Author(s)

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

Division of Clinical Epidemiology, Jikei University School of Medicine, Tokyo, Japan.
Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Hospital, Sendai, Japan.

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.

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

Ogawa, S. , Matsushima, M. , Okamura, M. , Senda, M. , Sakamoto, T. , Nako, K. and Ito, S. (2012) Urinary type IV collagen excretion predicts an increased urinary albumin-to-creatinine ratio in normoalbuminuric patients with diabetes. Journal of Diabetes Mellitus, 2, 413-426. doi: 10.4236/jdm.2012.24065.