Elevation of serum and urine levels of TIMP-1 and tenascin in patients with renal disease.
BACKGROUND
Chronic kidney disease is characterized by increased synthesis and inhibited destruction of collagenous and non-collagenous matrix proteins. Elevation of collagen fragments has been demonstrated in the serum and urine of patients with renal disease, but the dynamics of renal matrix deposition remain difficult to determine.


METHODS
To obtain a further insight into renal matrix metabolism we have assessed whether serum and urine concentrations of the non-collagenous protein, tenascin, and of the tissue inhibitor of metalloproteinases 1 (TIMP-1) are altered in association with renal disease. Serum and urine concentrations of both proteins were determined using a newly developed magnetic particle enzyme immunoassay and were compared with levels of N-terminal procollagen III-peptide (PIIINP) and related to the degree of renal failure and proteinuria.


RESULTS
Circulating levels of tenascin and TIMP-1 were moderately, but significantly, higher in patients with chronic renal disease (n=54; mean creatinine clearance, 62 ml/min) than in healthy controls (n=176). Urine concentrations per mg creatinine of tenascin and TIMP-1 were significantly lower than serum levels, but were on average six- and 18-fold higher, respectively, in patients with renal disease than in controls. Urinary concentrations increased with progressive reduction in renal function, but were unrelated to proteinuria. TIMP-1 concentrations in urine correlated with tenascin, which is compatible with the impact of TIMP-1 on the accumulation of matrix proteins. The concentrations of proteins measured did not differ depending on the aetiology of renal disease.


CONCLUSIONS
Urinary concentrations of tenascin and TIMP-1 are elevated in association with renal disease and may reflect specific aspects of renal fibrosis.
Hörstrup
Jan Henrik
JH
Department of Nephrology and Medical Intensive Care, Charité, Campus Virchow-Klinikum, Berlin, Germany.
Gehrmann
Mathias
M
Schneider
Birgit
B
Plöger
Angela
A
Froese
Peter
P
Schirop
Thea
T
Kampf
Dieter
D
Frei
Ulrich
U
Neumann
Rainer
R
Eckardt
Kai-Uwe
KU
D015415:Biomarkers / Q000097:blood / Q000652:urine; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007674:Kidney Diseases / Q000097:blood* / Q000145:classification / Q000652:urine; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000652:urine; D008297:Male; D011507:Proteinuria / Q000097:blood / Q000652:urine; D012016:Reference Values; D012044:Regression Analysis; D019063:Tenascin / Q000097:blood* / Q000652:urine; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood* / Q000652:urine
D015415:Biomarkers; D019063:Tenascin; D019715:Tissue Inhibitor of Metalloproteinase-1