Urinary type IV collagen: a specific indicator of incipient diabetic nephropathy.

OBJECTIVE

To determine whether urinary type IV collagen can serve as an indicator specific for diabetic nephropathy.

METHODS

Using a novel sandwich ABC-ELISA to measure type IV collagen directly, the 24-hour urinary type IV collagen excretion rate was determined in 120 diabetic patients and some groups of controls. Urinary albumin determinations were made with a RIA kit at the same time. A total of 13 diabetic patients with microalbuminuria underwent percutaneous renal biopsy for definitive diagnosis of diabetic nephropathy. Type IV collagen and TGF-beta 1 immunoreactivities were detected with ABC methods in renal biopsies.

RESULTS

Urinary type IV collagen excretion was significantly increased in diabetic patients with microalbuminuria, especially those with albumin excretion above 200 mg/24 h. By comparison, collagen excretion was equivalent to that in healthy controls when measured in diabetics with normalbuminuria and in patients with primary glomerular disease, primary hypertension, or coronary heart disease. Urinary type IV collagen excretion in diabetics was negatively correlated with creatinine clearance. In renal biopsies from subjects with elevated collagen excretion, the glomeruli showed pathological changes typical of diabetic nephropathy. Also, excessive type IV collagen and TGF-beta 1 immunoreactivity were detected in the glomeruli, Bowman's capsule and interstitium.

CONCLUSIONS

Excretion of type IV collagen, possibly reflecting increased production or decreased degradation of this protein, may be a clinically useful indicator of incipient diabetic nephropathy.