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

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.

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).

Figure 2

Correlation between urinary type IV collagen and annual decline in eGFR (Spearman coefficient γ = −0.34, P < 0.001). The log-transformed values of urinary type IV collagen were used in this plot because the raw values showed a skewed distribution.

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).