James A. Pederson

Relief of Idiopathic Generalized Pruritus in Dialysis Patients Treated with Activated Oral Charcoal

The effect of oral charcoal on idiopathic generalized pruritus in 11 stable patients undergoing maintenance hemodialysis was compared to that of placebo dextrose in a controlled, double-blind, cross-over study. Contrasted to placebo, charcoal, 6 g daily for 8 weeks, relieved pruritus subjectively in all but one patient (P = 0.01). Symptomatic relief from pruritus coincided with objective resolutions of active, scratch-induced skin lesions (P = 0.03). No significant alterations were noted in the serum concentrations of standard laboratory variables, including lipids, alkaline phosphatase, phosphorus, or calcium, during treatment with either charcoal or placebo. No adverse effects from the charcoal were noted during the study.

Chronic renal failure, dialysis, and neuropsychological function.

Hemodialysis patients, nondialyzed azotemic patients and control subjects with chronic physical disabilities were tested in psychometric measures of attention, memory, and visuomotor speed and coordination. There was relatively little difference between the performance of dialysis patients and controls and no significant correlations were found between years of dialysis treatment and performance on any task. In contrast, nondialyzed azotemic patients were impaired on 9 of 14 tasks relative to controls and/or dialysis patients. Measured levels of blood urea nitrogen (BUN) and serum creatinine were significantly correlated with the performance of nondialyzed azotemic patients on several tasks. These results demonstrate a relationship between degree of renal failure and cognitive and perceptual-motor functioning. The mild impairments evident in dialysis patients do not seem to be directly attributable to dialysis treatments. Rather, the onset of hemodialysis appears to have beneficial effects on neuropsychological function.

Apophysomyces elegans infection in a renal transplant recipient.

A 50-year-old cadaveric renal transplant recipient on immunosuppressive therapy is described with post-traumatic cutaneous infection caused by Apophysomyces elegans. He showed no evidence of hematogenous dissemination and recovered fully after therapy with extensive local debridement and amphotericin B lipid complex. An apparent drug-drug interaction between amphotericin B lipid complex and cyclosporine was encountered. The course of A elegans infection in transplant recipients may be similar to that described in immunocompetent hosts. A elegans infection should be considered in evaluation of post-traumatic cutaneous infection not readily responsive to antibacterial therapy.

Cefazolin Plasma Concentrations and Urinary Excretion in Patients with Renal Impairment

C EFAZOLIN is a new 7-aminocephalosporanic acid antibiotic active against various Gram-negative and Grampositive bacteria. Previous studies in man and animals without renal impairment demonstrated that the drug is primarily excreted by the kidneys, although approximately 3 per cent of the drug is excreted in bile.1’2 This study was performed to determine the effect of declining renal function on cefazolin plasma concentration, half-life, and urinary excretion. In addition, the effect of hemodialysis on plasma concentration and half-life was measured.

Effect of CAPD on Renal Osteodystrophy in Unmodified Patients Moving from Hemodialysis to CAPD

The effect of one year of CAPD on bone histology was studied in seven hemodialysis patients changing to CAPD. The course of these patients was not modified by oral calcium supplements, vitamin D or parathyroid ablation. An existing pattern of dialysis osteomalacia in three patients changed in two to osteitis fibrosa. This change was associated with decreased stainable aluminum in the bone biopsies obtained during CAPD. The specific role played by CAPD in effecting this change is uncertain. Progression and development of osteitis fibrosa in these patients was not prevented by a 7.0 mg/dl calcium containing dialysis solution. The observed persistence of abnormally high parathyroid hormone levels and increasing alkaline phosphatase concentrations supports the concept that a negative calcium balance may be a critical factor in progression of osteitis fibrosa among CAPD patients.

1618 CELLULAR MALNUTRITION IN UREMIA

Some of the cellular abnormalities of severe protein-calorie malnutrition in children (PCM), e.g., reduced energy-related enzyme activities, energy and protein synthesis levels and intracellular amino acid deficits, are also thought to occur in chronic uremics. Improvement of these abnormal cell bioactivities, characterizing cellular malnutrition, should stabilize and possibly retard progressive cellular deterioration in uremics. We have used the circulating granulocyte as a cell model to study energy-related enzyme activities (pyruvate kinase (PK), phospho-fructokinase (PFK), adenylate kinase (AK), energy charge (Ech=ATP+0.5ADP/(ATP + ADP + AMP)), protein synthesis (3 H-leucine incorp.) and amino acid pools in 52 adult uremics (9 not dialyzed (ND), 40 hemodialyzed (HD) and 13 peritoneally dialyzed (CAPD)) and 61 normal control (C) subjects. Gross clinical estimators of chronic malnutrition (Wt/Ht ratio, skinfolds, arm muscle area, plasma albumin and total lymphocyte count) were within normal limits for the dialyzed uremics. In the ND uremics, all clinical and cell measures were abnormal. In the HD uremics, cell PK, AK, ATP, Ech and PS were significantly (p < .05) better than ND but less than C. A significant reduction in branched-chain amino acids (BCAA=valine, leucine, isoleucine) and methionine (MET) were noted in both ND and HD patients. In the CAPD patients, after 18 ±9 (SD) months of dialysis PK, PS, BCAAs and MET levels were normalized. Ech was 90% of normal and >HD, but ATP and AK were not improved. We conclude that cellular malnutrition occurs in apparently stabilized adult uremics without clinical signs of malnutrition. CAPD seems to improve many cell bioactivities, and therefore, cellular malnutrition in uremics.

PROTEIN SYNTHESIS, ENERGY LEVEL AND CELL AMINO 1617 ACID IMBALANCE IN CHRONIC UREMICS

To improve protein synthesis (PS) and Energy charge (Ech) should require correction of imbalanced intracellular amino acid levels. In 40 adult chronic uremics stabilized by hemodialysis, multiple regression analysis identified combinations of cell amino acid levels predicting intracellular PS (3 H-Leucine incorp) (PS=10.8 + 0.02 ASP -0.127 VAL + 0.54 ILE + 0.032 ORN -0.12 LYS -0.10 TRP (R2= 0.40, p=0.019)) and Energy charge (Ech=ATP + 1/2 ADP/ATP + ADP + AMP) (Ech (x 103) = 766 -0.75 ASP + 0.18 GLU + 0.59 GLY + 0.53 ORN -0.33 ARG (R2=0.33, p=0.036)). PS and Ech were reduced compared to 32 normals. The leukocyte (∼90% Pm neutrophils) was used as the cell model. 18 adult chronic uremics, stabilized on 3x/wk hemodialysis, were infused with 500ml 10% amino acid solution after each dialysis, dialyzer detached, for 3 months, receiving in toto ≅ 1.5-1.9kg synthetic amino acids. Baseline studies showed decreased (p<.05) PS, Ech and in vitro glycolytic flux (glucose → lactate). The amino acid infusions led to decreased blood pressure and plasma cholesterol level, but did not significantly improve cell bioactivities. The intracellular amino acid imbalance worsened: valine, isoleucine, leucine, methionine, lysine and ornithine were reduced; arginine + glycine were increased. Only tyrosine and phenylalanine levels normalized. We ascribe failure to correct cell bioactivities to failure to correct the cell amino acid imbalance. The leukocyte is a useful cell model to formulate and evaluate therapies to correct abnormal cell metabolism in uremics.

1525 CELL FUNCTIONS IN UREMIA IMPROVED BY DIALYSIS AND AMINO ACID INFUSIONS

Chronic uremia is often associated with impaired utilization of glucose, presumably intracellularly, since it is not dependent on insulin or insulin redeptors. Using the circulating polymophonuclear leukocyte (PMNL) as a cell model, 9 nondialyzed & 26 stable, maintenance hemodialyzed adults with chronic uremia (residual Ccr < 5ml/min) had significantly reduced levels of glycolytic enzyme activities pyruvate kinase (PK) & glucose -6-PO4 dehydrogenese (G6PDH), ATP, & adenylate kinase (AK), protein (3 H Leu) & RNA (3H-URI) synthesis, compared to 32 normal control subjects (blood donors). Following in vitro incubation of isolated PMNL in Krebs-Henseleit medium with 5mM glucose, cell levels of the glycolytic metabolites G6P, F6P, & F-1-6-P were reduced, while DHAP, 3-PGA & PEP were increased, indicating a perturbation in glycolytic flux (GF), although lactate production was not impaired. Hemodialysis improved AK activity & protein synthesis (PS), but G6PDH & ATP decreased. Lactate production by incubated PMNL fell. The postdialysis changes reverted to predialysis values within 1 week. Stable maintenance hemodialysis patients got 500ml amino acid infusions (AAI) (Aminosyn 10%) at the end of each 3×/week dialysis. After 12 infusions (1 month), predialysis ATP levels & PS reached normal levels. GF lactate production was unaffected but triose phosphate levels increased. To the extent that PMNL s reflect cell metabolism, the data is consistent with a cellular defect in glycolysis & protein synthesis in chronic uremics. Dialysis, coupled with AAI, improves cell functions.