Diagnostic potential of serum protein pattern in Type 2 diabetic nephropathy

Yh, Yang; Zhang, S; Jf, Cui; Lu, Binfeng; Xh, Dong; Song, Xian‐Rong; Yk, Liu; Xx, Zhu; Rm, Hu

doi:10.1111/j.1464-5491.2007.02312.x

Cited by 16 publications

(8 citation statements)

References 26 publications

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“…Consequently, the likelihood of detecting nondiabetic renal disease or normal glomerular structure is observed with microalbuminuria patients [10]. Thus, more accurate biomarkers for incipient DN in type 2 diabetic patients are required that can differentiate incipient DN from other conditions in microalbuminuria patients, including cardiovascular disease, inflammation, and hypertension.…”

Section: Introductionmentioning

confidence: 99%

Differential Proteome Profiling Using iTRAQ in Microalbuminuric and Normoalbuminuric Type 2 Diabetic Patients

Jin

Kim

et al. 2012

Experimental Diabetes Research

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Diabetic nephropathy (DN) is a long-term complication of diabetes mellitus that leads to end-stage renal disease. Microalbuminuria is used for the early detection of diabetic renal damage, but such levels do not reflect the state of incipient DN precisely in type 2 diabetic patients because microalbuminuria develops in other diseases, necessitating more accurate biomarkers that detect incipient DN. Isobaric tags for relative and absolute quantification (iTRAQ) were used to identify urinary proteins that were differentially excreted in normoalbuminuric and microalbuminuric patients with type 2 diabetes where 710 and 196 proteins were identified and quantified, respectively. Some candidates were confirmed by 2-DE analysis, or validated by Western blot and multiple reaction monitoring (MRM). Specifically, some differentially expressed proteins were verified by MRM in urine from normoalbuminuric and microalbuminuric patients with type 2 diabetes, wherein alpha-1-antitrypsin, alpha-1-acid glycoprotein 1, and prostate stem cell antigen had excellent AUC values (0.849, 0.873, and 0.825, resp.). Moreover, we performed a multiplex assay using these biomarker candidates, resulting in a merged AUC value of 0.921. Although the differentially expressed proteins in this iTRAQ study require further validation in larger and categorized sample groups, they constitute baseline data on preliminary biomarker candidates that can be used to discover novel biomarkers for incipient DN.

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Section: Introductionmentioning

confidence: 99%

Differential Proteome Profiling Using iTRAQ in Microalbuminuric and Normoalbuminuric Type 2 Diabetic Patients

Jin

Kim

et al. 2012

Experimental Diabetes Research

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“…Regardless, most biomarker studies in T2DM and DN have been performed with the lower resolution and sensitivity SELDI-TOF-MS. Yang et al performed a SELDI-TOF-MS analysis of serum samples from 65 patients with DN and 65 without DN. The identified six m/z values that correlated with DN and confirmed this correlation in samples from a nested group 33. Yang et al did not use other mass spectrometry methods to identify the amino acid sequence of the candidate biomarker peaks.…”

Section: Proteomic Discovery Of Dn Biomarkers In T2dmmentioning

confidence: 83%

Proteomic Discovery of Diabetic Nephropathy Biomarkers

Merchant

Klein²

2010

Advances in Chronic Kidney Disease

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Diabetes mellitus (DM) is a complex systemic disease, with complications that result from both genetic predisposition and dysregulated metabolic pathways. DM is a highly prevalent disease with current estimates that there are 17.5 million diagnosed and 6.6 million un-diagnosed diabetics in the United States. DM and its complications impose a significant societal and economic burden. The medical costs of the most common microvascular complications of uncontrolled DM, diabetic nephropathy (DN) and diabetic retinopathy, account for 29% and 15% respectively of the $116 billion expenditures associated with diabetes. A substantial gap in our knowledge exists of the understanding these complications. In order to advance therapy and decrease the societal burden of DM there is a clear need for biomarkers that can diagnose DN early and predict its course. Proteomics has evolved into a high-throughput, analytical discipline used to analyze complex biological datasets. These openended, hypothesis generating approaches, when appropriately designed and interpreted, are well suited to the study of the pathogenic mechanisms of diabetic microvascular disease and the identification of biomarkers of DN. We will review here the evolving role that proteomics has played in expandingour understanding of the diagnosis and pathogenesis of DN.

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“…Along these lines, an increase in α1-anti-trypsin, UbA52 and type I collagen expression has been reported in patients with diabetic nephropathy [67–69]. In view of the above observations, it is conceivable that the panel of biomarkers identified in patients with diabetic nephropathy with their signatures in the serum and urinary proteins/peptides along with their unique pattern of expression and profiling could serve as a novel clinical diagnostic approach for the detection of early diabetic nephropathy [69, 70]. …”

Section: Proteomic Approachesmentioning

confidence: 99%

Discovery of Genes Related to Diabetic Nephropathy in Various Animal Models by Current Techniques

Wada

Sun²,

Kanwar³

2011

Contributions to Nephrology

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One of the major problems facing clinical nephrology currently throughout the world is an exponential increase in patients with end-stage renal disease (ESRD), which is largely related to a high incidence of diabetic nephropathy. The latter is characterized by a multitude of metabolic and signaling events following excessive channeling of glucose, which leads to an increased synthesis of extracellular matrix (ECM) glycoproteins resulting in glomerulosclerosis, interstitial fibrosis and ultimately ESRD. With the incidence of nephropathy at pandemic levels and a high rate of ESRD, physicians around the world must treat a disproportionately large number of diabetic patients with up-to-date innovative measures. In this regard, identification of genes that are crucially involved in the progression of diabetic nephropathy would enhance the discovery of new biomarkers and could also promote the development of novel therapeutic strategies. Over the last decade, we focused on the recent methodologies of high-throughput and genome-wide screening for identification of relevant genes in various animal models, which included the following: (1) single nucleotide polymorphism-based genome-wide screening; (2) the transcriptome approach, such as differential display reverse transcription polymerase chain reaction (DDRT-PCR), representational difference analysis of cDNA (cDNA-RDA)/suppressive subtractive hybridization, SAGE (serial analysis of gene expression) and DNA Microarray; and (3) the proteomic approach and 2-dimensional polyacrylamide gel electrophoresis (2D-PAGE) coupled with mass spectroscopic analysis. Several genes, such as Tim44 (translocase of inner mitochondrial membrane-44), RSOR/MIOX (renal specific oxidoreductase/myo-inositol oxygenase), UbA52, Rap1b (Ras-related GTPase), gremlin, osteopontin, hydroxysteroid dehydrogenase-3β isotype 4 and those of the Wnt signaling pathway, were identified as differentially expressed genes in kidneys of diabetic rodents. Functional analysis of these genes and the subsequent translational research in the clinical settings would be very valuable in the prevention and treatment of diabetic nephropathy. Future trends for identification of the biomarkers and therapeutic target genes should also include genome scale DNA/histone-methylation profiling, metabolomic approaches (e.g. metabolic phenotyping by 1H spectroscopy) and lectin microarray for glycan profiling along with the development of robust data-mining strategies.

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Diagnostic potential of serum protein pattern in Type 2 diabetic nephropathy

Cited by 16 publications

References 26 publications

Differential Proteome Profiling Using iTRAQ in Microalbuminuric and Normoalbuminuric Type 2 Diabetic Patients

Differential Proteome Profiling Using iTRAQ in Microalbuminuric and Normoalbuminuric Type 2 Diabetic Patients

Proteomic Discovery of Diabetic Nephropathy Biomarkers

Discovery of Genes Related to Diabetic Nephropathy in Various Animal Models by Current Techniques

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