Association Between Urinary Type IV Collagen Level and Deterioration of Renal Function in Type 2 Diabetic Patients Without Overt Proteinuria

Abstract

OBJECTIVECross-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 METHODSJapanese 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.RESULTSAt baseline, urinary type IV collagen levels were higher in patients with microalbuminuria than in those with normoalbuminuria and correlated with urinary β2-microglobulin (β = 0.57, P < 0.001), diastolic blood pressure (β = 0.15, P < 0.01), eGFR (β = 0.15, P < 0.01), and urinary albumin excretion rate (β = 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 (γ = −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.CONCLUSIONSOur 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.

Urinary biomarkers of diabetic nephropathy

“…Similar results were shown in a Japanese cohort with type 2 DM without overt proteinuria. 19 This finding was also replicated in a prospective study of type 1 DM patients which showed an association between collagen type IV and a decline in estimated GFR, while albuminuria did not show an association. 20 However, as most of these studies were done in the Asian population, validation in other ethnic groups would be important.…”

Association Between Urinary IgG and Relative Risk for Factors Affecting Proteinuria in Type 2 Diabetic Patients

“…The bared GBM has been suggested for the increased susceptibility for renal fibrosis as it promotes invasion of numerous plasma molecules into GBM, which further promotes invasion of cells [9,10]. These pathways create kidney lesions without microalbuminuria, leads to increase collagen catabolism and excrete hydroxiproline peptides in urine, thus it reflects deterioration of renal function [11,12]. In addition, deteriorated glomerular endothelial surface layer precisely Podocytes cells detachment leads to increase urinary excretion of macromolecules [13,14], which is further facilitated by nonenzymatic glycation of proteins [15].…”

Renal Allograft Fibrosis: Biology and Therapeutic Targets

“…Increased urinary and serum concentrations of procollagen type III N-terminal propeptide (PIIINP) reflecting the expression of collagen type III, a typical scar collagen up-regulated in renal fibrosis, may also reflect fibrogenesis in renal allografts (400-402). Collagen type IV, a major constituent of the renal basement membrane, was shown to be elevated in the urine and to be associated with renal function in diabetic nephropathy and patients with glomerulonephritides (403)(404)(405)(406). Interestingly, although several other collagens and ECM proteins are deposited in renal fibrosis and undergo disease-specific modifications, including crosslinking, this has not yet been widely exploited as a potential source of biomarkers.…”