A cohort study to investigate sex-specific differences in ANCA-associated glomerulonephritis outcomes

Abstract

Data surrounding sex-specific differences in ANCA-associated vasculitis glomerulonephritis (ANCA-GN) outcomes is sparse. We hypothesised that the previously observed increased risk of end-stage kidney disease (ESKD) in males is driven by sex-specific variation in immunosuppression dosing. Patients were recruited to the Irish Rare Kidney Disease Registry or followed by the Royal Free Hospital vasculitis team (2012–2020). Inclusion criteria: prior diagnosis of ANCA-GN (biopsy proven pauci-immune glomerulonephritis) and positive serology for anti-MPO or -PR3 antibodies. Renal and patient survival, stratified by sex and Berden histological class, was analysed. The cumulative- and starting dose/kilogram of induction agents and prednisolone, respectively, was compared between sexes. 332 patients were included. Median follow-up was time 40.2 months (IQR 17.3–69.2). 73 (22%) reached ESKD and 47 (14.2%) died. Overall 1- and 5-year renal survival was 82.2% and 76.7% in males and 87.1% and 82.0% in females, respectively (p 0.13). The hazard ratio for ESKD in males versus females, after adjustment for age, ANCA serology, baseline creatinine and histological class was 1.07 (95% CI 0.59–1.93). There was no difference between sexes in the dose/kilogram of any induction agent. We did not observe a strong impact of sex on renal outcome in ANCA-GN. Treatment intensity does not vary by sex.

Comprehensive Analysis of Sex Differences at Disease Manifestation in ANCA-Associated Glomerulonephritis

“…The most crucial sex difference has been reported in crescentic class ANCA GN, representing active glomerular lesions and supporting the concept that observed outcome differences are caused by sex-specific inflammatory differences and responses to immunosuppressive therapy. In contrast, no significant sex-specific difference in ANCA GN outcomes has been observed when combining ESKD and death as a composite outcome in Irish and British patients with ANCA GN ( 18 ). These observations might potentially be attributed to the known latitudinal gradient of ANCA specificity ( 17 , 18 ).…”

“…In contrast, no significant sex-specific difference in ANCA GN outcomes has been observed when combining ESKD and death as a composite outcome in Irish and British patients with ANCA GN ( 18 ). These observations might potentially be attributed to the known latitudinal gradient of ANCA specificity ( 17 , 18 ). Our observation of sex-specific differences in tubulointerstitial inflammation is relevant since tubulointerstitial inflammation has previously been associated with active glomerular lesions ( 35 ).…”

“…With regard to outcomes, males show a higher risk of progression to ESKD, especially in crescentic class ANCA GN (16). However, recent evidence suggests that PR3-ANCA is more prevalent than MPO-ANCA in males without any outcome differences regarding sex, potentially attributed to the known latitudinal gradient of ANCA specificity (17,18). Besides investigations focusing on renal outcomes, sex differences in association with distinct clinical and histopathological findings in ANCA GN have not been systematically investigated (18).…”

“…However, recent evidence suggests that PR3-ANCA is more prevalent than MPO-ANCA in males without any outcome differences regarding sex, potentially attributed to the known latitudinal gradient of ANCA specificity (17,18). Besides investigations focusing on renal outcomes, sex differences in association with distinct clinical and histopathological findings in ANCA GN have not been systematically investigated (18). Therefore, we systematically analyzed sex differences in patients with biopsy-proven ANCA GN, emphasizing laboratory parameters, systematic scoring of renal histopathology including glomerular and tubulointerstitial lesions, and extrarenal manifestations of AAV.…”

Relationship Between Gender and 1-Year Mortality in ANCA-Associated Vasculitis Patients: A Single-Center Retrospective Analysis and Meta-Analysis

“…Patients with AAV have a 1-year mortality rate of up to 80% in the natural disease course they do not receive treatment (14), and even with intensive treatment, patients still carry a 2.7-fold increased risk of death compared with the general population (15,16). Although several studies have shown that the predictors of poor prognosis for patient survival were dialysis dependency or high creatinine level at initial diagnosis, high Birmingham vasculitis activity score (BVAS), and older age (17)(18)(19), the specific mechanism remains unknown.…”