Multimarkers based response to SGLT2 inhibitors in patients with chronic kidney disease

Background and Aims Chronic kidney disease (CKD) is a group of disorders defined by the presence of abnormalities of kidney structure or function for a minimum of 3 months with implications for health. The sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a new therapeutic option with a proven cardio and nephroprotective efficacy in patients with or without type 2-diabetes mellitus (T2DM) and preserved or reduced kidney function. Method We conducted a retrospective, observational study at the Nephrology, Dialysis and Transplantation Units of Sant'Orsola Hospital of Bologna and Santissima Annunziata Hospital of Cosenza. We enrolled 118 patients since 2020 affected by CKD, with or without T2DM. We aimed at investigating the efficacy of current SGLT2i through the analysis of estimated glomerular filtration rate (eGFR), uric acid, hemoglobin, serum potassium and systolic pressure from baseline to month 6 visit. Results After 6 months of therapy, a significant correlation between variation of proteinuria and eGFR was found. Proteinuria significantly decreased from baseline (953 mg/die IQR 450–2600) to 6-month visit (621 mg/die IQR 289–1900) (P = 0.0001) with the greatest reduction of proteinuria observed in patients who also experienced a reduction of the eGFR. Estimated GFR (P = 0.898), serum potassium (P = 0.689) and blood pressure (P = 0.829) did not significantly change. Hb increased at visit 2, as for treatment effect moving from 13.8 ± 1.7 g/dL to 14.2 ± 1.8 g/dL (P = 0.0008). Uric acid significantly decreased from 6.1 ± 1.4 mg/dL at baseline to 5.4 ± 1.3 mg/dL at follow-up visit (P = 0.0004) and a positive correlation between uric acid reduction and eGFR increase from baseline to follow-up visit was found (P = 0.037) (Fig. 1). No significant correlations between proteinuria and the other parameters analysed were observed. Conclusion In our real-life experience a 30% reduction of proteinuria and a stabilization of eGFR were observed after the initiation of SGLT2i therapy. Concomitantly we observed a change of other parameters that was mainly independent from change in proteinuria. Change in eGFR was associated with change in uric acid concentration. We suggest to monitor multiple parameters before taking decision to continue or withdraw SGLT2 inhibitors, in clinical practice.