Damage of charge-dependent renal tubular reabsorption causes diabetic microproteinuria.
More negatively-charged proteins are harder to pass through the glomerular charge barrier (GCB) and to be reabsorbed by renal tubules. Although the glycation of albumin increases its negative charge compared to non-glycated albumin, the glycation of transferrin does not change its charge. This difference enabled us to examine the charge-dependent renal function in diabetic proteinuria. The percentage of urinary glycated transferrin (serum %G-transferrin) positively correlated with serum fructosamine concentrations and the percentage of serum glycated albumin (serum %G-albumin) in all subjects. Urinary concentrations of transferrin and beta 2-microglobulin strongly correlated in diabetic patients with microproteinuria, while no significant correlation was observed in subjects with diabetic macroproteinuria or non-diabetic proteinuria. Urine/serum (U/S) ratio of %G-albumin in the patients with diabetic proteinuria was significantly lower than that in subjects with non-diabetic proteinuria, while no difference of the U/S ratio of %G-transferrin was observed between any groups. Furthermore, U-%G-transferrin/U-%G-albumin ratio was highest in the diabetic patients with microproteinuria. These results lead to the conclusion that the initial damage in diabetic kidney causing microproteinuria starts with the dysfunction of charge-dependent tubular reabsorption prior to a loss of GCB.
Kunika
K
K
Clinical Laboratory, Kensei General Hospital, Ibaraki, Japan.
Yamaoka
T
T
Itakura
M
M
D000042:Absorption; D000118:Acetylglucosaminidase / Q000652:urine; D000328:Adult; D000368:Aged; D000419:Albuminuria; D003920:Diabetes Mellitus / Q000652:urine*; D004594:Electrophysiology; D005260:Female; D017127:Glycation End Products, Advanced; D006031:Glycosylation; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism / Q000503:physiopathology*; D007684:Kidney Tubules / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D011507:Proteinuria / Q000209:etiology*; D012709:Serum Albumin / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism / Q000652:urine; D001613:beta 2-Microglobulin / Q000652:urine; D000093423:Glycated Serum Albumin
D017127:Glycation End Products, Advanced; D012709:Serum Albumin; D014168:Transferrin; D001613:beta 2-Microglobulin; D000118:Acetylglucosaminidase; D000093423:Glycated Serum Albumin