TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Division of Nephrology and Hypertension, University of Utah Health, Salt Lake City, UT.
Diabetes Care. 2023 Oct 1;46(10):1807-1815. doi: 10.2337/dc23-0492.
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.
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.
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 (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 Chronic Kidney Disease Prognosis Consortium risk prediction model.
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.
开发一种风险评估工具，以识别 2 型糖尿病（T2D）患者中肾脏疾病进展风险较高且可能从钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂中获益更多的患者。
来自四项血栓溶解心肌梗死（TIMI）临床试验的 41204 例 T2D 患者被分为推导队列（70%）和验证队列（30%）。采用多变量 Cox 回归选择肾脏疾病进展的候选预测因素（估计肾小球滤过率[eGFR]持续下降≥40%、终末期肾病或肾脏死亡的复合终点）。在 Dapagliflozin 对心血管事件的影响（DECLARE）-TIMI 58 中，根据风险类别（低：<0.5%；中：0.5-<2%；高：≥2%）评估达格列净的疗效。
中位随访 2.4 年后共发生 695 例事件。最终模型包含肾脏疾病进展的 8 个独立预测因素：动脉粥样硬化性心血管疾病、心力衰竭、收缩压、T2D 病程、糖化血红蛋白、eGFR、尿白蛋白/肌酐比值和血红蛋白。推导队列和验证队列的 c 指数分别为 0.798（95%CI，0.774-0.821）和 0.798（95%CI，0.765-0.831）。验证队列中预测风险与观察风险的校准图斜率（十分位数）为 0.98（95%CI，0.93-1.04）。虽然达格列净的相对风险降低在风险类别之间没有差异，但在基线风险较高的患者中，绝对风险降低更大，在风险最高的患者中（≥1%/年），4 年内肾脏疾病进展的绝对风险降低了 3.5%。使用 2022 年慢性肾脏病预后联盟风险预测模型得到了相似的结果。
可以在 T2D 患者中应用肾脏疾病进展风险模型进行风险分层，并确定那些从 SGLT2 抑制中获益更大的患者。
