Factors underlying abnormal zinc metabolism in uremia.

Zinc balance studies were completed in ten hemodialyzed adult uremic patients and five normal controls to determine the cause of abnormal zinc metabolism in uremia. Subjects were fed standard hospital foods providing nutrients in amounts recommended for adult stable hemodialyzed patients. The amount of zinc in the diet was kept constant at 10 mg per day. After one week of stabilization, blood, urine, used dialysate (in patients on dialysis days) and stool samples were collected daily for the next two weeks. In comparison to controls, patients had lower plasma zinc levels (mean +/- SD, 112 +/- 10 vs. 82 +/- 12 micrograms/dl, P less than 0.01), lower urinary zinc excretion (560 +/- 120 vs. 40 +/- 20 mg/24 hrs, P less than 0.001) and higher fecal zinc losses (8.1 +/- 0.7 vs. 10.2 +/- 0.6 mg/24 hrs, P less than 0.01). Dialytic zinc losses were minimal (26 +/- 4 micrograms/treatment). During the study period, patients were in a negative zinc balance while normal controls maintained a positive zinc balance on 10 mg dietary zinc intake. These results demonstrate that augmented fecal zinc excretion in the presence of hypozincemia contributes to the negative zinc balance in hemodialyzed uremic patients.

Elevated plasma copper in chronic renal failure.

Hypercupremia has been described in patients undergoing chronic dialysis. To further characterize dialysis-associated hypercupremia, we studied plasma copper (PCu) and ceruloplasmin (Cp) in patients on hemodialysis (n = 20) and peritoneal dialysis (n = 25), in uremic patients (n = 10) not yet on dialysis, and in normal age-matched control subjects (n = 20). PCu was significantly elevated in all three patients groups (mean +/- SD) (20.6 +/- 4.1, 19.8 +/- 4.6, 19.8 +/- 4.9 mumol/L, respectively) vs control subjects (16.5 +/- 2.7 mumol/L). However, Cp levels were not significantly different among the four study groups (330 +/- 60, 320 +/- 70, 370 +/- 100, and 360 +/- 90 mg/L, respectively). Calculated nonceruloplasmin copper was significantly higher in all uremic groups. The measurement of chelatable Cu confirmed the presence of significantly higher extractable Cu in hemodialysis (2.7 +/- 0.6 mumol/L) and peritoneal dialysis patients (2.4 +/- 0.5 mumol/L) than control subjects (1.5 +/- 0.3 mumol/L). Cu is elevated in uremia regardless of dialysis status and this elevation is not accounted for by an increase in plasma ceruloplasmin.

Effect of nonsupressible insulin-like protein on glomerular protein synthesis.

Partially purified preparations of NSILP were evaluated for effect on incorporation of labeled precursors into protein, collagen, and basement membrane by isolated rat renal glomeruli. Dowex-adsorbed NSILP (0.5 mU/mg) inhibited the secretion of protein and collagen and resulted in a significant diminution of incorporation of labeled lysine into glomerular basement membrane. Glomerular protein and collagen secretion were also inhibited in the presence of Sephadex G-200 NSILP (4.5 mU/mg), but an effect on incorporation of radiolabeled proline, hydroxyproline, lysine, and hydroxylysine into glomerular basement membrane was not observed. The in vitro response of renal glomeruli to NSILP constitutes another "insulin-like" effect of this substance.

Somatomedin on insulin-dependent diabetes mellitus.

Somatomedin activity in sera from twelve insulin-dependent diabetics was measured by the chick embryo cartilage assay system. All patients required insulin for control of hyperglycemia, and had been continuously treated with exogenous insulin for 3 to 25 years. Mean fasting somatomedin activity was elevated in this group of diabetics, and activity did not correlate with the simultaneous blood glucose concentrations. No significant differences were demonstrable between levels in diabetics with and without retinopathy or in patients with and without proteinuria.