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Augmenting solute clearance in peritoneal dialysis. Background. The 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. Methods . A 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. Results . The 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... [ABSTRACT FROM AUTHOR]

Addition of the nitric oxide (NO) donor nitroprusside to 1.36% glucose dialysate enlarges the effective peritoneal surface area during four-hour dwells. The theoretical positive effect on ultrafiltration is, however, counteracted by an increase in glucose absorption. The absorption of the glucose polymer icodextrin is much lower in comparison with glucose-based dialysis solutions, due to its high molecular weight. In the present study 7.5% icodextrin dialysis solution with and without the addition of 4.5 mg/liter nitroprusside was studied during eight-hour CAPD dwells. Two Standard Peritoneal permeability Analyses, adapted for eight-hour dwells, were performed in 10 stable CAPD patients. Nitrate and cGMP were measured as parameters of NO synthesis. The transcapillary ultrafiltration increased in a linear way with icodextrin (ICO) and was even higher after the addition of nitroprusside (NP): 666 (ICO) versus 834 (NP) ml/8 hr, P = 0.03. The effective lymphatic absorption rate was not different. The resulting net ultrafiltration increased with nitroprusside: 344 (ICO) versus 540 (NP) ml/8 hr, P < 0.01. The mass transfer area coefficient of urea increased 15% and that of creatinine 26% with nitroprusside, consistent with the expected enlargement of the vascular peritoneal surface area. The increase in protein clearances was more pronounced the larger the protein: beta 2-microglobulin 19%, albumin 47%, IgG 63% and alpha 2-macroglobulin 95%. Dialysate/plasma (D/P) ratios of nitrate were not higher than the expected values on the basis of its molecular weight (P < 0.001). They increased 19% with nitroprusside. Also, the D/P ratio cyclic guanosine monophosphate (cGMP) after four hours increased with nitroprusside (0.39, range 0.13 to 0.55 ICO, and 0.82, range 0.36 to 1.39 NP, P = 0.01). With nitroprusside the D/P ratio cGMP was higher than expected after four and eight hours (P < 0.001). This points to local generation of NO after addition of nitroprusside. The nitroprusside induced increase in the mass transfer area coefficients (MTAC) of creatinine and in the ultrafiltration caused an increase in the creatinine clearance from 4.2 ml/min to 5.0 ml/min during the eight-hour dwell. This means that nitroprusside adds 3 liters/week to the peritoneal clearance of creatinine. The adequacy of peritoneal dialysis can therefore be improved by the addition of nitroprusside to 7.5% icodextrin, used for the long exchange. [ABSTRACT FROM AUTHOR]