5921 COMPLEMENT FACTOR H RELATED PROTEINS AND IGA NEPHROPATHY: CLINICAL CORRELATION

Abstract Background and Aims Complement Factor H (FH) function is modulated by their homologous FH related proteins (FHRs), which compete with FH for binding to certain ligands on plasma and on cellular surfaces. Genetic variants in the CFH-CFHRs region (coding for FH and the FHRs) confer susceptibility or protection to complement-mediated renal diseases, such as IgA nephropathy (IgAN). The CFHR3-CFHR1 deletion provides a strong protection against IgAN, while protein levels of FHR-1 and FHR-5 are higher in plasma samples from IgAN patients than in controls. The contribution of other FHR proteins to IgAN is so far unknown. The objective of this study is to determine the role of FH and FHR proteins in the renal progression of IgAN, and to establish whether plasma levels of these proteins could at least partially explain the heterogeneity observed in the patients. Method Plasma levels of FH, FHR-1, FHR-2, FHR-4A and FHR-5 was carried out in patients diagnosed with IgAN by renal biopsy (n = 45), and compared with a control group (n = 45). Protein levels observed in the IgAN patients were subsequently compared according to renal progression. Results Forty-five IgAN patients with a mean age of 46±18 years and 71% male were included. 15% of patients were hypertensive and 4% were diabetic. 90% had antiproteinuric treatment, and 44% immunosuppressive treatment. In renal biopsy according to Oxford classification: M1: 11,4%, E1:8,8%, S1:22%; T1:10,5%. The basal creatinine was 1.3 ± 0.47mg/dl (eFG 67; IQR 16-116 ml/min/1.73m2), and proteinuria (uPCR) 500 mg/g (IQR 30-3220). The patients were followed for a median of 83 months (IQR 0-111 months). Seven patients progressed, defined as a loss of >40% of glomerular filtration rate (GFR). FH and FHR-1 plasma levels were significantly higher in IgAN cases (FH: cases 2400±650 nM vs controls 1980±573 nM, p = 0.002), (FHR-1: cases 497±256 vs controls 379±152 nM; p = 0.011), but the patients had a lowest FH/FHR-1 ratio (FH/FHR-1 cases 5.4±2.58 vs controls 6.3±3.67, p = 0.061). The levels of FHR-2 and FHR-4A were also elevated in IgAN cases (FHR-2: cases 214±127 vs controls 132±71 nM, p