Studies on Copper Metabolism. XI. Copper and Iron Metabolism in the Nephrotic Syndrome 1

Abstract

The metabolism of copper and iron in the nephrotic syndrome has received little attention. In view of the fact that copper in the plasma is bound almost exclusively to an a2-globulin (ceruloplasmin) with a molecular weight of approximately 151,000 (1, 2) while iron is bound to a #l,-globulin (transferrin) with a molecular weight of about 90,000 (3), it would seem not unlikely that these two metal-binding proteins might be excreted in large quantities in the urine of patients with pronounced proteinuria. If this loss were great and extended over a prolonged period, it is conceivable that depletion of the body stores of these two elements might occur or the capacity of the body to synthesize these two proteins might be exceeded, with the consequence that the plasma level of ceruloplasmin and transferrin would be reduced.In the course of investigations in this laboratory concerning the anemia associated with infection (4), a patient was studied who, while afflicted with chronic osteomyelitis, developed the nephrotic syndrome. In association with the severe hypoproteinemia and proteinuria, the plasma copper level decreased from 246 ug. per 100 ml., the high levels usually found with infection, to 40 JUg. per 100 ml. in'spite of the continued presence of osteomyelitis. More recently (5) we observed hypocupremia in two of three children with the nephrotic syndrome. Munch-Petersen (6) has reported that the urinary excretion of copper is increased in patients with proteinuria and that the amount of copper excreted is greatest in those with the highest concentration of protein in the urine. Although he did not record the plasma copper values he stated that there was no correlation between the plasma copper concentration and the amount of copper in the urine.

Studies on Copper Metabolism. Xiv. Copper, Cerulo-Plasmin and Oxidase Activity in Sera of Normal Human Subjects, Pregnant Women, and Patients With Infection, Hepatolenticular Degeneration and the Nephrotic Syndrome 1

“…per of 108 ,ug/per 100 ml. corresponds well with the normal mean determined previously in this Pregnancy laboratory in a much larger group (14). LikeStudies were made in 10 women.…”

“…In 1951 an apparently normal and healthy 28-year-old male physician was found to have a plasma copper level of 68 ug per 100 ml. This value was the lowest we had found in a total of 228 normal subjects (14,23). Re-examination of the serum of this individual in 1954 and again in 1955 revealed a plasma copper level of 68 and 69 ,ug per 100 ml.…”

“…The methods for the determination of total serum copper (5), the direct-reacting fraction of serum copper (5), urine copper (14), tissue copper (18), and urine protein (14) have been described in previous publications. The oxidase activity of the serum was estimated by the method of Holmberg and Laurell (2) employing paraphenylene diamine as a substrate.…”

“…It is now known that hypocupremia is present in most patients with Wilson's disease (8,12,13) and in some patients with the nephrotic syndrome (14). In Wilson's disease it has been demonstrated that there is a marked decrease in the indirect-reacting fraction of plasma copper and an increase in the direct-reacting fraction (13).…”

“…In 1498 the nephrotic syndrome (14), it has been suggested that the hypocupremia is the consequence of the loss of ceruloplasmin in the urine. Although patients with the nephrotic syndrome have been found to excrete increased quantities of copper in the urine, it has not been demonstrated conclusively that the copper is excreted as ceruloplasmin.…”