Lytvyn Yuliya, Burns Kevin D, Testani Jeffrey M, Lytvyn Andriy, Ambinathan Jaya Prakash N, Osuntokun Oluwatosin, Godoy Lucas C, Cherney David Z I, Parker John D
Toronto General Hospital Research Institute, Toronto, Ontario, Canada; Department of Medicine, Division of Nephrology, University of Toronto, Toronto, Ontario, Canada.
Kidney Research Centre, Division of Nephrology, Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
J Card Fail. 2022 Mar;28(3):385-393. doi: 10.1016/j.cardfail.2021.08.015. Epub 2021 Sep 4.
Understanding cardiorenal pathophysiology in heart failure (HF) is of clinical importance. We sought to characterize the renal hemodynamic function and the transrenal gradient of the renin-angiotensin-aldosterone system (RAAS) markers in patients with HF and in controls without HF.
In this post hoc analysis, the glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and transrenal gradients (arterial-renal vein) of angiotensin converting enzyme (ACE), aldosterone, and plasma renin activity (PRA) were measured in 47 patients with HF and in 24 controls. Gomez equations were used to derive afferent (R) and efferent (R) arteriolar resistances. Transrenal RAAS gradients were also collected in patients treated with intravenous dobutamine (HF, n = 11; non-HF, n = 11) or nitroprusside (HF, n = 18; non-HF, n = 5).
The concentrations of PRA, aldosterone and ACE were higher in the renal vein vs the artery in patients with HF vs patients without HF (P < 0.01). In patients with HF, a greater ACE gradient was associated with greater renal vascular resistance (r = 0.42; P 0.007) and greater arteriolar resistances (R: r = 0.39; P = 0.012; R: r = 0.48; P = 0.002). Similarly, a greater aldosterone gradient was associated with lower GFR (r = -0.51; P = 0.0007) and renal blood flow (RBF), r = -0.32; P = 0.042) whereas greater PRA gradient with lower ERPF (r = -0.33; P = 0.040), GFR (r = -0.36; P = 0.024), and RBF (r = -0.33; P = 0.036). Dobutamine and nitroprusside treatment decreased the transrenal gradient of ACE (P = 0.012, P < 0.0001, respectively), aldosterone (P = 0.005, P = 0.030) and PRA (P = 0.014, P = 0.002) in patients with HF only.
A larger transrenal RAAS marker gradient in patients with HF suggests a renal origin for neurohormonal activation associated with a vasoconstrictive renal profile.
了解心力衰竭（HF）中心肾病理生理学具有临床重要性。我们试图对HF患者和无HF的对照者的肾血流动力学功能以及肾素 - 血管紧张素 - 醛固酮系统（RAAS）标志物的跨肾梯度进行特征描述。
在这项事后分析中，测量了47例HF患者和24例对照者的肾小球滤过率（GFR）、有效肾血浆流量（ERPF）以及血管紧张素转换酶（ACE）、醛固酮和血浆肾素活性（PRA）的跨肾梯度（动脉 - 肾静脉）。使用戈麦斯方程推导入球（R）和出球（R）小动脉阻力。还收集了接受静脉注射多巴酚丁胺（HF组n = 11；非HF组n = 11）或硝普钠（HF组n = 18；非HF组n = 5）治疗患者的跨肾RAAS梯度。
与无HF患者相比，HF患者肾静脉中PRA、醛固酮和ACE的浓度更高（P < 0.01）。在HF患者中，更大的ACE梯度与更高的肾血管阻力相关（r = 0.42；P = 0.007）以及更高的小动脉阻力（入球小动脉：r = 0.39；P = 0.012；出球小动脉：r = 0.48；P = 0.002）。同样，更大的醛固酮梯度与更低的GFR（r = -0.51；P = 0.0007）和肾血流量（RBF，r = -0.32；P = 0.042）相关，而更大的PRA梯度与更低的ERPF（r = -0.33；P = 0.040）、GFR（r = -0.36；P = 0.024）和RBF（r = -0.33；P = 0.036）相关。多巴酚丁胺和硝普钠治疗仅降低了HF患者ACE（分别为P = 0.012，P < 0.0001）、醛固酮（P = 0.005，P = 0.030）和PRA（P = 0.014，P = 0.002）的跨肾梯度。
HF患者中更大的跨肾RAAS标志物梯度表明与血管收缩性肾特征相关的神经激素激活起源于肾脏。
