Urinary monocyte chemoattractant protein-1 and hepcidin and early diabetic nephropathy lesions in type 1 diabetes mellitus

作者：Fufaa Gudeta D; Weil E Jennifer; Nelson Robert G; Hanson Robert L; Knowler William C; Rovin Brad H; Wu Haifeng; Klein Jon B; Mifflin Theodore E; Feldman Harold I; Vasan Ramachandran S; Kimmel Paul L; Kusek John W; Mauer Michael^*

来源：Nephrology Dialysis Transplantation, 2015, 30(4): 599-606.

DOI：10.1093/ndt/gfv012

• biomarkers
• diabetic nephropathy
• hepcidin
• interstitial fibrosis
• monocyte chemoattractant protein-1

aEuro broken vertical bar the residual risk of renal disease progression in patients with diabetic nephropathy is still extremely high despite current optimal treatment; innate immunity, MCP-1 and macrophage tissue infiltration seem very promising targets for future treatment of diabetic nephropathy on top of the standard of care with RAAS inhibition.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.
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/aS2 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.
Baseline mean age was 24.6 years, mean duration of T1D 11.2 years, median AER 6.4 A mu g/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.
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.

• 出版日期2015-4