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

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

Pathomechanism of Renal Damage in Type 2 Diabetes Mellitus Patients

“…(12) Ogawa et al in an observational study over a 2-year period also found a significant correlation between the increase of urinary albumin/creatinine ratio to urinary type IV collagen and that in normoalbuminuria subjects, in which type IV collagen levels higher evolved into albuminuria within 2 years. (19) This study found no correlation between HbA1c levels with urinary GGT (Table 3), as well as no significant correlation was found between urinary type IV collagen/ creatinine ratio and hs-CRP with urinary GGT. The role of GGT in this case was not likely occurs through inflammatory mechanisms and accumulation of ECM, to prove which a further study is needed.…”

Urinary biomarkers for early diabetic nephropathy in type 2 diabetic patients

“…A follow-up study showed that 76.8 % of normoalbuminuric type 2 diabetic patients in the high urinary type IV collagen group developed microalbuminuria as opposed to 22.6 % patients in the normal urinary type IV collagen group. This indicated that baseline urinary type IV collagen excretion may be an independent predictive factor for the development of DN in normoalbuminuric type 2 diabetic patients [ 36 ].…”

Role of type IV collagen in the development of diabetic nephropathy in patients with diabetes mellitus

“…У более чем 2/3 пациентов с СД 2 типа, имеющих нормоальбуминурию и находящихся в группе с повышенной мочевой экскрецией коллагена IV, регистрировалась микроальбуминурия, что позволяет предположить роль базовой экскреции коллагена IV типа в моче как независимого прогнозирующего фактора для развития ДН. В соответствии с официальными рекомендациями комитета по ДН (Diabetic Nephropathy Committee) Японии увеличение уровня коллагена IV типа в моче является одним из ранних диагностических критериев для постановки диагноза ДН [45].…”