Kalantari Kambiz, Sullivan Megan M, Herrera Hernandez Loren P, Bu Lihong, Cornell Lynn D, Nasr Samih H, Fervenza Fernando C, Montes Daniel, Mangaonkar Abhishek A, Go Ronald S, Kusne Yael N, Patnaik Mrinal M, Lasho Terra L, Olteanu Horatiu, Reichard Kaaren K, Warrington Kenneth J, Koster Matthew J
Department of Internal Medicine, Division of Nephrology, Mayo Clinic, Rochester, MN, USA.
Department of Internal Medicine, Division of Rheumatology, Mayo Clinic, Scottsdale, AZ, USA.
Rheumatology (Oxford). 2025 Apr 1;64(4):2027-2033. doi: 10.1093/rheumatology/keae465.
Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic (VEXAS) syndrome is an autoinflammatory disease caused by somatic mutation of UBA1 and affects multiple organ systems. Involvement of the kidneys is not well characterized. We aimed to investigate the incidence, risk factors and histopathologic features of acute kidney injury (AKI) in VEXAS syndrome.
Patients with genetically confirmed UBA1 mutation consistent with VEXAS were included. Charts were manually reviewed. Cox regression analysis was used to identify variables associated with time-to-first AKI event. For patients with a kidney biopsy, histopathologic findings were reviewed.
Eighty-one patients were included, all white men, with a mean age of 66.3 ± 8.6 years. Median (IQR) follow up was 3.5 (2.1-5.2) years during which 20 (25%) developed AKI and 22% died. AKI relapsed in 90% of cases for a median of 6 times during the follow up period. Cumulative incidence estimates (95% CI) for AKI at 1, 3 and 5 years were 6.2% (0.80-11.3%), 16.7% (7.5-25.0%) and 27.9% (14.9-38.9%), respectively. Age and baseline C-reactive protein (CRP) were significantly associated with time-to-first AKI event. Six patients underwent a kidney biopsy. Findings included, plasma cell-rich interstitial nephritis (n = 3), neutrophilic-rich interstitial inflammation (n = 1), leukocytoclastic peritubular capillaritis (n = 1) and acute tubular injury (n = 1). AKI responded well to treatment with glucocorticoids but had relapse upon tapering.
AKI is an underrecognized feature of VEXAS occurring in 25% of patients in this cohort. Age at diagnosis and CRP were associated with time to first AKI event during follow up. Plasma cell-rich interstitial nephritis was the most common histopathologic finding.
空泡、E1酶、X连锁、自身炎症性、体细胞（VEXAS）综合征是一种由UBA1体细胞突变引起的自身炎症性疾病，可累及多个器官系统。肾脏受累情况尚不明确。我们旨在研究VEXAS综合征中急性肾损伤（AKI）的发病率、危险因素和组织病理学特征。
纳入基因检测证实UBA1突变符合VEXAS的患者。人工查阅病历。采用Cox回归分析确定与首次发生AKI事件时间相关的变量。对进行肾活检的患者，回顾其组织病理学结果。
共纳入81例患者，均为白人男性，平均年龄66.3±8.6岁。中位（四分位间距）随访时间为3.5（2.1 - 5.2）年，在此期间20例（25%）发生AKI，22%死亡。90%的病例AKI复发，随访期间中位复发6次。1年、3年和5年时AKI的累积发病率估计值（95%置信区间）分别为6.2%（0.80 - 11.3%）、16.7%（7.5 - 25.0%）和27.9%（14.9 - 38.9%）。年龄和基线C反应蛋白（CRP）与首次发生AKI事件的时间显著相关。6例患者进行了肾活检。结果包括富含浆细胞的间质性肾炎（n = 3）、富含中性粒细胞的间质炎症（n = 1）、白细胞破碎性肾小管周围毛细血管炎（n = 1）和急性肾小管损伤（n = 1）。AKI对糖皮质激素治疗反应良好，但减量时复发。
AKI是VEXAS综合征中一个未被充分认识的特征，在该队列25%的患者中出现。诊断时的年龄和CRP与随访期间首次发生AKI事件的时间相关。富含浆细胞的间质性肾炎是最常见的组织病理学表现。
