Make Precision Medicine Work for Chronic Kidney Disease

Sun, Ling; Zou, Lu-Xi; Chen, Mao-Jie

doi:10.1159/000455101

Cited by 17 publications

(13 citation statements)

References 39 publications

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“…Proteomics metabolomics and genomics recently provided great input to the implementation of novel biomarkers [69][70][71]. The advantage of these "omics" techniques is to provide a combination of informative peptides/metabolites that are able to classify patients (hence, the appellation of classifiers) into significant clinical or risk categories.…”

Section: Prognostic Role Of Proteomics Metabolomics and Genomicsmentioning

confidence: 99%

Contribution of Predictive and Prognostic Biomarkers to Clinical Research on Chronic Kidney Disease

Provenzano

Rotundo

Chiodini

et al. 2020

IJMS

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Chronic kidney disease (CKD), defined as the presence of albuminuria and/or reduction in estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2, is considered a growing public health problem, with its prevalence and incidence having almost doubled in the past three decades. The implementation of novel biomarkers in clinical practice is crucial, since it could allow earlier diagnosis and lead to an improvement in CKD outcomes. Nevertheless, a clear guidance on how to develop biomarkers in the setting of CKD is not yet available. The aim of this review is to report the framework for implementing biomarkers in observational and intervention studies. Biomarkers are classified as either prognostic or predictive; the first type is used to identify the likelihood of a patient to develop an endpoint regardless of treatment, whereas the second type is used to determine whether the patient is likely to benefit from a specific treatment. Many single assays and complex biomarkers were shown to improve the prediction of cardiovascular and kidney outcomes in CKD patients on top of the traditional risk factors. Biomarkers were also shown to improve clinical trial designs. Understanding the correct ways to validate and implement novel biomarkers in CKD will help to mitigate the global burden of CKD and to improve the individual prognosis of these high-risk patients.

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Section: Prognostic Role Of Proteomics Metabolomics and Genomicsmentioning

confidence: 99%

Contribution of Predictive and Prognostic Biomarkers to Clinical Research on Chronic Kidney Disease

Provenzano

Rotundo

Chiodini

et al. 2020

IJMS

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“…[8,9] Second, the DKD research did have new breakthroughs in some fields, such as histopathological diagnosis, [10–13] therapeutic agents, [14–17] and biomarkers for early screening. [2,18–21] Third, with the development of internet technology, massive medical data were easier to be obtained and shared.…”

Section: Resultsmentioning

confidence: 99%

“…In recent years, research hotspots in pathology and etiology of DKD switched to “podocyte,” “apoptosis,” “fibrosis,” “inflammation,” and “nuclear factor kappa B.” With new technologies developing, identifying novel “biomarker” for DKD screening, diagnosis and prognosis had made great progress, such as the genome sequencing, epigenetics, and omics technologies. [2,18,19] For example, the CKD273 classifier, based on 273 urinary peptides, was well suited for early detection of DKD in patients with type 2 DM, who had no sign of DKD with normal estimated glomerular filtration rate (eGFR) and normo-albuminuria. [20,21] Some other biomarkers, such as α1-microglobulin (α1-MG), β2-microglobulin (β2-MG), inflammatory markers (e.g., C-reactive protein, interleukin-6, and tumor necrosis factor-α), as well as several angiogenic and anti-angiogenic factors (e.g., vascular endothelial growth factor (VEGF), VEGF receptors, angiopoietins and endostatin) were reported to play important roles in early detection, therapeutic prevention and implementation of DKD.…”

Section: Resultsmentioning

confidence: 99%

Global diabetic kidney disease research from 2000 to 2017

Zou

Sun

2019

Medicine

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Background: This study aimed to analyze the scientific outputs of diabetic kidney disease (DKD) research and explore its hotspots and frontiers from 2000 to 2017, using bibliometric methods. Methods: Articles in DKD research between 2000 and 2017 were retrieved from the Web of Science Core Collection (WoSCC). We used the VOSviewer 1.6.8 and CiteSpace 5.2 to analyze publication years, journals, countries, institutions, authors, references, and keywords. Keywords with citation bursts were used to analyze the research hotspots and emerging trends. Results: We identified 27,577 publications in DKD research from 2000 to 2017. The annual publication number increased with time. Nephrology Dialysis Transplantation published the highest number of articles. The United States was the most influential country with most publications and collaborations with other countries. Harvard University was the leading institute. Parving had the most cited publications. Keywords analysis indicated that the renin–angiotensin system inhibition used to be the most prevalent research topic, while recent research hotspots were podocyte, inflammation, and biomarker. The biomarkers for DKD screening, diagnosis, and prognosis could be a research frontier. Conclusions: The number of DKD related publications rapidly increased over the past 2 decades. Our study revealed the structure, hotspots, and evolution trends of DKD research. Further studies and more collaborations are needed.

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“…The first step was to find an activator of Rac1. We chose to investigate transforming growth factor β1 (TGFβ1), a pro-fibrotic cytokine that has been implicated in the pathogenesis of FSGS and is highly expressed in podocytes from patients with idiopathic FSGS [ 23 , 24 ]. Furthermore, TGFβ1 has been shown to activate Rac1 in glomerular mesangial cells [ 25 ].…”

Section: Resultsmentioning

confidence: 99%

The Role of Trio, a Rho Guanine Nucleotide Exchange Factor, in Glomerular Podocytes

Maier

Baldwin

Aoudjit

et al. 2018

IJMS

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Nephrotic syndrome is a kidney disease featured by heavy proteinuria. It is caused by injury to the specialized epithelial cells called “podocytes” within the filtration unit of the kidney, glomerulus. Previous studies showed that hyperactivation of the RhoGTPase, Rac1, in podocytes causes podocyte injury and glomerulosclerosis (accumulation of extracellular matrix in the glomerulus). However, the mechanism by which Rac1 is activated during podocyte injury is unknown. Trio is a guanine nucleotide exchange factor (GEF) known to activate Rac1. By RNA-sequencing, we found that Trio mRNA is abundantly expressed in cultured human podocytes. Trio mRNA was also significantly upregulated in humans with minimal change disease and focal segmental glomerulosclerosis, two representative causes of nephrotic syndrome. Reduced expression of Trio in cultured human podocytes decreased basal Rac1 activity, cell size, attachment to laminin, and motility. Furthermore, while the pro-fibrotic cytokine, transforming growth factor β1 increased Rac1 activity in control cells, it decreases Rac1 activity in cells with reduced Trio expression. This was likely due to simultaneous activation of the Rac1-GTPase activation protein, CdGAP. Thus, Trio is important in the basal functions of podocytes and may also contribute to glomerular pathology, such as sclerosis, via Rac1 activation.

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Make Precision Medicine Work for Chronic Kidney Disease

Cited by 17 publications

References 39 publications

Contribution of Predictive and Prognostic Biomarkers to Clinical Research on Chronic Kidney Disease

Contribution of Predictive and Prognostic Biomarkers to Clinical Research on Chronic Kidney Disease

Global diabetic kidney disease research from 2000 to 2017

The Role of Trio, a Rho Guanine Nucleotide Exchange Factor, in Glomerular Podocytes

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