#4476 PRIMARY GLOMERULAR DISEASES AND LONG-TERM RISKS OF CKD PROGRESSION, CARDIOVASCULAR EVENTS AND DEATH: A SWEDISH NATIONWIDE COHORT STUDY

Abstract Background and Aims Although glomerular diseases are the third most frequent cause of end-stage kidney disease worldwide (after diabetes and hypertension), little is known about their long-term risks and complications. Method Using data from the Swedish Renal Registry (SRR-CKD) 2005-2021, we compared clinical outcomes between patients with the four most frequent primary glomerular diseases (IgA nephropathy [IgAN], focal segmental glomerulosclerosis [FSGS], minimal change disease [MCD] and membranous nephropathy [MN]) and patients with CKD attributed to non-inflammatory etiologies (i.e. without systemic auto-immune, inflammatory, infectious, hematologic malignancy, genetic disease, or polycystic kidney disease). Poisson models were used to estimate adjusted incidence rate ratios (IRR) of all-cause and cause-specific hospitalizations (cardiovascular-, acute kidney injury-, thromboembolism- and infection-related). Cox proportional hazards models were used to estimate adjusted hazard ratios (HR) of kidney replacement therapy (KRT), major adverse cardiovascular events (MACE) and death. Results We identified 2967 patients with primary glomerular disease (71% men, age 57 years, eGFR 28 mL/min/1.73 m2, uACR 63 mg/mmol) and 40026 patients with a non-inflammatory CKD (64% men, age 74 years, eGFR 22 mL/min/1.73 m2, uACR 20 mg/mmol). As compared to non-inflammatory CKD, patients with primary glomerular diseases were younger, had a lower prevalence of cardiovascular disease, higher eGFR but higher albuminuria. Over median follow-up of 6.3 [3.3;9.9] years, there were median 3.0 [1.0;7.0] hospitalizations per patient, 9890 (23%) KRT, 11708 (27%) MACE, and 21091 (49%) deaths. As compared to non-inflammatory CKD, patients with primary glomerular disease had a lower risk of all-cause (IRR 0.77 [0.75;0.79]), and all cause-specific hospitalizations, MACE (HR 0.56 [0.50;0.63]) and death (HR 0.57 [0.52;0.62], but a similar risk of KRT (HR 1.02 [0.95;1.10]) or AKI (HR 0.84 [0.70;1.02]) (Figure 1). Within primary glomerular diseases and as compared to IgAN, patients with FSGS had a higher risk of death (HR 1.29 [1.03;1.60]) and MACE (HR 1.49 [1.12;1.97]), and patients with MN and MCD had a lower risk of KRT. Conclusion In this nationwide analysis of patients with advanced CKD undergoing nephrologist-care, those with primary glomerular disease have an observed lower risk of adverse clinical events compared to non-inflammatory CKD diseases. However, their risks of AKI or KRT are similar, emphasizing the need of adequate treatment strategies in this population. We speculate that the long-term continuous exposure to comorbidities like diabetes and hypertension in patients with non-inflammatory CKD might explain these differences. Within single primary glomerular disease etiologies, FSGS is associated with the highest risk of cardiovascular and fatal complications. The study received grant support from CSL Vifor.