Mass Transfer Area Coefficient Of Creatinine Research Articles

Peritoneal Protein Clearance Is Associated With Cardiovascular Events but Not Mortality in Peritoneal Dialysis Patients.

IntroductionAssociation of peritoneal protein clearance (Pcl) with outcomes in patients with peritoneal dialysis (PD) is uncertain. Thus, we aimed to investigate its impact on cardiovascular events and all-cause mortality in patients with PD and factors associated with Pcl.MethodsPrevalent patients with PD from January 2014 to April 2015 in the center of Renji Hospital were enrolled. At the time of enrollment, serum and dialysate samples were collected to detect biochemical parameters and Angiopoietin-2-Tie2 system cytokines. Mass transfer area coefficient of creatinine (MTACcr) and Pcl were calculated. Patients were dichotomized into two groups by the median Pcl level (68.5 ml/day) and were followed up prospectively until the end of the study (1 October 2018).ResultsA total of 318 patients with PD [51.2% men, mean age 56.7 ± 14.3 y, median PD duration 31.5 (12.1–57.2) months] were enrolled. Among them, 25.7% were comorbid with diabetes and 28.6% had a history of cardiovascular disease (CVD). After being followed up for up to 43.9 (24.2–50.3) months, 63 had developed cardiovascular events, and 81 patients were died. Among them, the high Pcl group had occurred 39 cardiovascular events and 51 deaths, and the low Pcl group had 24 cardiovascular events and 30 deaths. Kaplan-Meier analysis showed that both the occurrence of cardiovascular events and all-cause mortality were increased in patients with high Pcl. However, after adjusting for important confounders and serum Angiopoietin-2 (Angpt-2) level, Pcl was still an independent risk factor for cardiovascular events [hazard ratio (HR) = 1.006 (1.000–1.012), p = 0.038] but not mortality. On multivariate regression analysis, serum albumin, MTACcr, and body mass index (BMI) were found to be independently associated with Pcl.ConclusionHigh Pcl is an independent risk factor for cardiovascular events but not all-cause mortality. The prediction of cardiovascular events by Pcl was independent of serum Angpt-2.

Longitudinal Changes of NF-\u03baB Downstream Mediators and Peritoneal Transport Characteristics in Incident Peritoneal Dialysis Patients

The role of intra-peritoneal mediators in the regulation peritoneal transport is not completely understood. We investigate the relation between longitudinal changes in dialysis effluent level of nuclear factor kappa-B (NF-κB) downstream mediators and the change in peritoneal transport over 1 year. We studied 46 incident PD patients. Their peritoneal transport characteristics were determined after starting PD and then one year later. Concomitant dialysis effluent levels of interleukin-6 (IL-6), cyclo-oxygenase-2 (COX-2) and hepatocyte growth factor (HGF) are determined. There were significant correlations between baseline and one-year dialysis effluent IL-6 and COX-2 levels with the corresponding dialysate-to-plasma creatinine level at 4 hours (D/P4) and mass transfer area coefficient of creatinine (MTAC). After one year, patients who had peritonitis had higher dialysis effluent IL-6 (26.6 ± 17.4 vs 15.1 ± 12.3 pg/ml, p = 0.037) and COX-2 levels (4.97 ± 6.25 vs 1.60 ± 1.53 ng/ml, p = 0.007) than those without peritonitis, and the number of peritonitis episode significantly correlated with the IL-6 and COX-2 levels after one year. In contrast, dialysis effluent HGF level did not correlate with peritoneal transport. There was no difference in any mediator level between patients receiving conventional and low glucose degradation product solutions. Dialysis effluent IL-6 and COX-2 levels correlate with the concomitant D/P4 and MTAC of creatinine. IL-6 and COX-2 may contribute to the short-term regulation of peritoneal transport.

Different patterns of inflammatory and angiogenic factors are associated with peritoneal small solute transport and peritoneal protein clearance in peritoneal dialysis patients

BackgroundBoth peritoneal small solute transport and peritoneal protein clearance are closely linked to outcomes in peritoneal dialysis (PD) patients. However, the associated factors of these two components are not fully understood so far. This study aimed to investigate the association between a panel of systemic and peritoneal inflammatory and angiogenic factors and peritoneal solute transport properties.MethodsStable PD patients in PD center of Renji Hospital, School of Medicine, Shanghai Jiao Tong University were enrolled in present study. Serum and overnight effluent markers including angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), sTie-2, VEGF, IL-6 and IL-10 were determined. Mass transfer area coefficient of creatinine (MTACcr) and peritoneal protein clearance (Prcl) were calculated. Multivariable linear regression was used to examine the association between these markers and MTACcr as well as Prcl.ResultsA total of 320 patients were enrolled in present study, which consisted of 166 (51.9%) males with a mean age of 56.8 ± 14.2 years and a median PD duration of 32.5 (9.0–56.3) months. Multiple regression analyses showed that BSA, history glucose exposure, dialysate IL-6 AR and dialysate Ang-1 AR were independent associated factors of MTACcr, while BSA and serum Ang-1 were independent associated factors of Prcl.ConclusionsMTACcr representing peritoneal small-solute transport and Prcl representing peritoneal large molecular transport are associated with slightly different panels of inflammatory and angiogenic factors.

Peritoneal Albumin and Protein Losses Do Not Predict Outcome in Peritoneal Dialysis Patients

Peritoneal clearance of albumin-unlike the transport of small molecules-is defined by both vascular surface area and size-selective permeability. Few studies have supported a positive correlation between peritoneal albumin loss and mortality. The aim of this study was to investigate whether baseline peritoneal loss and clearance of albumin and other proteins is a risk factor of death in peritoneal dialysis patients. All incident peritoneal dialysis patients in our center during the last 15 years were included. Mass-transfer area coefficient of creatinine and peritoneal clearances of albumin, β₂-microglobulin, α₂-macroglobulin, and immunoglobulin G were calculated during a standard peritoneal permeability analysis. The total amount of albumin loss in the dialysate was also calculated. Overall mortality was studied with an intention-to-treat analysis. Two hundred fifty-seven patients were included. High baseline albumin clearance was associated with fast transport status, the presence of peripheral arterial disease, and a high comorbidity index, whereas C-reactive protein levels did not differ from the patients with low albumin clearance. Age, high comorbidity score, C-reactive protein levels >10 mg/L, and a low serum albumin were associated with mortality. Peritoneal albumin clearances and albumin loss were not associated with death in crude and adjusted analysis. Similarly, peritoneal clearances of immunoglobulin G, α₂-macroglobulin, and β₂-microglobulin were not determinants of survival. Baseline peritoneal albumin and protein clearances are associated with signs of comorbidity, but this does not have a measurable effect on patient survival.

Impact of systemic and local peritoneal inflammation on peritoneal solute transport rate in new peritoneal dialysis patients: a 1-year prospective study

The association between peritoneal solute transport rates (PSTRs) and inflammatory markers in patients on peritoneal dialysis (PD) is still under investigation. We aimed to elucidate their relationship during the first year on PD. We performed a prospective observational study with 187 incident PD patients who were treated with either biocompatible solution (BCS) or conventional solution (CS). Peritoneal dialysate effluent (PDE) and blood samples for the markers and the calculation of mass transfer area coefficient of creatinine (MTAC) were performed at 1, 6 and 12 months after commencing PD. Of the 187 enrolled patients, 110 completed a 1-year study protocol. All PDE markers [interleukin-6 (IL-6), transforming growth factor-beta (TGF-beta), TGF-beta-induced gene-h3 (beta ig-h3), vascular endothelial growth factor (VEGF)] except CA125 increased over time, whereas PSTRs, high-sensitivity C-reactive protein (hs-CRP) and serum IL-6 levels did not change. Serum albumin and log PDE appearance rates (ARs) of IL-6, TGF-beta and CA125 predicted MTAC. The Delta value (12-month minus 1-month) of PDE AR of IL-6 was correlated with those of all other PDE markers. Both 12-month IL-6 and Delta IL-6 ARs in PDE were highest in the upper Delta MTAC tertile. PSTRs in the CS group, unlike BCS, had a tendency to increase over time, demonstrating a time-by-group interaction. Solution type and MTAC were not associated with patient and technique survival. The change in PSTR during the first year of PD is related to PDE IL-6 AR, which may represent intraperitoneal inflammation; however, there does not seem to be a close association between PSTR and the degree of systemic inflammation.

The relationship between bone morphogenic protein-7 and peritoneal transport characteristics

After prolonged peritoneal dialysis (PD) and exposure to a non-physiological dialysis solution, peritoneal mesothelial cells undergo the epithelial-to-mesenchymal transition. In other biological systems, bone morphogenic protein-7 (BMP-7) is a key factor that controls this process. However, the role of BMP-7 in peritoneal physiology has not been studied. We studied the peritoneal transport characteristics of 50 consecutive new PD patients at 4 and 52 weeks after PD. Peritoneal permeability will be determined by the standard peritoneal equilibration test (PET). BMP-7 in PD effluent (PDE) at mRNA and protein level at 4 weeks was quantified. At 4 weeks, the mRNA expression of BMP-7 in PDE significantly correlated with peritoneal transport characteristics, including the dialysate-to-plasma creatinine ratio at 4 h (D/P4) (r = 0.422, P = 0.015) and mass transfer area coefficient (MTAC) of creatinine (r = 0.457, P = 0.008). The PDE BMP-7 level by ELISA also had marginal correlation with D/P4 (r = 0.287, P = 0.072) and MTAC creatinine (r = 0.287, P = 0.073), although the result did not reach statistical significance. For the subgroup of patients who remained free of peritonitis, the PDE BMP-7 level by ELISA had significant correlation with the change in D/P4 (r = 0.441, P = 0.017) and MTAC creatinine in 52 weeks (r = 0.415, P = 0.025). The PDE BMP-7 level remained independently associated with the change in peritoneal transport adjusting for age, sex, serum C-reactive protein and PDE transforming growth factor-beta level. In patients who had peritonitis during the study period, the PDE BMP-7 level did not affect the change in peritoneal transport. Conclusion. We find that the peritoneal BMP-7 level correlates with peritoneal transport characteristics, and a high PDE BMP-7 level is associated with a gradual increase in peritoneal transport parameters with time. It remains unclear, however, whether this effect is beneficial, and the therapeutic role of exogenous BMP-7 on peritoneal transport requires a further study.

Evaluation of peritoneal transport properties at onset of peritoneal dialysis and longitudinal follow-up

The clinical determinants of baseline peritoneal membrane (PM) transport characteristics, as evaluated by a hypertonic peritoneal equilibration test (PET), remain ill-defined. Likewise, the longitudinal evolution of PM transport properties in peritoneal dialysis (PD) patients given automated PD (APD) and icodextrin still needs to be determined precisely. The aims of the present study were (1) to determine the clinical and biological factors affecting PM transport characteristics at PD onset and (2) to assess the longitudinal evolution of these markers. Seventy-two consecutive patients performed a baseline 3.86% glucose dialysate PET and were enrolled. Subgroups of 35 and 18 patients underwent another PET 1 and 2 year(s) later, respectively, and were included in the longitudinal part. For each patient, clinical and biological data were reviewed and PM transport markers calculated. At onset of PD, angiotensin-converting enzyme (ACE) inhibitor intake (r = 0.31, P = 0.01), presence of a diabetes (r = 0.26, P = 0.03) and body surface area (BSA) (r = 0.26, P = 0.03) independently affected the mass transfer area coefficient (MTAC) of creatinine. Serum albumin (r = -0.46, P<0.001) and net ultrafiltration (r = -0.33, P = 0.009) inversely correlated with MTAC creatinine. Sodium sieving was inversely correlated with BSA (r = -0.33, P = 0.01). Serum albumin also inversely correlated with albumin clearance (r = -0.39, P = 0.02). Finally, the independent covariates that affected alpha2-macroglobulin clearance were age (P = 0.03), diabetes (P = 0.01) and the level of residual renal function (P<0.01). Serum albumin decreased with time on PD (P = 0.02). A rise in small solute transport and a decrease in net ultrafiltration, but no change in protein clearances, were also observed after 2 years of PD. Transport properties across the PM, as evaluated by MTAC creatinine and sodium sieving determinations, are correlated with anthropometric characteristics (BSA) and by comorbid conditions (witnessed by the presence of diabetes, a low serum albumin concentration and the prescription of an ACE inhibitor). The short-term evolution (2 years) of the PM transport properties of patients on APD and icodextrin is still characterized by a progressive increase in small solute transport and a loss of ultrafiltration capacity, as documented in ancient studies, but not with a modification in protein clearances. This conclusion merits, however, to be further evaluated in a larger cohort of PD patients after a longer follow-up.

Ultrafiltration and Small Solute Transport at Initiation of PD: Questioning the Paradigm of Peritoneal Function

Human peritoneal function on commencing peritoneal dialysis (PD) is not yet adequately understood. The objective of this study was to determine peritoneal functional patterns on commencing PD. 367 end-stage renal disease (ESRD) patients on PD for the first time were studied between their initial second to sixth weeks on PD. Urea and creatinine mass transfer area coefficients (MTAC) and standardized ultrafiltration (UF) capacity were determined. Mean parametric values were MTAC urea 22.9 +/- 7.04 mL/min, MTAC creatinine 10.31 +/- 4.68 mL/min, and UF 896 +/- 344 mL. Gender, patient size, and diabetes or kidney disease did not affect these parameters. The relationship between values of MTAC creatinine and UF reached statistical significance, although with a low value for Pearson's coefficient (r = -0.30, p = 0.001). Age showed a significant inverse linear correlation with UF capacity (r = -0.15, p = 0.003) and MTAC urea (r = -0.11, p < 0.05). Logistic regression analysis demonstrated that UF below 400 mL was independently related to a high MTAC creatinine and older age. Diabetes was least frequent in patients with the lowest UF. However, in the analysis of MTAC creatinine quintiles, UF values did not follow the expected inverse pattern. The lack of differences in UF between the second and third to fourth MTAC creatinine quintiles is remarkable; MTAC creatinine ranged from 6.71 to 13.54. The functional characteristics of human peritoneum varied markedly and there was a less intense than expected relationship between solute and water transports. This mild inverse relationship is intriguing and suggestive of the necessity of redefining some basic concepts. Age was associated with a lower peritoneal UF capacity, in part independently of small solute transport.

Determinants of Peritoneal Solute Transport Rates in Newly Started Nondiabetic Peritoneal Dialysis Patients

An overrepresentation of a fast peritoneal transport status in new peritoneal dialysis (PD) patients with extensive comorbidity has been reported in some studies. High mass transfer area coefficients (MTACs) of low MW solutes suggest the presence of a large effective peritoneal surface area. The mechanism is unknown. It might include comorbidity, chronic inflammation, or an effect of mesothelial cell mass on peritoneal transport by the production of vasoactive substances. To investigate their relative importance in early PD, peritoneal permeability characteristics in incident PD patients were analyzed for relationships with comorbidity, serum concentrations of inflammatory markers, and products of the mesothelial cells that can be detected in dialysate. A cross-sectional study. A university hospital. 46 patients who fulfilled the following inclusion criteria were analyzed: a standard peritoneal permeability analysis (SPA) within 6 months after the start of PD, no peritonitis prior to the SPA, older than 18 years, and without diabetes mellitus as a primary renal disease. The patients were divided into tertiles based on the MTAC creatinine: slow, medium, and fast transport groups. The Davies comorbidity score was used to assess comorbidity. Serum and dialysate samples obtained during the SPA were used to determine hyaluronan, interleukin (IL)-6, vascular endothelial growth factor (VEGF), and cancer antigen 125 (CA125). The dialysate concentrations of these substances were expressed as their dialysate appearance rates. No significant differences were present in the three transport groups for comorbidity, serum concentrations of inflammatory markers, or serum VEGF. Interleukin-6 and VEGF concentration attributed to local VEGF production were not different between the tertiles. Levels of VEGF were higher in the medium transport group compared to the slow transport group (p = 0.02); CA125 was higher in the fast transport group compared to the medium transport group (p= 0.01). When analyzed as continuous variables, MTAC creatinine was related to VEGF (r= 0.33, p < 0.05) and CA125 (r= 0.41, p = 0.03). In linear regression analysis, VEGF influenced the association between CA125 and MTAC creatinine; IL-6 weakened this association only marginally. A fast peritoneal transport status in incident nondiabetic PD patients was not related to comorbidity. The relationships found between VEGF, CA125, and MTAC creatinine may suggest a role of VEGF in the regulation of the vascular peritoneal surface area, possibly already before structural abnormalities have developed. Our analyses are consistent with the hypothesis that mesothelial cell mass is an important determinant of the peritoneal transport status in incident nondiabetic PD patients without previous peritonitis. Of the many potential mediators produced by mesothelial cells, VEGF was more important than the inflammation marker IL-6.

Analysis of the Prevalence and Causes of Ultrafiltration Failure during Long-Term Peritoneal Dialysis: A Cross-Sectional Study

Ultrafiltration failure (UFF) is a major complication of peritoneal dialysis (PD). It can occur at any stage of PD, but develops in time and is, therefore, especially important in long-term treatment. To investigate its prevalence and to identify possible causes, we performed a multicenter study in The Netherlands, where patients treated with PD for more than 4 years were studied using a peritoneal function test (standard peritoneal permeability analysis) with 3.86% glucose. UFF was defined as net UF < 400 mL after a 4-hour dwell. 55 patients unselected for the presence or absence of UFF were analyzed. Mean age was 48 years (range 18 - 74 years); duration of PD ranged from 48 to 144 months (median 61 months); UFF was present in 20 patients (36%). Patients with and without UFF did not differ in age or duration of PD. Median values for patients with normal UF compared to patients with UFF were, for net UF 659 mL versus 120 mL (p < 0.01), transcapillary UF rate 3.8 versus 2.1 mL/ minute (p < 0.01), effective lymphatic absorption 1.0 versus 1.6 mL/min (p < 0.05), mass transfer area coefficient (MTAC) for creatinine 9.0 versus 12.9 mL/min (p< 0.01), dialysate-to-plasma ratio (D/P) for creatinine 0.71 versus 0.86 (p < 0.01), glucose absorption 60% versus 73% (p < 0.01), maximum dip in D/P sodium (as a measure of free water transport) 0.109 versus 0.032 (p < 0.01), and osmotic conductance to glucose 3.0 versus 2.1 microL/min/mmHg (p < 0.05). As causes for UFF, high MTAC creatinine, defined as > 12.5 mL/min, or a glucose absorption > 72%, both reflecting a large vascular surface, a lymphatic absorption rate (LAR) of > 2.14 mL/min, and a decreased dip in D/P sodium of < 0.046 were identified. Most patients had a combination of causes (12 patients), whereas there was only a decreased dip in D/P sodium in 3 patients, only high MTAC creatinine in 1 patient, and only high LAR in 2 patients. We could not identify a cause in 2 patients. Both groups had similar clearances of serum proteins and peritoneal restriction coefficients. However, dialysate cancer antigen 125 concentrations, reflecting mesothelial cell mass, were lower in the UFF patients (2.79 vs 5.38 U/L). The prevalence of UFF is high in long-term PD. It is caused mainly by a large vascular surface area and by impaired channel-mediated water transport. In addition, these patients also had signs of a reduced mesothelial cell mass, indicating damage of the peritoneum on both vascular and mesothelial sites.

Free-water transport in fast transport status: A comparison between CAPD peritonitis and long-term PD

Ultrafiltration failure (UFF) in continuous ambulatory peritoneal dialysis (CAPD) is a transient phenomenon during acute peritonitis and a permanent complication in long-term peritoneal dialysis (PD). The high solute transport rates during acute peritonitis are probably caused by an increased number of perfused peritoneal capillaries. Long-term PD is associated with an increased number of peritoneal microvessels, leading to an enlargement of the anatomic vascular surface area. This leads to high mass transfer area coefficients (MTAC) and to UFF. Impaired conductance to glucose, leading to a reduction in free-water transport, may be a contributing factor to UFF in long-term PD. We hypothesized that UFF during acute peritonitis is, in the absence of permanent structural changes, only caused by an increased vascular surface area, while in long-term patients it is often the result of an increased surface area in combination with an impaired conductance to glucose. Therefore, the peritoneal transport parameters of patients with acute peritonitis were compared to those in long-term PD patients. A standard peritoneal permeability analysis (SPA) was done in 10 PD patients during the first 48 hours after the diagnosis of peritonitis. The results were compared to those obtained in 10 long-term PD patients matched for the MTAC creatinine. In addition, the results of 8 peritonitis patients were compared with SPA results of 8 recently started PD patients, matched for MTAC creatinine. Peritonitis patients had a deeper maximal dip in D/P sodium, corrected for diffusion, than long-term patients (0.058 vs. 0.039, P < 0.05). Most parameters of peritoneal fluid transport were not different, except that t50 (i.e., the time to reach 50% of the maximum transcapillary ultrafiltration) was reached earlier during the dwell in peritonitis than in long-term PD-128 versus 175 minutes, P < 0.05. This confirmed the difference in the shape of the intraperitoneal volume versus time curve, which was blunted in the long-term patients. No differences were found for the parameters of solute transport between peritonitis patients and recently started patients. In contrast to patients with long-term PD, the osmotic conductance to glucose is unaffected in peritonitis, despite the lower net ultrafiltration caused by high solute transport. This implies that impaired free- water transport in chronic PD must be regarded as a contributing factor to UFF.

Effluent CA 125 Concentration in Chronic Peritoneal Dialysis Patients: Influence of PD Duration, Peritoneal Transport and PD Regimen

In terms of the integrity of the peritoneal membrane in peritoneal dialysis (PD), the peritoneal mesothelial cells play a pivotal role since its monolayer constitutes the first line of the peritoneal membrane. Cancer antigen 125 (CA 125) is released by peritoneal mesothelial cells and correlates with the mesothelial cell mass in PD. Since its effluent concentration is easy to determine in chronic PD patients, CA 125 serves as an in vivo marker of biocompatibility. We performed a cross-sectional study to investigate the relation between PD duration, peritoneal transport and the PD regimen (CAPD/CCPD) on effluent CA 125 concentration in 22 chronic PD patients. We compared long-term (>6 months) with short-term PD treatment, patients with high small solute transport properties (MTAC >11 ml/min, d/p ratio of creatinine >0.72) to patients with low small solute transport and CAPD with APD patients. A peritoneal equilibration test was performed with 1.36% glucose. Dialysate/plasma (D/P) ratio and mass transfer area coefficient (MTAC) of creatinine were calculated and the 4-hour effluent concentration of CA 125 was determined. CA 125 tended to be lower in the long-term PD patients and also in APD patients, but statistical significance was missing. Effluent CA 125 was significantly increased in patients with an MTAC of creatinine >11 ml/min (40.2 ± 11.2 vs. 20.7 ± 1.2 U/ml) and in patients with a d/p ratio of creatinine >0.72 (48.2 ± 11.0 vs. 21.6 ± 1.6 U/ml). CA 125 and the d/p ratio of creatinine were positively correlated (r = 0.68). The positive correlation of CA 125 with peritoneal small solute transport especially in the early phase of PD treatment indicates an initial correlation of the mesothelial cell mass with the peritoneal surface area. A direct relation between the CA 125 concentration and peritoneal transport is unlikely. In our study the CA 125 effluent concentration tended to be lower in long-term PD patients and also in APD patients, possibly indicating a cell depletory influence of the conventional PD fluid.

Peritoneal Function and Adequacy Calculations: Current Programs versus PD Adequest 2.0

Our current programs (CPs) were compared to PD Adequest 2.0 (PD-A) for calculations of peritoneal membrane transport and dialysis adequacy. Thirty peritoneal equilibration tests (PETs) and 24-hour balances (24hBs) were conducted and calculated using our CPs and PD-A. Thirty hospital-controlled peritoneal dialysis (PD) patients were studied. The inclusion of correction factors (for glucose or plasmatic water) and of residual volume, and the use of 3 or 6 peritoneal samples were analyzed to discover the differences between programs. The main outcome measures were peritoneal permeability and adequacy parameters, evaluated by Student t-test (mean and paired comparisons) and linear regression for correlation. No significant differences were found in D/P values for small solutes. At the first step, mass transfer area coefficient (MTAC) urea and MTAC creatinine were significantly higher in DP-A than in CP, but MTAC glucose did not differ. The causes of differences were: (1) inclusion of a correction factor for aqueous plasmatic concentration of small solutes in CP; (2) lack of Inclusion of residual volume in peritoneal volumes in CP; and (3) use of 6 peritoneal samples in CP versus 3 in PD-A. At the second step, when the input data were made equivalent for both programs, the differences disappeared for MTAC urea, creatinine, and glucose (mean comparison), but creatinine and glucose remained different by paired comparison. Similar results were obtained when a correction for plasmatic aqueous concentration was applied to the data in both programs [MTAC urea: 22.60 +/- 4.27 ml/min (CP) vs 22.43 +/- 4.61 mL/min (PD-A), nonsignificant, r= 0.97; MTAC creatinine: 9.76 +/- 3.83 mL/min (CP) vs 10.61 +/- 3.07 mL/min (PD-A), nonsignificant, r = 0.98; MTAC glucose: 13.30 +/- 3.12 mL/min (CP) vs 11.87 +/- 3.41 m/min (PD-A), nonsignificant, r= 0.92]. Creatinine and glucose were different by paired t-test. No significant differences were found in Kt/V and urea generation rate. Weekly creatinine clearance [WCCr: 70.71 +/- 16.71 L (CP) versus 79.33 +/- 18.73 L (PD-A), p < 0.001] and creatinine generation rate [CrGR: 0.56 +/- 0.18 mg/min (CP) versus 0.61 +/- 0.19 mg/min (PD-A), p < 0.001) were significantly higher in PD-A than In CP owing to the lack of creatinine correction according to glucose concentration In the PD-A adequacy program. Finally, normalized protein nitrogen appearance according to Bergström [1.09 +/- 0.20 g/kg/d (CP) versus 1.03 +/- 0.21 g/kg/d (PD-A), p = 0.01] was different owing to the different algorithms and normalization method: standardized body weight in CP and actual body weight in PD-A. Provided that equivalent data are used, PD-A and CP yield similar results. The PD-A program needs external correction of data input: (1) for plasmatic water concentration in MTAC calculations, and (2) for peritoneal glucose interference with creatinine analysis (Jaffé method) In WCCr and CrGR calculations; otherwise, It may give falsely optimistic results.

Vascular endothelial growth factor in peritoneal dialysis: A longitudinal follow-up

In a previous study, vascular endothelial growth factor (VEGF) was found to be locally produced in the peritoneal tissue of patients undergoing peritoneal dialysis (PD) who were being treated with glucose-containing PD solutions. Locally produced VEGF (LVEGF) was positively related to the mass transfer area coefficient (MTAC) of creatinine and to glucose absorption, both of which are representative of the peritoneal vascular surface area. It was therefore hypothesized that VEGF is involved in the peritoneal neoangiogenesis found in long-term PD. The aim of the present study was to investigate the time course of peritoneal VEGF levels in PD patients treated with glucose-based PD solutions during longitudinal follow-up. We also studied the effect of the switch to glucose-free PD treatment on VEGF production. Forty standard peritoneal permeability analyses (SPAs) with 3.86% glucose-containing dialysis solution were investigated. The SPAs were performed in 10 PD patients with a median number of three SPAs per patient during a follow-up of 23 months. Duration of PD treatment at the last SPA was 74 months. All patients were initially treated with glucose-containing dialysis solutions. Four patients switched after 114 months of glucose-based PD to glucose-free PD and were followed for 7 months. A PD regimen of icodextrin, glycerol, and amino acid–based dialysis solutions was applied in these patients. Four SPAs were performed per patient in this period. To predict the VEGF dialysate-to-serum ratio (D/S), when diffusion would be the only explanation for the VEGF dialysate concentration, we calculated the power relationship between D/S ratios of serum proteins that are only transported across the peritoneum and the molecular weights of those proteins. The measured VEGF D/S ratio was higher than expected (P <.001) in each observation, pointing to local production of VEGF. LVEGF increased with duration of glucose PD, 11.7 ng/L to 23.45 ng/L (P <.03). LVEGF decreased in all 4 patients undergoing glucose-free PD, from 57.35 ng/L to 23.10 ng/L. A correlation (r = 0.83, P <.001) was found be-tween the differences in MTAC creatinine between the first and last SPA during glucose-based PD and the difference in LVEGF between these observations. A similar correlation was present between the difference in glucose absorption and the difference in LVEGF (r = 0.85, P <.001). This supports a pathogenetic role of high glucose dialysate concentrations in the development of changes in the peritoneum that are found in long-term PD. Treatment with non-glucose-based PD solutions may inhibit further development of these alterations. (J Lab Clin Med 2001;137:125-32)

A Comparison between 1.36% and 3.86% Glucose Dialysis Solution for the Assessment of Peritoneal Membrane Function

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. 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. 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. 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.

Longitudinal evaluation of transport kinetics in children receiving peritoneal dialysis.

Functional stability of the peritoneal membrane is necessary for maintenance of peritoneal dialysis (PD) as a therapeutic option. Few studies have investigated this issue in children. We evaluated the peritoneal membrane solute transport capacity longitudinally in 26 children (mean age 11.0+/-5.5 years) receiving long-term PD. Each patient underwent a standardized peritoneal equilibration test on two occasions (mean interval between studies 19.8+/-5.9 months) to determine solute dialysate to plasma (D/P) ratios, dialysate glucose to initial dialysate glucose (D/D(0)) ratios, and mass transfer area coefficients (MTAC). The correlation of transport capacity with peritonitis history was also assessed. No significant change in MTAC, D/P, or D/D(0) values were found when comparing original and follow-up data of the group overall. However, transport of creatinine and glucose was significantly (P<0.05) greater in the peritonitis group compared with the group without peritonitis, and differences in the change over time between the peritonitis groups was significant for MTAC creatinine (P=0.035) and D/D(0) glucose (P=0.020). In summary, this experience demonstrates functional stability of the peritoneal membrane in pediatric patients receiving PD. However, follow-up assessments of peritoneal solute kinetics may be necessary in patients with a history of peritonitis in order to permit early identification of those who may be at risk for ultrafiltration failure and sclerosing peritonitis.

A Simple Assessment of Peritoneal Transport in Stable Continuous Ambulatory Peritoneal Dialysis Patients

We studied the peritoneal transport properties in 175 stable continuous ambulatory peritoneal dialysis (CAPD) patients seeking a simple and handy assessment of peritoneal permeability to small solutes. Measurement of creatinine in biological fluid was known to suffer from interference by high glucose concentration in the sample. Furthermore, the interference is also affected by the creatinine concentration of the specimen. Peritoneal transport properties were studied by determining the dialysate to plasma ratio of creatinine concentration (D/P) at the fourth hour of the peritoneal equilibration test, and the mass transfer area coefficient of creatinine (MTACCr) or glucose (MTACGlu). The ratio of glucose concentration in peritoneal dialysate effluent (PDE) at 4 and 0 h (G4/G0) was examined and compared with various peritoneal parameters. There were significant logarithmic correlations between D/P or G4/G0 with MTACCr (r = 0.96 and 0.79, respectively, p < 0.0001). The correlation between G4/G0 and D/P was linear (r = –0.82, p < 0.0001). A fairly good agreement was present between G4/G0 and D/P by Bland and Altman’s method. The bias was –0.93% with 95% confidence interval –23.29% to 21.43% of the measured value. Systematic error was found when D/P or G4/G0 were compared with MTACCr. D/P under estimated MTACCr in the high range. The reverse happened for G4/G0. Net ultrafiltration (NUF) also correlated with MTACCr, D/P and G4/G0 (r = –0.32, p < 0.001; –0.26, p < 0.01; and 0.16, p < 0.05, respectively.In conclusion, the use of G4/G0 as a measure of peritoneal transport in CAPD is an acceptable alternative to D/P. It is highly reproducible and avoids correction of interference when creatinine transport parameters are measured. Because of the logarithmic relations of G4/G0 (or D/P) with MTACCr, the former should not be directly converted to MTACCr. Such a simple measure of peritoneal permeability is, however, most convenient for serial monitoring and can be useful to detect early loss of ultrafiltration or solute clearance.

Dialysate cell population and cancer antigen 125 in stable continuous ambulatory peritoneal dialysis patients: Their relationship with transport parameters

We investigated the total cell count and cell population of the overnight peritoneal dialysis effluent (PDE) by flow cytometry in 76 stable continuous ambulatory peritoneal dialysis (CAPD) patients. The mean percentage of mesothelial cells and macrophages was 4.4% and 57%, respectively. A higher percentage of dead cells among the mesothelial cells compared with other cell populations in the PDE was observed. Peritoneal transport properties were studied in every patient by determining the dialysate to plasma ratio of creatinine concentration (D/P) at the fourth hour of the peritoneal equilibration test, and the mass transfer area coefficient of creatinine (MTACCr) or glucose. Cancer antigen 125 (CA125), suggested as a bulk marker for the mesothelial mass in stable peritoneal dialysis patients, was determined in the PDE. No correlation was demonstrated between CA125 and the number of mesothelial cells, lymphocytes, or macrophages in the PDE. A significant correlation was observed between CA125 and different parameters of peritoneal transport (D/P and MTACCr). On the contrary, neither the history of peritonitis nor the duration of CAPD appeared to affect the CA125 concentration in the PDE. The lack of correlation between CA125 in the PDE and the duration of CAPD may be related to the early loss of peritoneal transport properties as a result of the use of hypertonic dialysate in the majority of our patients with small-volume CAPD (3 × 2 L daily exchange). Our findings suggest that CA125 may not necessarily correlate well with the number of mesothelial cells in PDE. In patients with vanishing of the mesothelial layer, the measurement of CA125 (as a bulk marker for the mesothelial mass in the peritoneum) may reflect the change of peritoneal transport properties.

Analysis of Ultrafiltration Failure in Peritoneal Dialysis Patients by Means of Standard Peritoneal Permeability Analysis

Ultrafiltration failure (UFF) is a complication of peritoneal dialysis (PD) treatment that occurs especially in long-term patients. Etiological factors include a large effective peritoneal surface area [measured as high mass transfer area coefficient (MTAC) of creatinine], a high effective lymphatic absorption rate (ELAR), a large residual volume, or combinations. The prevalence and etiology of UFF were studied and the contribution of transcellular water transport (TCWT) was analyzed. A new definition of UFF and guidelines for the analysis of its etiology were derived from the results. Peritoneal dialysis unit in the Academic Medical Center in Amsterdam. Cross-sectional study of standard peritoneal permeability analyses (4-hr dwells, dextran 70 as volume marker) with 1.36% glucose in 68 PD patients. Patients with negative net UF (change in intraperitoneal volume, dIPV < 0 mL) were analyzed further using 3.86% glucose, whenever possible. Among 68 patients (duration of PD 0.3-178 months), 39 had negative net UF with 1.36% glucose. These patients had greater MTAC creatinine and glucose absorption, and higher ELAR (p < 10(-4)) than the patients with positive UF. dIPV and transcapillary UF rate (TCUFR) were lower (p < 10(-5)). Twenty of these patients could be studied using 3.86% glucose. dIPV was greater than 400 mL/4 hr in this test in 12 patients, implying that no clinically important UFF was present. Ultrafiltration failure (dIPV < 400 mL) was found in 8 patients, giving a prevalence of 23%. This last group had been treated with PD for a longer period (p = 0.03), had higher ELAR (p = 0.07), but lower residual volume (p = 0.03), and lower TCUFR (p = 0.01). Ultrafiltration failure was associated with a high MTAC creatinine in 3 patients, a high ELAR in 4 patients, and a combination of factors in one. As an additional possible cause, TCWT was studied, using the sodium gradient in the first hour of the dwell, corrected for diffusion (dNA). Five patients had dNA > 5 mmol/L, indicating normal TCWT. The 3 patients with dNA < 5 mmol/L tended to be treated longer (p = 0.19) and had lower TCUFR (p = 0.04). A smaller difference was found between dIPV 3.86% and 1.36% (p = 0.04) compared to the dNA > 5 mmol/L group, but no differences were present for MTAC creatinine, ELAR, residual volume, or glucose absorption. In addition to known factors, impairment of TCWT can be a cause of UFF. A standardized dwell with 1.36% glucose overestimates UFF. Therefore, 3.86% glucose should be used for identification of patients with UFF, especially because it provides additional information on TCWT. Ultrafiltration failure can be defined as net UF < 400 mL/4 hr with 3.86% glucose during a 4-hour exchange.

Peritoneal Sclerosis in Chronic Peritoneal Dialysis Patients: Analysis of Clinical Presentation, Risk Factors, and Peritoneal Transport Kinetics

To analyze clinical features of peritoneal sclerosis (PS) in a group of peritoneal dialysis (PD) patients, and to compare potential risk factors and peritoneal transport characteristics with a control group matched for duration of PD. Study 1: Retrospective study of 16 PD patients with PS. Study 2: Case-control study comparing 10 patients with evident PS to 30 control patients who were matched for duration of PD. Continuous Ambulatory Peritoneal Dialysis unit in the Academic Medical Centre in Amsterdam. The incidence of PS was 3.5 per 1000 patient years. PS was diagnosed either during PD (n = 10), in patients on hemodialysis (n = 2), or after successful transplantation (n = 4). Presenting symptoms were bowel obstruction, ascites, blood-stained effluent, and impaired net ultrafiltration. Macroscopic confirmation of the diagnosis was possible in 13 patients. Sclerotic encapsulation was present in 8 of them. Patients with PS were divided into three groups based on clinical symptoms and typical macroscopical findings. In category I the diagnosis PS was obvious (10 patients), in category II the diagnosis was highly suggestive (3 patients), and in category III it was doubtful (3 patients). Treatment was conservative in most patients. Surgical treatment was only possible in four and immunosuppressive therapy was given in 5 patients. Peritoneal sclerosis was the direct cause of death in 1 patient. Five patients died during follow-up due to other causes. At present, 7 patients are well and 3 patients (all from category I) still have recurrent bowel obstruction. Compared to matched controls, no difference existed in peritonitis incidence, or in the percentage of patients with former renal transplantations. The number of patients treated with beta-blocking agents and the number of previous abdominal surgeries were not different. The number of catheter-related surgical procedures was higher in the PS patients than in the control group. The mass transfer area coefficient (MTAC) of creatinine was higher in PS patients and net ultrafiltration with 1.36% glucose was lower. The estimated cumulative glucose exposure until the diagnosis of PS was made was larger in PS patients than in their controls. This difference was already present in the first year of PD treatment in 8 of 10 patients. The initial values for the MTAC creatinine were similar in both groups. The presenting symptoms of PS were bowel obstruction, ascites, and blood-stained effluent, often in combination with loss of net ultrafiltration. Peritoneal sclerosis is a complication of long-duration PD and could also become manifest after a successful renal transplant. Treatment should be conservative unless complications require surgical intervention. Patients with PS had lower net ultrafiltration and higher transport rates compared to controls who were matched for duration of PD. Although peritonitis incidence was similar, a relation of PS with severe peritonitis may be present in some patients. Glucose exposure is likely to be an important risk factor for PS.