A total of 82 patients with ANCA-associated renal vasculitis diagnosed in Department of Nephrology, Renji Hospital, Shanghai Jiaotong University School of Medicine from January 2013 to September 2020 were included. 24 people who did not meet the inclusion criteria were excluded, and finally 58 people were involved for this study. Among them, 35 were in the standard-dose glucocorticoids group and 23 were in the reduced-dose glucocorticoids group. The ratio of male to female 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, and the baseline Scr was 251.35[155.53,445]μmo/L, and 42 cases 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 total included patients no matter the dose of corticosteroids.
A total of 9 patients developed to ESRD, 7 patients in the standard-dose glucocorticoids group and 2 patients in the reduced-dose glucocorticoids group (P=0.25), (figure 2), of these nine patients, all were positive for MPO-ANCA, with a baseline Scr of 460.22±141.20μmol /L, baseline UACR 796[523.2,1753.1]mg/g, BVSA score 12[12,17], 2 cases complicated with underlying pulmonary diseases, one was with pulmonary tuberculosis history, another was chronic obstructive pulmonary disease; 6 patients developed pulmonary infections within 3 months, and 4 patients had persistent hematuria for more than 6 months. The proportion of patients who developed ESRD in the standard-dose glucocorticoids group was significantly higher than that in the reduced-dose glucocorticoids group, but there is no significant statistical difference. (Table 1)
Secondary end points
A total of 19 adverse events occurred in 17 patients within first six months, 13 patients of pulmonary infection (2 of 13 patients were cryptococcal infection, the others were bacterial infections, and 1 of 13 patients simultaneously with elevated transaminase, 1 of 13 patient simultaneously with central serous chorioretinopathy), 2 patients of herpes, 1 patient was urinary tract infection, 1 patient was upper respiratory tract infection. 10 patients (17.24%) developed infection within first 3 months, out of 10 patients, 1 patient of upper respiratory tract infection, 1 patient of urinary tract infection, 1 patient of cryptococcal infection, and the remaining 7 patients were pulmonary bacterial infections. There were 9 patients (25.71%) in the standard-dose group, of which 1 patient developed cryptococcal infection, 1 patient (4.35%) in the reduced-dose group (P=0.035). The infection rate in the reduced-dose group was significantly lower than that of the standard-dose group. (Table 1)
45/58 patients (77.57%) had disappeared hematuria within 6 months, 26/35 patients (74.29%) of the standard-dose group, 19/23 patients (82.61%) of the reduced-dose group(P=0.46); 28/58 patients (48.28%) patients with ANCA turned negative within 6 months, 18/35 patients (51.43%) of standard-dose group, 10/23 patients (43.48%) of the reduced-dose group, (P=0.553); There was no significant statistical difference between the groups in the persistent hematuria and ANCA conversion within 6 months. Table 1
Risk predictors of ESRD
Age, baseline Scr, infection, Scr drop rate and ANCA turned negative within first 3 months, persistent hematuria for more than 6 months, baseline UACR, baseline albumin, baseline lymphocyte ratio, hypertension, diabetes, combined with chronic pulmonary disease were included in the Kaplan-Meier analysis,(Figure 3-7), and compared by Log rank test, (Table 2). Among them, the baseline Scr, infection and Scr drop rate within first 3 months, persistent hematuria for more than 6 months, and baseline UACR were significant correlated with endpoint event which P value were 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 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).