Impact of fill volume on peritoneal clearances and cytokine appearance in peritoneal dialysis

Background: Current adequacy guidelines for peritoneal dialysis encourage the use of large fill volumes for the attainment of small solute clearance targets. These guidelines have influenced clinical practice in a significant way, and adoption of higher fill volumes has become common in North America. Several studies, however, have challenged the relevance of increasing small solute clearance; this practice may result in untoward consequences in patients. Objective: The present study was designed to explore the relationship between dialysate volume and the clearance of different sized molecules, fluid dynamics, and appearance of peritoneal cytokines. Methods: Thirteen adult prevalent patients on continuous ambulatory peritoneal dialysis were studied. Three different dialysate volumes (2.0, 2.5, and 3.0 L) were infused on consecutive days in a random order. Several measurements of peritoneal fluid dynamics (intraperitoneal pressure, net ultrafiltration, fluid absorption), solute clearances (urea, creatinine, beta(2)-microglobulin, albumin, IgG, and transferrin), and appearance of interleukin-6 and tumor necrosis factor alpha (TNFalpha) were assessed. Results: Increase in dialysate fill volume (from 2 to 2.5 to 3 L) was examined in relationship to body surface area (BSA). The dialysate volume/BSA (DV/BSA) ratio increased from 1262 to 1566 to 1871 mL/m(2) on 2.0, 2.5, and 3.0 L dialysate volumes, respectively. In parallel, diastolic blood pressure increased from 82.7+/-8.8 to 87.0+/-9.5 to 92+/-8.3 mmHg (p<0.05). Net ultrafiltration rate also increased, from 0.46±0.48 to 0.72±0.42 to 0.97±0.49 mL/minute (p<0.01), despite a concomitant increase in fluid absorption, from 1.05+/-0.34 to 1.21+/-0.40 to 1.56+/-0.22 mL/min (p<0.01). Urea peritoneal clearance increased from 8.27±0.68 to 9.92±1.6 to 12.98±4.03 mL/min (p<0.01); creatinine peritoneal clearance increased from 6.69+/-1.01 to 7.64+/-1.12 to 8.69+/-1.76 mL/min (p<0.01). Clearance of the other measured molecules did not change. Appearance of interleukin-6 increased 17% and 43% (p<0.01), and TNFalpha appearance increased 14% and 50% (p<0.01) when dialysate volumes of 2.5 and 3.0 L were used, compared with 2.0 L. Conclusions: These results show that, with higher values of DV/BSA ratio, small solute peritoneal clearance is increased, but clearances of large molecules remain unchanged. With the use of higher volumes, fluid absorption rate and the appearance of proinflammatory cytokines in the dialysate are increased.