Increased collagen IV excretion in diabetes - A marker of compromised filtration function

OBJECTIVE - Increased albumin excretion in diabetes is believed to be derived from hemodynamic and/or permeability abnormalities, whereas mesangial matrix expansion gives rise to the reduction in glomerular filtration surface and decline in renal function in diabetic nephropathy. We postulated that the overproduction of extracellular matrix proteins underlying glomerulosclerosis in diabetes might he associated with the excretion of increased amounts of type IV collagen in the urine. RESEARCH DESIGN AND METHODS - To explore this hypothesis. we measured the urinary excretion of (human) collagen IV by immunoassay in 65 patients with type 1 or type 2 diabetes and various degrees of albuminuria and examined its relationship to filtration function assessed hy the reciprocal of the serum creatinine (RSC). RESULTS - Collagen IV excretion showed a significant (P < 0.001) inverse correlation (r = - 0.62) with the RSC, and this correlation pertained regardless of whether albumin excretion was in the low (<less than or equal to>100 mug/mg creatinine: r = -0.73) or high (>100 mug/mg; r = -0.53) range. In contrast. albumin excretion showed insignificant correlation with either collagen IV excretion (r = 0.12) or with the RSC (r = -0.20). Urinary collagen IV was significantly higher (P < 0.05) in patients with an RSC value <less than or equal to>100 (28.3 +/- 2.4 ng/mg creatinine) than in patients with an RSC value >100 (16.0 +/- 0.8 ng/mg creatinine). CONCLUSIONS - Because not all patients with microalbuminuria progress to declining renal function and some patients who develop nephropathy do not manifest albuminuria. the findings in this cross-sectional analysis suggest that measurement of urine collagen IV may be a useful noninvasive indicator to detect diabetic renal disease entering a phase of compromised renal function.