Sudesh K. Mahajan

Effect of Oral Zinc Therapy on Gonadal Function in Hemodialysis Patients: A Double-Blind Study

Zinc deficiency may account for the persistence of gonadal dysfunction in a majority of uremic men despite adequate dialysis. Twenty stable patients having hemodialysis three times a week completed a double-blind trial using either 50 mg of elemental zinc as zinc acetate (10 patients) or placebo (10 patients), orally. At the end of the 6-month study period, a significant increase in the mean (+/- SE) plasma zinc (75 +/- 2 micrograms/dL to 100 +/- 2 micrograms/dL, p less than 0.001), serum testosterone (2.8 +/- 0.3 ng/dL to 5.2 +/- 0.5 ng/mL, p less than 0.001), and sperm count (30 +/- 3 million/mL to 63 +/- 5 million/mL, p less than 0.001) occurred in the zinc-treated group, but not in those receiving the placebo. The zinc-treated group also had a significant fall in serum luteinizing hormone (92 +2- 10 mIU/mL to 49 +/- 26 mIU/mL, p less than 0.005) and follicle stimulating hormone (45 +/- 9 mIU/mL to 25 +/- 7 mIU/mL, p less than 0.05), not seen in the placebo group. Patients receiving zinc had an improvement in potency, libido, and frequency of intercourse not found in the placebo group. These results suggest that zinc deficiency is a reversible cause of gonadal dysfunction in patients having regular hemodialysis.

Influenza Vaccination in Kidney Transplant Recipients: Cellular and Humoral Immune Responses

Influenza infection in renal transplant recipients may cause either morbidity and mortality or acute allograft rejection; thus, routine annual influenza vaccination should be considered. We have studied the humoral and cellular immune responses to influenza virus antigens before and after trivalent vaccine administration in 13 patients and 16 control subjects. The patients, nine of whom were either on alternate-day or low-dose daily steroid therapy, showed highly significant serum hemagglutination-inhibition antibody responses to each influenza virus strain, There was no significant change in mean lymphocyte stimulation index to any influenza virus strain after vaccination in either group. There was no correlation in the patient group between hemagglutination-inhibition antibody titer or response, or lymphocyte stimulation index or response, and the degree of allograft function or dose or duration of immunosuppressive therapy. The vigorous antibody response and the evidence of cellular immunity support the efficacy of influenza vaccination in these patients.

Zinc Tolerance Test in Uremia: Effect of Ferrous Sulfate and Aluminum Hydroxide

The effects of ferrous sulfate and aluminum hydroxide on the oral zinc tolerance test after administration of 25 mg of elemental zinc as sulfate were studied in six hemodialysis patients and six normal controls. Fasting plasma zinc levels, the 2-hour plasma zinc peak, and the area under the plasma zinc curve were significantly lower in patients compared with values in controls (plasma zinc, 92 +/- 4 compared with 108 +/- 3 micrograms/dL, p less than 0.025; 2-hour plasma zinc peak, 159 +/- 8 compared with 228 +/- 17 micrograms/dL, p less than 0.025; and area under the curve, 193 +/- 41 compared with 316 +/- 39 micrograms h/dL, p less than 0.025). Ferrous sulfate (300 mg orally), when administered along with zinc sulfate, decreased the area under the curve significantly (in patients by 28%, in controls by 40%) in comparison with the results obtained when zinc sulfate was given alone. When 30 mL of aluminum hydroxide was administered orally with zinc sulfate, the area under the curve decreased by 60% in controls and 75% in patients (p less than 0.005). These results confirm the presence of diminished zinc absorption in patients with renal failure and show that ferrous sulfate and aluminum hydroxide, which worsen this defect, also impair zinc absorption in normal subjects.

Hypoxemia during Hemodialysis Using Acetate versus Bicarbonate Dialysate

To evaluate the extent and cause(s) of dialysis-related hypoxemia, we studied 10 patients, 7 days apart using acetate (AC) and bicarbonate dialysate (HCO3). We measured arterial blood gases, WBC, minute ventilation (VE) and inspired and expired gas concentrations and calculated the respiratory quotient (R) and the alveolar-arterial oxygen difference (A-a)DO2 before and during hemodialysis. 8 patients developed hypoxemia. Arterial PO2 (PaO2) dropped similarly at 30 min from 93 +/- 5 to 78 +/- 6 (p less than 0.05) and 89 +/- 4 to 79 +/- 5 mm Hg (p less than 0.05) with AC and HCO3, respectively. R and VE decreased during AC (p less than 0.05). (A-a)DO2 increased at 30 min and correlated with the drop in PaO2 during both AC (r = 0.68, p less than 0.025) and HCO3 (r = 0.76, p less than 0.025). The fall in PaO2 also correlated with the fall in WBC count for both AC and HCO3 (r = 0.63, p less than 0.005). The increase in arterial pH during HCO3 (up to 7.45 +/- 0.01) was significantly greater than that during AC (up to 7.42 +/- 0.01) (p less than 0.025), and coincided with a relative decrease in VE. We conclude that (1) HCO3 does not prevent hypoxemia, and (2) hypoventilation V/Q abnormalities and increase in arterial pH, contribute variably to dialysis related hypoxemia depending on the type of dialysate and the time during dialysis.

Effect of renal transplantation on zinc metabolism and taste acuity in uremia. A prospective study

The effect of successful renal transplantation on zinc metabolism and taste acuity was determined prospectively in 15 adult uremic patients. Before transplantation all patients had subnormal concentrations of zinc in plasma and hair, as well as abnormal taste detection and recognition thresholds for sodium (salty), sucrose (sweet), hydrochloric acid (sour), and urea (bitter). Following renal transplantation, abnormalities of taste acuity and zinc metabolism persisted and were accompanied by increased urinary zinc excretion in all patients. Normalization of zinc concentration in plasma and hair as well as taste acuity did not occur until one year after transplantation and was associated with a concomitant decrease in urinary zinc excretion. The plasma zinc levels and daily urinary zinc excretion were inversely related (r=0.62, P<.001) in all patients with normal allograft function. None of the zinc parameters was significantly related to azathioprine or corticosteroid dosage. The results of this study suggest that zinc deficiency and taste abnormalities of uremia persist up to one year posttransplant and may be related to increased urinary zinc losses. The mechanisms underlying post-transplant hyperzincuria as well as clinical significance of zinc deficiency following transplantation remain to be determined.

Comparability of Insulin Binding to Erythrocytes and Monocytes from Hemodialysis Patients and Healthy Subjects

Most studies relating alterations in insulin receptor binding to abnormalities of glucose tolerance in humans have used peripheral blood monocytes for the in vitro assay of insulin-binding kinetics. S

Zinc tolerance test in uremia: Effect of calcitriol supplementation

The effect of 1,25(OH)2D3 on zinc absorption was indirectly determined in hemodialysis patients using the oral zinc tolerance test. The increment in plasma zinc and the area under the curve following an oral zinc load of 25 mg were studied in seven patients, before and after 6 weeks of therapy with 1 microgram/day of 1,25(OH)2D3 [Rocaltrol(R)]. Before therapy, fasting plasma zinc, 2 hour plasma zinc, and the area under the curve (AUC) were subnormal (hemodialysis patients vs normals: 96 +/- 2 vs 105 +/- 3 micrograms/dl, p less than 0.05, 161 +/- 8 vs 222 +/- 16 micrograms/dl, p less than 0.025, and 188 +/- 25 vs 302 +/- 33 micrograms hr/dl, p less than 0.025, respectively). Following Rocaltrol, serum calcium level increased (8.9 +/- .12 to 9.8 +/- .4 mg/dl, p less than 0.05), parathyroid hormone levels decreased (20.4 +/- 8.9 to 13.6 +/- 7.2 ng/ml, p less than 0.05), but there was no significant change in fasting plasma zinc, 2 hour plasma zinc, or AUC (89 +/- 3 micrograms/dl, 149 micrograms/dl, and 176 +/- 18 micrograms hr/dl, respectively). These results suggest that short-term 1,25(OH)2D3 therapy had no significant impact on zinc absorption or plasma zinc level in uremics.

Glucose Tolerance, Insulin Release, and Insulin Binding to Monocytes in Kidney Transplant Recipients

In order to evaluate glucose tolerance following renal transplantation, intravenous glucose tolerance tests (IVGTT), with evaluation of hormonal responses to the intravenous glucose load and percent specific 125I-insulin binding to peripheral blood monocytes, were studied in eight clinically stable kidney transplant recipients. For comparison purposes, identical studies were done in eight control subjects and seven clinically stable hemodialysis patients. One transplant recipient was glucose intolerant, with fasting hyperglycemia, elevated HbA1C, and abnormal glucose decay constant. Impaired pancreatic insulin release appeared to be the major factor accounting for his glucose intolerance. The seven glucose-tolerant transplant recipients had significantly increased insulin release during IVGTT compared to control subjects, and significant correlations were found among insulin release, glucose decay constant, and fasting blood sugar in those patients. Insulin binding to monocytes was significantly greater in transplant recipients than control subjects due to an increase in insulin binding capacity per cell. A significant correlation was found between percent specific 125I-insulin binding and steroid dose, expressed as mg/kg body weight/day, in those patients. Thus, chronic steroid administration does not cause glucose intolerance in transplant recipients who manifest steroid-associated increases in pancreatic insulin release and cellular insulin binding capacity.