Quantification of free water transport in peritoneal dialysis

Quantification of free water transport in peritoneal dialysis.BackgroundIn peritoneal dialysis (PD) total net ultrafiltration (NUF) is dependent on transport through small pores and through water channels in the peritoneum. These channels are impermeable to solutes, and therefore, crystalloid osmotic-induced free water transport occurs through them. Several indirect methods to assess free water transport have been suggested. The difference in NUF between a 3.86% and a 1.36% solution gives a rough indication, but is very time consuming. The magnitude of the dip in dialysate/plasma (D/P) sodium in the initial phase of a 3.86% exchange is another way to estimate free water transport. In the present study, a method was applied to calculate free water transport by calculating sodium-associated water transport in one single 3.86% glucose dwell.MethodsForty PD patients underwent one standard peritoneal permeability analysis (SPA) with a 1.36% glucose solution, and another with a 3.86% glucose solution. At different time points intraperitoneal volume and sodium concentration were assessed. This made it possible to calculate total sodium transport. By subtracting this transport (which must have occurred through the small pores) from the total fluid transport, free water transport remained. These results were compared with the other methods to estimate free water transport.ResultsFor the 1.36% glucose dwell, total transcapillary ultrafiltration in the first hour (TCUF0-60) was 164 mL, transport through the small pores was 129 mL, and free water transport was 35 mL (21%). For the 3.86% glucose solution, total TCUF0-60 was 404 mL, transport through the small pores was 269 mL, and free water transport was 135 mL (34%). The contribution of free water transport in the first minute (TCUF0-1) was 39% of the total fluid transport. From the 40 patients, 11 patients had ultrafiltration failure (NUF <400 mL after 4 hours). For these patients the contribution of free water to TCUF0-1 was significantly lower than for those with normal ultrafiltration (20% vs. 48%, P < 0.05). A strong correlation was present between free water transport as a percentage of total fluid transport and the maximum dip in D/P sodium (r = 0.84). The correlation was not significant with the difference in net ultrafiltration of 3.86% and 1.36% solutions (r = 0.24, P = 0.3).ConclusionThe method applied here is the first direct quantification of free water transport, calculated from a single standard peritoneal function test. It offers a quick possibility to evaluate patients suffering from ultrafiltration failure. In these patients free water transport was impaired, but the origin of this impairment is still to be determined

Augmenting solute clearance in peritoneal dialysis

Augmenting solute clearance in peritoneal dialysis.BackgroundThe removal of low molecular weight solutes by peritoneal dialysis is less than by hemodialysis. The targets for Kt/Vurea and creatinine clearance formulated in the Dialysis Outcome Quality Initiative are unlikely to be achieved in a substantial portion of peritoneal dialysis patients. Possibilities to increase small solute clearances have therefore been subject to many investigations.MethodsA review of the literature and of recent new data on determinants of solute removal, such as residual renal function, the role of drained dialysate volume and manipulation of the diffusive capacity of the peritoneum are presented.ResultsThe contribution of residual GFR is more important for the clearance of creatinine than for Kt/Vurea. It is even more important for the removal of organic acids that are removed from the body by tubular secretion. High dosages of furosemide increase the urinary volume and the fractional Na+ excretion, but have no effect on the magnitude of residual GFR, renal creatinine clearance, renal urea clearance, and peritoneal transport characteristics. The drained dialysate volume per day is the main determinant of the peritoneal removal of urea. Its effect decreases the higher the molecular weight of a solute. It can be augmented by using large instillation volumes, by the application of more exchanges, and by increasing peritoneal ultrafiltration. A large exchange volume is especially effective in patients with an average transport state, but in those with high solute transport rates, Kt/Vurea is especially influenced by the number of exchanges. Possibilities to increase ultrafiltration are discussed. The diffusive capacity of the peritoneum can be augmented by using low dosages of intraperitoneally administered nitroprusside. This increases solute transport most markedly when it is applied in combination with icodextrin as osmotic agent.ConclusionsSmall solutes clearances cannot be increased by furosemide. Increasing the instilled volume of dialysis fluid and the number of exchanges both affect solute clearance. Studies are necessary on long-term effects of manipulation of the peritoneal membrane with nitroprusside

Quantification of free water transport in peritoneal dialysis

BACKGROUND: In peritoneal dialysis (PD) total net ultrafiltration (NUF) is dependent on transport through small pores and through water channels in the peritoneum. These channels are impermeable to solutes, and therefore, crystalloid osmotic-induced free water transport occurs through them. Several indirect methods to assess free water transport have been suggested. The difference in NUF between a 3.86% and a 1.36% solution gives a rough indication, but is very time consuming. The magnitude of the dip in dialysate/plasma (D/P) sodium in the initial phase of a 3.86% exchange is another way to estimate free water transport. In the present study, a method was applied to calculate free water transport by calculating sodium-associated water transport in one single 3.86% glucose dwell. METHODS: Forty PD patients underwent one standard peritoneal permeability analysis (SPA) with a 1.36% glucose solution, and another with a 3.86% glucose solution. At different time points intraperitoneal volume and sodium concentration were assessed. This made it possible to calculate total sodium transport. By subtracting this transport (which must have occurred through the small pores) from the total fluid transport, free water transport remained. These results were compared with the other methods to estimate free water transport. RESULTS: For the 1.36% glucose dwell, total transcapillary ultrafiltration in the first hour (TCUF(0-60)) was 164 mL, transport through the small pores was 129 mL, and free water transport was 35 mL (21%). For the 3.86% glucose solution, total TCUF(0-60) was 404 mL, transport through the small pores was 269 mL, and free water transport was 135 mL (34%). The contribution of free water transport in the first minute (TCUF(0-1)) was 39% of the total fluid transport. From the 40 patients, 11 patients had ultrafiltration failure (NUF <400 mL after 4 hours). For these patients the contribution of free water to TCUF(0-1) was significantly lower than for those with normal ultrafiltration (20% vs. 48%, P < 0.05). A strong correlation was present between free water transport as a percentage of total fluid transport and the maximum dip in D/P sodium (r= 0.84). The correlation was not significant with the difference in net ultrafiltration of 3.86% and 1.36% solutions (r= 0.24, P= 0.3). CONCLUSION: The method applied here is the first direct quantification of free water transport, calculated from a single standard peritoneal function test. It offers a quick possibility to evaluate patients suffering from ultrafiltration failure. In these patients free water transport was impaired, but the origin of this impairment is still to be determine

What can we do to preserve the peritoneum?

BACKGROUND: Long-term peritoneal dialysis may lead to peritoneal membrane failure. Loss of ultrafiltration is the most important clinical abnormality. Loss of ultrafiltration is associated with an increased number of peritoneal blood vessels, with fibrotic alterations, and with loss of mesothelium. Continuous exposure to bioincompatible dialysis solutions is likely to be important in the pathogenesis of these alterations. METHODS: This article reviews the toxicity of various constituents of dialysate, current assessments of interventions, and the results of interventions aimed at preserving the peritoneum. RESULTS: Glucose, possibly in combination with lactate, and glucose degradation products (GDPs) are likely to be the most toxic constituents of dialysate. Diabetiform peritoneal neoangiogenesis is likely to be mediated by vascular endothelial growth factor (VEGF). Release of VEGF might be influenced by glucose-induced cellular pseudohypoxia, which is likely to be increased by exposure to lactate. Glucose and GDPs are both toxic to peritoneal cells. Glucose degradation products induce the formation of advanced glycosylation end-products at a much faster rate than does glucose itself, but the relative importance of GDPs and glucose in clinical PD has not been clarified. The effects of interventions should first be assessed in long-term animal models, followed by clinical studies on peritoneal transport and on effluent markers that may reflect the status of the peritoneum. Possible interventions aim at reducing peritoneal exposure to glucose, GDPs, and lactate. Techniques include peritoneal resting, replacing some glucose-based exchanges with amino acid-based and icodextrin-based dialysate, using bicarbonate as a buffer, and administering solutions that have a low GDP content. Exposure to various dialysis solutions with a reduced GDP content has resulted in an increase in the effluent concentration of the mesothelial cell marker CA125, irrespective of the buffer used. Experimental studies in a long-term peritoneal exposure model in rats showed that the combination of a reduction in the concentration of lactate and replacement of lactate with pyruvate resulted in a reduction of the number of peritoneal blood vessels. Results of drug therapy have been studied in various animal models. Their use in patients is still experimental. CONCLUSIONS: Strategies to preserve the peritoneum aim at reducing membrane exposure to bioincompatible solutions. Currently available dialysis fluids that are more biocompatible are likely to have some beneficial effects. Further research on the development of dialysis solutions that use combinations of osmotic agents and alternative buffers is necessar

Peritoneal membrane failure in peritoneal dialysis patients

A review is given of the conditions associated with peritoneal membrane failure, and the possible causes. Ultrafiltration failure is the most important manifestation. It is mostly associated with high transport rates of low molecular weight solutes suggesting the presence of a large vascular surface area. Enlargement of the peritoneal surface area can be functional (effective surface area: more perfused microvessels) or anatomic (more microvessels). The former is likely to be present in some patients in the beginning of peritoneal dialysis, and also during peritonitis. The latter can develop in long-term peritoneal dialysi