#2932 Clinical characteristics and disease progression in primary IgA nephropathy patients in the Netherlands

Abstract Background and Aims Immunoglobulin A nephropathy (IgAN) is the most prevalent form of glomerulonephritis worldwide, characterized by the deposition of IgA in the glomeruli, leading to inflammation and disease progression. The rate of disease progression varies between patients, eventually leading to kidney failure in many patients. Few studies have investigated the clinical characteristics and disease progression of primary IgAN in a real world clinical setting in Europe. This study aims to describe the clinical characteristics and disease progression of patients with primary IgAN, using real-world data from the Netherlands. Method This retrospective cohort study in primary IgAN is based on longitudinal registry and electronic health record data from the PHARMO Data Network in the Netherlands. Data from adult patients with biopsy-confirmed IgAN as recorded in the Dutch Nationwide Pathology Databank between 2010–2022 were linked to hospital, out-patient pharmacy, and general practitioner (GP) data; additional data from clinical laboratories was linked where available. Patients with secondary IgAN or history of kidney transplantation were excluded. The index date was established as the date of initial biopsy confirming the diagnosis of IgAN. At index, we assessed demographic and clinical characteristics such as estimated glomerular filtration rate (eGFR), and urinary albumin-creatinine ratio (uACR). During follow-up, annualized rate of eGFR decline was assessed using age and sex-adjusted linear mixed models. Kaplan-Meier estimators were used to assess time to composite outcome (kidney failure, eGFR reduction ≥40% from baseline, or mortality), and time to hospitalization. Results A total of 161 adult biopsy-confirmed primary IgAN patients were included in the study (mean age 51 ± 17 years; 32% female). Median (interquartile range (IQR)) follow-up was 4.0 years (1.8–7.1). Median (IQR) eGFR at index date was 67 ml/min/1.73 m2 (54–87), and median (IQR) uACR was 0.8 g/g (0.3–1.8). The estimated linear rate of decline of eGFR over the follow-up period was 4.5 ml/min/1.73 m2 per year. The incidence rate (IR) for the composite outcome was 6.6 per 100 patient-years (95% CI 4.8–9.0). Approximately 50% of patients reached the composite outcome at 11.8 years. The incidence rate for all-cause hospitalization was 13 per 100 patient years of which cardiovascular disease was the most common reason for hospitalization with 3.1 per 100 patient-years. Conclusion This study showcased that among a cohort of primary IgAN patients of advanced age there is a significant decline in kidney function (4.5 ml/min/1.73 m2 per year) despite a proteinuria level of 0.8 g/g uACR (roughly equivalent to 1.2 g/g uPCR) at index. Time to reaching the composite endpoint of kidney failure, eGFR reduction ≥40%, or mortality is consistent with existing literature. Overall, notwithstanding limitations, these findings indicate that presentation of primary IgAN with risk factors of rapid progression can lead to kidney function loss and supports the need for more effective therapeutic interventions to slow disease progression.