Presumptive nickel dermatitis from hemodialysis.

Presumptive cutaneous hypersensitivity to nickel administered intravenously during hemodialysis was observed in a patient with nickel sensitivity. The source of the nickel was a 316 stainless-steel fitting that came in contact with 6N hydrochloride during dialysis. An in vitro experiment was performed to demonstrate the ability of nickel to be dialyzed into blood through a standard hemodialysis system. A plasma nickel level 89% higher than that of the original dialysate was achieved with a single cycle of dialysis. This is consistent with the plasma protein binding of nickel.

Clinical studies of a continuous extracorporeal cyanate treatment system for patients with sickle cell disease.

An extracorporeal carbamylation system was evaluated in two patients with sickle cell disease. Access was achieved with existing veins in one patient and an AV fistula in the second. Modifications in the treatment procedure were made as experience indicated. Levels of carbamylation of greater than 1 mol/mol of hemoglobin tetramer were achieved with 4 to 6 hr of treatment every 2 weeks. Cyanate returned to the patient averaged 68.5 mg per treatment. As expected, P50 values decreased and hemoglobin levels increased as the treatment progressed. Patterns of cyanate distribution among the red cell population were those predicted by computer calculations. These observations document the safety and reliability of the treatment system but do not permit conclusions as to efficacy.

Effect of incubation temperature on human red cell survival.

The effect of in vitro response of normal human erythrocytes to temperatures between 41 degrees C and 43 degrees C for two hours was determined. In vivo survival was measured employing 51Cr and 14C-cyanate as red cell tags. No significant difference was observed between cells exposed to these temperatures and erythrocytes incubated at 37 degrees C. The results of this study are of value in various types of extracorporeal blood treatment where an elevated temperature is desired.

Creatinine degradation. II: Mathematical model including the effect of extra-renal removal rates.

Previous models of the patient-artificial kidney system have neglected the contribution of creatinine degradation as a pathway for creatinine removal. Creatinine degradation can remove significant amounts of creatinine from dialysis patients, and models which neglect this mechanism are susceptible to error in predicting creatinine concentrations. In this study three models of the patient-artificial kidney system have been developed. The single pool model is the easiest to use since it requires a minimum of patient information, but it is the least accurate in predicting creatinine plasma concentrations. A two-pool model predicts experimental data within 5 percent, and appears to be the most useful model from the consideration of ease of use and accuracy. A three-pool model was derived that is suitable for use on a mini-computer or programmable calculator providing the device is capable of inverting a 3 x 3 matrix. The three-pool model predicts the measured plasma concentrations with 0.5 percent. These models provide a means to account for creatinine degradation and accurately predict creatinine concentrations in dialysis patients.

Creatinine degradation I: the kinetics of creatinine removal in patients with chronic kidney disease.

The existence of an alternative route of excretion for creatinine in subjects with chronic renal failure has been demonstrated. The data presented in this study confirm the hypothesis that creatinine is converted into other metabolites, probably by action of the gut flora. Creatinine degradation was quantitated in a group of subjects that spanned a wide range of kidney functions from normal to no renal function. Five patients were analyzed who were on maintenance dialysis, five were predialysis and two subjects were normal with respect to kidney function. Creatinine degradation expressed as a percentage of production varied from 13.9 to 27.7% in the dialysis patients, 0 to 42.3% in the pre-dialysis patients and was 0% in the controls. Creatinine degradation was correlated with plasma creatinine degradation was correlated with plasma creatinine levels in predialysis (r = 0.73, p less than 0.01), but not in dialysis patients. No correlation was found between creatinine degradation and production in either group. It is concluded that significant amounts of creatinine are degraded in dialysis patients, and this removal mechanism must be accounted for in models of the patient-artificial kidney system.

Creatinine production rate measured by whole body counting of 40K.

The creatinine production rate in dialysis patients was measured by potassium-40 whole body counting and carbon-14 creatinine injection. The correlation coefficient for the two methods was 0.96, p less than 0.005. An equation predicting whole body potassium (WBK) for normal subjects was found to accurately predict the WBK of dialysis patients as well. Two equations predicting creatinine production from WBK were compared with measured production rates and were found to agree within experimental error. It is thus possible to use the predictive equations to accurately estimate creatinine production without resorting to experimental measurements. These findings should simplify the use of computer models of the patient-artificial kidney system where accurate estimations of creatinine production rates are essential.

Measurement of the carbamylation kinetics and antisickling mechanism in hemoglobin S blood.

The kinetics of HbS carbamylation in whole blood have been investigated under conditions anticipated in extracorporeal treatment systems. The reaction was well represented by a bimolecular, irreversible, second-order mechanism, and the overall carbamylation rate was enhanced by increasing the temperature and decreasing the pH and PO2. An expression was developed to predict the carbamylation rate for a range of experimental conditions. The relative amount of beta chain carbamylation was increased for those conditions under which the overall carbamylation rate was lowered, i.e., lower temperature, higher PO2, and higher pH. Morphological examination of cells with predominantly beta chain carbamylation showed that the antisickling effect, as measured by this technique, could be accounted for entirely by an increase in the oxygen affinity. Although this observation does not exclude an effect independent of change in the oxygen affinity of carbamylated hemoglobin, such an effect, if it occurs, is not detectable by this method. The results of this study were used to design a reaction vessel for an extracorporeal treatment system for sickle cell anemia patients.

Carbamylation distributions in extracorporeal treatment of sickle cell anemia.

The extracorporeal exposure of blood from patients with sickle cell anemia results in the binding of different amounts of cyanate to the hemoglobin of individual erythrocytes. This distribution pattern of carbamylated hemoglobin may affect the efficacy of treatment. A computer model has been developed to predict the carbamylation distribution attained in batch ex vivo exposures. In addition, an autoradiographic technique has been developed whereby the actual distribution pattern of carbamylated hemoglobin in small volumes of blood can be determined. Agreement was demonstrated between the computer model predictions and the actual distribution patterns. The model was applied to published results of extracorporeal treatments of sickle cell patients, and profiles of loading were compared. With the use of such approaches it will be possible to test the importance of the erythrocyte distribution of carbamylated hemoglobin on clinical effects and to design protocols to achieve an optimum distribution. The procedure may be adapted to the distribution of other therapeutic agents as they become available.

Kinetics of the cyanate-hemoglobin reaction in whole blood.

The kinetics of the cyanate-hemoglobin reaction in normal whole blood have been investigated. The mechanism was found to be second order, irreversible, bimolecular. The influence of the temperature, pH, Po2, and Pco2 on the reaction rate constant was examined. A temperature change from 37 degrees to 42 degrees C, resulted in a 50 percent increase in the rate constant. The rate constant increased in proportion to the pH decrease, and deoxygenated whole blood was carbamylated approximately twice as fast as oxygenated blood. Carbon dioxide pressures had no influence on rates of carbamylation when a constant pH was maintained. A maximum rate constant of 3.7 M-U min.-u was obtained with conditions which were compatible with the red blood cells. This knowledge of the reaction mechanism and the influence of important system parameters on the reaction rate constant may be applied to the development of an extracorporeal system for the treatment of sickle cell anemia.