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

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posted on 2023-08-09, 19:42 authored by Filipe A. Moura, David D. Berg, Andrea Bellavia, Jamie P. Dwyer, Ofri Mosenzon, Benjamin A. Scirica, Stephen D. Wiviott, Deepak L. Bhatt, Itamar Raz, Mark W. Feinberg, Eugene Braunwald, David A. Morrow, Marc S. Sabatine

  

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. 

Funding

Funding and Assistance: SAVOR-TIMI 53 and DECLARE-TIMI 58 were supported by institutional research grants to Brigham and Women’s Hospital from AstraZeneca. FOURIER was supported by an institutional research grant to Brigham and Women’s Hospital from Amgen. CAMELLIA-TIMI 61 was supported by an institutional research grant to Brigham and Women’s Hospital from Eisai. F.A.M., S.D.W., B.M.S., D.A.M., and M.S.S. were supported for the present analysis by the American Heart Association Cardiometabolic Health & Type 2 Diabetes Mellitus Strategically Focused Research Network (20SFRN35120087). F.A.M. was supported by a T32 postdoctoral training grant from the National Heart, Lung, and Blood Institute (T32HL007604).

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