Serum Levels of Advanced Glycation Endproducts and Other Markers of Protein Damage in Early Diabetic Nephropathy in Type 1 Diabetes 英文参考文献.docVIP

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Serum Levels of Advanced Glycation Endproducts and Other Markers of Protein Damage in Early Diabetic Nephropathy in Type 1 Diabetes 英文参考文献.doc

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Serum Levels of Advanced Glycation Endproducts and Other Markers of Protein Damage in Early Diabetic Nephropathy in Type 1 Diabetes 英文参考文献

SerumLevelsofAdvancedGlycationEndproductsand OtherMarkersofProteinDamageinEarlyDiabetic NephropathyinType1Diabetes BruceA.Perkins1*.,NailaRabbani2.,AndrewWeston2,LindaH.Ficociello3, AntonysunilAdaikalakoteswari2,MonikaNiewczas3,JamesWarram3,AndrzejS.Krolewski3, PaulThornalley2 1Division of Endocrinology, University of Toronto, Toronto, Canada, 2Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry, UnitedKingdom,3SectiononGeneticsandEpidemiology,JoslinDiabetesCenter,Boston,Massachusetts,UnitedStatesofAmerica Abstract Objective: To determine the role of markers of plasma protein damage by glycation, oxidation and nitration in microalbuminuria onset or subsequent decline of glomerular filtration rate (termed ‘‘early GFR decline’’) in patients with type1diabetes. Methods:Fromthe1stJoslinKidneyStudy,weselected30patientswithlongstandingnormoalbuminuriaand55patients withnewonsetmicroalbuminuria.Patientswithmicroalbuminuriahad8–12yearsfollow-upduringwhich33hadstable GFRand22earlyGFRdecline.MeanbaselineGFRCYSTATIN Cwassimilarbetweenthethreegroups.Glycation,oxidationand nitration markers were measured in protein and ultrafiltrate at baseline by liquid chromatography-tandem mass spectrometryusingthemostreliablemethodscurrentlyavailable. Results:ThoughnoneweresignificantlydifferentbetweenpatientswithmicroalbuminuriawithstableorearlyGFRdecline, levels of 6 protein damage adduct residues of plasma protein and 4 related free adducts of plasma ultrafiltrate were significantly different in patients with microalbuminuria compared tonormoalbuminuria controls.Three protein damage adduct residues were decreased and 3 increased in microalbuminuria while 3 free adducts were decreased and one increasedinmicroalbuminuria. Themostprofound differenceswereofN-formylkynurenine (NFK)proteinadductresidue andNv-carboxymethylarginine(CMA)freeadductinwhichlevelsweremarkedlylowerinmicroalbuminuria(P,0.001for both). Conclusions:Complexprocessesinflue