P0355FAMILY HISTORY OF COMPLEX TRAITS IN THE CUREGN COHORT: ASSOCIATIONS WITH RENAL FUNCTION, COMORBIDITY BURDEN AND DISEASE PROGRESSION

Abstract Background and Aims Family history (FHx) of complex traits may reflect shared genetic/environmental risk. Few studies suggest associations with increased risk of comorbidities and worsening renal function, but this has not been examined in primary glomerulopathies (GNs). Herein, we studied the association of FHx of complex traits with presentation patterns, comorbidities and disease progression in a prospective cohort of patients with primary GN. Method The Cure Glomerulopathy Networ (CureGN) is a prospective multi-center observational study of GN patients (N=2474) affected by biopsy-proven Focal Segmental Glomerulosclerosis (FSGS), Minimal Change Disease (MCD), Membranous Nephropathy (MN) and IgA Nephropathy/Vasculitis (IgAN/V). Associations of self-reported FHx of diabetes (DM), coronary artery disease (CAD), cancer (C), clotting disorders (CD), and autoimmune diseases (AD) with eGFR, UPCR at diagnosis, and comorbidities prevalence were studied using linear and logistic regression models adjusted for age, sex, ethnicity, race, BMI and other relevant clinical covariates. Associations between FHx and ESRD/40%eGFR reduction were investigated with multivariate Cox models. Results FHx of DM was associated with lower eGFR and higher UPCR at diagnosis in the entire cohort (p=0.006 and p=0.03), lower eGFR in FSGS (p=0.02) and higher UPCR in IgAN/V (p=0.01). Regarding comorbidity burden (Table 1), FHx of DM was associated with higher prevalence of DM, heart failure and infections requiring hospitalization, FHx of C with cancer, FHx of CD with higher prevalence of thrombosis and FHx of AD with inflammatory bowel, celiac diseases, asthma and drug allergies. At the survival analysis adjusted for age, sex, ethnicity, race, BMI, diagnosis group, eGFR and UPCR at diagnosis, DM, hypertension, use of immunosuppressants and RAAS-inhibitors, FHx of DM was associated with higher risk of the composite outcome of ESRD/40%eGFR reduction in the entire cohort (HR 1.39, 95%CI 1.07-1.81, p=0.01), and specifically in FSGS (HR 1.76, 95%CI 1.08-2.85, p=0.02) and in the paediatric subgroup (HR 1.98, 95%CI 1.04-3.80, p=0.04). Conclusion FHx of complex traits are associated with higher prevalence of specific comorbidities. FHx of DM identifies patients with lower eGFR at diagnosis, higher prevalence of infections and higher risk of renal disease progression. These findings, which need to be confirmed in other cohorts, suggest that FHx could be an additional useful parameter for risk stratification and management of primary GN.