Urinary connective tissue growth factor excretion in patients with type 1 diabetes and nephropathy.
OBJECTIVE
Excretion of growth factors in the urine has been implicated in the pathogenesis of tubulointerstitial disease that characterizes proteinuric renal disease. In this cross-sectional study, we sought to examine the urinary excretion of the profibrotic cytokine connective tissue growth factor (CTGF) in type 1 diabetic patients with incipient and overt diabetic nephropathy.


METHODS
We recruited 31 subjects with type 1 diabetes from a hospital diabetes outpatient clinic. Of these, 10 subjects were normoalbuminuric, 8 were microalbuminuric and not receiving ACE inhibitor treatment, and 13 were macroalbuminuric, 8 of whom were receiving ACE inhibitor treatment. Urinary CTGF NH(2)-terminal fragment (CTGF-N) was determined by enzyme-linked immunosorbent assay and expressed relative to urinary creatinine.


RESULTS
Urinary CTGF-N was closely correlated with the degree of albuminuria (r = 0.76, P < 0.001). In comparison with normoalbuminuric subjects, urinary CTGF-N was increased 10- and 100-fold in micro- and untreated macroalbuminuric subjects, respectively (CTGF-N-to-creatinine ratio: normoalbuminuria 0.23 x// 1.3 ng/mg, microalbuminuria 2.1 x// 1.7 ng/mg, untreated macroalbuminuria 203 x// 3.8 ng/mg, and geometric mean x// tolerance factor; P < 0.05 for normoalbuminuria versus microalbuminuria, P < 0.001 for microalbuminuria versus macroalbuminuria). Urinary CTGF-N was lower (<30-fold) in macroalbuminuric subjects treated with ACE inhibitors (6.5 x// 1.7 ng/mg; P < 0.01 vs. untreated macroalbuminuria) compared with their untreated counterparts.


CONCLUSIONS
In this cross-sectional study, the magnitude of urinary CTGF-N excretion was related to the severity of diabetic nephropathy. In the context of its known profibrotic actions, these findings suggest that CTGF may contribute to the chronic tubulointerstitial fibrosis that accompanies proteinuric renal disease. Prospective and interventional studies will be needed to determine whether urinary CTGF-N may provide a reliable surrogate marker of renal injury and a meaningful indicator of response to therapy.
Gilbert
Richard E
RE
Department of Medicine, St Vincent's Hospital, University of Melbourne, Fitzroy, Australia. gilbert@medstv.unimelb.edu.au
Akdeniz
Aysel
A
Weitz
Stephen
S
Usinger
William R
WR
Molineaux
Christopher
C
Jones
Susan E
SE
Langham
Robyn G
RG
Jerums
George
G
D000328:Adult; D000419:Albuminuria; D015415:Biomarkers / Q000652:urine; D001794:Blood Pressure; D003404:Creatinine / Q000097:blood / Q000378:metabolism; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000503:physiopathology / Q000652:urine*; D003928:Diabetic Nephropathies / Q000097:blood / Q000503:physiopathology / Q000652:urine*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D016212:Transforming Growth Factor beta / Q000652:urine
D015415:Biomarkers; D003404:Creatinine; D006442:Glycated Hemoglobin; D016212:Transforming Growth Factor beta