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Matsubara, T., Abe, H., Arai, H., Nagai, K., Mima, A., Kanamori, H., Sumi, E., Takahashi, T., Matsuura, M., Iehara, N., Fukatsu, A., Kita, T. and Doi, T. (2006) Expression of Smad1 is directly associated with mesangial matrix expansion in rat diabetic nephropathy. Laboratory Investigation, 86, 357-368. doi:10.1038/labinvest.3700400

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• TITLE: Urinary type IV collagen excretion predicts an increased urinary albumin-to-creatinine ratio in normoalbuminuric patients with diabetes

  AUTHORS: Susumu Ogawa, Masato Matsushima, Masashi Okamura, Miho Senda, Takuya Sakamoto, Kazuhiro Nako, Sadayoshi Ito

  KEYWORDS: Type IV Collagen; Diabetic Nephropathy; Oxidative Stress; Monocyte Chemoattractant Protein-1

  JOURNAL NAME: Journal of Diabetes Mellitus, Vol.2 No.4, November 27, 2012

  ABSTRACT: Aims: We evaluated whether urinary excretion of type IV collagen (U-COL) may predict an increase in the urinary albumin-to-creatinine ratio (ACR) and what factors regulate U-COL in 145 normoalbuminuric patients with type 2 diabetes. Methods: We measured HbA1c, systolic blood pressure (SBP), urinary 8-hydroxydeoxyguanosine (8-OHdG) and monocyte chemoattractant protein (MCP)-1 at start of this study (Baseline), ACR and U-COL in addition to these measurements at one year later (Evaluation-1), and ACR and SBP after two years of the Evaluation-1 (Evaluation-2). The relationships were investigated between the increase of ACR and the U-COL. The effect of angiotensin receptor blockers (ARB) treatment on the correlations between U-COL and ACR at Evaluation-2 on one hand, and between U-COL and percent change of ACR on the other, was also analyzed. Furthermore, we investigated whether the increase in 8-OHdG and in MCP-1 in a year prior to the Evaluation-1 were risk factors of the rise in U-COL levels. Results: Both U-COL and SBP at Evaluation-1, but not ARB treatment, were independent risk factors for an increased ACR after 2 years. ARB treatment significantly suppressed the increase in ACR after 2 years in patients with higher U-COL excretion. The percentage changes in 8-OHdG (%8-OHdG) and MCP-1 (%MCP-1) in one year prior to Evaluation-1 measurements are independent risk factors for U-COL. HbA1c and SBP values one year prior to Evaluation-1 are independent risk factors not only for %8-OHdG but also, for baseline U-COL. The %8-OHdG is an independent risk factor for %MCP-1. Conclusions: U-COL may predict an increase in the ACR. The U-COL seems to be increased with oxidative stress and inflammation induced by past hyperglycemia.