Biomedical subjects
Publications and source records attributed to K D Nolph.
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Clinical studies with intraperitoneal nitroprusside were designed to examine drug effects on peritoneal clearances as a function of dose, frequency of administration and dwell times. Increases in clearances and protein losses were seen with 1 mg of nitroprusside per liter of dialysis solution, with progressively greater effects up to maximum doses of 4.5 mg/1. Maximum effects were seen at the high dose after 3 or more consecutive exchanges. Clearance effects promptly returned toward control during postdrug exchanges and, in some studies, even during alternate exchanges. Proportional effects on solute clearances appeared independent of dwell time, supporting previous studies suggesting area permeability alterations. Series of 12 or more consecutive exchanges showed little change in blood pressure. Increases in serum thiocyanate were not detected after multiple exchanges. Dialysate cell counts showed no evidence of chemical irritation.
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The peritoneal dialysis system is a sophisticated dialyser. It probably represents a capillary kidney regulating the number of capillaries perfused, the nature of capillaries perfused, and the overall permeability of its membranes. Its sophistication far exceeds that available with extracorporeal man-made haemodialysis systems. However, because of limited pore area and inaccessible fluid film resistances, it will never be an efficient dialyser for small solute removal. One way to overcome this intrinsic inefficiency is to utilise CAPD which trades efficiency for time. Our first two years of experience with CAPD have answered many initial questions, at least in a preliminary fashion. The future of CAPD has exciting potential, but many questions remain.
Peritoneal clearances were measured in multiple patients with different types of peritoneal dialysis solution to assess the effects of pH, choice of buffer anion (acetate versus lactate), and the effects of nitroprusside (a vasodilator) in combination with different buffer anions and varying pH. The studies show no differences in peritoneal clearances at very low solution pH (less than 6 as is commonly available) as compared to a pH nearer to 7 or above. There were no diffences between solutions with acetate as compared to those with acetate. Nitroprusside significantly increased clearances in all solutions to a similar extent.
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.
Topical application of dialysis solution to the rat microcirculation causes a transient vasoconstriction for 2 to 3 min. We assessed the clinical importance of this vasoconstriction by developing a dialysis solution without vasoactive properties, as assessed in the microcirculatory laboratory. The solution was of similar composition to human extracellular fluid. We tested its effects on Cur, Ccr, Cin, and dialysate protein concentration. We found that compared to commercial solutions, the lower osmolality of the NVS resulted in loss of ultrafiltration and decreases in clearance of urea and creatinine. The clearance of inulin was unchanged, and dialysate protein increased, suggesting a major increase in diffusive transport of large solutes. Increased diffusive transport of large solutes with NVS suggests that initial vasoconstriction seen in the rat could be present and clinically important during peritoneal dialysis in humans.
Intermittent peritoneal dialysis may provide borderline adequate dialysis in terms of clearance of small solutes. A number of disease processes could decrease clearances. Drug manipulations and other techniques to increase clearances primarily affect larger solutes. Since some small-molecular-weight solutes may be uremic toxins until proven otherwise, small solute clearance decreases during chronic intermittent peritoneal dialysis may require consideration of even more hours of intermittent peritoneal dialysis or initiation of CAPD.
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Peritoneal clearances of urea, creatinine, inulin and dialyzate protein concentration were compared in ten patients using dialysis solutions containing either lactate or acetate. No significant differences were found between solutions containing lactate or acetate.
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Clearances of sodium and B12 were measured with increasing ultrafiltration in two newer coils with new types of membrane support. In all other coil studies previously reported, clearance increases with ultrafiltration did not equal predictions from contributions of convection implying simultaneous decreases in diffusive solute transport with increasing transmembrane pressure. Such deterioration was attributed to masking of membrane surface area by the membrane support, widening of blood channels, and/or channeling of dialysate flow. In these newer coils, clearance increases were very near to predicted enhancement by convection while diffusion was stable in one type and decreased only modestly in the other. Coil volumes assessed with the kerosene technique increased with higher transmembrane pressure similar to findings in previous coils studies. Thus, although coil blood path dimensions are altered with increasing pressure as in older coils, diffusive clearances remain stable and increases in total clearances equal that predicted from convective solute transport. These results suggest that membrane masking is probably the major mechanism for decreases in diffusion with ultrafiltration in other coils and that the problem has been minimized with improved membrane supports.