Abstract
Effect of Caveolin-1 on Solute Transport and Ultrafiltration in Peritoneal Dialysis
Objectives: To investigate the influence of caveolin-1 (Cav1) deletion on macromolecular and micromolecular solute transport and ultrafiltration (UF) during peritoneal dialysis (PD).
Methods: We used age- and sex-matched Cav1-deficient (Cav1–/–) mice and wild type (Cav1+/+) mice for this study. We performed 2-hour peritoneal equilibration tests, depicting transport curves, calculating UF, examining biochemical parameters in PD effluent, and detecting the expression of key transport-related proteins endothelial nitric oxide synthase (eNOS) and aquaporin-1 (AQP-1).
Results: Cav1–/– mice had net UF (69 ± 3.1 μL/g vs. 71±2.9 μL/g, p > 0.05) and small-solute transport that were similar to those in Cav1+/+ mice [30-min dialysate-to-plasma ratio (D/P) of urea: 0.37 ± 0.01 vs. 0.34 ± 0.05; 120-min D/P urea: 0.79 ± 0.02 vs. 0.75 ± 0.05; 30-min end dialysate–to–initial dialysate (D/D0) glucose (Glu): 0.62 ± 0.02 vs. 0.58 ± 0.03; 120-min D/D0 Glu: 0.36 ± 0.01 vs. 0.35 ± 0.02; p > 0.05] and similar expression of eNOS and AQP-1. However, Cav1–/– mice had significantly higher total protein in PD effluent than did Cav1+/+ mice (1.14 ± 0.06 vs. 0.71 ± 0.10, p < 0.05).
Conclusions: Caveolin-1 does not influence water and small-solute transport, but its presence limits the transport of macromolecular protein.
Peritoneal Membrane Characteristics in Saudi Patients on Peritoneal Dialysis
Peritoneal dialysis (PD) is a well-established modality for end-stage renal disease with excellent rates of patient and technique survival. However, PD is being underutilized in most parts of the world.
In recent years, substantial data have been gathered on the characteristics of the peritoneal membrane and on the anatomic and pathophysiologic changes occurring with long-term PD, but there is a dearth of information available for PD patient characteristics as related to Middle Eastern and Arab populations. In Saudi Arabia, data collected by the Saudi Center for Organ Transplantation showed that, in 2007, PD patients accounted for a mere 4.8% of all patients receiving renal replacement therapy, including hemodialysis and renal transplant.
We followed a total of 52 patients [30 women, 23 men; mean age: 50.5 years (14 – 86 ± 19.4)] on continuous ambulatory PD (CAPD, n = 14) and automated PD (APD, n = 29) being treated in the peritoneal dialysis unit of King Khalid University Hospital, Riyadh. In these patients, average body mass index was 27.1 (12.5 – 38.5 ± 4.6) and mean body surface area was 1.7 m2 (1 – 2.11 ± 87 m2). In all patients, a standardized peritoneal equilibration test (PET) was performed 4 – 6 weeks after initiation of regular PD. Creatinine clearance (CCr) and Kt/V were measured 6 – 8 weeks after initiation of dialysis and at 3- to 4-month intervals subsequently. Residual renal function was measured as daily urine output (24-hour urine collection). Mean daily urine output was 610 mL (0 – 2833 ± 798), mean hemoglobin was 11.02 g/dL (7.21 – 15.8 ± 1.896 g/dL), and mean weekly dose of erythropoietin was 7000 U (7031.5, 2000 – 30000 ± 3577) in these patients. The average weekly total Kt/V was calculated to be 1.965 (0.79 – 5.48 ± 1.24), and weekly total CCr was 56.595 L (19.9 – 132.8 ± 24.8 L). According to the PET, 8% of subjects belonged to the high transport category; 44%, to the high-average category; 46%, to the low-average category; and 2%, to the low transport category. The characteristics and demographic parameters seen in this patient population are comparable to those seen in other studies in Middle East and worldwide, including data collected in Canada, New Zealand, and Mexico.
Change in Membrane Characteristics in Saudi Peritoneal Dialysis Patients
Ultrafiltration failure remains a leading cause of technique failure in peritoneal dialysis (PD) patients (pts). Studies have shown that peritoneal membrane (PM) undergoes morphology changes over time that increase the solute transport rate, induced by primary renal disease (especially diabetes), exposure to hypertonic glucose (glu) solution, residual renal function (RRF), and peritonitis (P).
Over a period of 3 years, we retrospectively followed 30 pts (15 men, 15 women) under treatment in the PD unit at King Khalid University Hospital. A standardized peritoneal equilibration test (PET) was performed 4 – 6 weeks after initiation of regular PD, and repeated at a mean interval of 13.64 months (11 – 19 ± 4.13). Based on the difference between initial and repeat PETs, pts were allocated either to group 1 [n = 16, no change or change of <0.1 in the 4-h dialysate-to-plasma ratio (D/P) of creatinine (Cr)] or group 2 (n = 14, increase of at least 0.1 in 4-h D/P Cr).
Results: In group 1, 37.5% pts had diabetes (DM), as compared with 64.3% in group 2. The two groups did not show any significant difference in age, sex, modality, use of icodextrin, RRF, or body mass index (BMI). The total daily exposure to glu in group 1 was 172.09 (81.6 – 289.4 ± 49.198) compared with 200.057 (104.6 – 579 ± 123.39) in group 2 (statistically nonsignificant). Mean weekly total Kt/V was 1.807 (1.02 – 2.74 ± 0.587) in group 1 and 1.981 (1.09 – 2081 ± 0.6928) in group 2. Mean weekly total CCr was 51.677 L (19.98 – 96.27 ± 41.257 L) in group 1 and 66.821 (40.09 – 126.2 ± 39.701 L) in group 2. There were 13 episodes of P in group 1 and 17 in group 2 (statistically nonsignificant). Changes in PM permeability included 5 pts who changed from low-average (LA) to high-average (HA); 2 from HA to high (H); 1 each from low (L) to LA, HA, and H; and 1 from LA to H. The other 3 showed no change in PET category, despite a change of >0.1 in D/P Cr.
Conclusions: Over a period of 3 years, 14 pts (46.6%) showed a change in PM permeability. This change was seen in all PM types, independent of pt age, sex, BMI, and other factors. Notably, DM was present in 64.3% of pts in the group that showed a change in PM permeability as compared with 37.5% in the group that showed no considerable change. Lack of a clear statistical difference between the groups could be a result of the small sample size or possibly of genetic or racial factors. Close to 50% of our pts underwent some change in PM characteristics. Such changes necessitate regular PETs and appropriate changes in the therapy regime. Further studies, with longer follow-up and a larger study population, are needed to further evaluate this process.
Peritoneal Membrane Characteristics in Vietnamese Patients on Continuous Ambulatory Peritoneal Dialysis
Background: Assessment of peritoneal membrane characteristics in continuous ambulatory peritoneal dialysis (CAPD) patients and therapy modification are essential for optimal outcomes in PD.
Methods: This prospective descriptive study followed 45 CAPD patients in 3 hospitals for 6 months. Peritoneal membrane classification at months 1 and 6 of CAPD was based on the standardized peritoneal equilibration test originally described by Zbylut J. Twardowski.
Results: The 45 end-stage renal disease patients [64.4% men, 35.6% women; mean age: 44.1 ± 14.4 years (range: 19 – 71 years)] were treated with CAPD in Bach Mai Hospital, 108 Central Military Hospital, and E Hospital in Hanoi City, Vietnam, from August 2007 to June 2008. In these patients, chronic glomerulonephritis caused 82.2% of the chronic kidney failure; other causes were diabetes (8.9%), hypertension (4.5%), tubulointerstitial nephritis (2.2%), and systemic lupus erythematosus (2.2%). Three cases of peritonitis occurred. Most patients (77.8%) were high-average and low-average transporters, suitable for CAPD. Another 17.8% were high transporters, and 4.4% were low transporters. Ultrafiltration at 4 hours was lowest in high transporters, higher in high- and low-average transporters, and highest in low transporters (p < 0.01). Urea clearance was the same in each group at different times, but the creatinine clearance varied between the groups (p < 0.01). Ultrafiltration over 24 hours was higher in the low transporters than in the other groups. The drain volume in the other groups wasn't different (p > 0.05) because high transporters used dextrose 2.5% in the night exchange.
The peritoneal membrane characteristics of these patients did not change in the first 6 months of CAPD, even in the patients experiencing peritonitis.
Factors Influencing Peritoneal Transport Rate of Continuous Peritoneal Dialysis Patients in Saiful Anwar Teaching Hospital, Malang, East Java, Indonesia
Measurement of peritoneal transport rate (PTR) is important for both characterization of functional state and prescription of the individual dialysis dose. Twardowski et al. presented a peritoneal equilibration test (PET) that is reproducible in developing countries such as Indonesia.
Objectives: To measure the PTR and analyze the factors influencing the PTR in continuous ambulatory peritoneal dialysis (CAPD) patients in Saiful Anwar Teaching Hospital, Malang, East Java.
Methods: Cross-sectional study. In 37 patients, we performed a PET and calculated the dialysate-to-plasma ratio (D/P) of creatinine at 4 hours. We collected data about age, sex, duration of CAPD, and diabetes mellitus.
Results: In the 37 patients [average age: 47.35 ± 12.84 years (range: 23 – 83 years)], duration of CAPD was 9.98 ± 8.96 months (range: 2 – 36 months), PTR (as D/P creatinine) was 0.73 ± 0.14 (range: 0.51 – 1.06), and membrane characteristics were 27.03% low-average transport, 43.24% high-average transport, and 29.71% high transport. Using multivariate analysis, the factors influencing PTR were age, sex, duration of CAPD, and diabetes mellitus.
Conclusions: In our center, high transporters are more prevalent than are low transporters. Age, sex, duration of CAPD, and diabetes mellitus are the factors influencing peritoneal transport rate in our CAPD patients.
Improving the Accuracy of the 2-Hour Peritoneal Equilibration Test as a Surrogate for the Standard 4-Hour Test in Asian Children
Objectives: Evaluation of peritoneal membrane transport capacity using the peritoneal equilibration test (PET) is important for determining the adequacy of a dialysis regimen. In young children, a PET measurement using the classical 4-hour test can be laborious and carries a risk of excessive ultrafiltration and hypotension. This study aimed to determine the accuracy of the short 2-hour PET in predicting peritoneal transport characteristics in Asian children.
Methods: A PET was performed using 25 samples with dwell volumes ranging from 1000 mL/m2 to 1100 mL/m2 from 16 subjects, age range 2 to 21 years. The dialysate-to-plasma ratio (D/P) of creatinine (Cr) and the ratio of dialysate glucose to baseline dialysate glucose (D/D0) at 2 and 4 hours were calculated. Kappa correlation and accuracy were calculated for both D/P Cr and D/D0 glucose, and discriminant analysis was performed.
Results: Following the standard 4-hour test, peritoneal transport was defined as 20% high, 20%high average, 36% low-average, and 24% low (D/P Cr), and 12% high, 36% low-average, and 52%low (D/D0 glucose). Kappa correlation and accuracy in the 2-hour PET was better for D/P Cr (0.780, 84%) than for D/D0 glucose (0.362, 56%). Using discriminant analysis adjusting for age, sex, body surface area, weight, height, and volume per m2, those results could be improved to 0.892 (92%) and 1.0 (100%) for D/P Cr and D/D0 glucose respectively. Upon further adjustment for volume infused and the 2-hour PET for D/D0 glucose, the results for D/P Cr prediction further increased to 0.945 (96%).
Conclusions: Our findings suggest that the short 2-hour PET could be used clinically with good accuracy as a surrogate for the standard 4-hour PET to define peritoneal transport characteristics in Asian children.
Icodextrin Can Improve Dialysate Cancer Antigen 125 Level in Peritoneal Dialysis Patients
Objectives: As an iso-osmotic solution, icodextrin (ICO) can reduce injury to the peritoneal membrane induced by high glucose (GLU) and high osmotic pressure. Conversely, the effect of ICO metabolites on the peritoneal membrane is unclear. Cancer antigen 125 (CA125) is known to be secreted by peritoneal mesothelial cells (PMCs). Changes in CA125 before and after ICO use can reflect the function of PMCs.
Methods: We randomized stable prevalent continuous ambulatory peritoneal dialysis (PD) patients to either 7.5% ICO or to GLU solution for 4 weeks. Peritoneal membrane function [dialysate-to-plasma ratio (D/P) of creatinine (Cr)] was determined at baseline. Ultrafiltration (UF) volume in the long dwell was measured at baseline and at 2 and 4 weeks. Creatinine clearance (CCr), UF, and CA125 in peritoneal effluent from the long night dwell were measured at baseline and after 4 weeks.
Results: The study enrolled 54 patients. Baseline conditions (sex, age, primary diseases, PD dosage, PD duration, and height, weight, Body surface area, D/P Cr, and other factors) were not different between the groups. After 2 and 4 weeks of therapy, UF in the long dwell was significantly higher in the ICO than in the GLU group (2 weeks: 494.2 ± 167.7 mL ICO vs. 345.8 ± 220.2 mL GLU, p < 0.05; 4 weeks: 520.4 ± 204.7 mL ICO vs. 316.2 ± 190.1 mL GLU, p < 0.001). Also, peritoneal CCr in the long dwell time was significantly higher in the ICO group (ICO: 2229.7 ± 246.2 mL/12 h at week 4 vs. 1969.3 ± 352.6 mL/12 h at week 0, p < 0.001; GLU: 1908.6 ± 298.3 mL/12 h at week 4 vs. 1858.1 ± 274.6 mL/12 h at week 0, p > 0.05). Additionally, CA125 in the long dwell was comparable between the groups at baseline (11.9 ± 4.8 U/mL ICO vs. 12.8 ± 7.2 U/mL, p > 0.05). After follow-up for 4 weeks, CA125 levels increased in the ICO group and decreased in the GLU group. As a result, CA125 was significantly higher in the ICO group (16.8 ± 8.6 U/mL ICO vs. 11.8 ± 7.0 U/mL GLU, p < 0.05). When ΔCA125 (CA125 at week 4 – CA125 at baseline) was used to evaluate PMC function, the difference between two groups became more significant (5.9 ± 6.3 vs. –0.7 ± 3.3, p < 0.001).
Conclusions: Compared with GLU-based solution, 7.5% ICO significantly improved UF and small-solute clearance, and increased the CA125 level in PD effluent.
Proteomic Study of Body Fluid in Peritoneal Dialysis Patients with Different Types of Peritoneal Membranes
Objectives: To analyze proteomic profiles and identify differential proteins in serum and peritoneal dialysate effluents from patients on continuous ambulatory peritoneal dialysis (CAPD) with different types of peritoneal membranes.
Methods: We performed a proteomic technique based on 2D gel. Serum and peritoneal dialysate effluents (PDEs) were obtained from CAPD patients with different membrane transport status. Samples were analyzed by 2D gel, and selected proteins were identified by mass spectrometry (MS), tandem mass spectrometry (MS/MS), and ELISA. The standard peritoneal equilibration test (PET) was used to evaluate peritoneal membrane transport function, which can be classified as high (H), high-average (HA), low-average (LA), and low (L).
Results: The study enrolled 27 incident CAPD patients, including 6 classified a H transporters, 8 as HA transporters, 8 as LA transporters, and 5 as L transporters. We identified 13 and 6 differential proteins, in PDE and serum respectively, from CAPD patients with different types of peritoneal membranes. In H transporters, levels of isoform 1 of α1 antitrypsin precursor, D-binding protein precursor, AMBP protein precursor, and complement C3 precursor (fragment) in PDE and concentrations of apolipoprotein E precursor and IGHM protein in serum were significantly higher. The proteomic data were confirmed by the ELISA analysis in PDE and serum samples from another 48 patients. The results were consistent with those obtained from 2DE approach.
Conclusions: Changes of differential proteins in body fluids may potentially be biomarkers for different types of peritoneal membranes. However, further studies are needed to investigate the sensitivity and specificity of these proteins for peritoneal transport properties.
Dynamic Mechanism of Sodium Transport in Peritoneal Dialysis
Objectives: Na retention is universal in peritoneal dialysis (PD) patients. It can cause many complications that reduce patient and technique survival rates. Dialysis is the main way to remove excess Na. Na transport through the peritoneum is still not completely understood. This study explored the dynamic mechanism of transperitoneal Na transport.
Methods: A mathematical model of K transport was established according to dialysis dynamics and the three-pore theory:
An equation of Na removal was established,
where C represents solute concentrations (mmol/L) and the subscripts D, P, and i represent dialysate, plasma, and solutes that can induce osmosis, including glucose and Na and its anions, among others. CD0, CD (t), and CP represent the initial, instant concentration of solutes in D and P (mmol/L) respectively. VD0 and VD(t) represent the initial and instant volume of D in the peritoneal cavity (mL). PS, LpS, s, σ, and α respectively represent the mass transport area coefficient (mL/min), hydraulic conductance (mL “min–1“mmHg–1), sieving coefficient, osmotic reflection coefficient, and ultrafiltration fraction. Q, Qu, Qa, and L respectively represent net ultrafiltration (UF), UF, and re-absorption (mL/min). During calculation, Q is set to 200 mL according to clinical practice and L to 0.3 mL according to Rippe et al. Δπ pro is the colloid osmotic pressure difference caused by P albumin (mmHg). ΔP is the mean hydrostatic pressure difference between blood capillaries and peritoneal cavity (mmHg). D/PK+ is the concentration ratio of K between D and P.
Results: The Na concentration in dialysis solution appeared noticeable sedimentation no matter the peritoneal permeability and dialysate concentration. It was more obvious with low transport and high dialysis solution. More Na was removed with higher-concentration dialysate in a single dwell, but it became inverse if UF was excluded, and Na removal was little only by the instilled volume. Na removal depended mainly on UF volume, which were positively correlated.
Conclusions: The “sedimentation” phenomenon during dialysis reduces the removal of Na. Na removal depends mainly on UF volume but not on instilled volume in PD.
Shan Y.S.,1,2 Xu FF.,2 Mao R.Y.,2 Ji J.,1
Influencing Factors and Relationships between the Transport of Large and Small Molecular Solutes in Continuous Ambulatory Peritoneal Dialysis Patients
Objectives: The key to improving the efficacy of peritoneal dialysis (PD) has been proposed to lie in how to increase the transportation of small molecular solutes and reduce the loss of protein. This study investigated the transport rates of both small and large molecular solutes and explored whether drugs [nitroprusside (NP) or salvia miltiorrhiza (SM)] and ventral movement can influence the transport rates of solutes and efficiency of PD.
Methods: The study included 6 groups of 20 patients (pts) without peritonitis during the preceding 6 weeks: group 1, pts on continuous ambulatory PD (CAPD) for only 30 days; group 2, pts on CAPD for more than 1 year; group 3, pts at various periods of CAPD (3 – 29 months) as controls to groups 4, 5, and 6 through self and pre–post control. The pts in group 3 sequentially received intraperitoneal injections of NP and SM or increased ventral vibration. Between each injection, the pts underwent routine CAPD for 1 month. Standard peritoneal equilibration tests (PETs) were performed, and mass transfer area coefficients (MTAC) were calculated after the drugs were added to the dialysate or after ventral vibration. Concentrations of total protein, albumin, and immunoglobulin G (IgG) were examined in effluent dialysate, and the drained volumes were recorded.
Results: Protein loss was not significantly different between the groups. Compared with pts whose PET dialysate-to-plasma ratio (D/P) of creatinine (Cr) was <0.65, pts with D/P Cr≥0. 65 had no significant protein loss. Protein loss was not different between pts with a urea clearance index of ≥2.0 and <2.0. The MTACs of blood urea nitrogen and Cr increased significantly in both the NP group and the vibration group (p < 0.05) as compared with controls, and the concentration of IgG in effluent was higher in the NP group than in controls (p < 0.05). However, total drained volume was not significantly different between the three groups.
Conclusions: This study further shows that large proteins and small solutes have different transport mechanisms. NP and vibration can increase peritoneal transport of small molecular solutes; vibration has less influence on the loss of protein in CAPD. These findings suggest that moderate movement may improve the removal of small molecules in CAPD pts.