Kidney Protective Effect of SGLT2 Inhibitors Based on Fractional Excretion of Total Protein

Background: An initial dipping in eGFR occurs after initiation of SGLT2 inhibitors (SGLT2i), reflecting a decrease in intraglomerular pressure. Changes in proteinuria in response to the initial dipping in eGFR are variable and the impact on renal prognosis is not clear. Fractional excretion of total protein (FETP) which was protein clearance divided by creatinine clearance is an indicator of protein leak that accounts for glomerular filtration rate. This study investigated the association between initial dipping in FETP after initiation of SGLT2i and renal prognosis in CKD. Methods: This retrospective observational study included 112 CKD patients who received SGLT2i from 2016 to 2022 at our Hospital. The FETP was calculated as follows: FETP = (urinary total protein / serum total protein) / (urinary creatinine / serum creatinine) %. According to the decline in FETP, patients were divided into two groups. The primary outcome was eGFR slope for 2 years (Figure1). Results: Their median age was 58.0 (interquartile range, 50.0–66.0) years, 69.6 % of which were male. eGFR was 45.0 (33.0–59.9) ml/min/1.73 m2, and FETP was 0.010 (0.004-0.024) %. The eGFR slope for 2 years was significantly slower in the FETP dipper group than in the non-dipper group (Figure 2). We found that initial dipping in FETP was an independent risk factor for eGFR slope for 2 years in multivariate analysis (P=0.030). Conclusion: We found that a greater initial dipping in FETP after initiation of SGLT2i was associated with a better renal prognosis. FETP may be a useful and convenient marker that accurately reflects changes in intraglomerular pressure after initiation of SGLT2i.Figure 1Figure 2