Renal handling of Zn α2 glycoprotein as compared with that of albumin and the retinol binding protein

Abstract

An unusual electrophoretic pattern of the urine from a patient with malignant lymphoma was observed. One of the major proteins, identified as Zn α2 glycoprotein (Zn α2), was isolated from the urine and partly characterized. The Stokes radius was found to be 3.24 nm and the molecular weight, determined by sodium dodecyl sulfate polyacrylamide electrophoresis, 42,000. The plasma level in healthy individuals was 39±7 (SD) mg/liter. In 12 of 25 healthy individuals, Zn α2 was measurable in the urine and was found to be 1.0±1.1 mg/liter. In 23 patients with chronic glomerulonephritis (CGN), in 9 with proximal tubular dysfunction (PTD), in 23 with various diseases (VRD), and in 10 with malignant lymphoma, the plasma level and the urinary excretion were compared with those of albumin (mol wt 67,000) and of the retinol binding protein (RBP, mol wt 21,000). A close correlation was found between the urine to plasma (U/P) ratios of Zn α2 and albumin in the patients with CGN, whereas in the PTD patients the U/P ratios of Zn α2 and RBP were correlated. No significant renal arteriovenous difference in Zn α2 could be demonstrated. The Zn α2 excretion was increased also in two patients with malignant lymphoma and proteinuria of a tubular pattern. The plasma Zn α2 varied inversely with the glomerular filtration rate in the patients with renal disease, but was normal in those with malignant lymphoma. The results are consistent with the assumption of a sieving coefficient of Zn α2, substantially exceeding that of albumin, but notably lower than that of smaller low molecular weight proteins. An increased excretion of Zn α2 may be due to increased glomerular permeability as well as to defective proximal tubular reabsorption.