Hypogeusia is a reported side effect of captopril. Linkage of hypogeusia to zinc deficiency has been suggested. We objectively assessed taste acuity using Henkin's three-drop stimulus technique and measured plasma zinc (PZn) level and urinary zinc excretion in 31 hypertensive patients. Of these, 11 were long-term, high-dose captopril recipients (more than 6 months, 266 +/- 34 mg/day), six were short-term captopril recipients (less than 6 months, 104 +/- 40 mg/daily dose), and the remaining 14 served as noncaptopril controls. Compared to controls, the long-term captopril group had significantly higher taste detection and recognition thresholds, lower PZn (91 +/- 3 vs. 100 +/- 3 micrograms/dl, P less than 0.05) and higher urinary zinc excretion (1017 +/- 89 vs. 609 +/- 76 micrograms/day, P less than 0.005). The short-term captopril group did not differ significantly from the noncaptopril group except for higher taste-recognition thresholds for NaCl and sucrose (P less than 0.05). Discontinuing captopril improved taste acuity and almost normalized zinc parameters in two patients on long-term captopril. These results suggest that abnormalities of taste are commonly associated with captopril therapy and may be related to changes in zinc metabolism. This is especially true in patients on long-term, high-dose captopril therapy.

Zinc clearance studies in anesthetized dogs were performed during hydropenia, mannitol infusion, and infusion of mannitol plus ZnSO4, ZnCL2, or cysteine. Mannitol expansion caused no significant change in Zn clearance. ZnSO4 infusion increased filtered Zn 13-fold without changing clearance. Zn excretion increased only sixfold, indicating increased net Zn reabsorption. Cysteine infusion increased urinary Zn excretion 86-fold, indicating net tubular Zn secretion, some of which derived from nonplasma sources. Stop-flow studies localized Zn reabsorption to the distal nephron during infusion of mannitol and mannitol plus ZnSO4 or ZnCl2. Net Zn secretion was shown to occur in the proximal tubule during cysteine infusion with reversal of the distal reabsorption pattern seen during ZnSO4 and ZnCl2 infusion. Despite increased urinary Zn excretion during ZnSO4 infusion, calcium excretion was unaltered. During cysteine infusion dissociation of tubular handling of CA2+ and Zn occurred in both the proximal and distal tubule. These experiments demonstrate that the nephron under these experimental conditions is capable of both proximal secretion and distal reabsorption of Zn.

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.

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.

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 (V_E) and inspired and expired gas concentrations and calculated the respiratory quotient (R) and the alveolar-arterial oxygen difference (A-a)DC·2 before and during hemodialysis. 8 patients developed hypoxemia. Arterial PO₂ (PaO₂) dropped similarly at 30 min from 93 ± 5 to 78 ± 6 (p < 0.05) and 89 ± 4 to 79 ± 5 mm Hg (p < 0.05) with AC and HCO₃, respectively. R and V_E decreased during AC (p < 0.05). (A-a)DC·2 increased at 30 min and correlated with the drop in PaO₂ during both AC (r = 0.68, p < 0.025) and HCO₃ (r = 0.76, p < 0.025). The fall in PaO₂ also correlated with the fall in WBC count for both AC and HCO₃ (r = 0.63, p < 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 < 0.025), and coincided with a relative decrease in V_E. We conclude that (1) HCO₃ does not prevent hypoxemia, and (2) hypo ventilation 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.