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Please prepare and upload your E-Poster no later than March 14, 2026 11.59PM CET. After this date, you will no longer be able to prepare and upload your E-poster and it will not be displayed and accessible on the congress website.
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Recently, we reported that urinary N-glycans recognized by two lectins, Erythrina cristagalli (ECA) and Narcissus pseudonarcissus (NPA) were significantly associated with the composite renal outcome in patients with IgA nephropathy (IgAN) during 3-year follow-up (Sci Rep. 2021;11(1):3394). However, the associations of such N-glycans in urine with long-term renal prognosis, especially after glucocorticoid (GC) therapy, remains unclear.
Among 157 patients diagnosed with isolated IgAN who underwent renal biopsy from December 2010 to August 2017 at Okayama University Hospital, 154 patients with the baseline estimated glomerular filtration rate (eGFR) more than 15 ml/min/1.73m2 were enrolled in this study. At baseline, we measured urinary levels of Cy3-labeled glycans that bound to 45 lectins with different specificities. The composite outcome was a decrease of the eGFR by ≥ 30% from baseline, commencement of dialysis for end-stage renal disease, and all cause of death. Cox proportional hazards analysis was employed to calculate hazard ratios (HRs) and 95% confidence interval (CIs) for the death-censored endpoint.
During a median follow-up period of 6.2 years (IQR: 2.7-10.2), the outcome was reached in 35 patients. The patients were 41.8 ± 16.2 years old, and 51% female. The mean baseline eGFR was 71.1 ± 26.0 ml/min/1.73 m2, and the distribution of baseline 24-h urinary protein, such as urinary protein (UP) <0.5g/day, 0.5g/day≤UP<3.5g/day, and UP≥3.5g/day was 42%, 50%, and 8%, respectively. The GC therapy with or without tonsillectomy after renal biopsy was decided based on the discussion among nephrologists at our hospital, and 69.5% of them received GC therapy. Pathologically, chronic lesions including interstitial fibrosis and tubular atrophy (IFTA) were severer in patients without GC therapy.
After adjustment for glucocorticoid therapy and known indicators of renal prognosis of IgAN, including baseline eGFR and proteinuria categories, the urine levels of glycans binding to ECA and Griffonia simplicifolia (GSL-II) were significantly associated with the primary outcome (+1SD for log[glycan signal intensity], HR for ECA: 1.85 [95% CI: 1.05-3.24], and HR for GSL-II: 2.08 [1.16-3.75], respectively). Of note, those urinary glycans were strongly associated with the outcome even in the group of patients without GC therapy (HR for ECA: 2.41 [95% CI: 1.04-5.58] and HR for GSL-II: 3.33 [1.04-10.65], respectively), whereas not in the group with GC therapy (HR for ECA: 1.36 [95% CI: 0.75-2.46] and HR for GSL-II: 1.54 [0.79-3.02], respectively).
The glycan Galβ1-4GlcNAc and fully agalactosylated N-glycans were reported to bind with ECA, while GlcNAc and agalactosylated tri/tetra antennary glycans were reported to bind with GSL-II. Neither of them binds fully galactosylated or sialylated N-type glycans, which is consistent with the pathogenesis of IgAN.
Urinary N-glycans recognized by ECA and GSL-II might be useful predictors of the renal prognosis in IgAN patients, especially with advanced chronic lesions leading to the follow-up without GC therapy.
