Urinary Proteomics in Diabetes and CKD

Steno Diabetes Center, Niels Steensens Vej 2, DK 2820 Gentofte, Denmark.
Journal of the American Society of Nephrology (Impact Factor: 9.34). 08/2008; 19(7):1283-90. DOI: 10.1681/ASN.2007091025
Source: PubMed


Urinary biomarkers for diabetes, diabetic nephropathy, and nondiabetic proteinuric renal diseases were sought. For 305 individuals, biomarkers were defined and validated in blinded data sets using high-resolution capillary electrophoresis coupled with electrospray-ionization mass spectrometry. A panel of 40 biomarkers distinguished patients with diabetes from healthy individuals with 89% sensitivity and 91% specificity. Among patients with diabetes, 102 urinary biomarkers differed significantly between patients with normoalbuminuria and nephropathy, and a model that included 65 of these correctly identified diabetic nephropathy with 97% sensitivity and specificity. Furthermore, this panel of biomarkers identified patients who had microalbuminuria and diabetes and progressed toward overt diabetic nephropathy over 3 yr. Differentiation between diabetic nephropathy and other chronic renal diseases reached 81% sensitivity and 91% specificity. Many of the biomarkers were fragments of collagen type I, and quantities were reduced in patients with diabetes or diabetic nephropathy. In conclusion, this study shows that analysis of the urinary proteome may allow early detection of diabetic nephropathy and may provide prognostic information.

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Available from: Petra Zürbig, Oct 04, 2015
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    • "However, the authors also stated the need for larger cohort studies to better establish the accuracy of using the urinary proteome to identify new biomarkers in LV dysfunction. The urinary proteome has also been used to identify conditions associated with hypertension, such as preeclampsia renal injury [89–91] and other pathologies associated with hypertension such as diabetes [92]. "
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    ABSTRACT: Left ventricle hypertrophy is a common outcome of pressure overload stimulus closely associated with hypertension. This process is triggered by adverse molecular signalling, gene expression and proteome alteration. Proteomic research has revealed that several molecular targets are associated with pathologic cardiac hypertrophy, including angiotensin II, Endotelin-1 and isoproterol. Several metabolic, contractile and stress-related proteins are shown to be altered in cardiac hypertrophy derived by hypertension. On the other hand, exercise is a non-pharmacologic agent used for hypertension treatment, where cardiac hypertrophy induced by exercise training is characterized by improvement in cardiac function and resistance against ischemic insult. Despite the scarcity of proteomic research performed with exercise, healthy and pathologic heart proteomes are shown to be modulated in a completely different way. Hence, the altered proteome induced by exercise is mostly associated with cardioprotective aspects such as contractile and metabolic improvement and physiologic cardiac hypertrophy. The present review, therefore, describes relevant studies involving the molecular characteristics and alterations from hypertensive induced and exercise induced hypertrophy, as well as the main proteomic research performed in this field. Furthermore, proteomic research into the effect of hypertension on other target-demerged organs is examined.
    BioMed Research International 04/2014; 2014(2). DOI:10.1155/2014/634132 · 3.17 Impact Factor
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    • "Collagen type I accumulation in fibrosis, as many other ECM molecules, is both due to decreased degradation and elevated synthesis [14,69]. Urinary proteome analyses could differentiate DN patients from healthy individuals and patients with other chronic kidney diseases [80]. Among the proteins differentially expressed, fragments of collagen type I were significantly less present in the urine of DN patients. "
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    ABSTRACT: Interstitial fibrosis is the common endpoint of end-stage chronic kidney disease (CKD) leading to kidney failure. The clinical course of many renal diseases, and thereby of CKD, is highly variable. One of the major challenges in deciding which treatment approach is best suited for a patient but also in the development of new treatments is the lack of markers able to identify and stratify patients with stable versus progressive disease. At the moment renal biopsy is the only means of diagnosing renal interstitial fibrosis. Novel biomarkers should improve diagnosis of a disease, estimate its prognosis and assess the response to treatment, all in a non-invasive manner. Existing markers of CKD do not fully and specifically address these requirements and in particular do not specifically reflect renal fibrosis. The aim of this review is to give an insight of the involvement of the extracellular matrix (ECM) proteins in kidney diseases and as a source of potential novel biomarkers of renal fibrosis. In particular the use of the protein fingerprint technology, that identifies neo-epitopes of ECM proteins generated by proteolytic cleavage by proteases or other post-translational modifications, might identify such novel biomarkers of renal fibrosis.
    Fibrogenesis & Tissue Repair 03/2014; 7(1):4. DOI:10.1186/1755-1536-7-4
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    • "Several recent reports demonstrated that urinary peptides and proteins can serve as specific biomarkers for e.g. chronic kidney diseases [10] [11], bladder cancer [12] [13], and prostate cancer [14]. Similarly to these previous studies and with the aim to identify early non-invasive urinary biomarkers of RCC, we have analyzed urine from RCC patients and age-matched controls using high resolution capillary electrophoresis coupled to mass spectrometry (CE–MS). "
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    ABSTRACT: Renal cell carcinoma (RCC) is often accompanied by non-specific symptoms. The increase of incidentally discovered small renal masses also presents a diagnostic dilemma. This study investigates whether RCC-specific peptides with diagnostic potential can be detected in urine and whether a combination of such peptides could form a urinary screening tool. For the discovery of RCC-specific biomarkers, we have employed CE-MS to analyze urine samples from patients with RCC (N=40) compared to non-diseased controls (N=68). Results and discussion 86 peptides were found to be specifically associated to RCC, of which sequence could be obtained for 40. A classifier based on these peptides was evaluated in an independent set of 76 samples, resulting in 80% sensitivity and 87% specificity. The specificity of the marker panel was further validated in a historical dataset of 1077 samples including age-matched controls (N=218), patients with related cancer types and renal diseases (N=859). In silico protease prediction based on the cleavage sites of differentially excreted peptides, suggested modified activity of certain proteases including cathepsins, ADAMTS and kallikreins some of which were previously found to be associated to RCC. RCC can be detected with high accuracy based on specific urinary peptides. Clear cell renal cell carcinoma (RCC) has the highest incidence among the renal malignancies, often presenting non-specific or no symptoms at all. Moreover, with no diagnostic marker being available so far, almost 30% of the patients are diagnosed with metastatic disease and 30-40% of the patients initially diagnosed with localized tumor relapse. These facts introduce the clinical need of early diagnosis. This study is focused on the investigation of a marker model based on urinary peptides, as a tool for the detection of RCC in selected patients at risk. Upon evaluation of the marker model in an independent blinded set of 76 samples, 80% sensitivity and 87% specificity were reported. An additional dataset of 1077 samples was subsequently employed for further evaluation of the specificity of the classifier.
    Journal of proteomics 12/2013; 98. DOI:10.1016/j.jprot.2013.12.010 · 3.89 Impact Factor
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