Unveiling the Role of Additional Histological Parameters in ANCA-Associated Vasculitis

医学 动脉炎 内科学 队列 血管炎 肾活检 环磷酰胺 美罗华 胃肠病学 肾功能 入射(几何) 活检 外科 化疗 疾病 淋巴瘤 光学 物理
作者
Vincenzo L’Imperio,Fabio Pagni
出处
期刊:Journal of The American Society of Nephrology 卷期号:33 (6): 1226-1227 被引量:1
标识
DOI:10.1681/asn.2022020208
摘要

In their recent report, Boudhabhay et al.1 demonstrated that the detection of arteritis in ANCA-associated vasculitis (AAV) at renal biopsy may improve the performance of the proposed renal risk score, predicting poor renal outcomes and mortality. Moreover, Aendekerk et al.2,3 independently validated these findings in a large cohort of patients, confirming the higher risk of all-cause mortality in AAV with confirmed arteritis. However, other possible additional clinical/histologic parameters are involved in the deterioration of renal function. In this setting, we recently described the improvement of the already-established renal risk score4 with the addition of a specific histologic feature, the Bowman’s capsule rupture (BCR), in stratifying patients with higher risk of mortality and poor renal outcome.5,6 Thus, we evaluated a selected series of 45 patients with biopsy specimen–proven AAV, diagnosed in a large Italian nephropathology center,7 for the effect of arteritis and BCR on outcome with a 12-month follow-up. In this cohort, we confirmed the incidence of arteritis already reported by Boudhabhay et al. (six of 45 patients, 13%; Figure 1). All of the patients had demonstrated concurrent glomerular involvement in the form of pauci-immune crescentic necrotizing GN. The patients with AAV and arteritis were treated with high-dose steroids, cyclophosphamide (two patients), and rituximab (one patient), or without immunosuppressive therapy. On the basis of the renal risk score, patients with AAV and arteritis were classified as being at low (n=1), medium (n=3), or high (n=2) risk, although no statistically significant differences in the distribution of risk scores were noted compared with the AAV group without arteritis (Table 1). Interestingly, in our cohort, the presence of arteritis correlated with baseline serum creatinine (P=0.0003) and with the related renal outcome measures (dialysis at diagnosis, serum creatinine at 6 and 12 months, P=0.002, 0.02, and 0.05, respectively), confirming the correlation with renal outcomes already reported by Boudhabhay et al. Moreover, we found a correlation with overall mortality in our cohort (P=0.005), further confirming the predictive value of this histologic feature. Finally, the presence of arteritis in this subset of patients was correlated with evidence of BCR on the biopsy specimen (P=0.05; Figure 1), which has not yet been investigated and could suggest a complementary role for these two features in improving the predictive performance of the already existing risk scores. For these reasons, we agree with the authors that further investigation on prospective and multicentric cohorts with comprehensive clinical and histologic data will shed further light on the role of these underestimated morphologic features.Figure 1.: Concurrent renal arteritis and BCR. (A) A medium-sized artery with transmural inflammation, mainly composed of lymphocytes, plasma cells, and neutrophils (top; hematoxylin and eosin) is seen in association with BCR in a glomerulus with cellular crescent and fibrinoid necrosis (white arrows, bottom; Jones methenamine silver stain). (B) A different specimen of a large artery in cross-section demonstrating circumferential involvement of inflammation (top; Periodic acid–Schiff) along with BCR (white arrows, bottom; Periodic acid–Schiff). Original magnification, ×20 in (A) top panel, ×40 in (A) bottom panel, ×5 in (B) top panel, ×40 in (B) bottom panel. Table 1. - Clinical and histologic characteristics of the cohort, comparing patients with or without evidence of arteritis Variables ANCA-Associated Vasculitis A+ ANCA-Associated Vasculitis A− P Value Patients, n (%) 6 (13%) 39 (87%) Males, n (%) 6 (100%) 22 (56%) — Age, yr, (mean±SD) 71.5±8.5 62.4±13.6 0.12 Clinical features Proteinuria, g/d, (mean±SD) 1.2±0.8 1.8±1.5 0.30 Microhematuria, n (%) 6 (100%) 38 (97%) — Baseline serum creatinine, mg/dl, (mean±SD) 7.2±3.7 3.2±2 0.0003 a Hypertension, n (%) 4 (67%) 25 (64%) 0.90 ANCA specificity MPO, n (%) 5 (83%) 24 (62%) 0.32 PR3, n (%) 1 (17%) 14 (36%) Double positive 0 1 (3%) ANCA titer, U/ml, (mean±SD) 94.7±44.3 139.5±241.7 0.66 Complement level, mg/dl, (mean±SD) C3 106.8±15.3 109.8±17.6 0.70 C4 23.7±8.8 27.9±8.8 0.28 Berden class, n (%) Focal 2 (33%) 10 (26%) 0.79 Crescentic 0 7 (18%) Mixed 3 (50%) 18 (46%) Sclerotic 1 (17%) 4 (10%) ANCA renal risk score, n (%) Low 1 (17%) 10 (26%) 0.43 Medium 3 (50%) 24 (62%) High 2 (33%) 5 (13%) Histology features, %, (median (IQR)) Normal glomeruli 35% (21%–49%) 25% (17%–48%) 0.28 Sclerosed glomeruli 11% (0%–24%) 13% (9%–33%) 0.49 BCR 19% (4%–30%) 0% (0%–7%) 0.05 a Interstitial fibrosis and tubular atrophy 20% (13%–20%) 15% (5%–35%) 0.30 Peritubular capillaritis 6 (100%) 14 (36%) — Outcome Dialysis at diagnosis, n (%) 4 (67%) 5 (13%) 0.002 a Serum creatinine at 6-month follow-up, mg/dl, (mean±SD) 4.8±2.9 2.5±2.0 0.02 a Serum creatinine at 12-month follow-up, mg/dl, (mean±SD) 4.5±3.1 2.5±2.2 0.05 a RRT at 12-month follow-up, n (%) 2 (33%) 7 (18%) 0.38 Mortality, n (%) 3 (50%) 3 (8%) 0.005 a Differences in continuous variables expressed as mean±SD were assessed using the independent samples t test; variables expressed as median (IQR) were compared using the Wilcoxon test. Differences in categoric variables were assessed using the chi-squared test. A+, patient with arteritis; A−, patient without arteritis; MPO, myeloperoxidase; PR3, proteinase 3; IQR, interquartile range.aP≤0.05. Disclosures F. Pagni reports serving on speakers bureaus and in an advisory or leadership role for Amgen, MSD, Novartis, and Roche. The remaining author has nothing to disclose. Funding None.
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