Urinary Excretion of Glycosaminoglycans in Patients with Early Diabetic Nephropathy

F. Pérez-Blanco, PO Box 752, E-18080 Granada (Spain) Table 1. Urinary excretion of GAG in patients with diabetes mellitus Group B C D n 52 63 37 29 Mean ± SD 16.8 ± 0.8 40.1 + 27.5 90.1 ± 62.0 193.3 + 83.9 p < O.Ol < 0.05 < O.Ol Dear Sir, The kidney undergoes structural and functional alterations throughout the course of diabetes, microalbuminuria being the first manifestation of nephropathy [1]. Albumin excretion depends mainly on glomerular hy-perfiltration and changes in charge selectivity and pore size in the glomerular basement membrane (GBM) [2]. Although the structural basis of diabetic nephropathy is unknown, it is related with expansion of the mesangium and thickening of the GBM. This membrane, which represents a selective barrier to glomerular filtration, is formed of a dense network of collagen filaments, poly-peptides of different chain structures, and glycosaminoglycans (GAG), heparan sulfate proteoglycan being the major type. The GAG play an important role as a selective filter in the GBM, ensuring that a negative charge is maintained. In diabetes mellitus, the negative charge on the GBM is reduced because of a decrease in heparan sulfate proteoglycan [3]. As a result, albuminuria and pore size are both increased. The early phase of nephropathy is characterized by an increase in the activity of the enzymes responsible for glycoprotein (n-ace-tylglucosaminidase) and mucopolysaccha-ride metabolism (ß-glucuronidase). These enzymes break down complex intracellular macromolecules and degrade glycoconju-gates on the endothelial membrane [4], leading to structural alterations in the GBM, and the abnormal excretion of GAG [5]. We investigated the urinary excretion of GAG in 129 patients in different stages of nephropathy caused by insulin-dependent diabetes: 63 patients without hypertension or microalbuminuria (group B), 37 patients without hypertension but with microalbuminuria (group C), and 29 patients with both (group D). As a control group we studied 52 healthy control subjects (group A).