Icodextrin with nitroprusside increases ultrafiltration and peritoneal transport during long CAPD dwells

Abstract

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.

Neoangiogenesis in the Peritoneal Membrane

“…This process is reversible after the inflammation is cured. A similar temporary increase can be provoked by intraperitoneal administration of the direct nitric-oxide donor nitroprusside (25,26).…”

Pathophysiology of Peritoneal Membrane Failure

“…Mean values for transcapillary UF during 4-hour dwells average 1.0 – 1.2 mL/min for 1.36%/1.5% glucose (25,37,43), and 3.4 mL/min for 3.86%/4.25% glucose (25). The transcapillary UF rate for 7.5% icodextrin is more or less constant during a 4-hour dwell and averages 1.4 – 2.2 mL/min (36,46). Knowledge of pressure gradients and maximum transcapillary UF rates makes it possible to calculate the peritoneal UF coefficient (PUFC), which is the product of the peritoneal surface area and its hydraulic permeability (L p S).…”

Predicting the Peritoneal Absorption of Icodextrin in Rats and Humans Including the Effect of α–Amylase Activity in Dialysate

“…The three-pore model used for humans was adapted from PD Adequest 2.0 (Baxter Healthcare Corporation, Deerfield, IL, USA), previously validated for predicting UF with icodextrin based on data from ten patients who performed 8-hour long exchanges (2,17). Icodextrin was modeled as described by Vonesh et al (2) using five distinct MW fractions representing the total icodextrin MW distribution.…”