Abstract

Abstract Background and Aims Glomerulonephritis related to antineutrophil cytoplasmic autoantibodies (ANCA) is typically referred to as “pauci-immune”, however, it is not unusual for kidney biopsies to exhibit some immune complex deposition within glomeruli on electron microscopic study. Such deposits in ANCA-glomerulonephritis have not been widely studied, and their potential pathologic and clinical significance is not clear, although a possible synergistic effect between immune complexes and ANCA in producing more severe glomerulonephritis is suggested in the literature. Method An observational retrospective study was conducted using a dataset comprising all patients with ANCA associated vasculitis diagnosis from a Portuguese Center between march 2011 and march 2023. Demographic and clinical data were collected from medical records. Electron microscopy reports from kidney biopsies were examined for the presence of electron-dense deposits. Descriptive statistics were used to describe all reports. The objective of this study was to explore associations between the presence or absence of such deposits and clinical data, including serum creatinine, urine protein-creatinine ratio levels (PCR) at the time of biopsy as well as overall survival and renal outcomes at follow-up. Non-parametric Mann-Whitney U test and the Chi-squared test were used for continuous and categorical variables respectively. Kaplan-Meier curves were used for assessing time to event data. All analyses were two-tailed and a p value ≤ 0.05 was considered significant. Results From a total of 39 patients with ANCA associated vasculitis diagnosis, 33 underwent at least one kidney biopsy, and among them, 17 were analysed by electron microscopy. 8 (47%) of biopsies showed glomerular immune complex deposits by electron microscopy; Table 1 describes demographic data of both groups (immune complex deposits—D; no-immune complex deposits—ND). The median numbers of glomeruli examined by electron microscopy were identical between the two groups. In group D there was less patients with positive titers for ANCA (p = 0.034) and serum creatinine levels were higher at admission (mean 7.1 mg/dL IQR: 5.6-8.1 versus 4.2 IQR 3.2-7.1), despite the lack of definitive statistical significance (p = 0.123). Urine protein-to-creatinine ratio did not differ between groups. The need for renal replacement therapy at admission was greater for patients with dense deposits on kidney biopsy (p = 0.008). At the end of follow-up (median 48, IQR 24-48 months), death and progression to end stage kidney disease occurred in 25.0% and 37.5% of group D patients versus 11.1% and 22.2% of ND patients, respectively (Fig. 1). Conclusion Immune complex deposits were found on electron microscopy in nearly half of kidney biopsies. Our data suggest that these immune complex deposits are common and might play a role in clinical presentation, overall survival and renal prognosis. The small sample size of our cohort is a limitation, as well as the retrospective nature of the study. Larger cohorts and more comprehensive electron microscopic studies are warranted to better characterize this population.

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