title: Urinary monocyte chemoattractant protein-1 (MCP-1) and connective tissue growth factor (CCN2) as prognostic markers for progression of diabetic nephropathy.
abstract: Profibrotic growth factors and inflammatory chemokines have been implicated in the pathogenesis of diabetic nephropathy (DN). However, measurement of urinary monocyte chemoattractant protein-1 (MCP-1) and connective tissue growth factor (CCN2) as prognostic markers has not previously been reported, and neither have two such molecules in urine been examined in a single study of DN. In this prospective observational study, 43 adult diabetic patients were studied, 40 were followed up for 6years. Urinary MCP-1/creatinine ratios were found to be significantly higher in patients with macroalbuminuria (3.3- and 2.1-fold higher (p<0.01) than normoalbuminuric and microalbuminuric patients, respectively). CCN2 exhibited a pattern different from that of urinary MCP-1. Urinary CCN2/creatinine ratios were greatly elevated in both microalbuminuric and macroalbuminuric patients (125- and 74-fold higher than normoalbuminuric patients, respectively, p<0.01 and p<0.05, respectively). Further, urinary CCN2, but not MCP-1, correlated with progression of microalbuminuria (R=0.49, p<0.05). In contrast, MCP-1, but not CCN2, correlated with the rate of eGFR decline for all patients (R=0.61, p<0.0001), reflective of its predictive value in patients with macroalbuminuria, but not for patients with microalbuminuria or normoalbuminuria. In conclusion, increased urinary CCN2 is associated with the early progression of DN, whereas MCP-1 is associated with later stage disease.
authors.affiliation: Imperial College Kidney and Transplant Institute, Renal Section, Division of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK. f.tam@imperial.ac.uk
authors.forename: Frederick W K
authors.initials: FW
authors.lastname: Tam
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Riser
authors.forename: Karim
authors.initials: K
authors.lastname: Meeran
authors.forename: JoAnn
authors.initials: J
authors.lastname: Rambow
authors.forename: Charles D
authors.initials: CD
authors.lastname: Pusey
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Frankel
mesh_terms: D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000652:urine; D015415:Biomarkers / Q000652:urine; D001794:Blood Pressure / Q000502:physiology; D018932:Chemokine CCL2 / Q000652:urine*; D055513:Connective Tissue Growth Factor / Q000652:urine*; D003404:Creatinine / Q000652:urine; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000652:urine; D003928:Diabetic Nephropathies / Q000175:diagnosis* / Q000503:physiopathology / Q000652:urine*; D003930:Diabetic Retinopathy / Q000652:urine; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018932:Chemokine CCL2; D055513:Connective Tissue Growth Factor; D003404:Creatinine; D006442:Glycated Hemoglobin; C111835:CCL2 protein, human; C526317:CCN2 protein, human; C517652:hemoglobin A1c protein, human