P0383A LONG-TERM RETROSPECTIVE OUTCOME ANALYSIS OF ANCA-NEGATIVE PAUCI-IMMUNE GLOMERULONEPHRITIS
Authors: O'Brien Jennifer , Tan Pek Ghe , Pusey Charles , McAdoo Stephen 
Published: June 2020

Background and Aims

Pauci-immune glomerulonephritis (GN), usually associated with circulating antineutrophil cytoplasm antibodies (ANCA), is one of the most common causes of rapidly progressive glomerulonephritis that results in high incidence of end-stage kidney disease (ESKD). Most of the existing large trials looking at treatment efficacies exclude ANCA-negative patients, and relatively few studies have reported their long-term outcomes. Therefore, we conducted a single-centre retrospective study to examine the long-term overall survival and renal outcome in this cohort of patients.

Method

All cases of newly diagnosed biopsy-proven pauci-immune GN from 2006 - 2019 were identified through a local histopathology database. Patients with negative anti-myeloperoxidase (MPO) and anti-proteinase-3 (PR3) serology were identified (ANCA-negative group) and comparisons made with the cohort of patients with positive serology (MPO/PR3 positive group). Patients with relapsing ANCA-GN, eosinophilic granulomatosis with polyangitis, other co-existing glomerulonephritis or missing data on induction therapy or outcome were excluded.

Baseline demographics, initial serum creatinine (sCr), estimated glomerular filtration rate (eGFR), systemic involvement and histopathology features including percentage normal glomeruli, and interstitial fibrosis/tubular atrophy score of &gt;25% were collected and compared.

Kaplan Meier survival analysis was used to compare overall survival and end-stage kidney disease (ESKD) progression rate between the two groups.

Results

178 patients were identified with a median follow-up of 44 months. 83 were female (47%) and median age was 62 years. 15 (8%) were ANCA-negative. 163 (92%) were MPO- and/or PR3-ANCA positive.

There were no differences in baseline characteristics such as age, gender and proportion of patients with normal glomeruli &lt;25% on initial histology. However, we observed a significantly higher proportion of patients with renal-limited vasculitis in the ANCA-negative group (67% vs 24% p=0.01) and more severe renal dysfunction at presentation (median sCr 309umol/L vs 204umol/L, p= 0.01). We also demonstrated a higher proportion of patients with an IFTA score of &gt;25% on renal biopsy (53% with &gt;25% IFTA in ANCA-negative cohort vs 27%, p =0.03). The ANCA-negative group were more likely to receive combination immunosuppressive therapy that included plasma exchange (47% vs 23%, p value 0.04).

When considering overall survival there was significantly higher mortality (40% vs 16%, p value 0.009) and rate of progression to ESKD (53% vs 18%, p value 0.001) in the ANCA-negative group as a whole. When we compared patients with renal-limited vasculitis only however, there was no significant difference in either overall survival or rate of progression to ESKD (p=0.85 and 0.84 respectively). We found that ANCA-negative patients with systemic disease did still have significantly higher rates of both progression to ESKD and overall mortality (p=0.002 and p=0.02 respectively).

Conclusion

In our cohort, patients with ANCA-negative pauci-immune GN have poorer renal function and higher IFTA scores on biopsy at presentation perhaps reflecting delayed diagnosis due to a lack of diagnostic serology and the higher proportion of renal-limited disease in this subgroup. Despite intensive immunosuppressive therapy, this study observed overall higher treatment failure rates in ANCA-negative patients, largely in those with systemic disease. This possibly relates to a different underlying disease process. Larger, prospective studies are required to enhance understanding of the disease pathogenesis to allow optimal tailored treatment for these patients.