Proteomic analysis for the assessment of diabetic renal damage in humans

被引:143
作者
Mischak, H
Kaiser, T
Walden, M
Hillmann, M
Wittke, S
Herrmann, A
Knueppel, S
Haller, H
Fliser, D [1 ]
机构
[1] Hannover Med Sch, Dept Internal Med, D-3000 Hannover, Germany
[2] Mosaiques Diagnost & Therapeut AG, Hannover, Germany
关键词
albuminuria; capillary electrophoresis coupled with mass spectrometry (CE/MS); nephropathy; proteomics; type II diabetes;
D O I
10.1042/CS20040103
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Renal disease in patients with Type II diabetes is the leading cause of terminal renal failure and a major healthcare problem. Hence early identification of patients prone to develop this complication is important. Diabetic renal damage should be reflected by a change in urinary polypeptide excretion at a very early stage. To analyse these changes, we used an online combination of CE/MS (capillary electrophoresis coupled with MS), allowing fast and accurate evaluation of up to 2000 polypeptides in urine. Employing this technology, we have examined urine samples from 39 healthy individuals and from 112 patients with Type II diabetes mellitus and different degrees of albumin excretion rate. We established a 'normal' polypeptide pattern in the urine of healthy subjects. In patients with Type II diabetes and normal albumin excretion rate, the polypeptide pattern in urine differed significantly from normal, indicating a specific 'diabetic' pattern of polypeptide excretion. In patients with higher grade albuminuria, we were able to detect a polypeptide pattern indicative of 'diabetic renal damage'. We also found this pattern in 35% of those patients who had low-grade albuminuria and in 4% of patients with normal albumin excretion. Moreover, we could identify several of the indicative polypeptides using MS/MS sequencing. We conclude that proteomic analysis with CE/MS permits fast and accurate identification and differentiation of polypeptide patterns in urine. Longitudinal studies should explore the potential of this powerful diagnostic tool for early detection of diabetic renal damage.
引用
收藏
页码:485 / 495
页数:11
相关论文
共 31 条
[1]  
BENNETT PH, 1995, AM J KIDNEY DIS, V25, P107
[2]   Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy [J].
Brenner, BM ;
Cooper, ME ;
de Zeeuw, D ;
Keane, WF ;
Mitch, WE ;
Parving, HH ;
Remuzzi, G ;
Snapinn, SM ;
Zhang, ZX ;
Shahinfar, S .
NEW ENGLAND JOURNAL OF MEDICINE, 2001, 345 (12) :861-869
[3]   Detection and analysis of urinary peptides by on-line liquid chromatography and mass spectrometry: application to patients with renal Fanconi syndrome [J].
Cutillas, PR ;
Norden, AGW ;
Cramer, R ;
Burlingame, AL ;
Unwin, RJ .
CLINICAL SCIENCE, 2003, 104 (05) :483-490
[4]  
Dolník V, 2001, ELECTROPHORESIS, V22, P4163, DOI 10.1002/1522-2683(200111)22:19<4163::AID-ELPS4163>3.0.CO
[5]  
2-9
[6]   The INSL3-LGR8/GREAT ligand-receptor pair in human cryptorchidism [J].
Ferlin, A ;
Simonato, M ;
Bartoloni, L ;
Rizzo, G ;
Bettella, A ;
Dottorini, T ;
Dallapiccola, B ;
Foresta, C .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2003, 88 (09) :4273-4279
[7]  
Hampel DJ, 2001, J AM SOC NEPHROL, V12, P1026, DOI 10.1681/ASN.V1251026
[8]  
Hochstrasser DF, 2002, PROTEOMICS, V2, P807, DOI 10.1002/1615-9861(200207)2:7<807::AID-PROT807>3.0.CO
[9]  
2-4
[10]   Probing proteomes using capillary isoelectric focusing-electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry [J].
Jensen, PK ;
Pasa-Tolic, L ;
Anderson, GA ;
Horner, JA ;
Lipton, MS ;
Bruce, JE ;
Smith, RD .
ANALYTICAL CHEMISTRY, 1999, 71 (11) :2076-2084