Association of Urinary Plasminogen-Plasmin with Edema and Epithelial Sodium Channel Activation in Patients with Nephrotic Syndrome
Association of Urinary Plasminogen-Plasmin with Edema and Epithelial Sodium Channel Activation in Patients with Nephrotic Syndrome
复制标题
尿纤溶酶原-纤溶酶与肾病综合征患者水肿及上皮钠通道激活的关系
DOI：
10.1159/000501059
复制
发表时间：
2019-01-01
影响因子：
4.2
通讯作者：
Wang, Hao
中科院分区：
文献类型：
--
作者：
Chen, Jun-Liang;Wang, Li;Wang, Hao
背景：先前的动物实验和小型人体研究表明，尿纤溶酶可以激活上皮钠通道（ENaC），并有助于肾病综合征（NS）的钠潴留，但这在临床环境中尚未得到很好的研究，其与水肿形成的相关性也未在人类中得到很好的表征。我们研究了尿纤溶蛋白与多病因NS患者临床表型之间的关系，旨在评估尿纤溶蛋白在钠处理和水肿形成中的作用。方法：取尿血标本203例NS患者，根据水肿严重程度分为轻、重度症状组。其中26例在免疫抑制治疗期间连续采集样本。检测纤溶酶原-纤溶酶水平及其他关键指标，并分析其与临床表现的相关性。结果：203例患者中有101例进行了肾活检，其结果包括所有常见的原发性肾性肾病和各种继发性肾性肾病。定量比较和多因素logistic回归分析发现，尿纤溶酶原-纤溶酶/肌酐比值（uPLG-PL/C）、血清白蛋白、d -二聚体和心功能障碍史是水肿的独立危险因素，但蛋白尿或24小时尿蛋白不是（p < 0.01）。在接受治疗并连续取样的患者中，upg - pl /C的降低被确定为水肿缓解的独立影响因素（p < 0.01）。最后，患者尿钠分数排泄（FENa）与钾分数排泄呈负相关（FEK; p< 0.001）， FEK/FENa比值与uPLG-PL/C呈正相关（p < 0.001），提示uPLG-PL与ENaC激活密切相关。结论：本研究确定upg - pl丰度是成人NS患者水肿的独立影响因素，支持纤溶蛋白依赖性ENaC激活是NS患者钠潴留和水肿形成的重要病理生理机制。
Background: Previous animal experiments and small human studies suggest that urinary plasmin can activate the epithelial sodium channel (ENaC) and contribute to sodium retention in nephrotic syndrome (NS), but this however is not well studied in clinical settings, and its relevance to edema formation is not well characterized in humans. We have investigated the association between urinary plasmin and clinical phenotypes in a large group of patients with NS from multiple etiologies, aiming to assess the role of urinary plasmin in sodium handling and edema formation. Methods: Two hundred and three NS patients with urine and blood samples were divided into mild and severe symptom groups based on their edema severity. Twenty six of them had serial samples collected during the course of immunosuppressive therapy. The plasminogen-plasmin level and other key parameters were assayed, and their association with clinical manifestations were analyzed. Results: One hundred and one of the 203 patients had renal biopsies performed, the results of which had included all the common types of primary NS and various types of secondary NS. Quantitative comparison and multivariate logistic regression analysis identified urinary plasminogen-plasmin to creatinine ratio (uPLG-PL/C), serum albumin, D-Dimer, and cardiac dysfunction history, but not albuminuria or 24-h urine protein, as independent risk factors for edema (p < 0.01). In patients who were treated and had serial samples, a decrease in uPLG-PL/C was identified as an independent influencing factor of edema remission (p < 0.01). Finally, the urinary fractional excretion of sodium (FENa) in patients was inversely correlated with the fractional excretion of potassium (FEK; p< 0.001), and FEK/FENa ratio was positively correlated with uPLG-PL/C (p < 0.001), suggesting a close association between uPLG-PL and ENaC activation. Conclusions: Our study identifies uPLG-PL abundance as an independent influencing factor of edema in adult NS patients, and supports the conclusion that plasmin-dependent ENaC activation is an important pathophysiological mechanism of sodium retention and edema formation in humans with NS.