FC058: Long-Term Renal Survival of Anca-Associated Vasculitis Patients Included in the Euvas Randomized Clinical Trials

Abstract

Abstract BACKGROUND AND AIMS Kidney involvement is common in ANCA-associated vasculitis (AAV) and prognosis is largely determined by the severity of the kidney damage at diagnosis and by the response to treatment. Rapidly progressive glomerulonephritis is the most common severe clinical manifestation of AAV. Current therapy with immunosuppressive and glucocorticoid treatment plays a crucial role to rescue kidney function, but the rate of patients reaching end-stage renal disease (ESRD) remains high. The aim of the study is to determine the renal prognosis and predictive factors of patients included in EUVAS randomized controlled trials (RCTs) by the European Vasculitis Society from 1995 to 2012: MEPEX, NORAM, CYCAZAREM, CYCLOPS, IMPROVE, RITUXVAS and MYCYC. METHOD Questionnaires were sent to the principal investigators of the original RCTs and 490 were returned (70% of the potential patients). The dataset comprised 848 patients, all newly diagnosed with AAV, well characterized at inclusion in the trials, as was the type and duration of induction therapy. RESULTS Median follow-up time for the entire cohort was 8 years [interquartile range (IQR): 2.9–13.6]. 478 (56%) patients had granulomatosis with polyangiitis (GPA) and 370 (47%) microscopic polyangiitis (MPA). Mean age at diagnosis was 57.5 ± 14.2 years. Renal involvement was detected in 644 (76%) patients at diagnosis, with a median eGFR of 42.1 (IQR: 16.2–88.6) mL/min/1.73 m2. At baseline, 199 patients had an eGFR <15 mL/min/1.73 m2 and another 144 an eGFR 15–30 mL/min/1.73 m2. A totla of 107 patients needed dialysis at initial presentation. However, 37 out of the 107 recovered renal function later and 11 patients were temporarily dialysis independent but needed subsequent dialysis. A total of 105 started renal replacement therapy (RRT) after the end of the initial RCTs. A total of 175 patients required RRT during long-term follow-up. A total of 35 patients received a kidney transplant and they showed better survival than patients receiving other modalities of RRT (LR: 42.2; P-value < 0.001) (Figure 1). Among patients with ESRD, 67 (38%) had GPA and 108 (62%) had MPA-RLV. Median baseline eGFR was 13.2 (IQR: 7.3–26) mL/min/1.73 m2. Patients with ESRD were older at entry (62.3 ± 13.4 versus 57 ± 14.1 years) (P-value < 0.001), had baseline lower hemoglobin level (9.2 ± 1.8 versus 10.3 ± 2 g/dL) (P-value < 0.001) and lower baseline platelets count (366 ± 182 versus 406 ± 164 *109/L) (P-value: 0.006). The cumulative incidence of ESRD at 5 and 10 years was 16.7% and 22.5%, respectively. A total of 118 deaths were found among the patients who developed ESRD (67.4%). Those with ESRD had reduced survival when compared with those with preserved kidney function (log-rank: 97.2; P-value < 0.001) (HR: 2.8; P-value < 0.001).The most frequent causes of death were infection (29.7%) followed by cardiovascular disease (16.9%) and malignancy (5.9%). GPA patients who had ESRD had better prognosis compared to MPA-RLV (HR: 5.4; P-value: 0.02) (Figure 2). When compared to a matched general population (matched by age, sex and country), even those patients with AAV and mild renal impairment (eGFR > 30 mL/min/1.73 m2) had a worse prognosis. CONCLUSION Our findings, which were derived from a large number of patients with AAV enrolled in EUVAS’ RCTs over the past 25 years, estimate the 5- and 10-year cumulative incidence of ESRD to 16.7% and 22.5%, respectively. ESRD is tightly associated with decreased patient survival.