SP158INTRAVENOUS STREPTOCOCCUS MUTANS IN RATS INDUCED GLOMELORONEPHLITIS LIKE IGA NEPHROPATHY OR INFECTION-RELATED GLOMERULONEPHRITIS

INTRODUCTION: IgA nephropathy (IgAN) is one of most common primary glomerulonephritis, whose pathogenesis had remained unclear. We had reported that Cnm-(+)Streptococcus mutans, a kinds of major dental caries bacteria. Cnm-(+)Streptococcus mutans had strong collagen binding ability, resulting in high pathogenicity. We reported that the prevalence of Cnm-(+)Streptococcu in IgA nephropathy is significantly higher than that in control (Misaki-T et al, Clin Exp Nephrol 2015; 19:844-50), and that Cnm-(+)Streptococcus mutans in IgA nephropathy was associated with proteinuria (Misaki-T et al, Sci Rep 2016). We also reported C.rectus and S.mutans increased proteinuria synergistically (Misaki-T et al, Nephron, 2018). In this point, there is no direct evidence that Cnm-(+)Streptococcus could induce IgA nephropathy. In this study, we evaluated the renal lesion in rats treated by intravenous Cnm-(+)Streptococcus to confirm the pathogenesis of IgA nephropathy like lesions induced by Cnm-(+)Streptococcus. METHODS: Cmn-(+)Streptococcus mutans from saliva of IgA nephropathy patients was administrated intravenously into 4 weeks old male Sprague-Dawley rats. At day 15, 30, 45, 60 after the infection, blood, urine, and kidney samples were evaluated. Kidney samples were stained by Periodic Acid-Schiff (PAS) , IgA, C3. Historical evaluation by electron microscope analysis was also performed. RESULTS: At day 30, BUN, proteinuria in infectious rats significantly elevated, compared with control rats (P<0.05) (Figure 1A). PAS staining revealed the significant mesangial proliferation at day 30 and day 45 (Figure 1B). At day 30, the prevalence of IgA deposition in infections rats was higher than that in control rats (36.4% vs 0%), and also the prevalence of C3 deposition in infectious rats was higher than that in control rats (27.3% vs 0%). At day 45, the prevalence of IgA deposition in infections rats was significantly higher than that in control rats (58.3% vs 0%, P=0.0147), and also the prevalence of C3 deposition in infectious rats was significantly higher than that in control rats (75.0% vs 0%, p=0.0014). Electron microscopy analysis revealed high dense deposit in mesangial areas, and hump in subepithelial areas. All these findings had become normal at day 60 after infection. CONCLUSIONS: Cmn-(+)Streptococcus mutans from saliva of IgA nephropathy patients could induce IgA-dominant infection-associated glomerulonephritis, or IgA nephropathy.