Abstract 9552: RNA Sequencing of Cardiac and Renal Tissue in a Rat Model of Chronic Kidney Disease Reveals Chronodisruption as Common Pathway

Abstract

Introduction: Chronic kidney disease (CKD) is often accompanied by cardiovascular disease, which is referred to as type 4 cardiorenal syndrome. Management is challenging due to the multifactorial nature of the condition, and treatment of one organ may negatively impact the other. Hypothesis: More insights into the common molecular disease processes in the heart and kidney might provide a source for new therapies. We used RNA sequencing to identify pathways that were dysregulated in both organs. Methods: Cardiac and renal tissue samples from four 5/6 th partial nephrectomized (NX) and four sham-operated (SHAM) female Sprague-Dawley rats were analyzed using RNA sequencing. Strand-specific and rRNA depleted cDNA libraries were generated and were sequenced on NovaSeq (Ilumina) with 20 million reads per library. Results: In comparison to SHAM, the kidneys of NX animals had 290 differentially expressed genes (DEGs), showing increased expression of genes that map to Gene Ontology terms including collagen fibril organization , circadian regulation of gene expression , mitotic cell cycle , neutrophil chemotaxis , and inflammatory response . Within the hearts of NX animals, 8 DEGs were found, including those related to circadian regulation of gene expression (Per2, Per3, Arntl/Bmal1, BHLHE41) , as well as the Adra1d , C2cd4b , Ubtd1 , and Atp2b2 genes. Four genes were differentially expressed in both organs. Three of them were related to circadian rhythm, with Per2 and Per3 being downregulated and Arntl/Bmal1 being upregulated. Furthermore, Adra1d was downregulated in both organs. Conclusions: This comprehensive RNA sequencing in a rat model of type 4 cardiorenal syndrome identified chronodisruption as a common pathway, suggesting that circadian rhythms could be a novel target for intervention. Figure Legend. (A) Venn diagram with number of DEGs and vulcano plots for heart (left) and kidney (right). (B) GO terms for heart. (C) GO terms for kidney.