Introduction: Understanding the molecular signals associated with the progression of kidney disease is vital for risk stratification and targeted treatment. Recent advances in RNA-sequencing technique has enabled us to characterize extracellular transcriptome profiles for precision diagnostics. Method: We evaluated the plasma mRNA profile of participants exhibiting slow (n=119) and fast (n=119) decline in estimated glomerular filtration rate (eGFR) among the Chronic Renal Insufficiency Cohort (CRIC) in a nested case control study. The two groups were matched for age, sex, race, baseline eGFR, proteinuria and diabetes status. The next generation sequencing data was analyzed using edgeR to identify differentially expressed genes (DEGs) and Ingenuity Pathway Analysis (IPA) was done to identify the associated pathways. We also compared the top plasma DEGs with gene expression in microdissected human CKD kidney. Results: We identified fragments from ~28,000 annotated genes, of which 783 transcripts exhibited differential expression between slow and fast CKD progressors. Among 629 protein coding genes, 469 were overexpressed in slow progressors, while 157 showed increased expression in fast progressors. Expression of GLI2, CUX1, NOTCH1 and LRP1 transcripts were amplified in slow progressors. Pathway analysis linked these differentially expressed genes to WNT/β-catenin signaling, IL-12 signaling and production in macrophages, Netrin-1 Signaling and Epithelial-Mesenchymal Transition pathways. Many of the plasma differentially expressed genes were also upregulated in microdissected human CKD kidney. Conclusion: Warranting further validation, circulating levels of aberrantly expressed transcripts hold potential to be used as biomarkers for fast CKD progression.

Anvesha Srivastava

Mark Maienschein-Cline

Richard L. Amdur

Katalin Susztak

Jeffrey Burnett Kopp

Haiming Cao

Divya Shankaranarayanan

Yoosif Abdalla

Ana Pabalan

Michael Gombert

Dominic Raj

American Journal of Nephrology

《美国肾脏病学杂志》是一份同行评审期刊，重点关注基础科学和临床研究中的及时主题。论文分为几个部分，包括：

The American Journal of Nephrology is a peer-reviewed academic journal that focuses on timely topics in basic science and clinical research. The articles are divided into several sections, including:

《美国肾脏病学杂志》是一份经过同行评审的学术期刊，专注于基础科学和临床研究中的重要主题。期刊中的论文分为多个部分，包括：

Category	Quartile
医学	3
医学, 泌尿学与肾脏学	2

Plasma transcriptome profile associated with CKD progression

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Journal Info

Category	Quartile
UROLOGY & NEPHROLOGY	1