Urinary Connective Tissue Growth Factor Excretion in Patients With Type 1 Diabetes and Nephropathy

Urinary Connective Tissue Growth Factor Excretion in Patients With Type 1 Diabetes and Nephropathy Richard E. Gilbert , MD, PHD 1 , Aysel Akdeniz , BSC 2 , Stephen Weitz , MD 3 , William R. Usinger , MD 3 , Christopher Molineaux , MD 3 , Susan E. Jones , MD 1 , Robyn G. Langham , MD, PHD 1 and George Jerums , MD 2 1 Department of Medicine, St. Vincent’s Hospital, University of Melbourne, Fitzroy, Australia 2 Fibrogen Inc., San Francisco, California 3 Department of Medicine, Austin and Repatriation Medical Centre, University of Melbourne, Heidelberg, Australia Address correspondence and reprint requests to Richard E. Gilbert, University of Melbourne, Department of Medicine, St. Vincent’s Hospital, 41 Victoria Parade, Fitzroy, Victoria, 3065, Australia. E-mail: gilbert{at}medstv.unimelb.edu.au Abstract 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. RESEARCH DESIGN AND 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 ×/÷ 1.3 ng/mg, microalbuminuria 2.1 ×/÷ 1.7 ng/mg, untreated macroalbuminuria 203 ×/÷ 3.8 ng/mg, and geometric mean ×/÷ tolerance factor; P < 0.05 for normoalbuminuria versus microalbuminuria, P < 0.001 for microalbuminuria versus macroalbuminuria). Urinary CTGF-N was lower (