Assessment of the size selectivity of peritoneal permeability by the restriction coefficient to protein transport.

Transport of serum proteins from the circulation to peritoneal dialysate in peritoneal dialysis patients mainly focused on total protein. Individual proteins have hardly been studied. We determined serum and effluent concentrations of four individual proteins with a wide molecular weight range routinely in the standardised peritoneal permeability analysis performed yearly in all participating patients. These include ß2-microglobulin, albumin, immunoglobulin G and α2-macroglobulin. The dependency of transport of these proteins on their molecular weight and diffusion coefficient led to the development of the peritoneal protein restriction coefficient (PPRC), which is the slope of the relation between the peritoneal clearances of these proteins and their free diffusion coefficients in water, when plotted on a double logarithmic scale. The higher the PPRC, the more size restriction to transport. In this review, we discuss the results obtained on the PPRC under various conditions, such as effects of various osmotic agents, vasoactive drugs, peritonitis and the hydrostatic pressure gradient. Long-term follow-up of patients shows an increase of the PPRC, the possible causes of which are discussed. Venous vasculopathy of the peritoneal microcirculation is the most likely explanation.

Bioimpedance spectroscopy for fluid status assessment in patients with decompensated liver cirrhosis: Implications for peritoneal dialysis.

Bioimpedance spectroscopy (BIS) is routinely used in peritoneal dialysis patients and might aid fluid status assessment in patients with liver cirrhosis, but the effect of ascites volume removal on BIS-readings is unknown. Here we determined changes in BIS-derived parameters and clinical signs of fluid overload from before to after abdominal paracentesis. Per our pre-specified sample size calculation, we studied 31 cirrhotic patients, analyzing demographics, labs and clinical parameters along with BIS results. Mean volume of the abdominal paracentesis was 7.8 ± 2.6 L. From pre-to post-paracentesis, extracellular volume (ECV) decreased (20.2 ± 5.2 L to 19.0 ± 4.8 L), total body volume decreased (39.8 ± 9.8 L to 37.8 ± 8.5 L) and adipose tissue mass decreased (38.4 ± 16.0 kg to 29.9 ± 12.9 kg; all p < 0.002). Correlation of BIS-derived parameters from pre to post-paracentesis ranged from R² = 0.26 for body cell mass to R² = 0.99 for ECV. Edema did not correlate with BIS-derived fluid overload (FO ≥ 15% ECV), which occurred in 16 patients (51.6%). In conclusion, BIS-derived information on fluid status did not coincide with clinical judgement. The changes in adipose tissue mass support the BIS-model assumption that fluid in the peritoneal cavity is not detectable, suggesting that ascites (or peritoneal dialysis fluid) mass should be subtracted from adipose tissue if BIS is used in patients with a full peritoneal cavity.

Assessment of the association between increasing membrane pore size and endotoxin permeability using a novel experimental dialysis simulation set-up.

BACKGROUND: Membranes with increasing pore size are introduced to enhance removal of large uremic toxins with regular hemodialysis. These membranes might theoretically have higher permeability for bacterial degradation products. In this paper, permeability for bacterial degradation products of membranes of comparable composition with different pore size was investigated with a new in vitro set-up that represents clinical flow and pressure conditions. METHODS: Dialysis was simulated with an AK200 machine using a low-flux, high-flux, medium cut-off (MCO) or high cut-off (HCO) device (n = 6/type). A polyvinylpyrrolidone-solution (PVP) was recirculated at blood side. At dialysate side, a challenge solution containing a filtrated lysate of two water-borne bacteria (Pseudomonas aeruginosa and Pelomononas saccharophila) was infused in the dialysate flow (endotoxin ≥ 4EU/ml). Blood and dialysate flow were set at 400 and 500 ml/min for 60 min. PVP was sampled before (PVPpre) and after (PVPpost) the experiment and dialysate after 5 and 55 min. Limulus Amebocyte Lysate (LAL) test was performed. Additionally, samples were incubated with a THP-1 cell line (24 h) and IL-1ß levels were measured evaluating biological activity. RESULTS: The LAL-assay confirmed presence of 9.5 ± 7.4 EU/ml at dialysate side. For none of the devices the LAL activity in PVPpre vs. PVPpost was significantly different. Although more blood side PVP solutions had a detectable amount of endotoxin using a highly sensitive LAL assay in the more open vs traditional membranes, the permeability for endotoxins of the 4 tested dialysis membranes was not significantly different but the number of repeats is small. None of the PVP solutions induced IL-1ß in the THP-1 assay. CONCLUSIONS: A realisitic in vitro dialysis was developed to assess membrane translocation of bacterial products. LAL activity on the blood side after endotoxin exposure did not change for all membranes. Also, none of the PVPpost solutions induced IL-1ß in the THP-1 bio-assay.

Changes of peritoneal transport parameters with time on dialysis: assessment with sequential peritoneal equilibration test.

BACKGROUND: Sequential peritoneal equilibration test (sPET) is based on the consecutive performance of the peritoneal equilibration test (PET, 4-hour, glucose 2.27%) and the mini-PET (1-hour, glucose 3.86%), and the estimation of peritoneal transport parameters with the 2-pore model. It enables the assessment of the functional transport barrier for fluid and small solutes. The objective of this study was to check whether the estimated model parameters can serve as better and earlier indicators of the changes in the peritoneal transport characteristics than directly measured transport indices that depend on several transport processes. METHODS: 17 patients were examined using sPET twice with the interval of about 8 months (230 ± 60 days). RESULTS: There was no difference between the observational parameters measured in the 2 examinations. The indices for solute transport, but not net UF, were well correlated between the examinations. Among the estimated parameters, a significant decrease between the 2 examinations was found only for hydraulic permeability LpS, and osmotic conductance for glucose, whereas the other parameters remained unchanged. These fluid transport parameters did not correlate with D/P for creatinine, although the decrease in LpS values between the examinations was observed mostly for patients with low D/P for creatinine. CONCLUSIONS: We conclude that changes in fluid transport parameters, hydraulic permeability and osmotic conductance for glucose, as assessed by the pore model, may precede the changes in small solute transport. The systematic assessment of fluid transport status needs specific clinical and mathematical tools beside the standard PET tests.

Dialysate interleukin-6 predicts increasing peritoneal solute transport rate in incident peritoneal dialysis patients.

BACKGROUND: Repeated exposure to peritoneal dialysis (PD) solutions contributes to cumulative intraperitoneal inflammation and peritoneal injury. The present study aimed to explore the capacity of dialysate interleukin-6(IL-6) to a) predict peritoneal membrane function and peritonitis in incident PD patients, and b) to evaluate the influence of neutral pH, low glucose degradation product (GDP) PD solution on dialysate IL-6 levels. METHODS: The study included 88 incident participants from the balANZ trial who had completed 24-months of follow-up. Change in peritoneal solute transport rate (PSTR) and peritonitis were primary outcome measures, and the utility of IL-6 and IL-6 appearance rate (IL-6 AR) in predicting these outcomes was analyzed using multilevel linear regression and Cox proportional hazards models, respectively. Sensitivity analyses were performed by analyzing outcomes in a peritonitis-free cohort (n = 56). RESULTS: Dialysate IL-6 concentration significantly increased from baseline to 24 months (mean difference 19.07 pg/mL; P < 0.001) but was not affected by the type of PD solution received (P = 0.68). An increase in PSTR from baseline was associated with higher levels of IL-6 (P = 0.004), the use of standard solutions (P = 0.005) and longer PD duration (P < 0.001). Baseline IL-6 level was not associated with a shorter time to first peritonitis (adjusted hazard ratio 1.00, 95% CI 0.99-1.00, P = 0.74). Analysis of IL-6 AR as well as sensitivity analyses in a peritonitis-free cohort yielded comparable results. CONCLUSION: Dialysate IL-6 concentration increased with longer PD duration and was a significant, independent predictor of PSTR. The use of biocompatible PD solutions exerted no significant effect on dialysate IL-6 levels but did abrogate the increase in PSTR associated with standard PD solutions. This is the first study to examine the impact of biocompatible solutions on the utility of IL-6 in predicting PSTR and peritonitis.

Novel peritoneal dialysis solutions--what are the clinical implications?

Novel low-glucose degradation products (GDP) peritoneal dialysis (PD) fluids have an improved biocompatibility profile as compared to standard fluids. Clinical studies suggest that their use may be associated with favorable clinical outcomes; however, large prospective randomized studies addressing clinical endpoints such as patient and technique survival are presently lacking. Nevertheless, as their only disadvantage is their cost, they are already being used as the standard treatment by many adult PD centers. This policy is also in line with the latest recommendations from the European Pediatric Dialysis Working Group which advises that conventional, single-chamber PD solutions should be replaced by PD solutions with reduced GDP content. The use of icodextrin, the glucose polymer PD solution, is recommended for patients with high or high-average peritoneal transport and/or ultrafiltration problems who otherwise would resort to hypertonic (3.86% glucose) exchanges.

Differences in corrective mode for divalent ions and parathyroid hormone between standard- and low-calcium dialysate in patients on continuous ambulatory peritoneal dialysis--result of a nationwide survey in Japan.

BACKGROUND: In patients on continuous ambulatory peritoneal dialysis (CAPD), dialysate calcium concentration has a strong influence on correction of serum calcium, phosphorus, and parathyroid hormone (PTH); however, the optimal concentration of Ca in PD solution is still uncertain. The aim of the survey reported here was to evaluate the prevalence of patients treated with standard- [SCD (approximately 3.25 - 4.0 mEq/L)] or low-calcium [LCD (approximately 1.8 - 2.5 mEq/L)] dialysate and differences in the clinical effects for correction of abnormalities in divalent ions and PTH. MATERIALS AND METHODS: We used a questionnaire to survey 333 peritoneal dialysis facilities nationwide in Japan. Then, we analyzed serum Ca, P, and PTH levels and the prescription rates for CaCO(3) as a P binder and for vitamin D (VitD) analogs. RESULTS: The 2384 CAPD patients enrolled in this analysis had a mean age of 60.5 +/- 14.2 years and a mean duration of CAPD of 44.1 +/- 39.2 months. The prevalences of SCD, LCD, and combination of SCD and LCD were, respectively, 49%, 50%, and 1% at initiation, and 40%, 38%, and 22% at the time of the survey. In 735 and 876 patients respectively, LCD and SCD had been prescribed from initiation to the time of the survey. In these two groups, we observed no difference in initiation and current serum levels of Ca and P. But prescription rates for CaCO(3) and VitD analogs were higher in the LCD group than in the SCD group, and PTH levels were higher in the LCD group than in the SCD group. CONCLUSIONS: A beneficial effect of LCD was revealed in the increased doses of CaCO(3) and VitD analogs seen in that group without the occurrence of hypercalcemia; however, PTH levels in that group were not maintained within an acceptable range. The survey suggests that more serious attention should be paid to the Ca concentration in peritoneal dialysate so as to lessen mineral and PTH disorders in CAPD.

A comparison between 1.36% and 3.86% glucose dialysis solution for the assessment of peritoneal membrane function.

OBJECTIVE: To assess peritoneal membrane function with respect to fluid transport, parameters of low molecular weight solute transport, and estimations of the function of peritoneal water channels, comparing the results from a 1.36%/1.5% glucose solution with those from a 3.86%/4.25% solution in standardized peritoneal function tests. DESIGN: The study was performed in 40 stable continuous ambulatory peritoneal dialysis (CAPD) patients [median age 50 years (range: 22-74 years); duration of CAPD 9 months (range: 2-45 months)] who underwent two standard peritoneal permeability analyses (SPAs) within 1 month. One SPA used 1.36% glucose; the other, 3.86% glucose. Mass transfer area coefficients (MTACs) and dialysate-to-plasma (D/P) ratios were compared for the two solutions. Also, two different methods of estimating aquaporin-mediated water transport were compared: the sieving of sodium (3.86% glucose) and the difference in net ultrafiltration (deltaNUF), calculated as NUF 3.86% SPA - NUF 1.36% SPA. RESULTS: Median NUF in the 1.36% glucose SPA was -46 mL (range: -582 mL to 238 mL); in the 3.86% SPA, it was 554 mL (range: -274 mL to 1126 mL). The median difference in NUF for the two SPAs was 597 mL (range: 90-1320 mL). No difference between the two solutions was seen for the MTAC of creatinine (11.4 mL/min for 1.36% vs 12.0 mL/min for 3.86%) and absorption of glucose (64% vs 65%, respectively). Also, D/P creatinine was not different: 0.77 (1.36%) and 0.78 (3.86%). However, the ratio of dialysate glucose at 240 minutes and at 0 minutes (Dt/D0) was 0.34 (1.36%) and 0.24 (3.86%), p < 0.01. Values of D/P creatinine from the two glucose solutions were strongly correlated. The intra-individual differences were small and showed a random distribution. Patient transport category was minimally influenced by the tonicity of the dialysate. The minimum D/P Na+ (3.86%) was 0.884, and it was reached after 60 minutes. After correction for Na+ diffusion, D/P Na+ decreased to 0.849 after 120 minutes. The correlation coefficient between the diffusion-corrected D/P Na+ and the deltaNUF was 0.49, p < 0.01. An inverse relationship was present between MTAC creatinine and D/P Na+ (p < 0.01) This correlation can be explained by the rapid disappearance of the osmotic gradient owing to a large vascular surface area. Such a correlation was not present between MTAC creatinine and deltaNUF. CONCLUSIONS: We conclude that a standardized 4-hour peritoneal permeability test using 3.86%/4.25% glucose is the preferred method to assess peritoneal membrane function, including aquaporin-mediated water transport. The D/P Na+ after correction for Na+ diffusion is probably more useful for the assessment of aquaporin-mediated water transport than is deltaNUF obtained with 3.86%/4.25% and 1.36%/1.5% glucose-based dialysis solutions.