#3999 PROTEINURIA AND PROGRESSION OF IGA NEPHROPATHY. HAVE WE REACHED THE POINT OF NO RETURN?

Abstract Background and Aims IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, associated with an incidence of 2.5/100.000 cases per year and progression to end-stage kidney disease (ESKD) in 20% patients within 10 years. Proteinuria has been identified as the greatest risk factor for ESKD in IgAN. The aim was to evaluate the correlation between proteinuria and major adverse renal events (MARE). We define MARE as 40% decline in glomerular filtration rate (eGFR), initiation of kidney replacement therapy (either dialysis or kidney transplantation) or death whether from renal cause or cardiovascular-related. Method In this retrospective observational single-center study, we included all biopsy-proven IgAN patients older than 18 years with proteinuria >500 mg/24h, diagnosed between 2006-2017 and followed up to January 2022. Clinical, analytical, and histological findings were collected at time of diagnosis and during follow-up. Uni and multivariable Cox regression were performed to establish correlation between our data and the main event. A linear mixed-effects model was used to estimate eGFR slope. Results A total of 124 patients were included. Mean age and eGFR were 40 ±15 years and 59 ml/min (IQR: 33-94 ml/min) respectively, with a median proteinuria of 1.44 g/24h (IQR 0.7-2.3). 64% of patients were treated with corticosteroids. In the multivariate analysis, we found that IFTA >25% had a statistically significant risk of MARE (IFTA T1 HR 3.1; 95% CI 1.52-6.6; p = 0.002; IFTA T2 HR 6.6; 95% CI 1.46-16.12; p<0.001), history of cardiovascular disease presented 3.7 times higher risk of MARE (HR 3.7; 95% CI 1.46-9.6 p = 0.015). Patients with proteinuria >3 g/24h showed significantly higher hazard ratio (HR 2.36 95%CI 1.16-4.8 p = 0.01) for MARE. In the 3-year linear mixed-effects model, patients with proteinuria above 3 g/24h had an annual eGFR slope of -6.3 ml/min (-9.6 to -3.1 95%CI). Nevertheless, proteinuria between 1.5 to 3 g/24h had an annual eGFR slope of -2.1 ml/min (-4.9 to 0.62 95% CI), finding no statistical difference in comparison to patients with proteinuria <1.5 g/24h. Conclusion Typically, the threshold of proteinuria >1 g/24h has been marked as the start of immunosuppression in this nephropathy. Several studies published in recent years (as example STOP IgAN) question this paradigm. According to our data, there is a strong association between proteinuria >3 g/24h and major adverse renal events. Patients with proteinuria between 1.5 to 3 g/24h had a similar behaviour as our reference group (proteinuria <1.5 g/24h). These results might provide new evidence supporting a more conservative approach and start receiving glucocorticoids if proteinuria is > 3 g/24h.