URINARY-EXCRETION RATE OF CERULOPLASMIN IN NON-INSULIN-DEPENDENT DIABETIC-PATIENTS WITH DIFFERENT STAGES OF NEPHROPATHY

The level of ceruloplasmin, which is a more negatively charged protein than albumin, was measured by an immunoradiometric assay in timed ove rnight urine and serum samples from patients with noninsulin-dependent diabetes mellitus and healthy controls. None of the plasma proteins e xamined showed any cross-reactivity in this assay. A linear correlatio n was seen between the ceruloplasmin level and the serial dilution of the sample. Western blot analysis using concentrated urine samples sho wed that the molecular weight of ceruloplasmin in the urine sample was the same as that of ceruloplasmin in the serum and standard samples. These findings indicated that the substance detected by this assay was truly ceruloplasmin. The urinary ceruloplasmin excretion rate (CER) a nd clearance of ceruloplasmin increased in parallel with the progressi on of albuminuria. The highest CER was found in macroalbuminuric patie nts, followed by micro- and normoalbuminuric patients and the healthy control subjects, the differences between the groups being significant . In view of the fact that the isoelectric point of ceruloplasmin (4.4 ) is more acidic than that of albumin, the present findings suggested that an enhanced CER was due either to the alteration of charge select ivity in the glomerular basement membrane with unaltered tubular funct ion or to a defect of the non-discriminatory pores (shunt pathway) wit h unaltered tubular function.