The history and current status of continuous ambulatory peritoneal dialysis.
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Biomedical subjects
Publications and source records attributed to R P Popovich.
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A mathematical model has been developed to study peritoneal fluid and solute transfer. The model uses the concept of a distributed capillary system within the peritoneal tissue. The model accounts explicitly for transport across the capillary membrane, through interstitial tissue, and across the mesothelium. The capillary and mesothelial membranes are modeled using pore theory and a dual pathway (through pores and across cells) for fluid transfer. The nonperitoneal tissues are modeled as a single body pool. Lymphatic uptake from the peritoneal cavity is included. Model parameters were found from the literature and by simultaneously fitting experimental data for dialysate volume and dialysate concentrations of blood urea nitrogen, glucose, creatinine, and inulin. The model was also shown to predict concentration gradients within several tissues surrounding the peritoneal cavity. Variation of the model parameters revealed the importance of the mesothelial cell layer in peritoneal ultrafiltration. The results of model simulations indicate an initial transfer of fluid from the tissue space to the peritoneal cavity followed by transcapillary fluid transfer.
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There is an increasing interest in CAPD for the treatment of chronic uremia. This technique uses long-dwell peritoneal exchanges lasting 4 hr or more. We have determined equilibration curves for multiple solutes during long exchanges with commercially available 1.5% and 4.25% dextrose dialysis solutions. For small solutes, rates of change of D/P ratios fall off dramatically after 3 hr of dwell time. For larger solutes, D/P ratios change more linearly. Some concentration gradients for net removal by diffusion persist well beyond 4 hr for all but the most highly diffusible solutes. Previously reported net sieving of sodium and chloride during hypertonic exchanges is still evident after many hours.
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Evaluation of permeance in peritoneal dialysis. Relations were developed to calculate permeance based on a minimum number of experimental measurements. Permeance is the product of the effective peritoneal area times its mass transfer coefficient. The relations were used on clinical data obtained with and without nitroprusside, a direct vasodilator, added to the dialysate. Nitroprusside increased permeance 34% for BUN and about 100% for creatinine and inulin. The equivalent increase in clearance in a 50 minute exchange protocol would be 24, 60, and 83%. Normalized consecutive concentration data obtained every ten minutes in several long exchanges agree well with calculated values supporting the adequacy of the approach. An expression is also given to calculate the residual dialysate volume left from the previous dialysate exchange. The values calculated ranged from 200 to 500 ml.
The technique of continuous ambulatory peritoneal dialysis was evaluated in nine patients during 136 patient weeks. The major objectives were to see if continuous ambulatory peritoneal dialysis would provide [1] acceptable control of serum chemistries by usual criteria, [2] adequate removal of sodium and water, [3] tolerable protein losses, and [4] a low prevalence of peritonitis with episodes responsive to therapy with continuing continuous ambulatory peritoneal dialysis. Preliminary findings suggest continuous ambulatory peritoneal dialysis represents an effective ambulatory, portable, internal dialysis technique. Larger-solute clearances per week may approach values six times greater than with most hemodialysis techniques. Small-solute clearances approach dialysate flow rate (8.3 ml/min) and are comparable to other dialysis techniques on a weekly basis. Edema is readily controlled and protein losses should be tolerable with adequate protein intake. Peritonitus occurs on the average every 10 weeks but responds to therapy promptly with continuing continuous ambulatory peritoneal dialysis. If the prevalence of peritonitis can be reduced, continuous ambulatory peritoneal dialysis appears to represent a very attractive dialysis technique.
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The transmittance coefficients of Cuprophan PT-150 and Rhone-Poulenc AN69 have been defined over a broad MW range. The results can be completely characterized by a simple Gaussian distribution employing 2 parameters, the selectivity and the mean molecular diameter. The selectivities of the membranes studies are identical. The mean MW at 50% cutoff for Cuprophan and RP69 are 2,500 and 11,500, respectively. A membrane model illustrating a semi-empirical correlation between permeability and transmittance has been developed.
A diffusion limited, multicompartment patient-artifical kidney transport model has been developed. The physiological transport parameters have been clincially elevated for radiosotopically tagged urea, creatinine, uric acid, vitamin B12, and inulin with anuric, chronic uremic patients. Concomitant hemodialysis simulations illustrate that a 3 compartment patient model is adequate to characterize physiological transport. However, because of the high value of the transcapillary mass transfer coefficient, it is concluded that a 2 compartment (intracellular/extracellular) model is adequate to define mass transfer in the patient-artifical kidney system: a single pool may be assumed for very low hemodialyzer (less than 20 ml/min) clearances. Dialysis simulations also demonstrate that a point of diminshing returns is reached with respect to increasing mass removal from the patient, via increasing dialyzer clearance for middle molecules. In a 5 hr hemodialysis simulation the system becomes limited by physiological mass transfer resistances for dialyzer clearances greater than 100 ml/min. It is concluded that physiological transport resistances significantly impeded the removal of middle molecules from the patient-artifical kidney system. As a result, a single, well mixed pool assumption is not generally adequate to describe solute transport. A consequence of this conclusion is that the M2-hr hypothesis, which is based on a single pool assumption, cannot be generally utilized to accurately adjust hemodialysis treatment schedules for equivalent middle molecule removal. We are currently analyzing the patient-artifical kidney system to define improved adjustments modes for equivalent mass removal employing a 2 pool patiemt model.
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