Risk Assessment of Kidney Disease Progression and Efficacy of SGLT2 Inhibition in Patients with Type 2 Diabetes
Diabetes Care Journal (ADA): August, 2023
Early identification of patients
with type 2 diabetes who are at risk of kidney disease progression is
particularly important in the context of new glucose-lowering medications such
as sodium-glucose cotransporter 2 (SGLT2) inhibitor (Dapagliflozin, Canagliflozin,
Empagliflozin, Ertugliflozin) that can modify the course of
chronic kidney disease.
TAKE-HOME MESSAGE
This study
sought to develop a clinical risk model to identify such patients by leveraging
data from multiple CVD clinical trials, totaling 41,204 participants. Kidney
disease progression was defined as a sustained ≥40% decline in eGFR, end-stage
kidney disease, or kidney death.
The model
performed well in patients with an eGFR of <60 mL/min/1.73 m2 and
≥60 mL/min/1.73 m2 and in those with and without albuminuria.
Dapagliflozin use was associated with a 3.5% absolute
risk reduction in kidney disease progression at 4 years in the highest-risk
group.
This novel clinical risk model to identify patients with type 2 diabetes who are at risk of kidney disease progression performed well and could be important in clinical settings to identify patients who may benefit most from SGLT2 inhibitor use.
CONCLUSIONS
Risk models for kidney disease
progression can be applied in patients with T2D to stratify risk and identify
those who experience a greater magnitude of benefit from SGLT2 inhibition.
Given the underuse of SGLT2 inhibitors in clinical practice, the need to balance risk/benefits as well as consideration of costs, a risk-based approach to administration of SGLT2 inhibitors is reasonable and encouraged.
Doctors Liked to Read More
Objective: To develop
a risk assessment tool to identify patients with type 2 diabetes (T2D) at
higher risk for kidney disease progression and who might benefit more from
sodium-glucose cotransporter 2 (SGLT2) inhibition.
Research design and methods: A total of
41,204 patients with T2D from four Thrombolysis In Myocardial Infarction (TIMI)
clinical trials were divided into derivation (70%) and validation cohorts
(30%). Candidate predictors of kidney disease progression (composite of
sustained ≥40% decline in estimated glomerular filtration rate [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 Dapagliflozin Effect on
Cardiovascular Events (DECLARE)-TIMI 58.
Results: There were
695 events over a median follow-up of 2.4 years. The final model comprised
eight independent predictors of kidney disease progression: atherosclerotic
cardiovascular disease, heart failure, systolic blood pressure, T2D duration,
glycated hemoglobin, eGFR, urine albumin-to-creatinine ratio, and hemoglobin.
The c-indices were 0.798 and 0.798 in the derivation and validation cohort,
respectively. The calibration plot slope (deciles of predicted vs. observed
risk) was 0.98 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 Chronic Kidney Disease 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 a greater magnitude of benefit from
SGLT2 inhibition.
Comments
You must login to write comment