#1646 Impact of sex in clinical presentation and outcomes of patients with ANCA-associated vasculitis with severe kidney disease
Authors: Moura Marta Casal , Liebana Marc P , Zubidat Dalia , Vargas Maria , Morales Nancy Daniela Valencia , Machado Miriam , Abouzahir Sana , Zand Ladan , Sethi Sanjeev , Fervenza Fernando Custodio , Romeo Maria José Soler 
Published: May 2024

Abstract

Background and Aims
Biological sex has been associated to a more rapid rate of chronic kidney disease progression (ie, speed of kidney function loss) in male than female [1]. Testosterone can increase oxidative stress, activate the renin angiotensin system, and aggravate renal fibrosis, whereas estrogens inhibit these pathological processes in the diseased kidney [2]. Several factors such as lower disease awareness and surveillance rates as well as disparities in health-care access result in late initiation or lack of kidney replacement therapy among females [3-5]. The impact of sex in the clinical presentation and outcomes of patients with anti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitis (AAV) with glomerulonephritis (AAV-GN) has not been studied, particularly in patients with severe kidney involvement at presentation (eGFR&lt;15 mL/min/1.73 m2).

Method
A retrospective cohort study on MPO- or PR3-ANCA positive patients with AAV (MPA or GPA) and eGFR&lt;15 ml/min/1.73 m2 or ESKD at presentation. Clinical presentation and outcomes (renal recovery, dialysis at presentation, and ESKD) were analyzed according with sex.

Results
We analyzed 166 patients with biopsy proven active AAV-GN and eGFR &lt;15 mL/min/1.73 m2 at the time of diagnosis (Fig. 1): 78 (47%) were females and 88 (53%) were males. Arterial hypertension was more frequently present in males (85.2% vs. 70.5%, p = 0.022). Median serum creatinine (SCr) was higher in males when compared with females (5.2 [IQR 4.2-7.4] vs. 3.6 [IQR 2.8-5.1] mg/dL, p &lt; 0.001) but there were no differences in eGFR at presentation. When analyzing only the 71 (24 females and 47 males) patients that started dialysis within 4 weeks, infections at 12 months were more common in females (75.0% vs. 36.2%, p = 0.017). The rate of dialysis initiation or progression to ESKD was not different between males (15, 62.5%) versus females (29, 61.7%) being on dialysis at 12 months. By multivariable logistic regression, factors related with dialysis initiation within 4 weeks in our cohort were SCr (OR1.478, [95% CI 1.231-1.776], p &lt; 0.001), alveolar hemorrhage (OR 2.726, [95% CI 1.099-6.763], p = 0.031) and PR3-ANCA (OR3.155, [95% CI 1.485-6.702], p = 0.003) adjusted to sex). Patients who remained on dialysis at 12 months more often had higher SCr at diagnosis (IRR 1.098 [95% CI, 1.026–1.175], p = 0.007), severe chronicity changes on kidney biopsies (IRR 2.469 [95% CI,1.205–5.061], p = 0.014), higher chronicity score (IRR 1.178 [95%CI, 1.062-1.308], p = 0.002) and lower hemoglobin (IRR 0.824 [95%CI, 0.683-0.994], p = 0.043). Minimal chronicity changes were protective for the achievement of this endpoint (IRR 0.228 [95% CI, 0.070-0.741], p = 0.014). Multivariable Cox regression showed that patients with higher SCr at diagnosis and moderate/severe chronicity changes on biopsy were at higher risk to evolve to ESKD at 12 months compared to patients with lower chronicity grades, even when adjusted to sex.

Conclusion
In our cohort, male patients presented with higher SCr, and dialysis was started within 4 weeks more frequently. However, this did not result in different outcomes in terms of kidney recovery, overall dialysis rates, and progression to ESKD in patients with AAV-GN and eGFR&lt;15 mL/min/1.73 m2 between groups.