The analysis of risk factors for diabetic nephropathy progression and the construction of a prognostic database for chronic kidney diseases

Abstract

Background Diabetic nephropathy (DN) affects about 40% of diabetes mellitus (DM) patients and is the leading cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD) all over the world, especially in high- and middle-income countries. Most DN has been present for years before it is diagnosed. Currently, the treatment of DN is mainly to prevent or delay disease progression. Although many important molecules have been discovered in hypothesis-driven research over the past two decades, advances in DN management and new drug development have been very limited. Moreover, current animal/cell models could not replicate all the features of human DN, while the development of Epigenetics further demonstrates the complexity of the mechanism of DN progression. To capture the key pathways and molecules that actually affect DN progression from numerous published studies, we collected and analyzed human DN prognostic markers (independent risk factors for DN progression). Methods One hundred and fifty-one DN prognostic markers were collected manually by reading 2365 papers published between 01/01/2002 and 12/15/2018. One hundred and fifteen prognostic markers of other four common CKDs were also collected. GO and KEGG enrichment analysis was done using g:Profiler, and a relationship network was built based on the KEGG database. Tissue origin distribution was derived mainly from The Human Protein Atlas (HPA), and a database of these prognostic markers was constructed using PHP Version 5.5.15 and HTML5. Results Several pathways were significantly enriched corresponding to different end point events. It is shown that the TNF signaling pathway plays a role through the process of DN progression and adipocytokine signaling pathway is uniquely enriched in ESRD. Molecules, such as TNF, IL6, SOD2, etc. are very important for DN progression, among which, it seems that “AGER” plays a pivotal role in the mechanism. A database, dbPKD, was constructed containing all the collected prognostic markers. Conclusions This study developed a database for all prognostic markers of five common CKDs, offering some bioinformatics analyses of DN prognostic markers, and providing useful insights towards understanding the fundamental mechanism of human DN progression and for identifying new therapeutic targets. Electronic supplementary material The online version of this article (10.1186/s12967-019-2016-y) contains supplementary material, which is available to authorized users.

Association of diabetic nephropathy with diabetic retinopathy in type 2 diabetes mellitus patients

“…This has been seen in earlier studies as well and re-emphasizes the importance of optimum glycemic control for preventing microvascular complications. 9,10 This study showed that common co-morbidities associated with DN were CAD, hypertension, dyslipidemia and obesity. This finding is similar to that seen in other studies.…”

Uncovering the Mechanism of Astragalus membranaceus in the Treatment of Diabetic Nephropathy Based on Network Pharmacology

“…The specific pathogenesis is still not fully clear. The incidence of DN accounts for 20%-40% of all diabetic patients, and it is also one of the main causes of death [4]. DN is characterized by edema, hyperglycemia, hypertension, and albuminuria.…”

Podocyte Lysosome Dysfunction in Chronic Glomerular Diseases

“…Diabetic nephropathy (DN) is the most common cause of end-stage renal disease (ESRD) worldwide [108]. Pathologic changes in the diabetic kidney including thickening of the glomerular basement membrane, mesangial expansion, proteinuria, inflammation, and fibrosis.…”