, and that the ANCA renal risk score remains the best tool for risk stratification in ANCA-associated vasculitis. However, in our study, the arteritis status was independently associated with renal survival, but also significantly improved the discrimination of previous risk scores. We believe the arteritis status could improve risk stratification of patients with AAV and should be used on top of these validated prognostic tools, especially for patients categorized as moderate risk. Nevertheless, we agree that prospective studies are warranted to confirm our results. In conclusion, with our study including two external validation cohorts and the additional data from Aendekerk et al., we now have four independent cohorts defining a new subtype of AAV with arteritis of small renal arteries, which should be routinely evaluated in clinical practice. Disclosures A. Karras reports having consultancy agreements with Alnylam, GlaxoSmithKline, Novartis, and Vifor; reports receiving honoraria from Amgen, AbbVie, AstraZeneca, Gilead, GSK, Pfizer, and Roche Pharmaceuticals; and reports being a scientific advisor or member of Novartis. All remaining authors have nothing to disclose. Funding None.