PMID- 19564150
OWN - NLM
STAT- MEDLINE
DCOM- 20100119
LR  - 20220316
IS  - 1535-9484 (Electronic)
IS  - 1535-9476 (Print)
IS  - 1535-9476 (Linking)
VI  - 8
IP  - 10
DP  - 2009 Oct
TI  - Identification and validation of urinary biomarkers for differential diagnosis 
      and evaluation of therapeutic intervention in anti-neutrophil cytoplasmic 
      antibody-associated vasculitis.
PG  - 2296-307
LID - 10.1074/mcp.M800529-MCP200 [doi]
AB  - Renal activity and smoldering disease is difficult to assess in anti-neutrophil 
      cytoplasmic antibody-associated vasculitis (AAV) because of renal scarring. Even 
      repeated biopsies suffer from sampling errors in this focal disease especially in 
      patients with chronic renal insufficiency. We applied capillary electrophoresis 
      coupled to mass spectrometry toward urine samples from patients with active renal 
      AAV to identify and validate urinary biomarkers that enable differential 
      diagnosis of disease and assessment of disease activity. The data were compared 
      with healthy individuals, patients with other renal and non-renal diseases, and 
      patients with AAV in remission. 113 potential biomarkers were identified that 
      differed significantly between active renal AAV and healthy individuals and 
      patients with other chronic renal diseases. Of these, 58 could be sequenced. 
      Sensitivity and specificity of models based on 18 sequenced biomarkers were 
      validated using blinded urine samples of 40 patients with different renal 
      diseases. Discrimination of AAV from other renal diseases in blinded samples was 
      possible with 90% sensitivity and 86.7-90% specificity depending on the model. 10 
      patients with active AAV were followed for 6 months after initiation of 
      treatment. Immunosuppressive therapy led to a change of the proteome toward 
      "remission." 47 biomarkers could be sequenced that underwent significant changes 
      during therapy together with regression of clinical symptoms, normalization of 
      C-reactive protein, and improvement of renal function. Proteomics analysis with 
      capillary electrophoresis-MS represents a promising tool for fast identification 
      of patients with active AAV, indication of renal relapses, and monitoring for 
      ongoing active renal disease and remission without renal biopsy.
FAU - Haubitz, Marion
AU  - Haubitz M
AD  - Department of Nephrology, Hannover Medical School, D-30625 Hannover, Germany. 
      Haubitz.Marion@MH-Hannover.de
FAU - Good, David M
AU  - Good DM
FAU - Woywodt, Alexander
AU  - Woywodt A
FAU - Haller, Hermann
AU  - Haller H
FAU - Rupprecht, Harald
AU  - Rupprecht H
FAU - Theodorescu, Dan
AU  - Theodorescu D
FAU - Dakna, Mohammed
AU  - Dakna M
FAU - Coon, Joshua J
AU  - Coon JJ
FAU - Mischak, Harald
AU  - Mischak H
LA  - eng
GR  - T32 GM008349/GM/NIGMS NIH HHS/United States
GR  - 5T32GM08349/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090628
PL  - United States
TA  - Mol Cell Proteomics
JT  - Molecular & cellular proteomics : MCP
JID - 101125647
RN  - 0 (Biomarkers)
RN  - 0 (Proteins)
RN  - 0 (Proteome)
SB  - IM
MH  - Adult
MH  - Anti-Neutrophil Cytoplasmic Antibody-Associated 
      Vasculitis/*diagnosis/pathology/*therapy/*urine
MH  - Area Under Curve
MH  - Biomarkers/*urine
MH  - Diagnosis, Differential
MH  - Female
MH  - Humans
MH  - Kidney/pathology
MH  - Male
MH  - Middle Aged
MH  - Proteins/analysis
MH  - Proteome/*analysis
MH  - Remission Induction
MH  - Reproducibility of Results
MH  - Treatment Outcome
MH  - Young Adult
PMC - PMC2758757
EDAT- 2009/07/01 09:00
MHDA- 2010/01/20 06:00
PMCR- 2010/10/01
CRDT- 2009/07/01 09:00
PHST- 2009/07/01 09:00 [entrez]
PHST- 2009/07/01 09:00 [pubmed]
PHST- 2010/01/20 06:00 [medline]
PHST- 2010/10/01 00:00 [pmc-release]
AID - S1535-9476(20)33952-9 [pii]
AID - M800529-MCP200 [pii]
AID - 10.1074/mcp.M800529-MCP200 [doi]
PST - ppublish
SO  - Mol Cell Proteomics. 2009 Oct;8(10):2296-307. doi: 10.1074/mcp.M800529-MCP200. 
      Epub 2009 Jun 28.