肾 intelX.dkd 的推导和独立验证：用于评估糖尿病肾病进展的预后测试。

Derivation and independent validation of kidneyintelX.dkd: A prognostic test for the assessment of diabetic kidney disease progression.

机构信息

Barbara T Murphy Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Division of Digital and Data Driven Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

出版信息

Diabetes Obes Metab. 2023 Dec;25(12):3779-3787. doi: 10.1111/dom.15273. Epub 2023 Sep 18.

DOI:10.1111/dom.15273

PMID:37722962

Abstract

AIMS

To develop and validate an updated version of KidneyIntelX (kidneyintelX.dkd) to stratify patients for risk of progression of diabetic kidney disease (DKD) stages 1 to 3, to simplify the test for clinical adoption and support an application to the US Food and Drug Administration regulatory pathway.

METHODS

We used plasma biomarkers and clinical data from the Penn Medicine Biobank (PMBB) for training, and independent cohorts (BioMe and CANVAS) for validation. The primary outcome was progressive decline in kidney function (PDKF), defined by a ≥40% sustained decline in estimated glomerular filtration rate or end-stage kidney disease within 5 years of follow-up.

RESULTS

In 573 PMBB participants with DKD, 15.4% experienced PDKF over a median of 3.7 years. We trained a random forest model using biomarkers and clinical variables. Among 657 BioMe participants and 1197 CANVAS participants, 11.7% and 7.5%, respectively, experienced PDKF. Based on training cut-offs, 57%, 35% and 8% of BioMe participants, and 56%, 38% and 6% of CANVAS participants were classified as having low-, moderate- and high-risk levels, respectively. The cumulative incidence at these risk levels was 5.9%, 21.2% and 66.9% in BioMe and 6.7%, 13.1% and 59.6% in CANVAS. After clinical risk factor adjustment, the adjusted hazard ratios were 7.7 (95% confidence interval [CI] 3.0-19.6) and 3.7 (95% CI 2.0-6.8) in BioMe, and 5.4 (95% CI 2.5-11.9) and 2.3 (95% CI 1.4-3.9) in CANVAS, for high- versus low-risk and moderate- versus low-risk levels, respectively.

CONCLUSIONS

Using two independent cohorts and a clinical trial population, we validated an updated KidneyIntelX test (named kidneyintelX.dkd), which significantly enhanced risk stratification in patients with DKD for PDKF, independently from known risk factors for progression.

摘要

目的

开发并验证 KidneyIntelX（kidneyintelX.dkd）的更新版本，以对 1 至 3 期糖尿病肾病（DKD）患者进行风险分层，简化检测以便临床应用，并支持向美国食品和药物管理局监管途径申请。

方法

我们使用来自宾夕法尼亚大学医学生物库（PMBB）的血浆生物标志物和临床数据进行训练，并使用独立队列（BioMe 和 CANVAS）进行验证。主要结局是肾功能进行性下降（PDKF），定义为在 5 年内随访期间肾小球滤过率持续下降≥40%或终末期肾病。

结果

在 573 名患有 DKD 的 PMBB 参与者中，有 15.4%的人在中位 3.7 年内经历了 PDPK。我们使用生物标志物和临床变量训练了一个随机森林模型。在 657 名 BioMe 参与者和 1197 名 CANVAS 参与者中，分别有 11.7%和 7.5%的人经历了 PDPK。根据训练截止值，BioMe 参与者中 57%、35%和 8%的人分别被归类为低、中、高危水平，而 CANVAS 参与者中 56%、38%和 6%的人分别被归类为低、中、高危水平。在这些风险水平上，BioMe 的累积发生率为 5.9%、21.2%和 66.9%，CANVAS 的累积发生率为 6.7%、13.1%和 59.6%。在临床危险因素调整后，BioMe 中的调整后的危险比分别为 7.7（95%置信区间 [CI] 3.0-19.6）和 3.7（95% CI 2.0-6.8），CANVAS 中的调整后的危险比分别为 5.4（95% CI 2.5-11.9）和 2.3（95% CI 1.4-3.9），高风险组与低风险组和中风险组与低风险组相比。