Cardiac and Inflammatory Biomarkers Are Associated with Worsening Renal Outcomes in Patients with Type 2 Diabetes Mellitus: Observations from SAVOR-TIMI 53.
Cardiac and Inflammatory Biomarkers Are Associated with Worsening Renal Outcomes in Patients with Type 2 Diabetes Mellitus: Observations from SAVOR-TIMI 53.
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DOI：
10.1373/clinchem.2018.298489
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发表时间：
2019-06
影响因子：
9.3
通讯作者：
Thomas A. Zelniker;D. Morrow;Ofri Mosenzon;Yared Gurmu;K. Im;A. Cahn;I. Raz;P. Steg;Lawrence A Leiter;E. Braunwald;Deepak L. Bhatt;B. Scirica
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作者：
Thomas A. Zelniker;D. Morrow;Ofri Mosenzon;Yared Gurmu;K. Im;A. Cahn;I. Raz;P. Steg;Lawrence A Leiter;E. Braunwald;Deepak L. Bhatt;B. Scirica
背景心脏和肾脏疾病通常发生双向相互作用。我们假设心脏和炎症生物标志物可能有助于识别肾功能恶化风险较高的2型糖尿病（T2 DM）患者。方法在SAVOR-TIMI 53的探索性分析中，测定了12310例患者基线血清样本中高敏心肌肌钙蛋白T（hs-TnT）、N末端B型利钠肽前体（NT-proBNP）和高敏C反应蛋白（hs-CRP）的浓度。该分析的主要终点是治疗结束（EOT）时估计的肾小球滤过率（eGFR）降低≥40%，中位时间为2.1年。使用校正的logistic和考克斯回归对生物标志物和终点之间的关系进行建模。结果在多变量校正（包括基线肾功能）后，每种生物标志物与EOT时eGFR降低≥40%的风险增加独立相关[四分位数（Q）Q4 vs Q1：hs-TnT校正的比值比（OR），5.63（3.49-9.10）; NT-proBNP校正OR，3.53（2.29-5.45）; hs-CRP校正OR，1.84（95%CI，1.27-2.68）;所有P值≤0.001]。此外，每种生物标志物与尿白蛋白-肌酐比值（UACR）类别恶化的风险较高独立相关（所有P值≤0.002）。在没有心力衰竭和eGFR >60 mL/min的患者中进行的敏感性分析提供了类似的结果。在校正的多标志物模型中，hs-TnT和NT-proBNP与两种肾脏结局均显著相关（所有P值均<0.01）。结论：hs-TnT、NT-proBNP和hs-CRP均与高危T2 DM患者的肾功能恶化[eGFR降低（≥40%）和UACR分级恶化]相关。心脏或炎症生物标志物高的患者不仅应治疗心血管结局风险，还应随访肾脏恶化。
BACKGROUND Cardiac and renal diseases commonly occur with bidirectional interactions. We hypothesized that cardiac and inflammatory biomarkers may assist in identification of patients with type 2 diabetes mellitus (T2DM) at high risk of worsening renal function. METHODS In this exploratory analysis from SAVOR-TIMI 53, concentrations of high-sensitivity cardiac troponin T (hs-TnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hs-CRP) were measured in baseline serum samples of 12310 patients. The primary end point for this analysis was a ≥40% decrease in estimated glomerular filtration rate (eGFR) at end of treatment (EOT) at a median of 2.1 years. The relationships between biomarkers and the end point were modeled using adjusted logistic and Cox regression. RESULTS After multivariable adjustment including baseline renal function, each biomarker was independently associated with an increased risk of ≥40% decrease in eGFR at EOT [Quartile (Q) Q4 vs Q1: hs-TnT adjusted odds ratio (OR), 5.63 (3.49-9.10); NT-proBNP adjusted OR, 3.53 (2.29-5.45); hs-CRP adjusted OR, 1.84 (95% CI, 1.27-2.68); all P values ≤0.001]. Furthermore, each biomarker was independently associated with higher risk of worsening of urinary albumin-to-creatinine ratio (UACR) category (all P values ≤0.002). Sensitivity analyses in patients without heart failure and eGFR >60 mL/min provided similar results. In an adjusted multimarker model, hs-TnT and NT-proBNP remained significantly associated with both renal outcomes (all P values <0.01). CONCLUSIONS hs-TnT, NT-proBNP, and hs-CRP were each associated with worsening of renal function [reduction in eGFR (≥40%) and deterioration in UACR class] in high-risk patients with T2DM. Patients with high cardiac or inflammatory biomarkers should be treated not only for their risk of cardiovascular outcomes but also followed for renal deterioration.