Peritoneal Dialysis Catheter Increases Leukocyte Recruitment in the Mouse Parietal Peritoneum Microcirculation and Causes Fibrosis

♦ Background:

The objective of this study was to examine the effects of a conventional dialysis solution and peritoneal catheter on leukocyte-endothelial cell interactions in the microcirculation of the parietal peritoneum in a subacute peritoneal dialysis (PD) mouse model.

♦ Methods:

An intraperitoneal (IP) catheter with a subcutaneous injection port was implanted into mice and, after a 2-week healing period, the animals were injected daily for 6 weeks with a 2.5% dextrose solution. Intravital microscopy (IVM) of the parietal peritoneum microcirculation was performed 4 hours after the last injection of the dialysis solution. Leukocyte-endothelial cell interactions were quantified and compared with catheterized controls without dialysis treatment and naïve mice.

♦ Results:

The number of rolling and extravascular leukocytes along with peritoneal fibrosis and neovascularization were significantly increased in the catheterized animals compared with naïve mice but did not significantly differ between the 2 groups of catheterized animals with sham injections or dialysis solution treatment.

♦ Conclusion:

The peritoneal catheter implant increased leukocyte rolling and extravasation, peritoneal fibrosis and vascularization in the parietal peritoneum independently from the dialysis solution treatment.     

Oral Astaxanthin Supplementation Prevents Peritoneal Fibrosis in Rats

♦ Background:

Preventing peritoneal damage during peritoneal dialysis is critical. Reactive oxygen species (ROS) have an important role in peritoneal damage; however, few studies have investigated this. We aimed to determine the effects of oral astaxanthin (AST) supplementation in a peritoneal fibrosis (PF) rat model.

♦ Methods:

Thirty-seven Sprague–Dawley rats were divided into 5 groups: Control 1 (fed a normal diet without stimulation), Control 2 (fed an AST-supplemented diet without stimulation), Group 1 (fed a normal diet with 8% chlorhexidine gluconate [CG] stimulation for 3 weeks), Group 2 (fed a 0.06% AST-supplemented diet with CG stimulation), and Group 3 (fed a 0.06% AST-supplemented diet that was initiated 4 weeks before CG stimulation). Peritoneal fibrosis, vascular proliferation, and fibrosis-related factor expression were examined.

♦ Results:

Peritoneal thickness was significantly suppressed by AST supplementation. Astaxanthin diminished the number of CD68-, 8-hydroxy-2′-deoxyguanosine (8-OHdG)-, and monocyte chemoattractant protein-1 (MCP-1)-positive cells. Type 3 collagen, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and MCP-1 mRNA expression was significantly lower in Group 3 than in Group 1. Increased transforming growth factor-β (TGF-β) and Snail mRNA expression, vascular density, and the number of α-smooth muscle actin (α-SMA)-positive cells were also decreased in Group 3.

♦ Conclusion:

Astaxanthin suppressed PF development through the inhibition of inflammation and oxidation in PF rats. It appears that the anti-oxidative agent AST may be useful for the prevention of peritoneal damage.     

Genetic Polymorphisms and Peritoneal Membrane Function

♦ Background:

Outcomes for peritoneal dialysis (PD) patients are affected by the characteristics of the peritoneal membrane, which may be determined by genetic variants. We carried out a systematic review of the literature to identify studies which assessed the association between genetic polymorphisms, peritoneal membrane solute transport, and clinical outcomes for PD patients.

♦ Methods:

The National Library of Medicine was searched using a variety of strategies. Studies which met our inclusion criteria were reviewed and data abstracted. Our outcomes of interest included: high transport status peritoneal membrane, risk for peritonitis, encapsulating peritoneal sclerosis (EPS), patient and technique survival. We combined data from studies which evaluated the same genetic polymorphism and the same outcome.

♦ Results:

We evaluated 18 relevant studies. All studies used a candidate gene approach. Gene polymorphisms in the interleukin (IL)-6 gene were associated with peritoneal membrane solute transport in several studies in different ethnic populations. Associations with solute transport and polymorphisms in endothelial nitric oxide synthase and receptor for advanced glycation end product genes were also identified. There was evidence of a genetic predisposition for peritonitis found in 2 studies, and for EPS in 1 study. Survival was found to be associated with a polymorphism in vascular endothelial growth factor and technique failure was associated with a polymorphism in the IL-1 receptor antagonist.

♦ Conclusions:

There is evidence that characteristics of the peritoneal membrane and clinical outcomes for PD patients have genetic determinants. The most consistent association was between IL-6 gene polymorphisms and peritoneal membrane solute transport.     

Development and Testing of Self-Management Scale for PD Patients

♦ Objectives:

To develop and evaluate the self-management scale for peritoneal dialysis (PD) patients.

♦ Methods:

The item pool was formulated based on literature reviews and in-depth interviews. An initial scale containing five factors and 44 items was constructed through two rounds of Delphi expert consultation and a preliminary test. A total of 313 PD patients from the Jiangsu-Zhejiang-Shanghai area were surveyed to test the reliability and validity of the scale.

♦ Results:

Five factors, namely solution bag replacement, troubleshooting during operation, diet management, complication monitoring, emotion management and return to social life, were extracted by exploratory factor analysis: the 28 items could explain 64.567% of the total variance; the content validity index was 0.963; the Cronbach’s α coefficient and split-half coefficient were 0.926 and 0.960 respectively; and test-retest reliability was 0.937.

♦ Conclusion:

The scale has been proved to be a reliable and valid tool which allows PD nurses to evaluate the self-management ability of PD patients. The evaluation outcomes can serve as a basis for individualized nursing plans and interventions so as to provide highly effective nursing care.     

Alterations of Intercellular Junctions in Peritoneal Mesothelial Cells from Patients Undergoing Dialysis: Effect of Retinoic Acid

♦ Background:

Dialysis patients are classified according to their peritoneal permeability as low transporter (LT, low solute permeability) or high transporter (HT, high solute permeability). Tight junction (TJ) proteins are critical to maintain ions, molecules and water paracellular transport through peritoneum. Exposure to peritoneal dialysis solutions causes damage to TJ in human peritoneal mesothelial cells (HPMCs). We analyzed the quantity, distribution and function of TJ proteins: claudin-1, -2 and -8, ZO-1 and occludin, in HPMC cultures from LT and HT patients. Since all-trans retinoic acid (ATRA) might modify the expression of TJ proteins, we studied its effect on HPMCs.

♦ Methods:

Control HPMCs were isolated from human omentum, while HT or LT cells were obtained from dialysis effluents. Cells were cultured in presence of ATRA 0, 50 or 100 nM. Transepithelial electrical resistance (TER) measurement, immunostaining and Western blot analyses were performed.

♦ Results:

HT exhibited lower TER than control and LT monolayers. Immunofluorescence for TJ was weak and discontinuous along the cell contour, in LT and HT. Furthermore, claudin-1, occludin and ZO-1 expressions were decreased. In all groups, claudin-2 was localized at nuclei. We observed that ATRA improved TJ distribution and increased TJ expression in HT. This retinoid did not modify claudin-2 and -8 expressions. All-trans retinoic acid decreased TER in HT, but had no effect in LT.

♦ Conclusions:

Tight junctions were altered in HPMCs from dialyzed patients. The HT monolayer has lower TER than LT, which might be associated with the peritoneal permeability in these patients. ATRA might be a therapeutic alternative to maintain mesothelial integrity, since it improved TJ localization and expression.     

Functional Disability in Older Adults Maintained on Peritoneal Dialysis Therapy

♦ Background:

Older in-center hemodialysis patients have a high burden of functional disability. However, little is known about patients on home chronic peritoneal dialysis (PD). As patients opting for home dialysis are expected to play a greater role in their own dialysis care, we hypothesized that a relatively low number of PD patients would require help with basic self-care tasks (ADL) and instrumental activities of daily living (IADL).

♦ Methods:

We used a cross-sectional study design to measure the proportion of patients aged 65 years and older undergoing outpatient PD who needed help with day-to-day activities. Patients living in nursing homes were excluded from the study. Functional dependence in ADL and IADL tasks were measured by the Barthel and Lawton Scales. Physical performance measures used included the timed up-and-go (TUG) test, chair stands and Folstein mini-mental score (MMSE).

♦ Results:

A total of 74 of 76 (97%) eligible PD patients participated. Patients had a mean age of 76.2 ± 7.5 years. Thirty-six percent had impaired MMSE scores, 69% were unable to stand from a chair without the use of their arms and 51% had abnormal TUG scores. Only 8 patients (11%) were fully independent for both ADL and IADL activities. Dependence in one or more ADL activity was reported by 64% of participants, while 89% reported dependence in one or more IADL.

♦ Conclusions:

Impaired physical and functional performance is common in older patients maintained on PD. Collaborative geriatric-renal programs may be beneficial within the dialysis community.     

Embedded Catheters: Minimizing Excessive Embedment Time and Futile Placement while Maintaining Procedure Benefits

♦ Background:

Embedding peritoneal catheters far in advance of anticipated need may successfully commit patients to their modality choice and reduce central venous catheter use but can be complicated by excessive embedment periods and futile catheter placement.

♦ Objective:

Embedded catheter outcomes were studied to identify factors that minimize inordinate embedment time and futile placement while maintaining procedure benefits.

♦ Methods:

Clinical and laboratory data were examined in 107 patients with embedded catheters that were either externalized, remained embedded, or were futilely placed.

♦ Results:

Externalization of 84 catheters was performed after a median embedment period of 9.4 months. Flow dysfunction occurred in 14.3% of externalized catheters. Overall function rate was 98.8% after laparoscopic revision. One patient changed their mind about modality choice. Except for 1 patient hospitalized acutely in a facility unfamiliar with embedded catheters, none remaining on a peritoneal dialysis pathway initiated dialysis with a central venous catheter. Including catheters with extremely long embedment periods, the incidence of futile placement was 13.1%. Multiple regression analysis identified estimated glomerular filtration rate (eGFR) and serum albumin as the 2 variables best associated with catheter embedment duration (r² = 0.44, p < 0.0001). Diabetic nephropathy was statistically more likely to be associated with lower serum albumin values (p < 0.0001); however, no association was noted between diabetic status and embedment duration (p = 0.62).

♦ Conclusions:

Timing of the embedment procedure should include appraisal of both eGFR and serum albumin. Appropriate consideration of these values together may help minimize excessive embedment periods and decrease futile placements while preserving procedure benefits.     

The Association of Effluent Ca125 with Peritoneal Dialysis Technique Failure

♦ Background and objectives:

Cancer antigen 125 (CA125) reflects the mesothelial cell mass lining the peritoneal membrane in individual patients. A decline or absence of mesothelial cells can be observed with duration of peritoneal dialysis (PD) therapy. Technique failure due to peritoneal membrane malfunction becomes of greater importance after 2 years of PD therapy in comparison to the initial period. In this study, we aimed to investigate the association between effluent CA125 and technique survival in incident PD patients with a PD therapy period of at least 2 years.

♦ Methods:

Within the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD), a Dutch multicenter cohort including 2,000 incident dialysis patients, we identified all PD patients who developed technique failure after 2 years of PD therapy and randomly selected a number of them as cases in a nested case-control study. Controls were PD patients matched on follow-up time without technique failure. Cases and controls were included if they had a dialysate specimen available within 24 ± 6 months of PD therapy for retrospective CA125 determinations. Odds ratios for technique failure related to CA125 were estimated. We used a prospective cohort with incident PD patients from the Academic Medical Center–University of Amsterdam (AMC) for replication of effect estimates. In these patients, absolute risk of technique failure was estimated and related to effluent CA125 levels.

♦ Results:

A total of 38 PD patients were selected from the NECOSAD cohort. From the AMC cohort as replication cohort, 91 PD patients were included. Incidence rates of PD technique failure per 100 patient-years were 16.3 in the NECOSAD cohort and 12.9 in the AMC cohort. In both study populations CA125 levels below 12 – 14 kU/L were associated with an increased risk for technique failure. Technique survival rates in the AMC were 87% in patients with levels of CA125 above 12.1 kU/L and 65% for those with CA125 levels below this threshold after a maximum 5-year follow-up.

♦ Conclusions:

Patients with high CA125 levels after at least 2 years of PD therapy tend to have better technique survival than patients with low CA125 levels. These results support the importance of effluent CA125 as a risk factor for dropout in long-term PD therapy.     

Identification of Targets for Prevention of Peritoneal Catheter Tunnel and Exit-Site Infections in Low Incidence Settings

♦ Background:

Peritoneal catheter tunnel and exit-site infection (TESI) complicates the clinical course of peritoneal dialysis (PD) patients. Adherence to recommendations for catheter insertion, exit-site care, and management of Staphylococcus aureus (SAu) carriage reduces, but does not abrogate the risk of these infections.

♦ Objective:

To reappraise the risk profile for TESI in an experienced center with a long-term focus on management of SAu carriage and a low incidence of these infections.

♦ Method:

Following a retrospective, observational design, we investigated 665 patients incident on PD. The main study variable was survival to the first episode of TESI. We considered selected demographic, clinical, and technical variables, applying multivariate strategies of analysis.

♦ Main results:

The overall incidence of TESI was 1 episode/68.5 patient-months. Staphylococcus aureus carriage disclosed at inception of PD (but not if observed sporadically during follow-up) (hazard ratio [HR] 1.53, p = 0.009), PD started shortly after catheter insertion (HR 0.98 per day, p = 0.011), PD after kidney transplant failure (HR 2.18, p = 0.017), lower hemoglobin levels (HR 0.88 per g/dL, p = 0.013) and fast peritoneal transport rates (HR 2.92, p = 0.03) portended an increased risk of TESI. Delaying PD ≥ 30 days after catheter insertion markedly improved the probability of TESI. Carriage of methicillin-resistant SAu since the start of PD was associated with a high incidence of TESI by these bacteria. On the contrary, resistance to mupirocin did not predict such a risk, probably due to the use of an alternative regime in affected patients.

♦ Conclusions:

Adherence to current recommendations results in a low incidence of TESI in PD patients. Interventions on specific risk subsets have a potential to bring incidence close to negligible levels. Despite systematic screening and management, SAu carriage is still a predictor of TESI. Antibiotic susceptibility patterns may help to refine stratification of the risk of TESI by these bacteria. Early insertion of the peritoneal catheter should be considered whenever possible, to reduce the risk of later TESI.     

Activation of p38 Mitogen-Activated Protein Kinase Promotes Peritoneal Fibrosis by Regulating Fibrocytes

♦ Background: Peritoneal fibrosis is a serious complication of long-term peritoneal dialysis, and yet the precise pathogenic mechanisms of peritoneal fibrosis remain unknown. Fibrocytes participate in tissue fibrosis and express chemokine receptors that are necessary for migration. The p38 mitogen-activated protein kinase (MAPK) pathway regulates the production of chemokines and has been demonstrated to contribute to the pathogenesis of various fibrotic conditions. Accordingly, we used an experimental mouse model of peritoneal fibrosis to examine the dependency of fibrocytes on p38MAPK signaling.♦ Methods: Peritoneal fibrosis was induced in mice by the injection of 0.1% chlorhexidine gluconate (CG) into the abdominal cavity. Mice were treated with {"type":"entrez-nucleotide","attrs":{"text":"FR167653","term_id":"258093044","term_text":"FR167653"}}FR167653, a specific inhibitor of p38MAPK, and immunohistochemical studies were performed to detect fibrocytes and cells positive for phosphorylated p38MAPK. The involvement of p38MAPK in the activation of fibrocytes also was also investigated in vitro.♦ Results: Fibrocytes infiltrated peritoneum in response to CG, and that response was accompanied by progressive peritoneal fibrosis. The phosphorylation of p38MAPK, as defined by CD45+ spindle-shaped cells, was detected both in peritoneal mesothelial cells and in fibrocytes. The level of peritoneal expression of CCL2, a chemoattractant for fibrocytes, was upregulated by CG injection, and treatment with {"type":"entrez-nucleotide","attrs":{"text":"FR167653","term_id":"258093044","term_text":"FR167653"}}FR167653 reduced the number of cells positive for phosphorylated p38MAPK, the peritoneal expression of CCL2, and the extent of peritoneal fibrosis. Pretreatment with {"type":"entrez-nucleotide","attrs":{"text":"FR167653","term_id":"258093044","term_text":"FR167653"}}FR167653 inhibited the expression of procollagen type I α1 induced by transforming growth factor-β1.♦ Conclusions: Our results suggest that p38MAPK signaling contributes to peritoneal fibrosis by regulating fibrocyte function.     

The First Peritonitis Episode Alters the Natural Course of Peritoneal Membrane Characteristics in Peritoneal Dialysis Patients

♦ Objective:

Little or no evidence is available on the impact of the first peritonitis episode on peritoneal transport characteristics. The objective of this study was to investigate the importance of the very first peritonitis episode and distinguish its effect from the natural course by comparison of peritoneal transport before and after infection.

♦ Participants:

We analyzed prospectively collected data from 541 incident peritoneal dialysis (PD) patients, aged > 18 years, between 1990 and 2010. Standard Peritoneal Permeability Analyses (SPA) within the year before and within the year after (but not within 30 days) the first peritonitis were compared. In a control group without peritonitis, SPAs within the first and second year of PD were compared.

♦ Main outcome measurements:

SPA data included the mass transfer area coefficient of creatinine, glucose absorption and peritoneal clearances of β-2-microglobulin (b2m), albumin, IgG and α-2-macroglobulin (a2m). From these clearances, the restriction coefficient to macromolecules (RC) was calculated. Also, parameters of fluid transport were determined: transcapillary ultrafiltration rate (TCUFR), lymphatic absorption (ELAR), and free water transport. Crude and adjusted linear mixed models were used to compare the slopes of peritoneal transport parameters in the peritonitis group to the control group. Adjustments were made for age, sex and diabetes.

♦ Results:

Of 541 patients, 367 experienced a first peritonitis episode within a median time of 12 months after the start of PD. Of these, 92 peritonitis episodes were preceded and followed by a SPA within one year. Forty-five patients without peritonitis were included in the control group. Logistic reasons (peritonitis group: 48% vs control group: 83%) and switch to hemodialysis (peritonitis group: 22% vs control group: 3%) were the main causes of missing SPA data post-peritonitis and post-control. When comparing the slopes of peritoneal transport parameters in the peritonitis group and the control group, a first peritonitis episode was associated with faster small solute transport (glucose absorption, p = 0.03) and a concomitant lower TCUFR (p = 0.03). In addition, a discreet decrease in macromolecular transport was seen in the peritonitis group: mean difference in post- and pre-peritonitis values: IgG: -8 μL/min (p = 0.01), a2m: -4 μL/min (p = 0.02), albumin: -10 μL/min (p = 0.04). Accordingly, the RC to macromolecules increased after peritonitis: 0.09, p = 0.04.

♦ Conclusions:

The very first peritonitis episode alters the natural course of peritoneal membrane characteristics. The most likely explanation might be that cured peritoneal infection later causes long-lasting alterations in peritoneal transport state.     

Peritoneal Dialysis Can Be an Option for Dominant Polycystic Kidney Disease: an Observational Study

♦ Background:

Autosomal dominant polycystic kidney disease (ADPKD) has been considered a relative contraindication for peritoneal dialysis (PD), although there are few specific studies available.

♦ Methods:

A multicenter historical prospective matched-cohort study was conducted to describe the outcome of ADPKD patients who have chosen PD. All ADPKD patients starting PD (n = 106) between January 2003 and December 2010 and a control group (2 consecutive patients without ADPKD) were studied. Mortality, PD-technique failure, peritonitis, abdominal wall leaks and cyst infections were compared.

♦ Results:

Patients with ADPKD had similar age but less comorbidity at PD inclusion: Charlson comorbidity index (CCI) 4.3 (standard deviation [SD] 1.6) vs 5.3 (SD 2.5) p < 0.001, diabetes mellitus 5.7% vs 29.2%, p < 0.001 and previous cardiovascular events 10.4% vs 27.8%, p < 0.001. No differences were observed in clinical events that required transient transfer to hemodialysis, nor in peritoneal leakage episodes or delivered dialysis dose. The cyst infection rate was low (0.09 episodes per patient-year) and cyst infections were not associated to peritonitis episodes. Overall technique survival was similar in both groups. Permanent transfer to hemodialysis because of surgery or peritoneal leakage was more frequent in ADPKD. More ADPKD patients were included in the transplant waiting list (69.8 vs 58%, p = 0.04) but mean time to transplantation was similar (2.08 [1.69 – 2.47] years). The mortality rate was lower (2.5 vs 7.6 deaths/100 patient-year, p = 0.02) and the median patient survival was longer in ADPKD patients (6.04 [5.39 – 6.69] vs 5.57 [4.95 – 6.18] years, p = 0.024).

♦ Conclusion:

Peritoneal dialysis is a suitable renal replacement therapy option for ADPKD patients.     

Novel Equations for Estimating Lean Body Mass in Peritoneal Dialysis Patients

♦ Objectives:

To develop and validate equations for estimating lean body mass (LBM) in peritoneal dialysis (PD) patients.

♦ Methods:

Two equations for estimating LBM, one based on mid-arm muscle circumference (MAMC) and hand grip strength (HGS), i.e., LBM-M-H, and the other based on HGS, i.e., LBM-H, were developed and validated with LBM obtained by dual-energy X-ray absorptiometry (DEXA). The developed equations were compared to LBM estimated from creatinine kinetics (LBM-CK) and anthropometry (LBM-A) in terms of bias, precision, and accuracy. The prognostic values of LBM estimated from the equations in all-cause mortality risk were assessed.

♦ Results:

The developed equations incorporated gender, height, weight, and dialysis duration. Compared to LBM-DEXA, the bias of the developed equations was lower than that of LBM-CK and LBM-A. Additionally, LBM-M-H and LBM-H had better accuracy and precision. The prognostic values of LBM in all-cause mortality risk based on LBM-M-H, LBM-H, LBM-CK, and LBM-A were similar.

♦ Conclusions:

Lean body mass estimated by the new equations based on MAMC and HGS was correlated with LBM obtained by DEXA and may serve as practical surrogate markers of LBM in PD patients.     

The Mutual Relationship Between Peritonitis and Peritoneal Transport

♦ Background:

Preservation of the peritoneum is required for long-term peritoneal dialysis (PD). We investigated the effect of multiple peritonitis episodes on peritoneal transport.

♦ Methods:

Prospectively collected data from 479 incident PD patients treated between 1990 and 2010 were analyzed, using strict inclusion criteria: follow-up of at least 3 years with the availability of a Standard Peritoneal Permeability Analysis (SPA) in the first year after start of PD and within the third year of PD, without peritonitis preceding the first SPA. For the purpose of the study, we only included patients who remained peritonitis-free (n = 28) or who experienced 3 or more peritonitis episodes (n = 16).

♦ Results:

At baseline the groups were similar with regard to small solute and fluid transport. However, the frequent peritonitis group had lower peritoneal protein clearances compared to the no peritonitis group, resulting in lower dialysate concentrations of proteins: albumin 196.5 mg/L vs 372.5 mg/L, IgG 36.4 mg/L vs 65.0 mg/L, and α-2-macroglobulin (A2M) 1.9 mg/L vs 3.6 mg/L, p <0.01. No differences in serum concentrations were present. A comparison between the transport slopes over time in both groups showed a positive time trend of mass transfer area coefficient (MTAC) creatinine (p = 0.03) and glucose absorption (p = 0.09) and a negative trend of transcapillary ultrafiltration (p = 0.06), when compared to the no peritonitis group. Frequent peritonitis did not affect free water transport.

♦ Conclusions:

Slow initial peritoneal transport rates of serum proteins result in lower dialysate concentrations, and likely a lower opsonic activity, which is a risk factor for peritonitis. Patients with frequent peritonitis show an increase in small solute transport and a concomitant decrease of ultrafiltration. In long-term peritonitis-free PD patients, small solute transport decreased, while ultrafiltration increased. This suggests that frequent peritonitis leads to an increase of the vascular peritoneal surface area without all the structural membrane alterations that may develop after long-term PD.     

Removal of Different Classes of Uremic Toxins in APD vs CAPD: A Randomized Cross-Over Study

♦ Aim:

In this study, we investigated, and this for the different classes of uremic toxins, whether increasing dialysate volume by shifting from continuous ambulatory peritoneal dialysis (CAPD) to higher volume automated peritoneal dialysis (APD) increases total solute clearance.

♦ Methods:

Patients on peritoneal dialysis were randomized in a cross-over design to one 24-hour session of first a CAPD regimen (3*2 L of Physioneal 1.36% and 1*2 L of icodextrin) or APD (consisting of 5 cycles of 2 L Physioneal 1.36 and 1 cycle of 2 L Extraneal), and the other week the alternate regime, each patient serving as his/her own control. Dialysate, blood and urine samples were collected and frozen for later batch analysis of concentrations of urea, creatinine, phosphorus, uric acid, hippuric acid, 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid, indoxyl sulfate, indole acetic acid, and p-cresyl sulfate. For the protein-bound solutes, total and free fractions were determined. Total, peritoneal and renal clearance (K) and mass removal (MR) of each solute were calculated, using validated models.

♦ Results:

In 15 patients (11 male, 3 diabetics, 56 ± 16 years, 8 on CAPD, time on peritoneal dialysis 12 ± 14 months, and residual renal function of 9.9 ± 5.4 mL/min) dialysate over plasma ratio for creatinine (D/P_crea) was 0.62 ± 0.10. Drained volume and obtained ultrafiltration were higher with APD vs CAPD (13.3 ± 0.5 L vs 8.5 ± 0.7 L and 1.3 ± 0.5 L vs 0.5 ± 0.7 L), whereas urine output was lower (1.0 ± 0.5 L vs 1.4 ± 0.6 L). Total clearance and MR tended to be higher for CAPD vs APD for all small and water soluble solutes, but mainly because of higher renal contribution, with no difference in the peritoneal contribution. For the protein-bound solutes, no differences in clearance or mass removal were observed.

♦ Conclusion:

Although the drained dialysate volume nearly doubled, APD did not result in better peritoneal clearance or solute removal vs classic CAPD. APD resulted in better ultrafiltration, but at the expense of residual urinary output and clearance.     

Low-Polydispersity Glucose Polymers as Osmotic Agents for Peritoneal Dialysis

♦ Background:

Peritoneal dialysis (PD) solutions containing icodextrin as the osmotic agent have advantages during long dwells. The glucose polymers that constitute icodextrin are a heterogeneous mix of molecules with a polydispersity [ratio of weight-average to number-average molecular weight (Mw/Mn)] of approximately 2.6. The present study evaluates whether modifications in the polydispersity and concentration of glucose polymers can improve ultrafiltration (UF) without an associated increase in carbohydrate absorption (CA).

♦ Methods:

Computer simulations using a three-pore model of peritoneal transport during a long dwell in PD patients predict that, in general, compared with 7.5% icodextrin, glucose polymers with a Mw greater than or equal to 7.5 kDa, a polydispersity less than 2.6, and concentrations greater than 7% could achieve higher UF without higher CA. Based on the simulations, we hypothesized that, compared with 7.5% icodextrin, glucose polymers with a Mw of 18 – 19 kDa and a polydispersity of 2.0 at 11% concentration could achieve higher UF without a higher CA. We tested this hypothesis in experimental studies using 8-hour dwells in New Zealand White rabbits. In those studies, UF was measured by complete fluid collection, and CA was measured by subtracting the total carbohydrate in the collected fluid from the carbohydrate initially infused.

♦ Results:

The UF was higher with 11% 19 kDa glucose polymer than with 7.5% icodextrin (mean ± standard deviation: 89 ± 31 mL vs 49 ± 15 mL; p = 0.004) without higher CA (5.2 ± 0.9 g vs 5.0 ± 0.9 g, p = 0.7). Similar results were seen with the 11% 18 kDa glucose polymer, which, compared with 7.5% icodextrin, resulted in higher UF (mean ± standard deviation: 96 ± 18 mL vs 66 ± 17 mL; p < 0.001) without higher CA (4.8 ± 0.7 g vs 5.2 ± 0.6 g, p = 0.2).

♦ Conclusions:

The findings demonstrate that, compared with 7.5% icodextrin solution, long-dwell PD solutions containing 11% glucose polymers with a Mw of 18–19 kDa and a polydispersity of 2.0 can provide higher UF without higher CA.     

Effects of Fructo-Oligosaccharide Supplementation on Constipation in Elderly Continuous Ambulatory Peritoneal Dialysis Patients

♦ Background:

Fructo-oligosaccharides (FOS) exhibit soluble-fiber properties that beneficially affect bowel function and relieve constipation. The effects of FOS supplementation on constipation and biochemical parameters were examined in elderly continuous ambulatory peritoneal dialysis (CAPD) patients.

♦ Methods:

This randomized, double-blind, placebo-controlled, cross-over study was performed in elderly CAPD patients (5 males and 4 females) with chronic constipation. All subjects were randomly assigned to receive either 20 g FOS or placebo daily for 30 days. After a 14-day washout period, the patients were switched to the other substance for 1 more month. Before and after each treatment period, frequency of defecation, characteristics of feces, and colonic transit were evaluated. Biochemical parameters were also assessed.

♦ Results:

Fructo-oligosaccharides significantly increased the frequency of defecation (10.5 ± 2.0 vs 6.2 ± 1.4 times per week, p < 0.005) and changed the feces'' appearance from type 1 (nut-like) to type 4 (sausage–like). The colonic transit determined by geometric center (GC) was augmented after FOS supplementation (3.9 ± 0.3 vs 3.2 ± 0.4, p < 0.05). Fructo-oligosaccharides had no effects on biochemical parameters. Fructo-oligosaccharides caused mild discomforts which were well tolerated after dose adjustment.

♦ Conclusions:

Fructo-oligosaccharide supplementation is effective, well tolerated, and can be an alternative to other laxatives in CAPD patients with constipation. Further studies are needed to better assess the biochemical effects of FOS in the chronic kidney disease population.     

The Impact of Timing of Dialysis Initiation on Mortality in Patients with Peritoneal Dialysis

♦ Background:

The impact of timing of dialysis initiation on mortality is controversial in patients with peritoneal dialysis (PD). In this study, we analyzed the impact of timing of dialysis initiation on mortality in the incident PD population.

♦ Methods:

Incident patients with PD were selected from the Clinical Research Center (CRC) registry for end-stage renal disease (ESRD), a prospective cohort study on dialysis in Korea. Patients were categorized into 3 groups according to the estimated glomerular filtration rate (eGFR) at the initiation of PD using the Modification of Diet in Renal Disease (MDRD) equation. Group A was defined as eGFR < 5 mL/min/1.73m², group B as eGFR 5 – 10 mL/min/1.73m², and group C as eGFR > 10 mL/min/1.73m². Cox regression analysis was used to calculate the adjusted hazard ratio (HR) of mortality with group B as the reference. The primary outcome was all-cause mortality.

♦ Results:

A total of 495 incident PD patients were included. The number of patients in group A was 109, group B was 279, and group C was 107. The median follow-up period was 23 months. Multivariate Cox regression analysis showed that group A had a significantly higher risk of all-cause mortality compared with group B (HR 4.13, 95% confidence interval [CI], 1.55 – 11.03, p = 0.005) after adjustment for age, gender, cause of ESRD, serum albumin level, diabetes mellitus, and cardiovascular disease. There was no significant difference in mortality between group C and group B (HR 1.50, 95% CI, 0.59 – 3.80, p = 0.398) after adjustment for clinical variables.

♦ Conclusion:

An eGFR < 5 mL/min/1.73m² at the initiation of PD was a significant risk factor for death, while an eGFR >10 mL/min/1.73m² at the initiation of PD was not associated with improved survival compared with an eGFR of 5 – 10 mL/min/1.73m² at the initiation of PD.