WHAT TO EXPECT WHEN DIAGNOSING ANCA-ASSOCIATED VASCULITIS? A PORTUGUESE CENTER PERSPECTIVE AND EXPERIENCE

ANCA-associated vasculitis (AAV) with glomerulonephritis (AAV-GN) carries poor prognosis despite treatment improvement. Current challenges include improving assessment of disease activity/severity and define risk factors for ESKD. We aim to characterize and determine factors associated with progression to ESKD or death.

Retrospective analysis of all AAV-GN cases of our Center. ESKD was considered as a composite outcome of eGFR<15 or dialysis dependency. Biopsies were classified by Berden’s classification (BC), Brix’s renal risk score (RRS), Mayo Clinic Chronicity Score (MCCS) and AAV-GN combined score (AAV-GN-CS). Categorical variables were analysed by non-parametric chi-square or fisher’s exact test; and continuous variables by Mann-Whitney U test. Cox regression models were applied for death and Kaplan-Meier estimator. Significance α=0.05 was considered.

A total of 74 patients, 56,8% male, 69yo median age were included. Of them, 81.2% were MPO, 11.6% PR3 and 7.2% negative. Clinical presentation with 35.3% alveolar haemorrhage, 13.4% GI and 66.7% constitutional manifestations. Initial median eGFR was 7.5 mL/min/1.73m2 (5.0-13.0), proteinuria 2.2g/g (0.45-4.17) and all had haematuria. Initial median ANCA titer (ATi) was 100 UI/mL (51-134) and at last follow-up 44 (15-101).

Of all, 64.2% of patients required dialysis at presentation. Of them, 14,0% recovered until discharge.

Kidney biopsy of 57 patients were analyzed. Per BC, 15.8, 40.4, 26.3, and 17.5% were focal, crescentic, mixed and sclerotic, respectively. ESKD risk were medium in 28.3% and high in 69.8 % by RRS; whereas low in 31%, intermediate in 42.3% and high in 19% by AAV-GN-CS.

Induction treatment (IT) was with CYC in 46.3%, 18.3% CYC+RTX and 3.3% RTX. Only 17 patients (26.2%) were added PLEX. Only 28% achieved kidney remission (KRm), 7% relapsed and 68.7% developed ESKD. Of them, 95.5% had eGFR<15 at diagnosis, 30% low C3, 37.5% crescentic pattern, 28.1% mixed and 28.1% sclerotic. 87% of ESKD patients had <25% normal glomeruli (NG), and 87.1% high risk (RRS). Progression to ESKD was associated with lower eGFR (p<0.001) and low C3 at diagnosis (p=0.026), lower %NG (p=0.004), higher %CG (p=0.004), higher %IFTA (p=0.011), worse BC (p=0.012), higher RRS (p<0.001) and MCCS categories (p=0.010). AAV-GN-CS was not. ATi reduction seems to determine better renal outcome (p=0.042). No significant differences were seen with IT or maintenance treatment, nor with PLEX. No patient treated with RTX or combined treatment developed ESKD.

Mortality was 32.8% and the best predictive model includes age, GI manifestations and KRm (p<0.001). Age (p=0.004), lower eGFR at diagnosis(p=0.016) and GI manifestations (p=0.003) were predictive of death, while achieving KRm improved survival (p=0.009).

Our results show that AAV-GN patients have poor kidney outcome if presenting with severe kidney dysfunction, high ANCA titers and low C3. A worse histological score is determinant of ESKD development. The prediction power of RRS and AAV-GN-CS must be demonstrated in large cohorts, adding clinical and laboratory data. RTX effectivity on kidney survival must be proved.

Patient survival is related with older age, clinical presentation, and achievement of kidney remission.