The analysis of risk factors for diabetic nephropathy progression and the construction of a prognostic database for chronic kidney diseases
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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.
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Longer duration of T2DM significantly escalates the risk of DKD.
“Extensive research indicates that a longer duration of T2DM significantly escalates the risk of DKD, a phenomenon that is intrinsically linked to the chronic renal damage induced by sustained hyperglycemia (83, 84).”
From Machine learning-based risk predictive models for diabetic kidney disease in type 2 diabetes mellitus patients: a systematic review and meta-analysis (2025) · cites this paper as [83]
The Background states that diabetic nephropathy (DKD) affects people with T1DM or T2DM and has peak incidence 10–20 years after diabetes onset. This supports a relationship with diabetes duration, but it does not establish that risk rises continuously with longer T2DM duration or report a statistically significant increase. (LLM, conf=0.82)
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“Extensive research indicates that a longer duration of T2DM signi fi cantly escalates the risk of DKD, a phenomenon that is intrinsically linked to the chronic renal damage induced by sustained hyperglycemia (83, 84).”
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- Authors
- Wang, G., Ouyang, J., Li, S., Wang, H., Lian, B., Liu, Z., & Xie, L.
- Affiliations
- Nanjing General Hospital of Nanjing Military Command (CN)
- Shanghai Academy of Science & Technology (CN)
- Corresponding author
- Liu, Zhihong
- Xie, Lu
- Venue
- Journal of Translational Medicine
- Published
- 2019-08-13
- Volume
- 17
- Issue
- 1
- Pages
- 264-264
- ISSN
- 1479-5876 (ISSN-L)
- PMC
- PMC6693179
- OpenAlex
- W2968804032
- Cited by
- 92
- References
- 63
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 13 · 2023: 7 · 2022: 23 · 2021: 23 · 2020: 7 · 2019: 1 · 2013: 1
- FWCI
- 10.43
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Journal of Translational Medicine (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Key Research and Development Program of China (2016YFC0904101)
- Topics
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Keywords
- diabetic nephropathy, chronic kidney disease, disease progression, prognostic factors, risk factors, end-stage renal disease, TNF signaling, adipocytokine signaling pathway, interleukin-6, manganese superoxide dismutase, AGER, therapeutic target
- MeSH terms
- Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Humans, Prognosis, Risk Factors, User-Computer Interface, Biomarkers, Disease Progression, Databases as Topic, Endpoint Determination, Renal Insufficiency, Chronic
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