Biomedical subjects
Publications and source records attributed to K D Nolph.
This article summarizes highlights of data from the National Institutes of Health Continuous Ambulatory Peritoneal Dialysis Registry Report released in early 1984. Follow-up data for 6,656 patients were collected from January 1981 through June 1983 and were analyzed for this report.
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Over a four-year period, 50 patients underwent continuous ambulatory peritoneal dialysis. After 24 months, 48 percent of the patients continued to receive continuous ambulatory peritoneal dialysis treatment (including those who underwent continuous ambulatory peritoneal dialysis with bottled solutions from 1977 to 1978). Using solutions in plastic bags, 63 percent of patients continued to undergo continuous ambulatory peritoneal dialysis after 24 months. The mortality rate at 24 months was 23 percent overall and 15 percent for those using plastic bags. There was an overall average of 2.4 episodes of peritonitis a year per patient and 1.3 episodes a year per patient from 1979 through 1980, when only the technique with plastic bags was used. The number of days a patient was hospitalized averaged 48 per year, and 37 days per year in 1979 and 1980. Fifty-five percent of catheters remained functional at 24 months. Other complications included 15 hernias, 15 skin and tunnel infections, 12 leaks, and five cuff extrusions. Improved catheters and further reductions in the incidence of peritonitis will most likely result in a decreased number of patients who withdraw from continuous ambulatory peritoneal dialysis therapy.
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Peritoneal clearance studies were performed in rats undergoing acute peritoneal dialysis. Some of these animals were then exposed to laparotomy and mechanical drying of the peritoneum. Peritoneal clearance studies were repeated at intervals up to 11 days. Another group of rats was placed on daily peritoneal dialysis and allowed to spontaneously develop peritonitis which was not treated. These rats underwent peritoneal transport studies at differing durations of infection. In all groups, animals were sacrificed at the time of the last transport studies for morphological assessment of the peritoneum by light microscopy, scanning electron microscopy, and transmission electron microscopy. The results showed similar decreases in drainage volume and increases in glucose absorption and protein losses with both infection and drying. Both types of injury resulted in extensive mesothelial structural changes. While drying caused mainly denudation of the mesothelial surface, infectious peritonitis was associated with separation of mesothelial cells, and the appearance of numerous white blood cells between and on mesothelial cells. Exposure to peritoneal dialysis alone had no obvious effects on anatomy. Although changes in the peritoneal microcirculation and deeper structures cannot be excluded as contributing to peritoneal transport alterations, the findings suggest that alterations of mesothelium might explain some of the changes in peritoneal transport properties under the conditions of these studies.
Intra-abdominal pressure (IAP), forced vital capacity (FVC), and forced expiratory volume at 1 sec (FEV1) were measured in 18 stable continuous ambulatory peritoneal dialysis (CAPD) patients maintained on 2-liter exchanges, in the supine, sitting, and upright positions after infusing dialysis solutions in 0.5-liter increments up to 4 liters as tolerated. Thereafter, five patients did not increase to 3-liter volumes (RUT-0), four used 3-liter volumes occasionally (RUT-1), and nine chose 3-liter volumes for routine dialysis (RUT-2). IAP was similar in all groups and dependent on the intraperitoneal volume (IPV). The mean IAP increased 2.0, 2.7, and 2.8 cm H2O/liter of IPV in the supine, upright, and sitting positions, respectively. The patients of the RUT-0 group had dramatic deterioration (up to 42%) of FVC and FEV1 in the supine position with IPV above 2 liters. The patients with the greatest deterioration of pulmonary functions could not continue the measurements above 3 liters of IPV. Two of these patients were switched to 1-liter overnight exchanges. Even in patients who tolerated up to 4 liters, FVC and FEV1 decreased significantly in the supine and sitting positions, with IPV greater than 3 or 4 liters, respectively. In the upright position, the values did not decrease significantly below those with the empty abdomen up to 4.6 liters of IPV. Each liter of IPV increased the abdominal girth by 2.1 cm. Exchange volume and frequency should be individualized. In our studies, 50% of the patients could increase daily dialysate volume from 8 to 9 liters while decreasing daily exchanges from 4 to 3.
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Peritoneal dialysis solutions contain glucose as an osmotic agent to obtain ultrafiltration. Due to rapid absorption, glucose does not sustain high ultrafiltration during long exchanges. Nonabsorbable polyanions might be effective as osmotic agents when suspended in electrolyte solution. Concentrations of freely diffusible ions should be in Gibbs-Donnan equilibrium with plasma electrolytes. The ideal proportion of diffusable to polymerbound cation concentrations is unknown. To obtain concentrations of free ions in equilibrium with plasma, it is assumed that the polymer solution dialyzed against a polyelectrolyte solution of the desired composition (with hydraulic pressure higher on the polymer side) will approach the same thermodynamic activity as the electrolyte solution. Subsequently, if transmembrane pressure is released, osmotic ultrafiltration will occur in proportion to the hydrostatic pressure applied during polymer solution preparation. Polyacrylate solution so prepared was compared with a commercial dextrose dialysis solution in an in vitro simulation of peritoneal dialysis. With dwell times up to 24 h, sustained ultrafiltration with polymer was observed, whereas, with dextrose, ultrafiltration ceased after 8 h. Concentrations of diffusible bivalent cations in polyacrylate were lower than intended due to avid polymer complexing; however, dextran sulfate solutions were developed to contain desired concentrations of diffusible electrolytes. The conclusion is that some polymer solutions might be useful in clinical settings when high sustained ultrafiltration is needed.
In 71 patients (41 men, 30 women) with advanced renal failure maintained on hemodialysis (HD), continuous ambulatory peritoneal dialysis (CAPD), or within 8 weeks after the commencement of dialysis therapy (ED), studies were performed searching for evidence of serositis and the blood levels of circulating immune complexes (CIC), measured by the polyethylene glycol precipitation method. Mean CIC levels were elevated in these patients compared to the 58 healthy subjects (mean +/- SEM 725 +/- 40, and 260 +/- 34 micrograms/ml, respectively). Serositides were significantly more prevalent in ED patients compared to both remaining groups, and tended to occur less frequently in CAPD than in HD patients. CIC levels were significantly lower in CAPD than in ED patients. The levels of CIC were significantly higher in patients with serositis compared to those without evidence of serosal inflammation (mean +/- SEM 868 +/- 71 and 677 +/- 53 micrograms/ml, respectively). In addition, immune complex-like materials were found in all of 4 effusate samples and in 10 of 27 peritoneal dialysates. It is suggested that immune complexes may be the 'uremic toxins' responsible for the serositis of renal failure, and may be secreted into serous effusions. Immune complex-like material can be removed in peritoneal dialysate, which may contribute to the lower CIC levels and lower incidence of serositis in the CAPD patients.
Sham and real trials of peritoneal dialysis were carried out in a double-blind crossover study design to test the efficacy of peritoneal dialysis as a treatment for psoriasis. The criteria for patients included having severe plaque-type psoriasis unresponsive to all conventional therapy including methotrexate. Patients were randomly assigned to 4 weeks of sham or real dialysis, 8 weeks of observation, 4 weeks of alternative real or sham dialysis and 8 weeks of observation. Topical therapy was continued during the trial. Real dialysis was done for 48 hours weekly with 1.5-hour cycle times and 2-litre exchanges by machine. Sham peritoneal dialysis was done recycling the same 2 litres of 1.5% continuous ambulatory peritoneal dialysis fluid with 1.5-hour cycle times for 48 hours weekly. After real dialysis, two patients completely cleared, two patients had greater than 75% clearing, and one patient had no substantial response. None of the five patients had a response to the sham dialysis procedure (p less than 0.01).
A radiotracer method to assess insulin binding to commercially available plastic peritoneal dialysis solution containers was developed. A peritoneal dialysis bag (bag 2) was emptied and attached to another full bag (bag 1) of the same kind. In the syringe-to-bag method, bag 1 was symmetrically injected through the bag wall with four syringes containing dialysis solution and radioactive insulin, with or without regular insulin. The radioactivity in each syringe was measured with a gamma counter before injection, and all of the samples were counted afterwards directly in the syringes. Using a bag-to-bag transfer method, bag 1 was agitated, eight samples were taken from different parts through the wall, and then the contents were transferred to bag 2. Bag 2 was then agitated and eight samples were taken and counted. In the bag-pieces method, pieces of bag wall were cut and the radioactivity on the walls was measured to determine the amount of binding. The syringe-to-bag method gave negative results, severely underestimating the amount of insulin binding. The bag-to-bag transfer method yielded positive results in all instances. Increasing the amounts of regular insulin had no demonstrable impact on percent of binding. When the bag-to-bag method was compared with the bag-pieces method, it gave only slightly higher values; however, the bag-to-bag method was considered more reliable because the counting can be controlled more effectively. A 15-minute delay in sampling was not found to influence insulin binding. A reliable method of assessing insulin binding must be based on the following two principles: (1) The transfer of samples to intermediate containers should be avoided, and (2) radiotracer concentrations in the samples should be similar.
The nature of insulin binding to plastic bags was evaluated to determine if it followed the physical laws of adsorption. To determine whether insulin is adsorbed on a liquid/air interface, the influence of foam in vials of radiolabeled insulin was evaluated. Using a bag-to-bag transfer method, the influence of regular insulin and detergent on radiotracer insulin binding was assessed. To evaluate the reversibility of the binding, bag pieces with bound radioactive insulin were washed with distilled water, detergent, and left to soak in detergent before measuring radioactivity. The radiolabeled insulin was adsorbed in the foam and then released into the bulk of the solution when the foam disappeared; hence, insulin can be entrapped in a liquid/air interface. The addition of regular insulin decreased the binding of the radiotracer insulin to the bag walls. The bound insulin could be removed by washing with water and detergent, but soaking in detergent did not remove a small residual quantity of the bound insulin, suggesting that minimal chemical binding or diffusion of the insulin into the plastic may occur. Insulin binding to plastic bags primarily follows the physical laws of adsorption.
The influence of temperature and time on insulin adsorption to plastic peritoneal dialysis bags was evaluated. A dialysis bag (1.5% dextrose, 2 liters) was injected with 25-microCi insulin I 125 and gently mixed. This bag was then attached to another empty bag of the same type. Following a bag-to-bag transfer method, the amount of insulin adsorbed on the plastic bags was measured at 24 degrees C and 37 degrees C, and after a 12-hour warming period at 37 degrees C. Regular insulin was added to the system in 40-unit increments up to 280 units. Radioactivity in all of the samples was measured in a gamma counter. As the amount of regular insulin increased, the percentage of insulin adsorbed decreased at both temperatures. More insulin was bound at 37 degrees C than at 24 degrees C for all levels of insulin. Data calculated according to the Langmuir isotherm equation showed that the maximum possible values of adsorption to the system at 24 degrees C and 37 degrees C were 17.8 and 18.4 units, respectively. The affinity constants at 24 degrees C and 37 degrees C were 0.0039 and 0.0065, respectively. The influence of prolonged warming at 37 degrees C was minimal. At the usual dosage of insulin (below 40 units) prescribed to the majority of dialysis patients, less than 9% (3.5 units) is adsorbed onto the dialysis bags.
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A patient developed a right pleural effusion soon after starting a program of continuous ambulatory peritoneal dialysis. The etiology of the effusion was unclear. 99mTc-labelled macroaggregated albumin was administered intraperitoneally, followed by 2 liters of dialysate. Trans-diaphragmatic leakage was clearly demonstrated, and confirmed by high count rates of pleural fluid with negligible blood count. This method can safely be used to demonstrate trans-diaphragmatic fluid leakage in peritoneal dialysis patients.
The use of sorbents in dialysate to increase solute clearances in continuous ambulatory peritoneal dialysis (CAPD) was investigated. With in vitro simulations of CAPD, the kinetics of irreversible binding of creatinine to activated charcoal were assessed. Cellulose dialyzer fibers were submerged in two liters of dialysate for 3-8 hour exchanges. Perfusate was pumped single pass through the fibers. Commercial dialysates with 1.5% and 4.25% dextrose as an osmotic agent were controls. Experimental exchanges contained either large or small particles of activated charcoal. Unencapsulated and collodion encapsulated large particles were also studied. From the perfusate side, creatinine, clearance and mass transfer were determined; dialysate/perfusate ratios (D/P) of free creatinine concentrations were assessed. We found that incorporation of small unencapsulated particles of activated charcoal would double both clearance and mass transfer of creatinine. It also maintained D/P values less than 0.6 even up to 8 hours. Small particles absorbed more than 10 times more creatinine per gram than large particles. Significant differences between encapsulated and unencapsulated large particles were not found. In summary, activated charcoal might double creatinine removal per exchange in CAPD. Animal studies of collodion encapsulated small particles and other sorbent-enzyme systems in CAPD dialysate solutions seem warranted.
In five patients, peritonitis caused by uncommon agents was acquired during continuous ambulatory peritoneal dialysis. Three patients had yeast (two Candida albicans, one C parapsilosis), one Aspergillus fumigatus, and one Nocardia asteroides infections. A review of the literature indicates that yeasts are the most common cause of peritoneal dialysis-associated fungal peritonitis; only one other possible case of Aspergillus sp and no Nocardia infections have been proved, to our knowledge. Observations are recorded in reference to diagnosis and suggested methods of treatment.