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尿小管生物标志物可预测微量白蛋白尿 2 型糖尿病患者的肾功能下降、心血管事件和死亡。

Urinary tubular biomarkers as predictors of kidney function decline, cardiovascular events and mortality in microalbuminuric type 2 diabetic patients.

机构信息

Steno Diabetes Center Copenhagen, Niels Steensens Vej 2, 2820, Gentofte, Denmark.

Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

出版信息

Acta Diabetol. 2018 Nov;55(11):1143-1150. doi: 10.1007/s00592-018-1205-0. Epub 2018 Aug 14.


DOI:10.1007/s00592-018-1205-0
PMID:30105469
Abstract

AIMS: Urinary levels of kidney injury molecule 1 (u-KIM-1) and neutrophil gelatinase-associated lipocalin (u-NGAL) reflect proximal tubular pathophysiology and have been proposed as risk markers for development of complications in patients with type 2 diabetes (T2D). We clarify the predictive value of u-KIM-1 and u-NGAL for decline in eGFR, cardiovascular events (CVE) and all-cause mortality in patients with T2D and persistent microalbuminuria without clinical cardiovascular disease. METHODS: This is a prospective study that included 200 patients. u-KIM-1 and u-NGAL were measured at baseline and were available in 192 patients. Endpoints comprised: decline in eGFR > 30%, a composite of fatal and nonfatal CVE consisting of: cardiovascular mortality, myocardial infarction, stroke, ischemic heart disease and heart failure based on national hospital discharge registries, and all-cause mortality. Adjusted Cox models included traditional risk factors, including eGFR. Hazard ratios (HR) are provided per 1 standard deviation (SD) increment of log2-transformed values. Relative integrated discrimination improvement (rIDI) was calculated. RESULTS: During the 6.1 years' follow-up, higher u-KIM-1 was a predictor of eGFR decline (n = 29), CVE (n = 34) and all-cause mortality (n = 29) in adjusted models: HR (95% CI) 1.68 (1.04-2.71), p = 0.034; 2.26 (1.24-4.15), p = 0.008; and 1.52 (1.00-2.31), p = 0.049. u-KIM-1 contributed significantly to risk prediction for all-cause mortality evaluated by rIDI (63.1%, p = 0.001). u-NGAL was not a predictor of any of the outcomes after adjustment. CONCLUSIONS: In patients with T2D and persistent microalbuminuria, u-KIM-1, but not u-NGAL, was an independent risk factor for decline in eGFR, CVE and all-cause mortality, and contributed significant discrimination for all-cause mortality, beyond traditional risk factors.

摘要

目的:尿肾损伤分子 1(u-KIM-1)和中性粒细胞明胶酶相关脂质运载蛋白(u-NGAL)的水平反映了近端肾小管的病理生理学变化,并已被提议作为 2 型糖尿病(T2D)患者发生并发症的风险标志物。我们澄清了 u-KIM-1 和 u-NGAL 对 T2D 患者持续微量白蛋白尿且无临床心血管疾病患者的 eGFR 下降、心血管事件(CVE)和全因死亡率的预测价值。

方法:这是一项前瞻性研究,纳入了 200 名患者。在基线时测量了 u-KIM-1 和 u-NGAL,192 名患者可获得这两种标志物的数据。终点包括:eGFR 下降>30%,致命和非致命 CVE 的综合指标,包括心血管死亡率、心肌梗死、中风、缺血性心脏病和心力衰竭,基于国家医院出院登记处,以及全因死亡率。调整后的 Cox 模型包括传统的危险因素,包括 eGFR。每增加 1 个标准差(SD)的对数转换值,风险比(HR)都会提供。计算相对综合判别改善(rIDI)。

结果:在 6.1 年的随访期间,较高的 u-KIM-1 在调整后的模型中是 eGFR 下降(n=29)、CVE(n=34)和全因死亡率(n=29)的预测因素:HR(95%CI)为 1.68(1.04-2.71),p=0.034;2.26(1.24-4.15),p=0.008;和 1.52(1.00-2.31),p=0.049。u-KIM-1 通过 rIDI(63.1%,p=0.001)对全因死亡率的风险预测有显著贡献。调整后,u-NGAL 不是任何结果的预测因素。

结论:在 T2D 合并持续微量白蛋白尿的患者中,u-KIM-1 是 eGFR 下降、CVE 和全因死亡率的独立危险因素,与传统危险因素相比,对全因死亡率的判别能力有显著提高。

相似文献

[1]
Urinary tubular biomarkers as predictors of kidney function decline, cardiovascular events and mortality in microalbuminuric type 2 diabetic patients.

Acta Diabetol. 2018-8-14

[2]
Markers of Glomerular and Tubular Damage in the Early Stage of Kidney Disease in Type 2 Diabetic Patients.

Mediators Inflamm. 2018-8-9

[3]
Urinary biomarkers of tubular injury to predict renal progression and end stage renal disease in type 2 diabetes mellitus with advanced nephropathy: A prospective cohort study.

J Diabetes Complications. 2019-5-25

[4]
Associations between urinary kidney injury biomarkers and cardiovascular mortality risk in elderly men with diabetes.

Ups J Med Sci. 2016-8

[5]
Nonalbuminuric proteinuria as a biomarker for tubular damage in early development of nephropathy with type 2 diabetic patients.

Diabetes Metab Res Rev. 2014-11

[6]
Urinary kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin as indicators of tubular damage in normoalbuminuric patients with type 2 diabetes.

Clin Biochem. 2016-2

[7]
Tissue expression of tubular injury markers is associated with renal function decline in diabetic nephropathy.

J Diabetes Complications. 2017-8-24

[8]
Clinical implication of urinary tubular markers in the early stage of nephropathy with type 2 diabetic patients.

Diabetes Res Clin Pract. 2012-3-21

[9]
Urinary tubular biomarkers in short-term type 2 diabetes mellitus patients: a cross-sectional study.

Endocrine. 2011-7-21

[10]
N-acteyl-ß-D-glucosaminidase and kidney injury molecule-1: New predictors for long-term progression of chronic kidney disease in patients with heart failure.

Nephrology (Carlton). 2016-6

引用本文的文献

[1]
Urinary non-albumin protein-creatinine ratio is an independent predictor of mortality in patients with type 2 diabetes: a retrospective cohort study.

Sci Rep. 2024-5-8

[2]
Precision prognostics for cardiovascular disease in Type 2 diabetes: a systematic review and meta-analysis.

Commun Med (Lond). 2024-1-22

[3]
Association between continuous glucose monitoring-derived glycemic control indices and urinary biomarkers of diabetic kidney disease: Hyogo Diabetes Hypoglycemia Cognition Complications study.

Acta Diabetol. 2024-4

[4]
THE INCREASED PLASMA LEVELS OF INTERMEDIN IN PATIENTS WITH TYPE 2 DIABETES MELLITUS.

Acta Endocrinol (Buchar). 2022

[5]
Acylcarnitines: Can They Be Biomarkers of Diabetic Nephropathy?

Diabetes Metab Syndr Obes. 2022-1-29

[6]
Novel Cardiovascular Risk Factors in Patients with Diabetic Kidney Disease.

Int J Mol Sci. 2021-10-17

[7]
Novel Urinary Glycan Biomarkers Predict Cardiovascular Events in Patients With Type 2 Diabetes: A Multicenter Prospective Study With 5-Year Follow Up (U-CARE Study 2).

Front Cardiovasc Med. 2021-5-24

[8]
The ratio and difference of urine protein-to-creatinine ratio and albumin-to-creatinine ratio facilitate risk prediction of all-cause mortality.

Sci Rep. 2021-4-12

[9]
Plasma trimethylamine N-oxide and its metabolic precursors and risk of mortality, cardiovascular and renal disease in individuals with type 2-diabetes and albuminuria.

PLoS One. 2021

[10]
Diabetic kidney diseases revisited: A new perspective for a new era.

Mol Metab. 2019-10-17

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