#1042 A real-life experience with dapagliflozin in the treatment of patients with IgA Nephropathy at high risk of progression

Abstract Background and Aims Even though IgA nephropathy is the most common primary glomerular disease worldwide, being accounted with 22% of kidney biopsy results in Europe and despite great advances in comprehending its pathogenesis, little has changed in the standard of care over the last decades. According to recent studies, dapagliflozin reduced the progression of chronic kidney disease in chronic forms of IgA Nephropathy. The study sought to investigate the impact of dapagliflozin use in a compiled cohort of patients diagnosed with IgA Nephropathy. Method This is a prospective, observational study, that included 52 patients with IgA Nephropathy, based on a prior kidney biopsy, actively monitored from 2021 to 2023, in the Nephrology Department of Fundeni Clinical Institute, Bucharest. The inclusion criteria were: patients with IgA nephropathy diagnosed upon evaluation of a kidney biopsy, with GFR30 ml/min/1.73 m2 and proteinuria above 0.3 g/day, who received dapagliflozin 10 mg, daily, with a follow-up of 6 and 12 months. The baseline parameters were considered those that were on the onset of SGLT2 inhibitors therapy with dapagliflozin. Results The study population had a mean age of 48 ± 11 years old and 69.2% were male. The mean value of baseline serum creatinine was 1.68 ± 0.75 mg/dl and the mean value of GFR was 54 ± 27 ml/min/1.73 m2, while the mean value of baseline proteinuria was 1.55 ± 2.1 g/day. Also, the risk of chronic kidney disease progression was very high in 59.6% cases, high in 34.6% cases and moderate in 5.8% cases. The majority of the study cohort (90.4%) already received a stable dose of angiotensin-converting-enzyme inhibitors or angiotensin receptor blocker. After 6 months of dapagliflozin administration, the absolute decline of proteinuria was 0.94 ± 1.9 g/day, while after 12 months was 1.06 ± 2.97 g/day, which in terms of percents translates as a decline of—44.7% and—50%, respectively. A mild decrease in GFR was observed, the absolute decline being represented by 4 (−6.25; 3) ml/min/1.73 m2 after 6 months and 3.5 (−9;2) ml/min/1.73 m2 after 12 months. Patients who had proteinuria less than 1 g/day at baseline experienced an absolute decline in GFR with 2.5 (−5.75; 3.75) ml/min/1.73 m2, while the study group with proteinuria above 1 g/day had an absolute decline in GFR of 5 (−7.2; 3) ml/min/1.73 m2 after 6 months, while after 12 months of treatment, the GFR drop was 4 (−8.5;1.5) ml/min/1.73 m2 and 3 (−9;2) ml/min/1.73 m2, respectively. A GFR decline over 30% was observed with a prevalence of 17.6% in the group with proteinuria above 1 g/day and 9.5% in the group with proteinuria under 1 g/day, while the prevalence was 8.7% in the group with GFR45 ml/min/1.73 m2 and 20% among the group with GFR45 ml/min/1.73 m2. The mean value of baseline proteinuria was 0.42 ± 0.21 g/day in the cohort with proteinuria1 g/day and 3.09 ± 2.53 g/day in the cohort with proteinuria1 g/day (p 0.001). At 6 months, the absolute decrease of proteinuria was 0.18 ± 0.18 g/day in the group with proteinuria under 1 g/day and with 1.79 ± 2.53 g/day in the group with proteinuria above 1 g/day (p 0.001), whereas after 12 months it was 0.15 ± 0.21 g/day and 2.17 ± 2.54 g/day (p 0.001); also, after 12 months, proteinuria was reduced with 1.42 ± 2.37 g/day at patients with GFR45 ml/min/1.73 m2 and with 0.48 ± 0.85 g/day at patients with GFR45 ml/min/1.73 m2, a difference which tends to reach statistical significance. Conclusion There was a decline in proteinuria after 6 months and 12 months of dapagliflozin treatment, with a statistically significant difference between the two groups: the patients with proteinuria above 1 g/day experienced a more remarkable reduction than the group with proteinuria under 1 g/day. Patients with GFR45 ml/min/1.73 m2 experienced a higher drop in proteinuria. A mild decrease of GFR was noticed during the follow-up period, with a higher prevalence of a GFR dip over 30% in the group with proteinuria above 1 g/day and with GFR45 ml/min/1.73 m2, but the difference was not statistically significant.