#5814 SGLT2 INHIBITORS IN IGA NEPHROPATHY: REAL-WORLD CLINICAL PRACTICE
Authors: Carro Clara García , Meneses Arianne Aiffil , Martínez Marina López , Velo Mercedes , Rodríguez-Moreno Antolina , Romeo Maria Jose Soler , Fructuoso Ana Sanchez 
Published: June 2023

Abstract

Background and Aims
Immunoglobulin A nephropathy (IgAn) is a common type glomerulonephritis that often progresses to advanced CKD despite the use of ACEi/ARBs and immunosuppression. DAPA CKD has demonstrated that dapagliflozin reduced the risk of CKD progression in patients with IgAn at high risk of progression (mean eGFR, 43.8 mL/min/1.73 m2, and median urinary albumin-to-creatinine ratio, 900 mg/g) for a median follow up of 2.1 years. EMPA KIDNEY demonstrated that empagliflozin was associated to a lower risk of progression of CKD than placebo in a pool of 853 patients with glomerular diseases also at higher risk of progression at 2 years of follow up. Based on both RCT, SGLT2i have been proposed as new therapeutic tools for management of IgAn. However, there is a lack of studies in real-world clinical practice. Thus, we aimed to evaluate the renal effect of SGTL2i at 12 months in a cohort of patients with biopsy proven IgAn.

Method
Multicenter retrospective observational study including all patients with biopsy proven IgAn who received SGLT2i in 2 hospitals in Spain.

Results
19 patients were included, followed up for 12 months. 73,7% were men with a mean age of 48,37±16,74 and a mean evolution of IgAn of 3,5 years before SGLT2i initiation. 21% presented type 2 DM. Oxford scores were: M0 68,42%, M1 26,31%; E0 78,95%, E1 5,79%; S0 68,42%, S1 26,31%; T0 84,21%, T15,26%, T2 5,26%. No patient presented with crescents, and 63-42% presented IF and TA. Before SGLT2i, 21% have received immunosuppression, and 2 were on steroids at the time of SGLT2i initiation (one budesonide). 94,7% were on ACEi/ARBs. 57,9% received dapagliflozin, 15,8% empagliflozin and 26,3% canagliflozin. At baseline, patients showed creatinine 1,10 (0,91-1,49) mg/dL, eGFR 69,84±28,446 ml/min/1.73 m2, and UACR 315,00 (210,75-590,75) mg/g. As showed in Table 1, there is a transient decline in eGFR at month 1 after SLGT2i but then, there was a tendency to an improvement in eGFR (from 69,84±28,446 at baseline to 87,83±31,33), and a tendency to a decrease in UACR from 315,00 (210,75-590,75) at baseline to 152,00 (86,75-423,75) at month 12. From month 3 after SGLT2i, a significant decrease in uric acid was observed, and, at month 6, better systolic and diastolic BP control was achieved. A tendency to higher Hb levels was also observed, as well as a decrease in weight at the end of follow up. Interestingly, SGLT2i withdrawal was only necessary in 1 patient who presented acute pyelonephritis and AKI, requiring dialysis (baseline eGFR 20 ml7min.1.73 m2 and previously known episodes of urinary tract infection). No other adverse events were found.

Conclusion
In a cohort of patients with IgAn at high risk of progression, a stabilization of renal function was found at 12 months after SGLT2i initiation, with no decrease in eGFR and no increase in UACR. Treatment with SGLTi was associated to a decrease in uric acid levels, a better blood pressure control, and to an increase in Hb levels. Thus, in real-world clinical practice, SGLT2i seem to be a promising therapy for modifying the clinical course of IgAn with a favorable safety profile.