Study population
This retrospective study was approved by the Ethics Committee of Xiangya Hospital, Center South University in accordance with the 1964 Declaration of Helsinki. Written informed consent was not required for a retrospective study. (ID: 202108374)
AAV patients with newly diagnosed MPA or GPA from Xiangya Hospital, Center South University between January 2010 and June 2021 were retrospectively included in this study. Diagnosis was made according to the 2007 European Medicines Agency-EMA- algorithm and the 2012 revised Chapel Hill Consensus Nomenclature of Vasculitides [2, 17]. Inclusion criteria were AAV patients with MPO-ANCA serology positive at initial diagnosis; Exclusion criteria were patients diagnosed with secondary vasculitis or other types of vasculitis, including EGPA, PR3-AAV and anti-glomerular basement membrane (GBM) disease.
Data Acquisition
We retrospectively collected the patient's demographic characteristics (age, sex), clinical presentation (duration of disease, BVAS [18], vasculitis type, organ involvement and comorbidities) and routine laboratory parameters (full blood examination, hemoglobin, serum albumin, serum globulin, serum creatinine (Scr), estimated glomerular filtration rate (eGFR), 24-hour proteinuria, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serum immunoglobulin, serum complement and ANCA serology) at the time of initial diagnosis obtained through the electronic medical records from Xiangya Hospital. We followed up the patients until they developed ESRD, or died or until November 2021 through telephone and/or Wechat.
Definition
ESRD was defined as eGFR < 15mL/(min*1.73m2) and requiring renal replacement therapy for more than 3 months or kidney transplantation [19]. Duration of disease was defined as the duration from onset to the time of diagnosis. Renal survival was defined as the duration from onset to the time of developing ESRD. Patient survival was defined as the duration from onset to the time of death. Renal and patient survival was defined as the duration from onset to the time of developing ESRD or death.
Renal Biopsy
A total of 151 patients received renal biopsy before receiving immunosuppressive therapy at the initial diagnosis of MPO-AAV. Two experienced pathologists scored the renal specimens independently and were blinded to the clinical data. Renal specimens were evaluated by direct immunofluorescence, light microscopy and electron microscopy [20]. According to the Berden classification [10], which is based on the proportion of glomerular lesions, the patients were divided into focal, crescentic, mixed and sclerotic classes. Renal specimens were also evaluated similarly by the histological characteristics as described previously [21], including fibrinoid necrosis, Bowman’s capsule rupture, periglomerular inflammation, granulomatous lesions, interstitial infiltrates and renal tubulointerstitial lesions. Interstitial infiltrates and renal tubulointerstitial lesions were scored semi-quantitatively according to the extent of involvement, which can be divided into none (score 0, range of involvement = 0%), mild (score 1, range of involvement < 25%), moderate (score 2, range of involvement between 25–50%) and severe (score 3, range of involvement > 50%) [22, 23].
Treatment Protocol
The treatment of AAV was divided into two stages: induction treatment and maintenance treatment [24]. All patients received glucocorticoid combined with CTX (0.5-0.75g/m2/months) or mycophenolate mofetil (MMF) (2g/d) during the induction period, and then were switched to maintenance therapy after remission was achieved, which consisted of MMF (1.5g-2g/d) or azathioprine (AZA) (1.5-2mg/kg/d) combined with low-dose prednisone (5-7.5mg/d). Maintenance treatment lasted at least 18 months. All patients were treated with oral prednisone, the initial dose was 1mg/ kg/d and gradually reduced according to the schedule as described previously [25].The dose of immunosuppressant was adjusted according to age, eGFR, adverse events and white blood cell count. According to the disease condition, some patients received high-dose methylprednisolone pulse therapy (5-10mg/kg/d) and plasma exchange.
Statistical Methods
The data types were divided into qualitative data and quantitative data. Qualitative data were presented as frequencies (percentage) and were compared by the χ2 test. Quantitative data were presented as meanplus standard deviation (SD) and compared by the Student’s t-test when they fitted a normal distribution, or they were presented as median with interquartile range (IQR) and compared by the Mann-Whitney U test or Kruskal-Wallis test when they were not normally distributed. Survival distribution was presented as Kaplan-Meier survival curves and compared by a log-rank test. All data analysis was performed using GraphPad Prism software (version 8) and SPSS Statistical software (version25). If the two-sided p value < 0.05, the difference was considered to be statistically significant.