Risk Assessment of Kidney Disease Progression and Efficacy of SGLT2 inhibition in Patients with Type 2 Diabetes

Objective:

To develop a risk assessment tool to identify patients with T2D at higher risk for kidney disease progression and who might benefit most from SGLT2 inhibition.

Research Design and Methods:

41,204 patients with T2D from 4 TIMI clinical trials were divided into derivation (70%) and validation cohorts (30%). Candidate predictors of kidney disease progression (composite of sustained ≥40% decline in eGFR, end-stage kidney disease, or kidney death) were selected with multivariable Cox regression. Efficacy of dapagliflozin was assessed by risk categories (low: <0.5%; intermediate: 0.5 to <2%; high ≥2%) in DECLARE-TIMI 58.

Results:

695 events occurred over a median follow up of 2.4 years. The final model was comprised of eight independent predictors of kidney disease progression: ASCVD, heart failure, SBP, T2D duration, HbA1c, eGFR, UACR, and hemoglobin. C-indices were 0.798 (95%CI, 0.774–0.821) and 0.798 (95%CI 0.765–0.831) in the derivation and validation cohort, respectively. The calibration plot slope (deciles of predicted vs. observed risk) was 0.98 (95%CI 0.93–1.04) in the validation cohort. Whereas relative risk reductions with dapagliflozin did not differ across risk categories, there was greater absolute risk reduction in patients with higher baseline risk, with a 3.5% absolute risk reduction in kidney disease progression at 4 years in the highest risk group (≥1%/year). Results were similar with the 2022 CKD Prognosis Consortium risk prediction model.

Conclusions:

Risk models for kidney disease progression can be applied in patients with T2D to stratify risk and identify those who experience greater magnitude of effect from SGLT2 inhibition.