Objective ANCA-associated vasculitis (AAV) is a small vessel vasculitis that commonly presents in the elderly. However, there are few long-term outcome data for these patients. Here, we assessed long-term outcomes in a single-centre cohort of elderly patients with AAV. Additionally, we tested whether a pre-morbid frailty score could aid prognosis. Methods Using a prospectively-compiled dataset, we investigated patients over the age of 65 who presented with AAV between 2005 and 2017 to a regional vasculitis centre. We used a Cox model to determine the factors associated with mortality. We also compared outcomes in pre-specified subgroups stratified by baseline frailty score, ANCA serotype and induction immunosuppression (with cyclophosphamide, rituximab or mycophenolate mofetil used as the main glucocorticoid-sparing agent). Results 83 patients were included in the study and were followed for a median of 1203 days. Median age was 74 years (range 65–92). Two- and five-year survival in the overall cohort were 83% (95% CI 75, 92%) and 75% (95% CI 65, 86%), respectively. The median cumulative dose of oral prednisolone was 2030 mg during the first three months. Only one patient received intravenous glucocorticoids. Age, frailty score and CRP at presentation were independently associated with mortality; all deaths occurred in patients aged over 75 at presentation. Patients treated with a cyclophosphamide-based induction regimen tended to be younger than those treated with rituximab or mycophenolate mofetil. Survival was better in the cyclophosphamide-treated group. Conclusion In the contemporary era, the overall prognosis of AAV in elderly patients is good. Baseline frailty associates with disease outcomes including mortality. A low-dose glucocorticoid regimen (avoiding intravenous methylprednisolone) can be used to treat AAV effectively in elderly patients.

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Background and Aims Outcomes in ANCA vasculitis remain difficult to predict and therapeutic decision-making can be challenging. We aimed to establish if a renal risk score (RRS) could predict outcomes in this population. Method The Scottish Renal Biopsy Registry is a complete national dataset of all renal biopsies performed in Scotland. Those who had a first renal biopsy between 01/01/2014 and 31/12/2017 with evidence of ANCA vasculitis were included. Demographic data, treatment regimens, episodes of relapse and patient and kidney survival were recorded, retrospectively. The RRS was calculated using the system proposed by Brix et al (1). Each patient was categorised according to % of normal glomeruli (N0 >25%, N1 10 to 25%, N2 <10%), % of tubular atrophy/interstitial fibrosis (T0 ≤25%, T1 >25%) and eGFR (CKD-EPI) at time of biopsy (eGFR: G0 >15 mL/min/1.73 m2, G1 ≤15 mL/min/1.73 m2). Individual scores were summated and patients defined as low, medium or high risk. Cox proportional hazard models were created for survival to ESKD, relapse and death, stratified by risk category. Analyses were conducted using R statistical software. Results Two-hundred and forty-six patients with biopsy proven ANCA vasculitis were identified. Fifty percent (n=123), 46% (n=112) and 5% (n=11) were stratified as low, medium and high risk respectively. Fifty-two percent (n=129) were male and mean age at biopsy was 66.7±12.2 years. This was similar across the risk categories. Mean eGFR was lower in the high-risk category (High risk 8.6±6.1 ‘v’ Low risk 45.7±26.0 ml/min/1.73m2, p<0.001) and proteinuria was higher (High risk 405 (IQR 170-767) ‘v’ Low risk 81 (IQR 41-155) mg/mmol, p<0.001). Thirty-seven percent (n=91) were PR3 antigen positive, 2% (n=5) had dual positivity. In the high risk category, 8 (73%) were PR3 or dual positive. Eighteen (n=7%) patients experienced pulmonary haemorrhage; representation similar across all risk categories. Those categorised as medium or high risk were more likely to receive plasma exchange and/or haemodialysis at presentation (p<0.001) compared with the low risk category. Overall, 16% (n=40) of patients relapsed with a trend to higher risk of relapse in the low risk group (27% of these patients, p=0.05). Thirty seven (15%) patients developed ESKD. Cox proportional hazard model for development of ESKD (Figure 1) shows that those in high risk ‘v’ low risk category were more likely to reach ESKD (HR 124.8, 95% CI 26.4-590.3, p<0.001). Patient survival was similar between risk categories. Conclusion A simple RRS, using routinely reported data, in patients with renal biopsy proven ANCA vasculitis can help to predict development of ESKD. It may also be predictive of future relapse in those with a lower RRS, most likely explained by reduced irreversible damage in this group. The RRS could inform monitoring and treatment decisions. Whilst the numbers are small, a unique strength of this data is that it is based on a complete national dataset making it less susceptible to bias from regional variations in diagnostic and therapeutic practice.

Background and Aims Reliable prediction tools are needed to improve prognostication and personalisation of treatment in anti-neutrophil cytoplasmic antibody (ANCA) glomerulonephritides (GN). We aimed to validate and update the ANCA Renal Risk Score (ARRS) prediction model. Method The ARRS working group collated a retrospective multicentre international longitudinal cohort from referral centres and registries across the globe to revise the ARRS in a validation and recalibration study. The primary endpoint was end stage kidney disease (ESKD) and patients were censored at last follow-up. Cox proportional hazards models were used to reweight risk factors and develop a modified scoring system. Kaplan-Meier estimates, Harrell's C statistics and calibration plots were used to assess model performance. Results Of a total of 1591 patients, 1439 were included in the final analyses (959 in the development cohort, 52% male, median age 64 years). The ARRS demonstrated a discrimination of C = 0.800, comparable to the original cohort. Updating the model found an additional useful cut-off for kidney function (K), and serum creatinine replaced glomerular filtration rate which provided higher reliability (K0: <250 μmol/l = 0 points, K1: 250-450 μmol/l = 4 points, K2: >450 μmol/l = 11 points). The risk points for the percentage of normal glomeruli (N) and interstitial fibrosis and tubular atrophy (T) were also reweighted (N0: >25% = 0 points, N1: 10-25% = 4, N2: < 10% = 7, T0: none, mild or < 25% = 0 points, T1: ≥ mild-moderate or ≥ 25% = 3 points). We created four risk groups based on the sum of points: low (0 – 4 points), moderate (5 – 11), high (12 – 18) and an additional very high-risk (21). The model discrimination was C = 0.831 and a supplemental continuous model was developed to supply a patient-specific annual risk. Three-year kidney survival was 96%, 79%, 54%, and 19%, respectively. The ARRS23 performed similarly well in the validation cohort with excellent calibration. Conclusion We demonstrated the out-of-sample validity of the ARRS and present here the modified and improved score to optimise prognostication and risk stratification for clinical practice and trials.