Glycosyl albumin and diabetic microalbuminuria: demonstration of an altered renal handling.

In attempt to elucidate the link between the nonenzymatic glycosylation of proteins and the diabetic functional nephropathy, renal handling of glycosyl albumin has been evaluated in 15 normal subjects and 29 insulin-dependent diabetic patients divided in three groups according to their urinary excretion rates of albumin (Ualb): (group A) ten diabetic patients with Ualb less than 10 micrograms/m', (group B) 12 patients with Ualb between 10 and 100 micrograms/m', and (group C) seven patients with Ualb greater than 100 micrograms/m'. Albumin was purified with Blue-Sepharose CL-6B. The carbohydrate bound to albumin was determined chemically with thiobarbituric acid after the acid hydrolysis of the protein. Serum glycosyl albumin concentration in normal subjects was 0.1256 +/- 0.009 nmoles of hydroxymethylfurfural per nanomole of albumin, in group A, 0.1900 +/- 0.0124; in group B, 0.2199 +/- 0.0177; and in group C, 0.2224 +/- 0.02732. Urinary glycosyl albumin concentration was 1.8467 + 0.2132 in normal subjects, 1.4369 +/- 0.3355 in group A, 1.008 +/- 0.1584 in group B, and 0.2614 + 0.0295 in group C. In normal subjects and patients without apparent nephropathy (groups A and B), the clearance of albumin correlated with the serum concentration of glycosyl albumin. In all patients (groups A, B, and C) the urinary-serum glycosyl albumin concentration ratio was correlated inversely with albumin clearance. These data show that in normal subjects and diabetic patients with normal excretion rates of albumin and microalbuminuric diabetic patients the passage of glycosyl albumin through the glomerular wall is facilitated in contrast to normal albumin and that glycosyl albumin plays an important role in the pathogenesis of diabetic functional nephropathy.