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Title: The role of lymphatic absorption in peritoneal dialysis
Author: MacTier, Robert Alexander
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1987
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Studies of peritoneal dialysis kinetics have focused on fluid and solute exchange between the peritoneal microcirculation and the hypertonic dialysis solution instilled into the peritoneal cavity. The intraperitoneal fluid, however, is also absorbed continuously by convective flow into the peritoneal cavity lymphatics. Thus, measured net ultrafiltration at the end of each exchange (drain volume minus infusion volume) represents the difference between total net transcapillary fluid transport into and lymphatic drainage out of the peritoneal cavity during the dwell time. Lymphatic absorption from the peritoneal cavity occurs mainly via stomata on the undersurface of the diaphragm and exceeds 50 ml/hour in patients with ascites unless the subdiaphragmatic or mediastinal lymphatics are obstructed by tumour or fibrosis. Lymphatic absorption in the iatrogenic "ascites" of peritoneal dialysis may also be significant and thus merits investigation. The role of lymphatic absorption during peritoneal dialysis was evaluated in a rat model and in adults and children on continuous ambulatory peritoneal dialysis (CAPD). Lymphatic absorption was calculated from the rate of removal of albumin added to the infused dialysis solution, and net transcapillary ultrafiltration was estimated from the dilution of the initial dialysate albumin concentration. Intraperitoneal volume and lymphatic absorption were determined serially during six hour exchanges in rats using 15% dextrose dialysis solution. The net transcapillary ultrafiltration rate decreased exponentially to zero after 330 minutes, whereas lymphatic absorption proceeded at an almost linear rate throughout the exchanges, averaging 4.7 +/- 0.9 (SEM) ml/hour. Peak ultrafiltration volume was observed before osmolar equilibrium between serum and dialysate was reached and occurred when the net transcapillary ultrafiltration rate had decreased to equal the lymphatic absorption rate. Thereafter, the net fluid absorption rate represented lymphatic absorption in excess of concurrent net transcapillary ultrafiltration. Measured net ultrafiltration at the end of the exchanges averaged 24 +/- 2 ml and represented only 46 +/- 5% of total net transcapillary ultrafiltration during the dwell time. Standardised four hour exchanges using 2 litres of 2.5% dextrose dialysis solution were performed in 18 adult CAPD patients. Cumulative lymphatic absorption averaged 343 +/- 39 ml and reduced potential net ultrafiltration at the end of the exchanges by 56 +/- 6%. Extrapolated to four x six hour exchanges per day, lymphatic absorption reduced potential daily net ultrafiltration by 82 +/- 9%, daily drain volumes by 18 +/- 2%, daily urea clearances by 14 +/- 1% and daily creatinine clearances by 13 +/- 1%. These findings indicate that net ultrafiltration and solute clearances are reduced significantly by lymphatic absorption in all CAPD patients. Eight of the patients had transperitoneal solute transport rates indicative of high peritoneal permeability x area. Absolute lymphatic absorption did not differ between patients with average and high peritoneal permeability x area, but caused a proportionately greater reduction in net ultrafiltration in patients with high peritoneal permeability x area (p < 0. 005) since these patients had more rapid glucose absorption from the dialysate (p < 0.001) and lower cumulative net transcapillary ultrafiltration (p < 0.05). Patients with high peritoneal permeability x area had daily net fluid absorption from the dialysis solution even though daily net transcapillary ultrafiltration averaged 2.1 +/- 0.4 litres. Failure of peritoneal ultrafiltration in CAPD, in the absence of a dialysate leak, occurs when daily lymphatic absorption exceeds daily net transcapillary ultrafiltration. Four hour exchanges using 40 ml/Kg of 2.5% dextrose dialysis solution were performed in six children on peritoneal dialysis. Cumulative lymphatic absorption averaged 10.4 +/- 1.6 ml/Kg and reduced total net transcapillary ultrafiltration by 73 +/- 10%. Extrapolated to four x six hour exchanges per day, lymphatic absorption reduced potential daily drain volumes by 27 +/- 5%, daily urea clearances by 24 +/- 4% and daily creatinine clearances by 22 +/-5%. The infusion volumes of dialysis solution, corrected for body surface area, were similar in children and adults. Net ultra- filtration, scaled for body surface area, was lower in children than in adults with average peritoneal permeability x area (p < 0.05) due to a combination of relatively higher lymphatic absorption and lower net transcapillary ultrafiltration. Thus, lymphatic absorption caused a proportionately greater reduction in net ultrafiltration and solute clearances in children than in adults. These studies emphasise the important contribution of lymphatic absorption to loss of ultrafiltration and solute clearances after long-dwell peritoneal dialysis exchanges. Thus, reappraisal of current understanding of peritoneal dialysis kinetics is required to incorporate the role of lymphatics. Pharmacological reduction of lymphatic absorption may provide an alternative means of improving the efficiency of peritoneal dialysis without altering transperitoneal transport of water and solutes into the peritoneal cavity.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available