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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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Kaplan-Meier curves for development of microalbuminuria in patients with normoalbuminuria (A) and progression of overt proteinuria in those with microalbuminuria (B) grouped according to the median cutoff value of urinary type IV collagen level. The difference between two subgroups was compared by a log-rank test. ——, patients above the value (6.36 μg/g Cr; n = 127); – – –, patients below the value (<6.36 μg/g Cr; n = 127).
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Figure 1: Kaplan-Meier curves for development of microalbuminuria in patients with normoalbuminuria (A) and progression of overt proteinuria in those with microalbuminuria (B) grouped according to the median cutoff value of urinary type IV collagen level. The difference between two subgroups was compared by a log-rank test. ——, patients above the value (6.36 μg/g Cr; n = 127); – – –, patients below the value (<6.36 μg/g Cr; n = 127).

Mentions: We explored the predictive effect of urinary type IV collagen on worsening of diabetic nephropathy. During the follow-up period (median 8 years; range 3–9 years), 16 of the 185 diabetic subjects with normoalbuminuria and 9 of the 69 with microalbuminuria progressed to more advanced stages of diabetic nephropathy. Among subjects with normoalbuminuria at baseline, urinary type IV collagen levels were not different between those who progressed to microalbuminuria (6.04 μg/g Cr [IQR 4.73–7.67 μg/g Cr]) and those who did not (5.62 μg/g Cr [3.06–8.07 μg/g Cr], P = 0.46, by Mann-Whitney U test). In contrast, the median urinary AER was significantly higher in those who progressed (10.6 μg/min [8.0–13.0 μg/min]) than in those who did not (7.1 μg/min [5.1–9.8 μg/min], P = 0.002). Among the subjects with microalbuminuria, the urinary type IV collagen level was not different between those who progressed to overt proteinuria (5.52 μg/g Cr [4.33–8.25 μg/g Cr]) and those who did not (7.68 μg/g Cr [5.86–12.21 μg/g Cr], P = 0.11), whereas urinary AER tended to be different in these two subgroups (55.7 [35.8–131.3] vs. 42.9 μg/min [31.9–64.5 μg/min], respectively, P = 0.07). Furthermore, urinary type IV collagen above the median cutoff point (≥6.36 μg/g Cr) was neither predictive for future development of microalbuminuria in patients with normoalbuminuria nor for progression to overt proteinuria in those with microalbuminuria, as examined with the Kaplan-Meier method (log-rank test: P = 0.90 for normoalbuminuria, P = 0.84 for microalbuminuria) (Fig. 1).


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)

Kaplan-Meier curves for development of microalbuminuria in patients with normoalbuminuria (A) and progression of overt proteinuria in those with microalbuminuria (B) grouped according to the median cutoff value of urinary type IV collagen level. The difference between two subgroups was compared by a log-rank test. ——, patients above the value (6.36 μg/g Cr; n = 127); – – –, patients below the value (<6.36 μg/g Cr; n = 127).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2909066&req=5

Figure 1: Kaplan-Meier curves for development of microalbuminuria in patients with normoalbuminuria (A) and progression of overt proteinuria in those with microalbuminuria (B) grouped according to the median cutoff value of urinary type IV collagen level. The difference between two subgroups was compared by a log-rank test. ——, patients above the value (6.36 μg/g Cr; n = 127); – – –, patients below the value (<6.36 μg/g Cr; n = 127).
Mentions: We explored the predictive effect of urinary type IV collagen on worsening of diabetic nephropathy. During the follow-up period (median 8 years; range 3–9 years), 16 of the 185 diabetic subjects with normoalbuminuria and 9 of the 69 with microalbuminuria progressed to more advanced stages of diabetic nephropathy. Among subjects with normoalbuminuria at baseline, urinary type IV collagen levels were not different between those who progressed to microalbuminuria (6.04 μg/g Cr [IQR 4.73–7.67 μg/g Cr]) and those who did not (5.62 μg/g Cr [3.06–8.07 μg/g Cr], P = 0.46, by Mann-Whitney U test). In contrast, the median urinary AER was significantly higher in those who progressed (10.6 μg/min [8.0–13.0 μg/min]) than in those who did not (7.1 μg/min [5.1–9.8 μg/min], P = 0.002). Among the subjects with microalbuminuria, the urinary type IV collagen level was not different between those who progressed to overt proteinuria (5.52 μg/g Cr [4.33–8.25 μg/g Cr]) and those who did not (7.68 μg/g Cr [5.86–12.21 μg/g Cr], P = 0.11), whereas urinary AER tended to be different in these two subgroups (55.7 [35.8–131.3] vs. 42.9 μg/min [31.9–64.5 μg/min], respectively, P = 0.07). Furthermore, urinary type IV collagen above the median cutoff point (≥6.36 μg/g Cr) was neither predictive for future development of microalbuminuria in patients with normoalbuminuria nor for progression to overt proteinuria in those with microalbuminuria, as examined with the Kaplan-Meier method (log-rank test: P = 0.90 for normoalbuminuria, P = 0.84 for microalbuminuria) (Fig. 1).

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