揭秘：為何末期腎病患者的心臟風險評估不能忽視利尿肽

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末期腎病(ESKD)患者中，利尿肽特別是B型利尿肽(BNP)及其N末端前體(NT-proBNP)長期被視為血容量超載及心衰排除工具。儘管這些指標因腎功能排泄受限而普遍升高，近期研究顯示其與心臟疾病、異常心臟結構或功能及死亡率之間存在中度至強烈相關，指出其在ESKD患者風險分層中的潛在重要性。

利尿肽在末期腎病患者中的病理生理學及其重要性

Pathophysiology and significance of natriuretic peptides in patients with end-stage kidney disease

Wen-ling Yang a b c, Magid Fahim b c, David W. Johnson b c d
aDepartment of Nephrology, Peking University Third Hospital, Beijing, China
bDepartment of Nephrology, Princess Alexandra Hospital, Brisbane, Australia
cCentre for Kidney Disease Research, The University of Queensland, Queensland, Australia
dTranslational Research Institute, Brisbane, Australia
Received 3 December 2019, Revised 24 May 2020, Accepted 25 May 2020,

Available online 5 June 2020, Version of Record 10 August 2020.

https://www.sciencedirect.com/science/article/abs/pii/S0009912019312986

Abstract

Natriuretic peptides (NP), especially B type (BNP) and its N-terminal pro-B type natriuretic peptide (NT-proBNP), have long been regarded as biomarkers of volume overload and tools to exclude heart failure in the general population. However, their role in end-stage kidney disease (ESKD) is less certain given that BNP and NT-proBNP are excreted by the kidney and so serum concentrations of NPs are nearly universally elevated compared to controls. Nevertheless, the accumulated evidence suggests that serum concentrations of NPs in patients with ESKD show moderate or strong positive relationships with underlying heart disease, abnormal cardiac structure or function and mortality. Limited evidence also supports the role of BNP including NT-proBNP, ANP in some studies, rather than CNP or DNP in risk stratification among ESKD patients as well as the utility of BNP samplings pre- and post- hemodialysis. However, studies of the cut-off values of NPs have yielded inconsistent results, such that further large-scale studies are needed to clarify these issues. This review summarizes the pathophysiology and significance of NPs in ESKD patients, especially their potential role as risk stratification biomarkers in clinical management.

摘要

利尿肽（NP），尤其是B型（BNP）及其N末端前B型利尿肽（NT-proBNP），長期以來被視為體液過多的生物標誌物和在一般人群中排除心力衰竭的工具。然而，對於末期腎病（ESKD）患者而言，其角色較為不確定，因為BNP和NT-proBNP是由腎臟排泄的，所以與對照組相比，NP的血清濃度幾乎普遍升高。儘管如此，累積的證據表明，ESKD患者的NP血清濃度與潛在的心臟疾病、異常的心臟結構或功能以及死亡率呈中度或強烈正相關。有限的證據還支持BNP（包括NT-proBNP）、在某些研究中的ANP，而非CNP或DNP，在ESKD患者的風險分層中的作用，以及BNP在血液透析前後取樣的實用性。然而，關於NP的截止值的研究結果不一致，因此需要進一步的大規模研究來澄清這些問題。本文綜述了NP在ESKD患者中的病理生理學和重要性，尤其是它們作為臨床管理中風險分層生物標誌物的潛在角色。

導言

據信，利尿肽（NP）家族為了共同的體液、滲透壓和循環系統壓力調節的家庭目的而進化。升高的NP有助於在一般人群中建立心力衰竭（HF）的初步診斷，識別那些需要進一步心臟檢查的人。然而，由於NP由腎臟排泄，絕大多數末期腎病（ESKD）患者的血清NP水平總是升高，對於NP在這一設置中的臨床效用仍存在不確定性。在本綜述中，我們將總結NP的病理生理學和重要性，重點關注B型（或腦型）NP（BNP）以及最近的文獻，在慢性腎病（CKD）第5期，即ESKD患者中，尤其是它們作為臨床管理中風險分層生物標誌物的潛在角色。

人類已知的NP系統包括≥6種心血管肽，包括A型（或心房型，ANP）、BNP、C型（CNP）、D型（DNP）和V型（VNP）NP，以及一種腎肽，尿促進素[1]，[6]，[7]，[8]，[9]，[10]。所有人類的利尿肽都含有一個保留的17個氨基酸（aa）殘基的環結構，形成一個內分子二硫鍵，這可能是負責受體結合的[7]，[8]。存在≥3種NP受體（PRs）。NPR-A，其中

心臟NP的分泌受到心臟壓力和體積的影響[1]，反之亦然。在慢性腎病（包括接受慢性透析的患者）的患者中[3]，[5]，[17]，[36]，[58]，[59]，[60]，研究表明基線NP與心血管疾病[5]，[38]，[61]或各種超聲心動圖指標，如左室質量指數（LVMI）[3]，[36]，[38]，[57]，[59]，[62]，左室射血分數（LVEF）[3]，[36]，[38]，[47]

值得認識的是，ESKD患者的NP值升高不僅提示潛在的心臟疾病、異常心臟結構和功能，也是一個強烈的負面預後發現（表2）。即使負面預後發現可能被腎功能[10]，[37]，[39]，[72]，肥胖[28]，心肌缺血[17]，心房顫動和感染/炎症性肺疾病[73]等共存因素混淆，多項研究已

對於排除HF或預測ESKD患者較差預後的血NP濃度閾值存在不確定性和巨大變異性。DeFilippi等[75]推薦的NT-proBNP切點為<50歲為450，50–75歲為900及>75歲為1800 pg/mL，無需進一步根據腎功能調整，除了<50歲且有嚴重CKD的患者，在這種情況下，對於HF指示的切點為1200 pg/mL。對於CKD患者，截斷

儘管由於腎排泄減少，ESKD患者中的NP，特別是ANP和BNP的血液水平在大多數患者中都升高，但這些水平仍然顯示與體液過多、異常心臟結構和功能、心血管疾病、心臟事件和死亡率有關。因此，單次或重複測定NP，特別是BNP和NT-proBNP，是ESKD患者管理中風險分層的有用生物標誌物。當前有限的文獻

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