Human Urine Proteomics: Analytical Techniques and Clinical Applications in Renal Diseases

Kalantari, Shiva; Jafari, Ameneh; Moradpoor, Raheleh; Ghasemi, Erfan; Khalkhal, Ensieh

doi:10.1155/2015/782798

Cited by 63 publications

(65 citation statements)

References 131 publications

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“…Urine is an ideal sample source for the clinical setting, as it can be obtained easily, is relatively stable and the collection of samples is non-invasive. In addition, urine contains a relatively small number of proteins which are present at lower concentrations compared with serum or plasma therefore making them easier to detect (8,9). Despite the relative simplicity of urine this method is complicated by the difficulty in standardising urine samples across individuals to determine the clinically relevant concentration of any particular urinary biomarker.…”

Section: Urinary Diagnostic Proteomic Markers For Dynapenia In Cancermentioning

confidence: 99%

Urinary diagnostic proteomic markers for dynapenia in cancer patients

et al. 2018

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Abstract. Dynapenia is defined as the age-related loss of muscle strength, and plays a significant role in the loss of physical function and increased risk of disability among older individuals. The need for an early diagnosis supports the search for a biomarker that reflects muscle 'weakening'. This has previously proven difficult due to patient heterogeneity at presentation and lack of understanding of the underlying molecular mechanisms. The aim of the present study was to identify potential urinary biomarkers of dynapenia in patients undergoing potentially curative surgery for upper gastrointestinal cancer. Maximum isometric knee extensor strength (strain gauge) and maximum leg extensor power (Nottingham power rig) measurements were taken. Cut-off values for dynapenia were based on the Allied Dunbar national fitness survey. Values below the 5th percentile for the population matched for age and sex on the Allied Dunbar national fitness survey were used to stratify the cohort into dynapenic or normal. Urine samples taken at induction of anaesthesia were analysed by SELDI-TOF mass spectrometry using CM10 and IMAC30 chip-types to establish statistically significant m/z peak fingerprint patterns, followed by in-gel LC-MS/MS to identify molecular constituents. Statistical analysis of decision-tree calculations using Biomarker Pattern software resulted in models with sensitivities of 86 and 96%, specificities of 81 and 89%, and overall correctness of 84 and 93%, when applied to the entire cohort for power and strength measurement-based stratifications using the IMAC30 chip-type and the CM10 chip-type, respectively. The molecular identities of 10 peaks of interest were further investigated. After subtraction of potentially unrelated proteins, they were identified as fragments of Annexin A1, collagen α-1 (XV), perlecan and myotrophin. These results demonstrate that urinary screening can be used to define cancer-associated muscle weakness, and the identification of potential biomarkers could be invaluable in establishing a rapid test to measure and assess dynapenia in the clinical setting.

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Section: Urinary Diagnostic Proteomic Markers For Dynapenia In Cancermentioning

confidence: 99%

Urinary diagnostic proteomic markers for dynapenia in cancer patients

et al. 2018

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“…Gel-based or gel-free methods are suitable for urinary proteome analysis. In particular, liquid chromatography-tandem MS and capillary electrophoresis-MS perform rapid separation of protein species in the sample, after preconcentration and enrichment of the low abundant fraction, providing a more accurate analysis especially for peptides and small proteins (<20 kDa) [13,15,29]. …”

Section: Proteomic Strategies and Applications In Iemsmentioning

confidence: 99%

Integration of Proteomics and Metabolomics in Exploring Genetic and Rare Metabolic Diseases

et al. 2017

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Background: Inherited metabolic disorders or inborn errors of metabolism are caused by deficiency of enzymatic activities in the catabolism of amino acids, carbohydrates, or lipids. These disorders include aminoacidopathies, urea cycle defects, organic acidemias, defects of oxidation of fatty acids, and lysosomal storage diseases. Inborn errors of metabolism constitute a significant proportion of genetic diseases, particularly in children; however, they are individually rare. Clinical phenotypes are very variable, some of them remain asymptomatic, others manifest metabolic decompensation in neonatal age, and others encompass mental retardation at later age. The clinical manifestation of these disorders can involve different organs and/or systems. Some disorders are easily managed if promptly diagnosed and treated, whereas in other cases neither diet, vitamin therapy, nor transplantation appears to prevent multi-organ impairment. Summary: Here, we discuss the principal challenges of metabolomics and proteomics in inherited metabolic disorders. We review the recent developments in mass spectrometry-based proteomic and metabolomic strategies. Mass spectrometry has become the most widely used platform in proteomics and metabolomics because of its ability to analyze a wide range of molecules, its optimal dynamic range, and great sensitivity. The fast measurement of a broad spectrum of metabolites in various body fluids, also collected in small samples like dried blood spots, have been facilitated by the use of mass spectrometry-based techniques. These approaches have enabled the timely diagnosis of inherited metabolic disorders, thereby facilitating early therapeutic intervention. Due to its analytical features, proteomics is suited for the basic investigation of inborn errors of metabolism. Modern approaches enable detailed functional characterization of the pathogenic biochemical processes, as achieved by quantification of proteins and identification of their regulatory chemical modifications. Key Message: Mass spectrometry-based “omics” approaches most frequently used to study the molecular mechanisms underlying inherited metabolic disorders pathophysiology are described.

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“…Brojne studije pokazale su da metode proteomike koje se temelje na masenoj spektrometriji imaju velik potencijal u identifikaciji novih proteinskih biljega bubrežne disfunkcije, stoga predstavljaju važnu komponentu u toksikološkim ispitivanjima [13][14][15] . Istraživanje proteoma urina otežavaju brojni izazovi koji se pojavljuju tijekom analize urina poput varijabilnosti u sastavu i koncentraciji proteina u urinu različitih osoba do kojih dolazi zbog razlika u unosu tekućine i hrane te zbog tjelovježbe, načina života i cirkadijalnog ritma, a istraživanje je dodatno otežano i zbog činjenice da se proteom urina ne razlikuje samo među pojedincima već i kod iste osobe u različito vrijeme 11,16 . Standard u vezi vremena uzorkovanja urina još uvijek ne postoji, no preporučuje se uzimanje urina nakon odmaranja te uvijek u isto doba dana, kako bi se smanjila varijabilnost proteoma 17,18 .…”

Section: Uvodunclassified

Proteomics analysis of potential biomarkers of acute kidney injury in urine from patients receiving vancomycin

et al. 2017

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Sažetak. Cilj: Vankomicin je antibiotik koji se koristi za liječenje infekcija uzrokovanih Gram--pozitivnim bakterijama, no kod nekih pacijenata uzrokuje ozljedu bubrega. Budući da standardni biomarkeri ozljede bubrega ne pokazuju dovoljnu osjetljivost i specifičnost, potrebno je pronaći nove biomarkere kako bismo mogli ranije detektirati poremećaje bubrežne funkcije te pravovremenim prekidom ili promjenom terapije spriječiti daljnje ozljede bubrega. Cilj je rada bio usporediti proteomske profile urina dviju pacijentica oboljelih od upale pluća koje su primale terapiju vankomicinom sa i bez kliničkih znakova ozljede bubrega uzrokovanih navedenim antibiotikom, kako bismo identificirali nove potencijalne proteinske biomarkere akutne ozljede bubrega uzrokovanog vankomicinom. Prikaz slučaja: Uzorci urina prikupljeni su treći i sedmi dan terapije vankomicinom od pacijentice sa i pacijentice bez kliničkih znakova bubrežne disfunkcije te su analizirani dvodimenzionalnom gel elektroforezom kombiniranom s MALDI-TOF/TOF masenom spektrometrijom. Vidljive razlike u proteomskim profilima urina između dviju pacijentica javljaju se treći, a naročito su izražene sedmi dan terapije. Dvodimenzionalna gel elektroforeza kombinirana s masenom spektrometrijom potvrdila je već ranije dokazanu ulogu proteina neutrofilnog lipokalina povezanog s gelatinazom (NGAL, engl. neutrophil gelatinase-associated lipocalin) kao biomarkera akutne ozljede bubrega, te otkrila ekspresiju citoskeletnog keratina 1 tipa II i retinol-vezujućeg proteina 4 (RBP4, engl. retinol-binding protein 4) samo u urinu pacijentice kod koje je terapija vankomicinom uzrokovala poremećaj bubrežne funkcije. Zaključci: Citoskeletni keratin 1 tipa II i retinol-vezujući protein 4 mogli bi predstavljati nove potencijalne biomarkere ozljede bubrega uzrokovane vankomicinom. Potrebne su daljnje studije na većem broju pacijenata kako bi se validirali dobiveni rezultati i utvrdio njihov potencijalni dijagnostički i klinički značaj.Ključne riječi: akutna ozljeda bubrega; biomarkeri; dvodimenzionalna gel elektroforeza; masena spektrometrija; urin; vankomicin Abstract. Aim: Vancomycin is an antibiotic used to treat infections caused by Gram-positive bacteria which can induce renal injury in some patients. Since standard biomarkers of kidney injury lack sufficient sensitivity and specificity, there is an unmet need for novel biomarkers that would enable early detection of renal injury and timely cessation or modification of treatment to prevent more severe kidney injury. The goal of this paper was to compare proteomics profiles of urine samples collected from two vancomycin-treated patients suffering from pneumonia with and without clinical symptoms of drug-induced renal dysfunction as to identify novel potential protein biomarkers of vancomycin-induced kidney injury. Case report: Urine samples were collected on the third and seventh day of vancomycin therapy from patients with and without clinical signs of acute kidney injury. Samples were analysed by two-dimensional gel electrophores...

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Human Urine Proteomics: Analytical Techniques and Clinical Applications in Renal Diseases

Cited by 63 publications

References 131 publications

Urinary diagnostic proteomic markers for dynapenia in cancer patients

Urinary diagnostic proteomic markers for dynapenia in cancer patients

Integration of Proteomics and Metabolomics in Exploring Genetic and Rare Metabolic Diseases

Proteomics analysis of potential biomarkers of acute kidney injury in urine from patients receiving vancomycin

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