Irene Capelli, Daniele Vetrano, Danilo Ribichini, Michele Provenzano, Sasha Albertini, Sabrina Berti, Ilirjana Sanfilippo, Valentina Vicennati, Uberto Pagotto, Gaetano La Manna, Giuseppe Cianciolo
In this real-world CKD cohort, SGLT2 inhibitor initiation was associated with favorable changes in renal risk scores and with changes in cardiovascular risk estimates, particularly among patients with diabetes and at higher baseline risk. These findings should be interpreted as exploratory changes in predicted risk rather than as evidence of reduction in observed cardiovascular events.
BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have become the standard of care in managing chronic kidney disease (CKD) and heart failure (HF), both in patients with and without type 2 diabetes mellitus (T2DM). Nonetheless, identifying those at persistent high cardiovascular (CV) and renal risk remains critical.
METHODS: We conducted a retrospective, 1:1 propensity-matched cohort study involving 132 CKD patients (66 with T2D and 66 without). Participants were followed for 12 months after SGLT2i initiation. Cardiovascular and renal risk were assessed using three validated tools-PREVENT, SCORE2 with CKD Add-on (SCORE2-CKD), and Kidney Failure Risk Equation (KFRE)-calculated at baseline and at 12-month follow-up. Changes in risk scores were analyzed, and logistic regression was used to identify predictors of improvement.
RESULTS: After 12 months, PREVENT scores declined significantly in the diabetic subgroup (Δ -2.95, P = .001), whereas non-diabetic patients showed no significant change (Δ -0.80, P = .396). SCORE2-CKD also decreased in diabetics (Δ -3.85, 95% CI -4.35 to -3.35, P = .023) but unexpectedly increased in non-diabetic patients (Δ + 3.25, P = .044). Importantly, individuals at higher baseline risk exhibited the most pronounced declines in both PREVENT and SCORE2-CKD. KFRE-derived renal risk decreased significantly in both groups. Across the entire cohort, variation in estimated glomerular filtration rate (eGFR) and proteinuria were independent predictors of CV risk-score improvement.
CONCLUSIONS: In this real-world CKD cohort, SGLT2 inhibitor initiation was associated with favorable changes in renal risk scores and with changes in cardiovascular risk estimates, particularly among patients with diabetes and at higher baseline risk. These findings should be interpreted as exploratory changes in predicted risk rather than as evidence of reduction in observed cardiovascular events.