Alterations in urinary collagen peptides in lupus nephritis subjects correlate with renal dysfunction and renal histopathology.
BACKGROUND
The excessive accumulation of extracellular matrix (ECM) in the renal tubulointerstitium is a key component of chronic renal damage in lupus nephritis (LN) and a critical determinant of the disease progression to renal failure. Detection of fibrosis requires renal biopsy and is therefore limited by high risks associated with an invasive procedure. This study explores whether a unique LN urinary peptidome can be identified and whether LN-specific alteration reflects the underlying fibrogenic process of altered ECM turnover.


METHODS
Urinary peptides were analyzed for 36 LN and 35 nonrenal systemic lupus erythematosus (SLE) subjects and 58 healthy volunteers (HVs).


RESULTS
In total, 70 collagen and 230 noncollagen peptides were significantly changed between LN and nonrenal SLE and between LN and HV and defined as 'LN peptides'; 14 proteases associated with observed LN collagen peptides were identified and activities in 9 proteases were significantly different between LN and nonrenal SLE; 28 collagen peptides were correlated with at least one parameter of clinical renal dysfunction or histolopathology.


CONCLUSIONS
Urinary peptidomic alterations likely reflect pathogenic pathways involving ECM turnover in LN kidneys and potentially could be developed as biomarkers to monitor renal disease progression.
Department of Research and Development, Biogen Inc., Cambridge, MA, USA.
Ru
R
Wei
Department of Research and Development, Biogen Inc., Cambridge, MA, USA.
Benbo
B
Gao
Department of Research and Development, Biogen Inc., Cambridge, MA, USA.
Fei
F
Shih
Department of Research and Development, Biogen Inc., Cambridge, MA, USA.
Ann
A
Ranger
Department of Research and Development, Biogen Inc., Cambridge, MA, USA.
Andrea
A
Dearth
Research and Development, Mosaiques Diagnostics GmbH, Hannover, Germany.
Harald
H
Mischak
Research and Development, Mosaiques Diagnostics GmbH, Hannover, Germany.
Justyna
J
Siwy
Clinical Development Immunology, Biogen, Maidenhead, Berkshire, UK.
Nicolas
N
Wisniacki
Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Michelle
M
Petri
Department of Research and Development, Biogen Inc., Cambridge, MA, USA.
Linda C
LC
Burkly
D000328:Adult; D015415:Biomarkers / Q000652:urine*; D016022:Case-Control Studies; D003094:Collagen / Q000652:urine*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000175:diagnosis* / Q000209:etiology / Q000652:urine; D008180:Lupus Erythematosus, Systemic / Q000150:complications*; D008181:Lupus Nephritis / Q000150:complications*; D008297:Male; D010446:Peptide Fragments / Q000652:urine*
D015415:Biomarkers; D010446:Peptide Fragments; D003094:Collagen
biomarkers; fibrosis; lupus nephritis; proteomics; systemic lupus erythematosus