Patient characteristics
A total of 82 patients with ANCA-associated renal vasculitis diagnosed in the Department of Nephrology, Renji Hospital, Shanghai Jiaotong University School of Medicine from January 2013 to September 2020 were included. Twenty-four people who did not meet the inclusion criteria were excluded, and 58 people were involved in this study. Among them, 35 were in the standard-dose glucocorticoid group, and 23 were in the reduced-dose glucocorticoid group. The ratio of males to females among 58 people was 16/42, the average age was 62.45±12.70 years, the ratio of PR3-ANCA to MPO-ANCA was 5/53, the baseline Scr was 251.35 [155.53,445] μmo/L, and 42 patients underwent renal biopsy. The median follow-up time was 17 [7.5, 31.25] months, and the cumulative cyclophosphamide dose was 1.2 [0.6, 1.6] g at 3 months and was 2.4 [1.6, 3.7] g at 6 months in all included patients regardless of the dose of glucocorticoids.
Primary outcomes
A total of 9 patients developed ESRD within 24 months, 7 patients in the standard-dose glucocorticoid group and 2 patients in the reduced-dose glucocorticoid group (P=0.25) (figure 2). Of these nine patients, all were positive for MPO-ANCA, with a baseline Scr of 460.22±141.20 μmol/L, baseline UACR 796[523.2,1753.1] mg/g, BVSA score 12[12,17], 2/9 cases complicated with underlying pulmonary diseases (one had pulmonary tuberculosis history, another had chronic obstructive pulmonary disease); 6/9 patients developed pulmonary infections within 3 months, and 4/9 patients had persistent hematuria for more than 6 months. The proportion of patients who developed ESRD in the standard-dose glucocorticoid group was significantly higher than that in the reduced-dose glucocorticoid group, but there was no significant difference due to the limited sample size. (Table 1)
Secondary end points
Ten patients (17.24%) developed infection within the first 3 months, out of 10 patients, 1 patient developed upper respiratory tract infection, 1 patient developed urinary tract infection, 1 patient developed cryptococcal infection, and the remaining 7 patients developed pulmonary bacterial infections. There were 9/10 patients (25.71%) in the standard-dose group, of whom 1/9 developed cryptococcal infection, and 1/10 developed cryptococcal infection (4.35%) in the reduced-dose group (P=0.035). The secondary infection rate in the reduced-dose group was significantly lower than that of the standard-dose group. Twenty-eight/58 patients (48.28%) with ANCAs became negative within the first 3 months, 18/35 patients (51.43%) in the standard-dose group, and 10/23 patients (43.48%) in the reduced-dose group (P=0.553). There was no significant difference between the groups in the rate of ANCA conversion. (Table 1)
A total of 19 adverse events occurred in 17 patients within the first six months: 13 patients had pulmonary infection (2 of 13 patients had cryptococcal infection, and the others had bacterial infections; 1 of 13 patients simultaneously had elevated transaminase, and 1 of 13 patients simultaneously had central serous chorioretinopathy), 2 patients had herpes, 1 patient had urinary tract infection, and 1 patient had upper respiratory tract infection. Forty-five/58 patients (77.57%) had disappeared hematuria within 6 months, 26/35 patients (74.29%) in the standard-dose group, and 19/23 patients (82.61%) in the reduced-dose group (P=0.46). (Table 1)
Risk predictors of ESRD
Age, baseline Scr, infection, Scr drop rate and ANCA became negative within the first 3 months, persistent hematuria for more than 6 months, baseline UACR, baseline albumin, baseline lymphocyte ratio, hypertension, diabetes, and chronic pulmonary disease were included in the Kaplan-Meier analysis (Figure 3-7), and the renal survival rate was compared by the log rank test (Table 2). Among them, the baseline Scr, infection and Scr drop rate within the first 3 months, persistent hematuria for more than 6 months, and baseline UACR were significantly correlated with endpoint events with P values less than 0.05 and were included in the multivariate Cox proportional hazard model. The results showed that baseline Scr[HR 1.008, 95%CI[1.001, 1.014], P=0.014], infection within first 3 months[HR 9.835, 95%CI[2.137, 45.270], P=0.003], and persistent hematuria for more than 6 months[HR 5.603,95%CI[1.355, 23.181], P=0.017] were risk predictors of ESRD, there is no significant relationship between baseline UACR, baseline lymphocyte ratio, combined hypertension, diabetes, chronic pulmonary disease and ESRD (Table 3). ROC curves were designed to prove the value of different factors in predicting the primary outcome. The AUCs for baseline Scr, infection within the first 3 months, and persistent hematuria were 0.82 (P=0.002, 95% CI 0.71-0.93), 0.79 (P=0.006 95%CI 0.60-0.98) and 0.565(P=0.541,95%CI 0.35-0.78). (Figure 8).