P0370RELATIONSHIP BETWEEN ATTENUATION OF C3 GLOMERULAR DEPOSITION AND CLINICAL PROGNOSIS IN IGA NEPHROPATHY: REPEAT-BIOPSY BASED OBSERVATION

Abstract

Abstract Background and Aims In IgA nephropathy (IgAN), mesangial IgA deposition activates the complement systems and amplifies the local inflammation, resulting in renal injuries. Although previous studies based on repeat biopsies suggested that the change of MEST-C scores of Oxford classification might be related to the prognosis, there have been few reports about immunofluorescence (IF) changes in repeat biopsies. In this study, we aimed to elucidate the relationship between the changes in the degree of glomerular IgA and C3 depositions and clinical prognosis of IgAN based on repeat biopsy observation. Method Fifty-five patients with IgAN who underwent repeat biopsies at our hospital between 2000 and 2019 were analyzed retrospectively. IF staining in each case was graded with a semiquantitative scale from 0 to 3 (0, negative; 1, weak; 2, moderate; 3, strong staining). MEST-C scores of the Oxford classification were also evaluated. When each score of IF staining or MEST-C in second biopsy was less compared with that in the first biopsy, it was regarded as “improved”. The primary outcome was the time to achieve complete remission (CR), which is defined as disappearance of both urinary protein (UP) (<0.3 g/gCr) and microhematuria (<5/HPF). The secondary outcome was disappearance of microhematuria, disappearance of UP and the rate of eGFR decline. Multivariate analyses were conducted using Cox proportional hazards regression models or linear regression models, adjusted for age, sex and eGFR at the first biopsy. Results Twenty-seven patients (48%) were male. At the first biopsy, median age and eGFR were 38.5 years (Interquartile ratio (IQR) 17-49) and 92 mL/min/1.73 m2 (IQR 63-108). Median urinary protein creatinine ratio was 0.6 g/gCr (IQR 0.3-1.7) and 45 patients (80%) had microhematuria. Thirty-three patients (59%) were treated by renin angiotensin system inhibitors and forty-three patients (78%) were treated by immunosuppressive therapy. Median period between the two biopsies was 36 months (IQR 25-55). Median IF scores of glomerular IgA and C3 were 2 (IQR 2-3) and 2 (IQR 1-2) in the first biopsies and 2 (IQR 1-2) and 1 (IQR 1-2) in the second biopsies, respectively. During the median 55 months (IQR 17-99) follow up period, disappearance of UP and microhematuria were observed in 47 (84%) and 36 (64%). Thirty-three (59%) patients reached CR. Improvement of the degree of C3 deposition between two biopsies was significantly associated with CR (Hazard ratio (HR) 0.37; 95% confidential interval (CI) 0.17-0.80, p=0.012), while that of IgA deposition had no association (HR 057; CI 0.27-1.19, p=0.125). Improvement of the degree of C3 deposition was also significantly associated with disappearance of microhematuria (HR 0.45; 95%CI 0.24-0.86, p=0.016), but not with disappearance of UP (HR 0.60; 95%CI 0.34-1.2, p=0.15). Multivariate linear regression revealed that the rate of eGFR decline was not related to IF scores. Any of the Oxford classification scores were not associated with these outcomes. Conclusion Attenuation of glomerular C3 deposition is associated with CR. This suggest that C3 deposition, rather than IgA deposition, may be related with the clinical prognosis of IgAN.