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

Abstract

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a small vessel vasculitis affecting multiple organ systems, including the kidney. Besides investigations focusing on renal outcomes, sex differences associated with distinct clinical and histopathological findings in ANCA glomerulonephritis (GN) have not been systematically investigated. Therefore, we here aimed to systematically analyze sex differences in patients with AAV and biopsy-proven ANCA GN. We provide a comprehensive analysis of 53 kidney biopsies with ANCA GN retrospectively included between 2015 and 2020 and identified specific sex differences in ANCA GN concerning laboratory parameters and systematic scoring of renal histopathology glomerular and tubulointerstitial lesions, and extrarenal manifestations of AAV. We did not observe any correlation between sex and short-term clinical AAV course or disease severity by comparing general AAV parameters. AAV manifestations in females occurred at an older age with more joint involvement. Regarding histopathological findings, we, again, observed no sex difference among ANCA GN classification, but a significant correlation between females and distinct histopathological findings with less tubulointerstitial inflammation and vasculitis of peritubular capillaries. Finally, we here identified fewer associations between clusters of clinical, laboratory parameters, and histopathological findings in females as compared to males. These findings are of great relevance and further improve our understanding of sex differences in the pathogenesis of ANCA GN. While future studies about specific sex differences and conclusions in these clusters are crucial, our observations further support that sex differences are relevant, affect distinct parameters, and influence clinical, laboratory parameters, and histopathological findings in AAV, particularly ANCA GN.

Sex and Gender in Glomerular Disease

“…83,84 There are limited data exploring differences between the sexes with respect to clinical presentations of AAV. Tampe et al 85 found no sex-specific associations between clinical characteristics or with serum or urinary parameters. They also reported that systemic disease activity does not differ between the sexes.…”

C-Reactive Protein Levels Are Associated with Complement C4 Deposits and Interstitial Arteritis in ANCA-Associated Renal Vasculitis

“…A cohort of 53 kidney-biopsy-confirmed cases of ANCA-associated renal vasculitis was retrospectively enrolled between 2015 and 2020 in a single-center observational study at the University Medical Center Göttingen, Göttingen, Germany [ 51 , 52 , 53 , 54 , 55 ]. In addition, a total of 138 disease controls—including AL amyloidosis, tubulointerstitial nephritis, diabetic kidney disease, focal segmental glomerulosclerosis (FSGS), immunoglobulin A (IgA) nephropathy, IgA vasculitis, hypertensive nephropathy, lupus nephritis, membranous nephropathy, minimal change disease, monoclonal dense deposit disease (DDD), post-infectious glomerulonephritis (GN), and thrombotic microangiopathy—were also evaluated.…”

Low levels of hemoglobin associate with critical illness and predict disease course in patients with ANCA-associated renal vasculitis

“…A total number of 53 cases admitted the University Medical Center Göttingen with confirmed ANCA-associated renal vasculitis retrospectively included between 2015 till 2020, the patient cohort has in part previously been described 23 – 27 . None of the patients required mechanical ventilation due to respiratory failure, and 1 patient was ventilated due to status epilepticus.…”

“…Particularly, data on critical illness during the initial course of disease are scarce and remains poorly determined. Therefore, the purpose of this retrospective study was to identify predictors of critical illness in a previously described cohort of patients with biopsy-proven ANCA-associated renal vasculitis 23 – 27 .…”