PMID- 25648911 OWN - NLM STAT- MEDLINE DCOM- 20160531 LR - 20220409 IS - 1460-2385 (Electronic) IS - 0931-0509 (Print) IS - 0931-0509 (Linking) VI - 30 IP - 4 DP - 2015 Apr TI - Urinary monocyte chemoattractant protein-1 and hepcidin and early diabetic nephropathy lesions in type 1 diabetes mellitus. PG - 599-606 LID - 10.1093/ndt/gfv012 [doi] AB - BACKGROUND: Urinary monocyte chemoattractant protein-1 (MCP-1) and hepcidin are potential biomarkers of renal inflammation. We examined their association with development of diabetic nephropathy (DN) lesions in normotensive normoalbuminuric subjects with type 1 diabetes (T1D) from the Renin-Angiotensin System Study. METHODS: Biomarker concentrations were measured in baseline urine samples from 224 subjects who underwent kidney biopsies at baseline and after 5 years. Fifty-eight urine samples below the limit of quantitation (LOQ, 28.8 pg/mL) of the MCP-1 assay were assigned concentrations of LOQ/ radical2 for analysis. Relationships between ln(MCP-1/Cr) or ln(hepcidin/Cr) and morphometric variables were assessed by sex using multiple linear regression after adjustment for age, T1D duration, HbA1c, mean arterial pressure, albumin excretion rate (AER) and glomerular filtration rate (GFR). In models that examined changes in morphometric variables, the baseline morphometric value was also included. RESULTS: Baseline mean age was 24.6 years, mean duration of T1D 11.2 years, median AER 6.4 microg/min and mean iohexol GFR 129 mL/min/1.73 m(2). No associations were found between hepcidin/Cr and morphometric variables. Higher MCP-1/Cr was associated with higher interstitial fractional volume at baseline and after 5 years in women (baseline partial r = 0.244, P = 0.024; 5-year partial r = 0.299, P = 0.005), but not in men (baseline partial r = -0.049, P = 0.678; 5-year partial r = 0.026, P = 0.830). MCP-1 was not associated with glomerular lesions in either sex. CONCLUSIONS: Elevated urinary MCP-1 concentration measured before clinical findings of DN in women with T1D was associated with changes in kidney interstitial volume, suggesting that inflammatory processes may be involved in the pathogenesis of early interstitial changes in DN. CI - Published by Oxford University Press on behalf of ERA-EDTA 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US. FAU - Fufaa, Gudeta D AU - Fufaa GD AD - National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ, USA. FAU - Weil, E Jennifer AU - Weil EJ AD - National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ, USA. FAU - Nelson, Robert G AU - Nelson RG AD - National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ, USA. FAU - Hanson, Robert L AU - Hanson RL AD - National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ, USA. FAU - Knowler, William C AU - Knowler WC AD - National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ, USA. FAU - Rovin, Brad H AU - Rovin BH AD - Ohio State University, Columbus, OH, USA. FAU - Wu, Haifeng AU - Wu H AD - Ohio State University, Columbus, OH, USA. FAU - Klein, Jon B AU - Klein JB AD - University of Louisville, Louisville, KY, USA. FAU - Mifflin, Theodore E AU - Mifflin TE AD - University of Pennsylvania, Philadelphia, PA, USA. FAU - Feldman, Harold I AU - Feldman HI AD - University of Pennsylvania, Philadelphia, PA, USA. FAU - Vasan, Ramachandran S AU - Vasan RS AD - Boston University, Boston, MA, USA. FAU - Kimmel, Paul L AU - Kimmel PL AD - National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA. FAU - Kusek, John W AU - Kusek JW AD - National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA. FAU - Mauer, Michael AU - Mauer M AD - Department of Pediatrics and Medicine, University of Minnesota, Minneapolis, MN 55454, USA. CN - CKD Biomarkers Consortium and the RASS Investigators LA - eng GR - U01DK085660/DK/NIDDK NIH HHS/United States GR - U01DK085688/DK/NIDDK NIH HHS/United States GR - U01DK85649/DK/NIDDK NIH HHS/United States GR - U01 DK085673/DK/NIDDK NIH HHS/United States GR - ImNIH/Intramural NIH HHS/United States GR - U01DK085651/DK/NIDDK NIH HHS/United States GR - U01 DK085649/DK/NIDDK NIH HHS/United States GR - U01 DK085689/DK/NIDDK NIH HHS/United States GR - U01 DK096927/DK/NIDDK NIH HHS/United States GR - U01 DK085688/DK/NIDDK NIH HHS/United States GR - U01 DK085660/DK/NIDDK NIH HHS/United States GR - U01DK085689/DK/NIDDK NIH HHS/United States GR - U01DK085673/DK/NIDDK NIH HHS/United States GR - U01 DK085651/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Multicenter Study PT - Research Support, N.I.H., Extramural PT - Research Support, N.I.H., Intramural DEP - 20150203 PL - England TA - Nephrol Dial Transplant JT - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JID - 8706402 RN - 0 (Biomarkers) RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Hepcidins) SB - IM CIN - Nephrol Dial Transplant. 2015 Apr;30(4):525-7. PMID: 25801635 MH - Adolescent MH - Adult MH - Aged MH - Biomarkers/*urine MH - Blood Pressure MH - Chemokine CCL2/*urine MH - Diabetes Mellitus, Type 1/*complications/physiopathology MH - Diabetic Nephropathies/*diagnosis/urine MH - Female MH - Glomerular Filtration Rate MH - Hepcidins/*urine MH - Humans MH - Kidney Glomerulus/pathology MH - Male MH - Middle Aged MH - Renin-Angiotensin System MH - Young Adult PMC - PMC4402379 OTO - NOTNLM OT - biomarkers OT - diabetic nephropathy OT - hepcidin OT - interstitial fibrosis OT - monocyte chemoattractant protein-1 FIR - Zinman, Bernard IR - Zinman B FIR - Donnelly, Sandra IR - Donnelly S FIR - Canada, Toronto IR - Canada T FIR - Gardiner, Robert IR - Gardiner R FIR - Suissa, Samy IR - Suissa S FIR - Drummond, Keith IR - Drummond K FIR - Goodyer, Paul IR - Goodyer P FIR - Sinaiko, Alan IR - Sinaiko A FIR - Strand, Trudy IR - Strand T FIR - Gubler, Marie Claire IR - Gubler MC FIR - Klein, Ronald IR - Klein R EDAT- 2015/02/05 06:00 MHDA- 2016/06/01 06:00 PMCR- 2016/04/01 CRDT- 2015/02/05 06:00 PHST- 2015/02/05 06:00 [entrez] PHST- 2015/02/05 06:00 [pubmed] PHST- 2016/06/01 06:00 [medline] PHST- 2016/04/01 00:00 [pmc-release] AID - gfv012 [pii] AID - 10.1093/ndt/gfv012 [doi] PST - ppublish SO - Nephrol Dial Transplant. 2015 Apr;30(4):599-606. doi: 10.1093/ndt/gfv012. Epub 2015 Feb 3.