#1307 Glomerular galactose-deficient IgA1 (KM55) positive may be associated with poor prognosis in DKD patients

Abstract Background and Aims Diabetic kidney disease (DKD) and IgA nephropathy (IgAN) are prevalent renal diseases with a high incidence rate, and the prognosis is notably poorer when these two diseases coexist. However, it remains uncertain whether the pathological changes associated with DKD combined with IgA deposition (DKD-IgA deposition) are linked to a worsened prognosis. Method To address this question, we conducted an analysis comparing the clinicopathological characteristics and prognosis of DKD-IgA deposition patients to DKD patients as controls (Fig. 1). Results The results revealed that DKD-IgA patients exhibited higher cholesterol levels compared to DKD patients (6.2 ± 2.0 vs. 5.4 ± 1.9 mmol/L, p = 0.042). The group with DKD-IgA deposition had a significantly shorter follow-up duration (10.9 ± 10.6 months) compared to the control group (20.4 ± 18.7 months, p = 0.029). However, they exhibited higher levels of serum creatinine at the end of the follow-up period (343.8 ± 328.0 μ mol/L vs. 182.1 ± 124.6 μmol/L, p = 0.031). Kaplan-Meier analysis showed a higher cumulative incidence of poor events in the DKD-IgA deposition group (p = 0.036) (Fig. 2). In addition, we also detected galactose deficient IgA1 (KM55) in the kidneys and serum of patients with DKD-IgA deposition. Of the 24 patients with DKD-IgA deposition, 54.5% (24/44) showed positive glomerular KM55 results. Immunofluorescence analysis revealed that KM55 and IgA were predominantly colocalized in the mesangial and capillary regions (Fig. 3). Furthermore, the subgroup with KM55 positivity had a shorter disease duration compared to the KM55 negative subgroup (66.0 vs. 120.0 months, p = 0.048). The serum levels of galactose-deficient IgA1 (Gd-IgA1) (6296.4 ± 1535.4 vs. 4057.4 ± 1082.0 ng/mL, p = 0.010) and C4 (0.4 ± 0.1 vs. 0.3 ± 0.1 g/L, p = 0.020) were significantly higher in the KM55 positive subgroup than in the KM55 negative subgroup. Furthermore, it was observed that the KM55 positive subgroup exhibited a considerably higher incidence of reaching the renal endpoint compared to the control group (64.3% vs. 20.0%, p = 0.047). Conclusion These study results suggest that individuals with DKD who display glomerular IgA deposition alongside KM55 positivity may experience a more unfavorable prognosis.