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Association between urinary type IV collagen level and deterioration of renal function in type 2 diabetic patients without overt proteinuria.

Araki S, Haneda M, Koya D, Isshiki K, Kume S, Sugimoto T, Kawai H, Nishio Y, Kashiwagi A, Uzu T, Maegawa H - Diabetes Care (2010)

Bottom Line: However, the level of urinary type IV collagen inversely correlated with the annual decline in eGFR (gamma = -0.34, P < 0.001).Multivariate regression analysis identified urinary type IV collagen, eGFR at baseline, and hypertension as factors associated with the annual decline in eGFR.Our results indicate that high urinary excretion of type IV collagen is associated with deterioration of renal function in type 2 diabetic patients without overt proteinuria.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan. araki@belle.shiga-med.ac.jp

ABSTRACT

Objective: Cross-sectional studies have reported increased levels of urinary type IV collagen in diabetic patients with progression of diabetic nephropathy. The aim of this study was to determine the role of urinary type IV collagen in predicting development and progression of early diabetic nephropathy and deterioration of renal function in a longitudinal study.

Research design and methods: Japanese patients with type 2 diabetes (n = 254, 185 with normoalbuminuria and 69 with microalbuminuria) were enrolled in an observational follow-up study. The associations of urinary type IV collagen with progression of nephropathy and annual decline in estimated glomerular filtration rate (eGFR) were evaluated.

Results: At baseline, urinary type IV collagen levels were higher in patients with microalbuminuria than in those with normoalbuminuria and correlated with urinary beta(2)-microglobulin (beta = 0.57, P < 0.001), diastolic blood pressure (beta = 0.15, P < 0.01), eGFR (beta = 0.15, P < 0.01), and urinary albumin excretion rate (beta = 0.13, P = 0.01) as determined by multivariate regression analysis. In the follow-up study (median duration 8 years), urinary type IV collagen level at baseline was not associated with progression to a higher stage of diabetic nephropathy. However, the level of urinary type IV collagen inversely correlated with the annual decline in eGFR (gamma = -0.34, P < 0.001). Multivariate regression analysis identified urinary type IV collagen, eGFR at baseline, and hypertension as factors associated with the annual decline in eGFR.

Conclusions: Our results indicate that high urinary excretion of type IV collagen is associated with deterioration of renal function in type 2 diabetic patients without overt proteinuria.

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Annual decline in eGFR. Subjects were categorized as being above or below the median cutoff of urinary type IV collagen level (6.36 μg/g Cr) and urinary AER (20 μg/min). N+L, patients with normoalbuminuria and less than the median cutoff value of urinary type IV collagen (n = 103, −0.78 ± 0.11 ml/min per 1.73 m2/year); N+H, patients with normoalbuminuria and above the median cutoff value (n = 82, −1.68 ± 0.15 ml/min per 1.73 m2/year); M+L, patients with microalbuminuria and less than the median cutoff value (n = 24, −0.97 ± 0.27 ml/min per 1.73 m2/year); M+H, patients with microalbuminuria and above the median cutoff value (n = 45, −1.69 ± 0.22 ml/min per 1.73 m2/year). Data are mean ± SEM. *P < 0.01 vs. patients with normoalbuminuria and below the median value (ANOVA with Scheffé test).
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Figure 3: Annual decline in eGFR. Subjects were categorized as being above or below the median cutoff of urinary type IV collagen level (6.36 μg/g Cr) and urinary AER (20 μg/min). N+L, patients with normoalbuminuria and less than the median cutoff value of urinary type IV collagen (n = 103, −0.78 ± 0.11 ml/min per 1.73 m2/year); N+H, patients with normoalbuminuria and above the median cutoff value (n = 82, −1.68 ± 0.15 ml/min per 1.73 m2/year); M+L, patients with microalbuminuria and less than the median cutoff value (n = 24, −0.97 ± 0.27 ml/min per 1.73 m2/year); M+H, patients with microalbuminuria and above the median cutoff value (n = 45, −1.69 ± 0.22 ml/min per 1.73 m2/year). Data are mean ± SEM. *P < 0.01 vs. patients with normoalbuminuria and below the median value (ANOVA with Scheffé test).

Mentions: Next, we analyzed the relationship between urinary type IV collagen and deterioration of renal function. Univariate regression analysis showed that the level of urinary type IV collagen inversely correlated with the annual decline in eGFR (γ = −0.34, P < 0.001) (Fig. 2), whereas urinary AER correlated weakly with this decline (γ = −0.14, P = 0.03). Multivariate regression analysis with a stepwise forward method identified log urinary type IV collagen (β = −0.28, P < 0.001), eGFR at baseline (β = −0.18, P = 0.002), and hypertension (β = −0.13, P = 0.03) as factors associated with the annual decline in eGFR. When the patients were divided according to the median cutoff level of urinary type IV collagen, the mean value of eGFR at the end of study was significantly lower in the patients above the median cutoff level (≥6.36 μg/g Cr) than in those below the median cutoff level (69.6 ± 16.3 vs. 73.8 ± 15.8 ml/min per 1.73 m2; P = 0.039), whereas the mean value of eGFR at baseline was not different in the two subgroups (83.2 ± 15.4 vs. 81.9 ± 13.8 ml/min per 1.73 m2; P = 0.50). Interestingly, those above the median cutoff level showed a rapid decline of eGFR in the follow-up compared with those who were below (−1.69 ± 1.40 vs. −0.82 ± 1.15 ml/min per 1.73 m2/year; P < 0.001). Finally, the annual decline in eGFR was compared in four subgroups of patients according to the stage of diabetic nephropathy and the median cutoff level of urinary type IV collagen (Fig. 3). In patients with normoalbuminuria, the annual decline in eGFR was significantly larger in those with urinary type IV collagen level above the median cutoff level than in those with who were below the median value. Similarly, the annual rate in eGFR of those with microalbuminuria and above the median cutoff value was larger than that in those with normoalbuminuria below the median value, although the annual decline in those with microalbuminuria and below the median value was not different.


Association between urinary type IV collagen level and deterioration of renal function in type 2 diabetic patients without overt proteinuria.

Araki S, Haneda M, Koya D, Isshiki K, Kume S, Sugimoto T, Kawai H, Nishio Y, Kashiwagi A, Uzu T, Maegawa H - Diabetes Care (2010)

Annual decline in eGFR. Subjects were categorized as being above or below the median cutoff of urinary type IV collagen level (6.36 μg/g Cr) and urinary AER (20 μg/min). N+L, patients with normoalbuminuria and less than the median cutoff value of urinary type IV collagen (n = 103, −0.78 ± 0.11 ml/min per 1.73 m2/year); N+H, patients with normoalbuminuria and above the median cutoff value (n = 82, −1.68 ± 0.15 ml/min per 1.73 m2/year); M+L, patients with microalbuminuria and less than the median cutoff value (n = 24, −0.97 ± 0.27 ml/min per 1.73 m2/year); M+H, patients with microalbuminuria and above the median cutoff value (n = 45, −1.69 ± 0.22 ml/min per 1.73 m2/year). Data are mean ± SEM. *P < 0.01 vs. patients with normoalbuminuria and below the median value (ANOVA with Scheffé test).
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Figure 3: Annual decline in eGFR. Subjects were categorized as being above or below the median cutoff of urinary type IV collagen level (6.36 μg/g Cr) and urinary AER (20 μg/min). N+L, patients with normoalbuminuria and less than the median cutoff value of urinary type IV collagen (n = 103, −0.78 ± 0.11 ml/min per 1.73 m2/year); N+H, patients with normoalbuminuria and above the median cutoff value (n = 82, −1.68 ± 0.15 ml/min per 1.73 m2/year); M+L, patients with microalbuminuria and less than the median cutoff value (n = 24, −0.97 ± 0.27 ml/min per 1.73 m2/year); M+H, patients with microalbuminuria and above the median cutoff value (n = 45, −1.69 ± 0.22 ml/min per 1.73 m2/year). Data are mean ± SEM. *P < 0.01 vs. patients with normoalbuminuria and below the median value (ANOVA with Scheffé test).
Mentions: Next, we analyzed the relationship between urinary type IV collagen and deterioration of renal function. Univariate regression analysis showed that the level of urinary type IV collagen inversely correlated with the annual decline in eGFR (γ = −0.34, P < 0.001) (Fig. 2), whereas urinary AER correlated weakly with this decline (γ = −0.14, P = 0.03). Multivariate regression analysis with a stepwise forward method identified log urinary type IV collagen (β = −0.28, P < 0.001), eGFR at baseline (β = −0.18, P = 0.002), and hypertension (β = −0.13, P = 0.03) as factors associated with the annual decline in eGFR. When the patients were divided according to the median cutoff level of urinary type IV collagen, the mean value of eGFR at the end of study was significantly lower in the patients above the median cutoff level (≥6.36 μg/g Cr) than in those below the median cutoff level (69.6 ± 16.3 vs. 73.8 ± 15.8 ml/min per 1.73 m2; P = 0.039), whereas the mean value of eGFR at baseline was not different in the two subgroups (83.2 ± 15.4 vs. 81.9 ± 13.8 ml/min per 1.73 m2; P = 0.50). Interestingly, those above the median cutoff level showed a rapid decline of eGFR in the follow-up compared with those who were below (−1.69 ± 1.40 vs. −0.82 ± 1.15 ml/min per 1.73 m2/year; P < 0.001). Finally, the annual decline in eGFR was compared in four subgroups of patients according to the stage of diabetic nephropathy and the median cutoff level of urinary type IV collagen (Fig. 3). In patients with normoalbuminuria, the annual decline in eGFR was significantly larger in those with urinary type IV collagen level above the median cutoff level than in those with who were below the median value. Similarly, the annual rate in eGFR of those with microalbuminuria and above the median cutoff value was larger than that in those with normoalbuminuria below the median value, although the annual decline in those with microalbuminuria and below the median value was not different.

Bottom Line: However, the level of urinary type IV collagen inversely correlated with the annual decline in eGFR (gamma = -0.34, P < 0.001).Multivariate regression analysis identified urinary type IV collagen, eGFR at baseline, and hypertension as factors associated with the annual decline in eGFR.Our results indicate that high urinary excretion of type IV collagen is associated with deterioration of renal function in type 2 diabetic patients without overt proteinuria.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan. araki@belle.shiga-med.ac.jp

ABSTRACT

Objective: Cross-sectional studies have reported increased levels of urinary type IV collagen in diabetic patients with progression of diabetic nephropathy. The aim of this study was to determine the role of urinary type IV collagen in predicting development and progression of early diabetic nephropathy and deterioration of renal function in a longitudinal study.

Research design and methods: Japanese patients with type 2 diabetes (n = 254, 185 with normoalbuminuria and 69 with microalbuminuria) were enrolled in an observational follow-up study. The associations of urinary type IV collagen with progression of nephropathy and annual decline in estimated glomerular filtration rate (eGFR) were evaluated.

Results: At baseline, urinary type IV collagen levels were higher in patients with microalbuminuria than in those with normoalbuminuria and correlated with urinary beta(2)-microglobulin (beta = 0.57, P < 0.001), diastolic blood pressure (beta = 0.15, P < 0.01), eGFR (beta = 0.15, P < 0.01), and urinary albumin excretion rate (beta = 0.13, P = 0.01) as determined by multivariate regression analysis. In the follow-up study (median duration 8 years), urinary type IV collagen level at baseline was not associated with progression to a higher stage of diabetic nephropathy. However, the level of urinary type IV collagen inversely correlated with the annual decline in eGFR (gamma = -0.34, P < 0.001). Multivariate regression analysis identified urinary type IV collagen, eGFR at baseline, and hypertension as factors associated with the annual decline in eGFR.

Conclusions: Our results indicate that high urinary excretion of type IV collagen is associated with deterioration of renal function in type 2 diabetic patients without overt proteinuria.

Show MeSH
Related in: MedlinePlus