Empagliflozin Slows Change in eGFR Slope in CKD

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Treatment with the sodium-glucose cotransporter-2 (SGLT2) inhibitor empagliflozin slows progression of chronic kidney disease (CKD) across a range of patient characteristics, according to randomized clinical trial data reported in The Lancet Diabetes & Endocrinology.

The researchers present a prespecified secondary analysis from the multicenter, international Study of Heart and Kidney Protection with Empagliflozin (EMPA-KIDNEY). In that trial, 6609 patients with CKD were assigned to treatment with empagliflozin (10 mg/day) or placebo. Enrolled patients had an estimated glomerular filtration rate (eGFR) between 20 and 45 mL/min/1.73 m2 or an eGFR between 45 and 90 mL/min/1.73 m2 with a urinary albumin-to-creatinine ratio (UACR) of at least 200 mg/g. The main EMPA-KIDNEY results showed significant reduction in progressive kidney diseases or cardiovascular death among patients assigned to empagliflozin.

The new analysis focused on the tertiary outcome of an annualized rate of change in the eGFR slope, which has been proposed as a potential surrogate for CKD progression. Outcome analysis included the acute eGFR slope (from baseline to 2 months) and the chronic slope (from 2 months onward).

Median follow-up was 2 years. Patients were “broadly representative” of patients with CKD with risk of disease progression and a range of eGFR and UACR values. Among the total patients, 46% were diabetic.

Empagliflozin treatment was associated with an acute dip in eGFR (2.12 mL/min/1.73 m2) for a relative reduction of 6%. After 2 months, the chronic slope was reduced by about half (from −2.75 to −1.37 mL/min/1.73 m2 per year).

Effects on the chronic slope varied according to diabetes status as well as baseline eGFR and UACR. Patients with lower initial UACR had a lower absolute difference in chronic slope. However, because this group had a slower rate of CKD progression, they had a larger relative difference in chronic slope: 86% among patients with a baseline UACR less than 30 mg/g compared with 29% among those with an initial UACR of 2000 mg/g or greater.

The findings suggest substantial slowing of long-term progression of CKD with empagliflozin treatment.

“If widely implemented, use of SGLT2 inhibitors could have a substantial effect on the public health impacts of chronic kidney disease,” the investigators conclude. They cite a companion paper (see reference 12 in the article) reporting broadly similar effects of empagliflozin in patients with different types of primary kidney diseases [EMPA-KIDNEY Collaborative Group. Effects of empagliflozin on progression of chronic kidney disease: A prespecified secondary analysis from the EMPA-KIDNEY trial. Lancet Diabetes Endocrinol 2024; 12:39–50. doi: 10.1016/S2213-8587(23)00321-2].