#3701 MESANGIAL C3 DEPOSITION ASSOCIATES WITH CHRONIC LESIONS AND RENAL OUTCOME IN PATIENTS WITH IGA NEPHROPATHY

Abstract

Abstract Background and Aims Mesangial C3 deposition is frequently observed in patients with IgA nephropathy (IgAN). We sought to investigate whether the extent of mesangial C3 deposition predicts long-term renal function. Method We conducted a retrospective, observational study that included all patients with biopsy-proven IgAN between 1999 and 2021 and a follow-up period of at least 12 months. All renal biopsy specimens were reviewed and scored according to the 2016 revised Oxford Classification by two independent pathologists. In addition, mesangial C3 deposits were assessed by immunofluorescence (IF) staining of C3 deposition and scored semi-quantitatively as: absent, mild (1+), moderate (2+) and intense (3+). The study composite endpoint was defined as doubling of serum creatinine or ESRD, whichever came first. Results 197 patients were followed for a median of 51.7 months (IQR:19.9-84.3 months). The mean eGFR and median 24-hour proteinuria were 54.4 ± 31.3 ml/min/1.73 m2 and 1.5 g/day (IQR: 0.8-3.35), respectively. 29.9% of the patients reached the composite endpoint. The percentage of patients with M1, E1, S1, T1 and T2 were 77.2%, 24.4%, 57%, 27.9% and 16.8%, respectively. 13.7% of patients showed crescents in less than 25% of glomeruli (C1), while 6.6% of them had over 25% of glomeruli involved (C2). In terms of mesangial C3 deposits, 7.7% had absent, 9.5% mild, 19.6% moderate and 63.1% intense IF staining. Compared to patients with mild-moderate or absent C3 staining on IF, those with intense C3 staining had more frequently M1 (83% vs. 73.5% vs. 38.5%, p = 0.04), S1 (64.2% vs. 49% vs. 30.8%, p = 0.03) and T1-2 (51.9% vs. 32.6% vs. 7.7%, p = 0.01). Similarly, the percentage of global glomerulosclerosis was significantly higher in patients with intense C3 staining (20.7% vs. 12.5% vs. 0%, p = 0.04). In terms of clinical variables, patients with intense C3 staining had a greater degree of proteinuria [1.8 (IQR: 0.9-3.6) vs. 1.2 (0.6-2.1) vs. 0.5 (IQR: 0.1-4.9), p = 0.04] and a tendency for a worse kidney function at baseline (52 ± 32 vs. 58 ± 32 vs. 66 ± 40 ml/min, p = 0.3). There was a tendency for patients with mesangial C3 deposits to have an increased serum IgA level, but the extent of deposits did not correlate with serum C3 level. Regarding the renal outcome, there was a significantly higher proportion of patients with intense C3 deposition to have a doubling of serum creatinine (23.6% vs. 12.2% vs. 0%, p = 0.05) and a tendency for a worse composite endpoint (35.8% vs. 22.4% vs. 23.1%, p = 0.1). Accordingly, the odds ratio for doubling of serum creatinine and for the composite endpoint in patients with intense C3 deposition were 2.88 (95%CI, 1.11-7.47, p = 0.02) and 1.91 (95%CI, 0.94-3.91, p = 0.07), respectively. Conclusion In our study, the extent of mesangial C3 deposition associated with clinical variables and chronic lesions of MESTC score. In addition, identification of intense C3 staining on IF could predict a worse renal outcome in patients with IgA nephropathy.