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Background Arteriovenous fistulae (AVFs) are the gold standard for vascular access in those requiring hemodialysis but may put an extra hemodynamic stress on the cardiovascular system. The complex interactions between the heart, kidney, and AVFs remain incompletely understood. Methods and Results We characterized a novel rat model of five-sixths partial nephrectomy (NX) and AVFs. NX induced increases in urea, creatinine, and hippuric acid. The addition of an AVF (AVF+NX) further increased urea and a number of uremic toxins such as trimethylamine N-oxide and led to increases in cardiac index, left and right ventricular volumes, and right ventricular mass. Plasma levels of uremic toxins correlated well with ventricular morphology and function. Heart transcriptomes identified altered expression of 8 genes following NX and 894 genes following AVF+NX, whereas 290 and 1431 genes were altered in the kidney transcriptomes, respectively. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis revealed gene expression changes related to cell division and immune activation in both organs, suppression of ribosomes and transcriptional activity in the heart, and altered renin-angiotensin signaling as well as chronodisruption in the kidney. All except the latter were worsened in AVF+NX compared with NX. Conclusions Inflammation and organ dysfunction in chronic kidney disease are exacerbated following AVF creation. Furthermore, our study provides important information for the discovery of novel biomarkers and therapeutic targets in the management of cardiorenal syndrome.

背景

动静脉瘘（AVF）是需要血液透析患者血管通路的金标准，但可能会给心血管系统带来额外的血液动力学压力。心脏、肾脏和 AVF 之间的复杂相互作用仍不完全清楚。

方法和结果

我们构建了一个新的六分之五部分肾切除术（NX）和动静脉瘘大鼠模型。NX 导致尿素、肌酐和马尿酸增加。添加动静脉瘘（AVF+NX）进一步增加了尿素和一些尿毒症毒素，如三甲胺氧化物，并导致心指数、左右心室容积和右心室质量增加。尿毒症毒素的血浆水平与心室形态和功能密切相关。心脏转录组学鉴定出 NX 后有 8 个基因和 AVF+NX 后有 894 个基因的表达发生改变，而肾脏转录组学分别有 290 个和 1431 个基因发生改变。基因本体论和京都基因与基因组百科全书分析显示，两个器官的基因表达变化与细胞分裂和免疫激活有关，心脏的核糖体和转录活性受到抑制，肾脏的肾素-血管紧张素信号和chronodisruption 发生改变。除后者外，AVF+NX 比 NX 中的改变更为严重。