1型心肾综合征的早期诊断及生物标志物研究进展

doi:10.3877/cma.j.issn.2095-3216.2022.02.011

1型心肾综合征(CRS1)被定义为急性心功能恶化导致的急性肾损伤(AKI)，其病理机制复杂、临床表现多种多样，早期诊断和防治AKI对改善CRS1患者的预后至关重要。AKI诊断的传统方法主要依赖血清肌酐(SCr)和尿量评估，可能导致对AKI的诊断延迟、以及入院率和死亡率增加。本文对CRS1的亚型和病理生理进行了描述，并讨论了早期诊断CRS1的重要潜在生物标志物，包括B型钠肽(BNP)、氨基末端BNP前体(NT-proBNP)、心肌肌钙蛋白(cTn)、可溶性基质裂解素2(sST2)、半乳糖凝集素3(Gal-3)、胱抑素C、中性粒细胞明胶酶相关载脂蛋白(NGAL)、肾损伤分子1(KIM-1)、脂肪酸结合蛋白(FABP)、金属蛋白酶组织抑制剂2(TIMP-2)与胰岛素样生长因子结合蛋白7(IGFBP7)乘积、N-乙酰-β-D-氨基葡萄糖苷酶(NAG)、成纤维细胞生长因子23(FGF-23)、白细胞介素18(IL-8)及微小RNA等，以便为CRS1患者的临床早期诊断和风险评估、进而改善预后提供参考。

关键词: 1型心肾综合征, 病理生理, 早期诊断, 生物标志物

Cardiorenal syndrome type 1 (CRS1) is defined as acute kidney injury (AKI) caused by acute cardiac function deterioration. Its pathological mechanism is complex and clinical manifestations are diverse. Early diagnosis and prevention of AKI are crucial to improving the prognosis of CRS1 patients. The traditional method for AKI diagnosis mainly relies on the assessment of serum creatinine (SCr) and urine volume, which may lead to delayed diagnosis of AKI and increased hospital admission and mortality. This article described the subtypes and pathophysiology of CRS1, and discussed important potential biomarkers for early diagnosis of CRS1, including B-type natriuretic peptide (BNP), N-terminal proBNP (NT-proBNP), cardiac troponin (cTn), soluble stromelysin 2 (sST2), galectin 3 (Gal-3), cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), fatty acid-binding protein (FABP), the product of tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7), N-acetyl-β-D-glucosaminidase (NAG), fibroblast growth factor 23 (FGF-23), interleukin-18 (IL-8), and microRNA (miRNA), etc, in order to provide a reference for the early clinical diagnosis, risk assessment, and prognosis improvement of CRS1 patients.

Key words: Cardiorenal syndrome type 1, Pathophysiology, Early diagnosis, Biomarker

表1 心肾综合征的分型^[1,9]

CRS	定义	描述	举例
CRS 1型	急性CRS	急性心功能恶化引起肾脏损伤和/或功能障碍	AHF或ACS引起的AKI
CRS 2型	慢性CRS	慢性心功能异常导致肾脏损伤或功能障碍	CHF导致的CKD
CRS 3型	急性肾心综合征	急性肾功能恶化引起心脏损伤和/或功能障碍	AKI引起的AHF
CRS 4型	慢性肾心综合征	CKD导致的心脏损伤、疾病和/或功能障碍	CKD导致的CHF
CRS 5型	继发性CRS	全身其他系统性疾病导致心力衰竭和肾衰竭	脓毒血症引起的心脏和肾脏功能衰竭

表1 心肾综合征的分型^[1,9]

CRS	定义	描述	举例
CRS 1型	急性CRS	急性心功能恶化引起肾脏损伤和/或功能障碍	AHF或ACS引起的AKI
CRS 2型	慢性CRS	慢性心功能异常导致肾脏损伤或功能障碍	CHF导致的CKD
CRS 3型	急性肾心综合征	急性肾功能恶化引起心脏损伤和/或功能障碍	AKI引起的AHF
CRS 4型	慢性肾心综合征	CKD导致的心脏损伤、疾病和/或功能障碍	CKD导致的CHF
CRS 5型	继发性CRS	全身其他系统性疾病导致心力衰竭和肾衰竭	脓毒血症引起的心脏和肾脏功能衰竭

表2 KDIGO标准定义的AKI阶段^[9]

AKI阶段	SCr水平	尿量
1	48 h内升高0.3 mg/dl (26.5 μmmol/L)	<0.5 ml/(kg·h), 6~12 h
	或升高至1.5~1.9倍基线水平
2	2.0~2.9倍基线水平	<0.5 ml /(kg·h)，≥12 h
3	3.0倍基线	<0.3 ml/(kg·h)，≥24 h
	或血清肌酐增加至≥353.6 μmmol/L(4.0 mg/dl)	无尿12 h
	或开始肾脏替代治疗
	或在患者<18岁群体中，eGFR降至<35 ml/(min·1.73 m²)

表2 KDIGO标准定义的AKI阶段^[9]

AKI阶段	SCr水平	尿量
1	48 h内升高0.3 mg/dl (26.5 μmmol/L)	<0.5 ml/(kg·h), 6~12 h
	或升高至1.5~1.9倍基线水平
2	2.0~2.9倍基线水平	<0.5 ml /(kg·h)，≥12 h
3	3.0倍基线	<0.3 ml/(kg·h)，≥24 h
	或血清肌酐增加至≥353.6 μmmol/L(4.0 mg/dl)	无尿12 h
	或开始肾脏替代治疗
	或在患者<18岁群体中，eGFR降至<35 ml/(min·1.73 m²)

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Advances in early diagnosis and biomarkers of cardiorenal syndrome type 1

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