INTERSTITIAL FIBROSIS IN ANCA-ASSOCIATED VASCULITIS: MPO VERSUS PR3: A SINGLE-CENTER EXPERIENCE

Abstract BACKGROUND AND AIMS Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a necrotizing vasculitis characterized by inflammation of small blood vessels, being the kidney one of the most frequently affected organs. AAV has a high morbidity and mortality, developing rapidly progressive renal failure that could lead to end-stage renal disease (ESRD). The pathogenesis is complex and multifactorial; macrophages have turned out to be a key element in inflammation and also in fibrosis. As already described in previous publications, PR3-AAV and MPO-AAV show clinical-demographic differences and different renal phenotypes on kidney biopsy. Histopathological subgrouping into four classes (focal, crescentic, mixed and sclerotic, as defined by Berden et al.) was proposed to predict long-term renal survival rates, poorest in the sclerotic class. This classification, validated by our group and multiple others, is still under review. The aim of this study is to demonstrate whether interstitial fibrosis in AAV is at least as important as glomerular sclerosis in renal prognosis, being a differentiating element between MPO and PR3 vasculitis. METHOD We performed a retrospective single-center study of 95 AAV-patients (78 MPO-AAV and 17 PR3-AAV) diagnosed by renal biopsy from 1991 to 2021 and at least 1-year follow-up. Clinical and laboratory variables, presence and type of ANCA, immunosuppressant therapy and renal/patient survival were evaluated. Sixty-two kidney biopsy samples have been analyzed: histomorphometric quantification has been carried out using MetaMorph® software on trichrome-stained slides in order to measure the degree of fibrosis. Continuous variables were described using measures of central tendency and dispersion (mean and standard deviation), and categorical variables using frequency tables and percentages. Student's t-tests or Mann–Whitney U tests, as appropriate, were performed to evaluate differences in mean values, and chi-squared tests were used to evaluate differences in qualitative variables. Statistical significance was defined as P-values <.05. All P-values were two-sided. RESULTS PR3-AAV population was predominantly male (70%) with a mean age at diagnosis of 62 years and a mean follow-up of 54 months, while MPO-AAV population was mainly female (65.8%), mean age 66 years and follow-up 65 months. There were no statistically significant differences in renal function between MPO and PR3-AAV at diagnosis. However, our data showed that MPO-AAV had worse renal function than PR3-AAV at the end of follow-up (P = .01). Furthermore, it should be highlighted that renal function improved throughout the follow-up (P < .01 and P = .05 in MPO and PR3-AAV, respectively). From a histological point of view: MPO-AAV manifests more interstitial fibrosis at diagnosis than PR3-AAV (P = .01). However, there were no statistically differences in the amount of glomerular sclerosis. It is noteworthy that PR3-AAV showed more crescentic proliferation at diagnosis (P = .03) but less fibrotic crescents than MPO-AAV (not reaching statistical significance). CONCLUSION The method we used allows a quantitative assessment of renal fibrosis. Our data confirm that renal prognosis is better in PR3-AAV than in MPO-AAV, which could be explained by a greater interstitial fibrosis, as well as more fibrotic crescentic in MPO-AAV at diagnosis.