Effects of intercurrent illnesses on nitrogen metabolism in uremic patients.
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Biomedical subjects
Publications and source records attributed to M J Blumenkrantz.
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The application of sorbent technology to the treatment of uremia has been limited by the inability to adsorb urea adequately. Conversion of urea to ammonium carbonate and adsorption by zirconium phosphate provides a practical means of removing urea. This combination, together with hydrated zirconium oxide and carbon, removes uremic waste products from dialysate. Over 1500 patients are undergoing maintenance hemodialysis with this system. The dialysate composition can be modified for the treatment of patients with acute renal failure. This sorbent system is now being used for the regeneration of peritoneal dialysate. Twenty patients have undergone a total of 90 dialyses, each of 4 to 24 hours duration. One home patient has been solely on this system for two months. The application of sorbent technology to peritoneal dialysis may be the most promising approach to a wearable dialysis system.
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Obtaining informed consent for clinical investigations represents a major legal, ethical, and moral consideration in human experimentation. Mechanisms for informing the patient vary widely, and usually no system exists to confirm the degree of information retained by the patient. A Veterans Administration Cooperative Study, begun in 1975, has used a videotape information package in addition to a standard written consent form to ensure uniformity. Each presentation was followed by a questionnaire to assess the amount of material learned before attempting randomization. Repeated showings were occasionally necessary and did not affect the rate of randomization. A videotape presentation, especially in cooperative studies, ensures uniformity, makes allowance for varying educational levels of patients, and provides documentation of the degree of informed consent.
Fourteen patients are described with a syndrome of methicillin-induced interstitial nephritis. In all patients severe renal dysfunction developed with an average peak serum creatinine of 8 mg/100 ml. An increased total peripheral eosinophil count was found in all patients. All patients had sterile pyuria and each of nine patients studied by Wright's stain of urine sediment had marked eosinophiluria. These findings are suggestive of methicillin-induced interstitial nephritis, although proteinura was a variable finding in our patients. Eight of 14 patients in our study received prednisone therapy for their interstitial nephritis, and the time lapse between maximal and final base line serum creatinine levels was statistically less in the prednisone-treated compared to the nontreated groups. Clinical manifestations of this syndrome are discussed, and the light and electron microscopic and immunofluorescent findings on renal biospy are described.
In the United States, 10,000 to 18,000 new patients require therapy for end-stage renal disease each year. A combination of medical and psychosocial criteria can be used to predict whether renal transplantation or maintenance hemodialysis or peritoneal dialysis may be the most efficacious treatment. In most cases, dialysis therapy should be initiated when signs and symptoms of uremia are only subtle, usually when creatinine clearance is between 3 and 6 ml/min. One mode of therapy can be exchanged for another to suit changing needs, and vascular access should be created even in patients who ultimately will undergo peritoneal dialysis or receive a transplant.
Malnutrition is frequently present in patients with acute renal failure and may affect morbidity and mortality in this condition. When adequate nourishment cannot be given through the gastrointestinal tract, total parental nutrition with amino acids and hypertonic glucose may have beneficial results. Total parenteral nutrition has been reported to stabilize or reduce serum urea nitrogen, potassium and phosphorus levels, improve wound healing, enhance survival from acute renal failure, and possibly increase the rate of recovery of renal function. The optimal composition of the total parenteral nutrition infusate is unknown. Preliminary results of a double-blind study are reported in which one man received hypertonic glucose alone, two received glucose with essential amino acids (21 g/day), and three received glucose with essential (21 g/day) and nonessential (21 g/day) amino acids. All infusates were isocaloric. No differences were observed in serum urea nitrogen levels, serum urea nitrogen/creatinine ratios or urea appearance rates. Nitrogen balance was negative in all patients. The ratio of essential amino acids/nonessential amino acids were higher and the tyrosine/phenylalanine ratios were lower in plasma in the two patients receiving glucose with essential amino acids. No patient survived the hospitalization. In view of the markedly negative nitrogen balance frequently observed in these and earlier studies, the use of a different composition or quantity of amino acids, a higher energy intake, and anabolic hormones deserve further investigation.
A sorbent regenerative dialysate system for peritoneal dialysis has been developed (Pericycle). Clinical results and data demonstrate that the sorbent system provides a suitable dialysate. The sorbents effectively remove uraemic metabolites from the dialysate. Calcium and magnesium removed by the cartridge and glucose metabolised by the patient are replaced by the infusion system. The machine pumps regenerated dialysate into and spent dialysate out of the patients. A pressure sensor in the patient line prevents excessive inflow and outflow pressures by stopping the inflow or outflow pump respectively. The Pericycle provides a simple, safe, portable method for conducting peritoneal dialysis in the home or hospital.
Until the last few years, maintenance peritoneal dialysis (PD) often was associated with progressive wasting due to frequent episodes of peritonitis, loss of considerable amounts of protein into the dialysate, and poor nutritional intake. Recently, available techniques have made PD a feasible alternative for the long-term care of the patient with end-stage renal failure. The incidence of peritonitis has been markedly reduced, and protein loss is only 4 to 20 gm. per dialysis treatment. Preliminary studies have shown no differences in the nutritional status of patients undergoing PD or hemodialysis, although both groups have evidenced malnutrition. In the patient undergoing PD, daily intakes of 1.2 to 1.5 gm. protein and 35 kcal per kilogram body weight are recommended. During times of stress, parenteral administration of nutrients may be necessary. Dietary supplements may often be required chronically. Careful studies are needed to difine the nutritional needs of the patient undergoing PD.
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Thirty-one patients with Candida isolated from peritoneal fluid were examined. Twenty-two were considered to have Candida peritonitis. The data on these 22 patients, plus 12 additional patients described in the literature, were reviewed. This infection was observed as a complication of peritoneal dialysis, gastrointestinal surgery or perforation of an abdominal viscus. Recent antibiotic administration seemed to be an important predisposing factor. The disease usually remained localized intra-abdominally, although disseminated candidiasis was also noted in three cases. Clinically significant infection could be differentiated from peritoneal contamination with Candida by the presence and persistence of fever, peritoneal signs, peripheral leukocytosis, positive peritoneal cultures for Candida, abnormal films of the abdomen and purulent ascitic fluid. Surgical interventions and removal of infected peritoneal fluid were the cornerstones of therapy. Short-term, low-dose systemic and/or intraperitoneally administered amphotericin B appeared promising in the treatment of unremitting infection. Mortality in treated patients was low and was comparable to that in patients with bacterial peritonitis.
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The effects of supplemental histidine on the anaemia of 16 chronically uraemic patients and 26 patients undergoing maintenance dialysis were assessed. Patients were given either L-histidine 4 g/day or placebo for a mean of 17-5 weeks in a randomized double-blind controlled study. Haemoglobin and packed cell volume increased slightly and to a similar degree in the patients on dialysis receiving placebo and histidine, but this change was statistically significant only in those on placebo. Plasma histidine rose significantly in the histidine-treated patients undergoing dialysis and decreased in the uraemic patients receiving placebo. These results suggest that supplementary L-histidine in patients with uraemia or patients undergoing maintenance dialysis does not improve anaemia.
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