Clinical Investigation

Kidney International (1984) 25, 565–570; doi:10.1038/ki.1984.55

Glycosyl albumin and diabetic microalbuminuria: Demonstration of an altered renal handling

Gian Marco Ghiggeri1, Giovanni Candiano1, Gerolamo Delfino1, Franco Bianchini1 and Carlo Queirolo1

1Department of Internal Medicine and Service of Hemodialysis, Hospital of Lavagna, Genoa, Italy

Correspondence: Dr G M Ghiggeri, Divisione di Medicina Interna e Servizio di Emodialisi, Ospedale di Lavagna, via Don Bobbio, 16033 Lavagna, (GE)Italy

Received 30 December 1982; Revised 23 May 1983.

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Abstract

Glycosyl albumin and diabetic microalbuminuria: Demonstration of 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 < 10 microg/m', (group B) 12 patients with Ualb between 10 and 100 microg/m', and (group C) seven patients with Ualb > 100 microg/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 plusminus 0.009 nmoles of hydroxymethylfurfural per nanomole of albumin, in group A, 0.1900 plusminus 0.0124; in group B, 0.2199 plusminus 0.0177; and in group C, 0.2224 plusminus 0.0273. Urinary glycosyl albumin concentration was 1.8467 + 0.2132 in normal subjects, 1.4369 plusminus 0.3355 in group A, 1.008 plusminus 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.

Albumine glycosylée et microalbuminurie diabétique: Démonstration d'une anomalie de l'excrétion renale. Dans une tentative d'élucider la liaison entre la glycosylation nonenzymatique des protéines et la néphropathie fonctionnelle diabétique, l'excrétion rénale d'albumine glycosylée a été évaluée chez 15 sujets normaux et 29 malades diabétiques insulino-dépendants, divisés en trois groupes selon leur excrétion urinaire d'albumine (Ualb): (groupe A) dix malades diabétiques avec Ualb10 < microg/m', (groupe B) 12 malades avec Ualb entre 10 et 100 microg/m', et (groupe C) sept malades avec Ualb > 100 microg/m'. L'albumine a été purifiée sur Blue-Sépharose CL-6B. Les hydrates de carbone liés à l'albumine ont été déterminés chimiquement avec de l'acide thiobarbiturique après hydrolyse acide des protéines. La concentration sérique d'albumine glycosylée chez les sujets normaux était de 0,1256 plusminus 0,009 nmoles d'hydroxymethylfurfural par nanomoles d'albumine, dans le groupe A, de 0,1900 plusminus 0,0124; dans le groupe B, 0,2199 plusminus 0,0177; et dans le groupe C, de 0,2224 plusminus 0,0273. La concentration urinaire d'albumine glycosylée était de 1,8467 plusminus 0,2132 chez les sujets normaux, 1,4369 plusminus 0,3355 dans le groupe A, 1,008 plusminus 0,1584 dans le groupe B, et 0,2614 plusminus 0,0295 dans le groupe C. Chez les sujets normaux et les malades sans néphropathie apparente (groupes A et B), la clearance de l'albumine était corrélée avec la concentration sérique d'albumine glycosylée. Chez tous les malades (groupes A, B, et C), le rapport des concentrations urinaires et sériques d'albumine glycosylée était inversement corrélé avec la clearance de l'albumine. Ces données indiquent que chez les sujets normaux et les malades diabétiques avec des débits d'excrétion d'albumine normaux, et chez des diabétiques microalbuminuriques, le passage d'albumine glycosylée à travers la paroi glomerulaire est facilité par rapport à l'albumine normale, et l'albumine glycosylée joue un rôle important dans la pathogénie de la néphropathie fonctionnelle diabétique.

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