Zinc-induced enhancement of lymphocyte function and viability in chronic uremia.

Spontaneous and phytohemagglutinin (PHA)-induced lymphocyte blastogenesis (LB) was measured by the incorporation of 3H-thymidine into lymphocytes from zinc-treated (group I) and non-zinc-treated (group II) patients on maintenance hemodialysis and from normal controls. The results were expressed as disintegrations per minute (dpm) per 200,000 cells. Spontaneous LB was comparable in the 3 groups. LB in response to PHA was impaired in group II (mean dpm 28,244 +/- 13,499 SEM) as compared to group I (163,407 +/- 14,325; p less than 0.001) or controls (193,711 +/- 9,406; p less than 0.001). In 5 group II patients the mean dpm rose from (45,630 +/- 26,334 SD to 211,795 +/- 78,231; p less than 0.025) after zinc therapy. The mean percentages of viable lymphocytes after 72 h of culture were 53.8, 85.8 and 85.5 in groups II, I, and controls, respectively. These results clearly indicate that zinc therapy improves lymphocyte function and viability in uremia and suggest that abnormal zinc metabolism may play a role in the impaired cellular immunity in this disorder.

Erythrocytosis in patients on long-term hemodialysis.

Erythrocytosis was seen in two men during maintenance hemodialysis therapy for end-stage renal disease secondary to apparent chronic glomerulonephritis. Nonrenal causes of erythrocytosis such as polycythemia vera, chronic hypoxemia, high-oxygen affinity hemoglobin, and hepatoma were excluded by appropriate clinical studies. A computed tomographic scan of the abdomen showed numerous renal cysts in each patient consistent with acquired cystic disease of end-stage kidneys. Peripheral serum erythropoietin levels were elevated as measured by sensitive radioimmunoassay. The findings suggest that the erythrocytosis is caused by an erythropoietic mechanism related to the diseased kidneys. A review of the literature failed to show previous reports of this clinical association.

Zinc tolerance tests in chronic uremia.

The intestinal absorption of zinc was investigated in 12 control subjects and in 20 patients or maintenance hemodialysis by means of a zinc tolerance test during fasting. Ten patients (Group I) were on long-term vitamin D therapy and 10 (Group II) were not receiving vitamin D. After baseline plasma zinc measurements, a single dose of 50 mg zinc was ingested and plasma zinc levels were measured at hourly intervals for 4 hours thereafter. Peak plasma zinc levels were significantly lower in Group II patients than in controls or patients in Group I suggesting impaired absorption. No significant difference was found between controls and Group I patients. Two patients had normal zinc tolerance tests while on vitamin D therapy, but abnormal tests while off vitamin D. We conclude that the intestinal absorption of zinc may be impaired in chronic uremia, probably secondary to abnormal metabolism of vitamin D.

The effect of zinc on cellular immunity in chronic uremia.

Delayed hypersensitivity to mumps was examined in 25 apparently well-nourished men receiving regular hemodialysis, each of whom had a history of mumps. A positive reaction was observed in eight of nine patients already under therapy with zinc added to the dialysis bath. In contrast, 11 of 16 untreated patients were anergic. Four of the anergic patients were subsequently treated with zinc resulting in restoration of sensitivity in three patients. There were no significant differences in lymphocyte, monocyte, or T-cell counts between the two groups of patients. Consequently, zinc probably acts by improving the function of one or more of these cell types. Protracted zinc deficiency may be a major cause of impaired cellular immunity in chronic renal failure.

Urinary zinc in relation to other cations and flow during volume expansion and intravenous chlorothiazide.

Urinary excretion of zinc, sodium, potassium, and calcium was studied in anesthetized dogs under conditions of volume expansion by saline infusion and volume expansion plus chlorothiazide administration. Zinc excretion was positively correlated to the fractional water excretion, as well as to th excretion of the other cations, during volume expansion. Chlorothiazide administration during volume expansion increased the zinc, sodium, and potassium excretion without changing that of calcium. The enhanced zinc excretion during chlorothiazide diuresis was equal to that expected on the basis of the increase in fractional water excretion alone. The urinary concentration of zinc appeared inversely related to the urine flow rate, reaching a minimum below that of the plasma ultrafilterable zinc concentration. The ratio of the clearance of zinc to that of sodium was 0.28, indicating a greater degree of net reabsorption for zinc than for calcium. These findings suggest that zinc and sodium reabsorption may be inhibited to a similar degree at chlorothiazide-sensitive sites in the tubule. Furthermore, the zinc reabsorptive mechanism seems capable of lowering urinary zinc concentration below that of ultrafiltrate and appears related in some way to sodium reabsorption.

Reversal of uraemic impotence by zinc.

In eight impotent haemodialysed men with low plasma-zinc levels sexual function, including potency, frequency of intercourse, libido, and plasma testosterone, follicle-stimulating hormone, and luteinising hormone levels, was determined before and after therapy with zinc (four patients) or placebo (four patients). Dialytic administration of zinc strikingly improved potency in all patients and raised the plasma-testosterone to normal in the two with low pretreatment plasma-testosterone levels. Placebo did not improve sexual function in any patient. Zinc deficiency is a reversible cause of gonadal dysfunction in uraemia.