Initial change in fractional excretion of total protein after SGLT2 inhibitors predicts renal prognosis in patients with chronic kidney disease.

Background: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) reduce glomerular hyperfiltration, resulting in an initial estimated glomerular filtration rate (eGFR) dip in chronic kidney disease (CKD). The association between the initial eGFR dip after SGLT2i and proteinuria reduction has not been explored. Fractional excretion of total protein (FETP) is an index of protein leakage corrected for GFR and may be useful in addressing this issue.

Methods: FETP was calculated as (serum creatinine × urine protein)/(serum protein × urine creatinine) (in %) and the initial FETP dip was defined as 3 months/baseline FETP. The patients were divided into three groups according to the initial FETP dip tertile: FETP acute dipper, moderate dipper and riser. The association between initial FETP dip after SGLT2i and the eGFR slope over the subsequent 2 years was retrospectively investigated.

Results: The study involved 238 patients, including 105 with diabetes mellitus. The patients' median age was 57.0 years and eGFR was 43.0 ml/min/1.73 m². The initial FETP dip was associated with the baseline eGFR, protein:creatinine ratio and FETP. The eGFR slope in the FETP acute dipper was -0.2 ml/min/1.73 m²/year, which was less than those of the moderate dipper and riser (-1.0 and -1.3 ml/min/1.73 m²/year; P < .001). Multivariate regression analyses revealed that the initial FETP dip was associated with the eGFR slope independent of potential confounders (P < .001).

Conclusions: An FETP acute dip after SGLT2i is associated with a favourable renal prognosis in CKD, indicating that FETP is a useful index for assessing the efficacy of SGLT2i.