John T. Daugirdas

Suppression of neutrophil superoxide production by conventional peritoneal dialysis solution.

The pH of conventional peritoneal dialysis solution is normally in the range of 5.0 to 5.5, because acid has been added during the manufacturing process to prevent caramelization of dextrose during sterilization. We studied the effects of normalizing the pH of conventional peritoneal dialysis solution on superoxide production by normal human neutrophils. At a pH of 6.0, superoxide generation was 4.07±2.56 (SD) nanomoles per million cells. With normalization of pH to 7.4, superoxide production was 19.3± 7.3 (p < 0.001). The results suggest that the unphysiologic acidity of conventional peritoneal dialysis solution has deleterious consequences on neutrophil superoxide formation.

Hyperosmolar Coma: Cellular Dehydration and the Serum Sodium Concentration

Excerpt Nonketotic hyperosmolar coma is a syndrome found mostly in diabetic patients with marked hyperglycemia; the relative pathogenetic roles of hyperglycemia, hyperosmolality, and cellular (espe...

IgE against ethylene oxide-altered human serum albumin in patients with anaphylactic reactions to dialysis☆

We have measured total antibody and IgE directed against ethylene oxide-altered human serum albumin (ETO-HSA) in the sera of 24 patients who have experienced anaphylaxis during hemodialysis and of 41 patients who have not had such episodes during hemodialysis. ETO is used to sterilize dialyzers and other medical equipment. The geometric mean level of IgE to ETO-HSA in patients with reactions (0.9 ng ETO-HSA bound to IgE per milliliter of serum) is significantly higher than in nonreacting patients (0.1 ng/ml, p less than 0.0001). Sixteen of 24 patients with reactions had detectable levels of IgE to ETO-HSA, whereas only three of 41 nonreacting patients had detectable levels (p less than 0.0001 chi-square). The geometric mean level of total antibody to ETO-HSA is also significantly higher in patients with reactions (270 ng ETO-HSA bound per milliliter) than in nonreacting patients (31 ng/ml, p less than 0.0001). Fourteen of 24 patients with reactions but only four of 39 nonreacting patients had total antibody binding of ETO-HSA (p less than 0.0001 chi-square). These data extend our previous observations on a small group of 13 patients receiving hemodialysis (seven patients with reactions, and six nonreacting patients) and clearly demonstrate an association between the presence of IgE or total antibody to ETO-HSA and immediate anaphylactic reactions in this group of 65 patients receiving hemodialysis.

Involvement of Renal Allograft by Fabry’s Disease

A man with Fabrys disease received a renal allograft from a heterozygous sister. Renal allograft dysfunction necessitated an allograft biopsy 5.5 years after transplantation. Extensive accumulation of Fabrys disease deposits in the glomeruli, tubules, blood vessels and interstitium was noted.

Amantadine Hydrochloride Pharmacokinetics in Hemodialysis Patients

To study the fate of amantadine hydrochloride in patients with renal failure, we gave 100 mg orally to 12 such patients immediately after hemodialysis. Plasma levels did not decrease between 24 and 44 hours after drug ingestion, suggesting an extremely poor total body clearance. Apparent volume of distribution was 5.1 +/- 0.2 (SEM) L/kg of body weight. Between 44 and 48 hours, as a result of 4 hours of hemodialysis, the mean plasma drug level decreased from 268 to 225 ng/mL (P less than 0.001). Dialyzer clearance was 67.0 +/- 3.9 mL of plasma per minute. The total quantity of drug removed by the dialysis treatment, however, was only 3.9 +/- 0.25 mg. The average half-life of amantadine in eight patients studied while receiving maintenance hemodialysis was 24.3 +/- 2.4 h of dialysis administered over approximately 13 days. Plasma half-life in six nonuremic control subjects was 12.2 +/- 1.6 h. Amantadine is poorly excreted in dialysis patients and has a large volume of distribution. The amount removed by a single dialysis is only a small fraction of the total body store.

Poststreptococcal Crescentic Glomerulonephritis in a Patient with Preexisting Membranous Glomerulonephropathy

An adult male with idiopathic membranous glomerulonephropathy who developed crescentic glomerulonephritis after an episode of streptococcal pharyngitis is described.

Plasma Protein-Binding of Amantadine in Maintenance Hemodialysis Patients

Mean 267.6±58.7 109.0±24.2 40.9±6.2 59.1 ±6.1 REFERENCES It can be seen that in azotemic plasma, approximately 40% of amantadine is present free whereas the remaining 60% is bound to plasma proteins. Thus, amantadine behaves similarly to other basic drugs which show an affinity for plasma proteins (7). Because amantadine is largely protein-bound, the plasma free drug fraction rather than the plasma total drug level might be the more useful guide to optimum dosage in patients with renal functional impairment.

Treatment of refractory hemodialysis ascites with maintenance peritoneal dialysis.

In 5 patients who were receiving maintenance hemodialysis, ascites developed that was refractory to treatment by ultrafiltration during hemodialysis. Use of sequential isolated ultrafiltration and hemodialysis therapy either precipitated side effects or else required prolongation of total treatment time which the patients declined to accept. In 4 of the patients, ascites was believed to be primarily responsible for severe, progressive cachexia. Maintenance peritoneal dialysis was instituted in all patients, and abdominal fluid was removed gradually, over a period of 2 to 3 days. Ascites resolved promptly in each case. Three patients noted a dramatic improvement in appetite after relief of abdominal distension. Follow-up periods ranged from 6 to 4 1/2 years. Our results suggest that maintenance peritoneal dialysis can successfully control hemodialysis ascites.

An Alternate Base for Hemodialysis: The Promise of l-Lactate

Acetate dialysis solution, especially when used in a high-efficiency dialysis setting, has been associated with hypotension and with symptoms such as nausea, vomiting, and fatigue (1, 2). At present, bicarbonate is the dialysis solution base of choice in highefficiency dialysis. Bicarbonate, however, has prob lems as well, such as the requirement for a relatively complex dual concentrate delivery system adding to the cost of dialysis. In addition, the danger of bacterial contamination exists with bicarbonate concentrate solutions (3, 4). The thinking of the dialysis community with regard to potential bases has been largely bipolar: the choice is either acetate or bicarbonate. However, it has long been recognized that bicarbonate-generating compounds other than acetate are available. Liang and Lowenstein ( 5 ) found that the infusion of pyruvate into dogs was associated with less cardiovascular effects than that of acetate. Wathen et al. (6) demonstrated the bicarbonate-generating ability of pyruvate and m-lactate infused into anesthetized dogs while Gonzalez et al. (7) made similar observations with intravenous succinate. During the past several years, our group has focused on the possibility of using lactate as a dialysis solution base. Our interest in lactate began with studies of the vasorelaxant effects of various potential bicarbonate-generating bases in isolated vascular tissue. In the rat caudal artery, we found that lactate caused far less vasorelaxation than acetate (8). In other studies, we confirmed that acetate has potent vasodilator (9, 10) and cardiodepressant effects (1 1) at concentrations commonly achieved during dialysis. In conscious dogs, acetate, when used in a dialysis setting, and with plasma acetate levels of only 2 to 3 mM, was associated with a substantial decrease in total peripheral resistance. In fact, in sympathectomized dogs, acetate dialysis, but not ’ bicarbonate dialysis, was associated with transient cardiovascular collapse (12). All of these findings suggest that use of alternative agents to acetate may be beneficial. We began feasibility studies in patients using DLlactate as a dialysis solution base. We found that a dialysis solution containing 40 mM DL-lactate resulted in insufficient correction of acidosis ( 13, 14). A reduction in symptoms with lactate was not found

Preventing Influenza in Chronic Renal Disease

Theoretically, vaccination could worsen certain kinds of renal disease by stimulating the immune system, but this fear has not been substantiated by clinical experience, Thus in a study of 36 children with various forms of renal disease, Sheth et al, found that a bivalent vaccine did not precipitate proteinuria in any of the 29 patients who initially had normal protein excretion levels; while of seven children with proteinuria, four developed a transient rise in protein excretion, returning to pre-immunization levels within one week (3), In adult patients with renal insufficiency, Pabico et aL also found no deterioration in renal function (4), Influenza vaccines have been given to patients suffering from systemic lupus erythematosus (with or without lupus nephritis); the incidence of influenza-like illnesses after immunization was no higher than that in healthy control subjects, and no major flares of systemic lupus erythematosus itself were encountered (5-8). The interesting association between virus infection and renal allograft dysfunction (9-13) calls into question the safety of immunizing renal allograft recipients with influenza virus products. For example, Briggs and associates reported an outbreak of influenza in a renal transplant unit; of 5 transplant recipients contracting influenza infection, 3 developed acute allograft dejection (12). However, influenza vaccines have been given to many transplant recipients with no significant adverse effects (14-16) one possible exception being an inci-