Abstract
The use of plasma proteins for the diagnosis and management of various diseases in humans has been known since the days of Hippocrates. Recently, a new protein, Urine protein 1 (UP1), has been isolated by Dakopatts Immunoglobulin, Copenhagen, from patients with renal tubular dysfunction. This study reports an investigation into the clinical significance of the protein. The purification, antibody production and semi-characterisation of the protein has also been undertaken. A sensitive, reproducible enzyme-linked immunosorbent assay has been set up and validated for the estimation of UP1. UP1 has been shown to be a stable, negative, low molecular weight (LMW) glycoprotein, with alpha-2 electrophoretic mobility on cellulose acetate. It is suggested that the protein be called alpha-2 glycomicroglobulin (a[2]GM). a[2]GM has been shown to be synthesised in the liver, and, like many other LMW proteins, cleared by the glomeruli, reabsorbed and catabolised mainly by the proximal convoluted tubules. It shows no acute phase reaction, and its serum levels are not significantly affected by pathological states such as myeloma, Hodgkins disease, leukaemia and teratoma, unless there is associated impairment in renal function. Patients with end-stage renal failure showed the highest serum increases. Serum levels of a[2GM were not found to be significantly affected by haemodialysis. Clinically, a[2]GM has been shown to be useful in the diagnosis and assessment of the course of progression of renal disease. It has also been demonstrated that a[2]GM has great potential in the identification, characterisation and monitoring of rejection episodes, and in the assessment of allograft function. Compared to other LMW plasma proteins, a[2]GM indicated clearly superior sensitivity and may be useful in monitoring tubular function in cancer patients on cisplatin chemotherapy. a[2]GM has also been shown to be a useful analyte in the assessment of early renal tubular involvement in diabetics.