Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis

To establish intraperitoneal pressure (IPP) in a relatively large pediatric study group and to study the effects of a 3.86% glucose solution and a 7.5% icodextrin solution on IPP during a 4-hour dwell.

IPP was measured with the patient in a supine position. The intraperitoneal volume (IPV) was 1200 mL/m² with a 1.36% glucose solution. The influence of dialysis solutions was obtained by performing two 4-hour peritoneal equilibration tests (PETs) with 3.86% glucose and 7.5% icodextrin as test solution, using an IPV of 1200 mL/m² and dextran 70 as volume marker. IPP was measured at two consecutive time points (t = 0 and t = 240 minutes). Transcapillary ultrafiltration, net ultrafiltration, and marker clearance were calculated.

IPP was established in 30 patients with median age of 4.5 years (range 1.0 – 14.9 years). Influence of dialysis solutions on IPP was studied in 9 children with median age of 4.2 years (range 1.7 – 10.9 years) and median treatment period of 12 months (range 5.6 – 122.3 months).

Mean IPP was 12.0 ± 6.5 cm H₂O. Significant relations were found between the change in IPP and transcapillary ultrafiltration and body surface area during the PET with 3.86% glucose. No relations were seen during the PET with icodextrin.

IPP was established in a large pediatric study group and was similar to previously published values of IPP in a small number of patients. Differences in fluid kinetics have different effects on the change in IPP during a 4-hour dwell period.

Atherosclerotic vascular diseases are the major cause of mortality in patients with end-stage renal disease (ESRD) treated with chronic peritoneal dialysis (CPD), even in children. Adiponectin (ADPN) is a recently discovered adipocyte-derived plasma protein having anti-atherogenic properties. ADPN levels are elevated in ESRD but it has been reported that ESRD patients with low plasma ADPN levels have a high risk of cardiovascular death.

To clarify the atherosclerotic risk and especially the significance of ADPN levels in pediatric patients on CPD.

Cross-sectional study in the pediatric peritoneal dialysis unit of a university hospital.

18 children, aged 12.6 ± 5.6 years, being treated with CPD and 20 healthy age- and sex-matched control subjects were enrolled in this study.

Serum ADPN levels and other risk factors, including blood pressure, blood glucose, serum lipid/lipoprotein fractions, apolipoprotein B, C-reactive protein (CRP), lipoprotein(a), and homocysteine levels, were studied in CPD patients and compared to the controls.

Serum ADPN levels were three times higher in the CPD group compared to the control subjects, as was previously reported. Apolipoprotein B and CRP levels were also high in the CPD group. No significant difference was found in other atherosclerotic parameters, including lipoprotein(a) and homocysteine levels. Interestingly, we found a negative correlation between log ADPN and creatinine levels among the CPD patients (r = –0.54, p < 0.05). There was no correlation between log ADPN and duration of CPD. Creatinine and low-density lipoprotein levels could account for 54% of the total variation in ADPN levels.

Among pediatric CPD patients, serum levels of the anti-atherogenic protein, ADPN, were inversely associated with creatinine. ADPN level might be a novel marker to predict prognosis in pediatric CPD patients.

Peritoneal dialysis (PD) patients are at risk for 25(OH) vitamin D deficiency due to effluent loss in addition to traditional risk factors.

To measure 25(OH) vitamin D deficiency in prevalent PD patients, to evaluate a replacement dose, and to determine the effects of correction.

25(OH) vitamin D levels were drawn on prevalent PD patients. Patients deficient in 25(OH) vitamin D were given ergocalciferol, 50 000 IU orally once per week for 4 weeks. Patients scored muscle weakness, bone pain, and fatigue on a scale of 0 (none) to 5 (severe). Serum calcium, phosphate, parathyroid hormone (PTH), and 25(OH) vitamin D, and 1,25(OH)₂ vitamin D levels were obtained before and after treatment.

25(OH) vitamin D levels were measured in 29 PD patients. Deficiency (<15 ng/mL) was found in 28/29 (97%); 25/29 (86%) had undetectable levels (<7 ng/mL). One course of ergocalciferol corrected the deficiency in all but 1 patient, who required a second course. Scores for muscle weakness and bone pain fell from pre- to posttreatment (p < 0.001). 1,25(OH)₂ vitamin D levels rose post ergocalciferol (from 20 to 26 pg/mL, n = 20, p = 0.09). Serum calcium, phosphate, and PTH levels did not change with ergocalciferol.

Most PD patients had marked 25(OH) vitamin D deficiency, which was readily and safely corrected with one course of 50000 IU ergocalciferol, having no effect on serum calcium, phosphorus, or PTH, but complaints of muscle weakness and bone pain decreased. A prospective, placebo-controlled double-blinded study is needed to determine whether replacement of 25(OH) vitamin D is beneficial in PD patients.

Conflicting literature exist regarding the patient characteristics that may confer an increased risk for anatomic complications of the peritoneal cavity boundaries.

We collected data from 75 randomly selected units in the United States and Canada, representing a total of 1864 peritoneal dialysis (PD) patients.

200 of these patients experienced a total of 217 anatomic complications between July 2000 and June 2001; 16 patients had more than 1 complication. Hernias comprised 60.4% of all complications: 24.9% inguinal, 18.9% umbilical, 13.8% ventral, 2.3% femoral, and 0.5% intrathoracic. Other complications included pericatheter or subcutaneous leak (25.3%), hydrothorax (6.0%), and miscellaneous (8.3%). Peritoneal dialysis modalities in use at the time of complication were automated PD (52.3%), continuous ambulatory PD (38.6%), and nocturnal intermittent PD (9.1%). The overall incidence of hernias was 7%.

Logistic regression analysis found no association between hernias and age, body surface area, PD modality, volume of dialysate, time of largest dwell (day/upright vs night/recumbent), or type of catheter used. Cystic disease conferred a 2.5-fold increase in risk for anatomic complications (p < 0.001); female gender conferred an 80% reduction in risk (p < 0.0001), and Kt/V ≥2.0 conferred a 52% reduction in risk (p < 0.05) for hernia.

We studied the clinical characteristics that influence the risk of dialysis-related peritonitis complication in incident Chinese patients undergoing continuous ambulatory peritoneal dialysis (CAPD).

A single center, retrospective, observational cohort study was carried out to examine the risk factors of developing a first episode of dialysis-related peritonitis.

Between 1995 and 2004, 246 incident CAPD patients were recruited for analysis. During the study period of 897.1 patient-years, 85 initial episodes of peritonitis were recorded. The median peritonitis-free time for diabetic subjects was significantly worse than for nondiabetic subjects (49.0 ± 10.5 vs 82.3 ± 12.6 months, p = 0.0019). The difference was due mainly to a higher likelihood of developing peritonitis with gram-negative organisms in patients with diabetes mellitus (p = 0.038). Low serum albumin concentration was also associated with worse peritonitis-free survival. There was a nonsignificant trend toward an increased risk for peritonitis in the group of patients with cerebrovascular disease. According to multivariate Cox proportional hazards model for the analysis of time to first peritonitis episode, the two independent risk factors were presence of diabetes mellitus and initial serum albumin concentration. In particular, diabetes mellitus was associated with a hazard ratio of 1.50 and a 95% confidence interval of 1.05 – 2.40 (p = 0.030) to develop an initial peritonitis. Lower serum albumin level at the start of CAPD was a significant predictor of peritonitis, with hazard ratio of 1.67 for every decrease of 10 g/L, and 95% confidence interval 1.08 – 2.60 (p = 0.021).

Our results confirm the susceptibility of diabetic CAPD and hypoalbuminemic patients to peritonitis, and highlight the role of further studies in reducing this complication.

This study determined the pharmacokinetics of intraperitoneal (IP) cefepime in automated peritoneal dialysis (APD) patients.

A prospective pharmacokinetic study was performed in 6 noninfected adult APD patients. All patients were administered a single IP dose of cefepime (15 mg/kg) over a 6-hour dwell. Patients then underwent a fixed APD regimen consisting of the first 6-hour dwell, followed by an 8-hour dialysate-free period and a subsequent series of 3 overnight APD exchanges. Blood and dialysate samples were collected at t = 0, 1, 2, 4, 6 (end of dwell), and 24 hours. Any urine produced during the study period was collected. Cefepime concentrations in serum, dialysate, and urine were determined by liquid chromatography mass spectrometry. Pharmacokinetic parameters were calculated assuming a mono-exponential model.

One hour after IP administration, serum cefepime levels exceeded the minimum inhibitory concentration (8 μg/mL) for susceptible organisms. The mean serum and dialysate concentrations at 24 hours were 15.8 ± 3.6 and 6.2 ± 2.3 μg/mL respectively. Bioavailability was 84.3% ± 6.2%, volume of distribution 0.34 ± 0.07 L/kg, and serum half-life 13.8 ± 3.2 hours. Total, peritoneal, and renal clearances were 16.5 ± 4.4, 4.3 ± 0.7, and 3.5 ± 2.5 mL/minute, respectively.

IP cefepime dosed at 15 mg/kg resulted in adequate serum concentrations in APD patients at 24 hours post dose. Pharmacokinetic predictions suggest that most APD and CAPD patients would achieve adequate serum cefepime concentrations if treated with standard doses of 1000 mg given IP once daily. Patients using APD regimens different from that used in this study, anuric patients, and those with significant residual renal function may require a more individualized approach.

In peritoneal dialysis (PD), neutrally buffered PD fluids with lower concentrations of glucose degradation products (GDP) have tested superior to conventional fluids in terms of biocompatibility. However, conventional in vitro studies provoke debate because, due to the lack of subsequent equilibration with the blood, they do not resemble the true intraperitoneal situation of PD.

We established a double-chamber cell culture system with peritoneal mesothelial cells seeded on top of a permeable membrane, with a physiological buffer below. Thus adequately reflecting the in vivo equilibration pattern, we compared a conventional fluid with a neutral bicarbonate/lactate-buffered PD solution. Using an exchange pattern adapted from an 8-hour continuous ambulatory PD regimen, cell viability was assessed with an MTT assay, and cell function via constitutive and stimulated interleukin (IL)-6 release. As an indicator of potential induction of fibrosis and as a parameter of mesothelial cell integrity, respectively, transforming growth factor-beta 1 (TGF-β1) generation and cancer antigen 125 (CA125) release were measured.

The conventional solution significantly compromised mesothelial cell viability and function in terms of mitochondrial activity (p < 0.05) and stimulated IL-6 release (p < 0.05). The bicarbonate/lactate fluid had no effect on cell viability or IL-6 release and turned out to be equivalent to the properties of the growth medium. Whereas lactate-incubated cells did not respond to IL-1β stimulation, bicarbonate/lactate-treated cells adequately increased IL-6 release after stimulation (p < 0.0005). Release of TGF-β1 and CA125 did not differ between the different fluids and the control.

Due to the sustained equilibration process, the double-chamber cell culture model allows a more realistic insight into mesothelial cell viability and function in terms of PD. As in classic in vitro studies, an adverse effect of conventional PD solutions on mesothelial cells was overt in the present cell culture system. The neutral bicarbonate/lactate-buffered fluid with low GDP content, however, did not interfere with mesothelial cell vitality or function, indicating superior biocompatibility.

Clinical studies have demonstrated that the intraperitoneal (IP) complement and coagulation systems are activated in peritoneal dialysis (PD) patients. In animal models, low molecular weight heparin (LMWH) was seen to inhibit peritoneal angiogenesis, and related compounds have increased ultrafiltration volumes after repeated administration to PD patients. The present study evaluated the effects of LMWH on ultrafiltration, coagulation, and complement activation during a single PD dwell.

Rats were exposed to a single dose of 20 mL 2.5% glucose-based, filter-sterilized PD fluid, with or without supplementation with LMWH. The PD fluid was administered either as an IP injection or as an infusion through an indwelling catheter. The dwell fluid was analyzed 2 hours later concerning activation of the complement and coagulation cascades, chemotactic activity, neutrophil recruitment, ultrafiltration volume, and glucose and urea concentrations.

Exposure to PD fluid induced activation of IP complement [formation of C3a(desArg) and increase of C5a-dependent chemotactic activity] and coagulation (formation of thrombin–antithrombin complex) and recruitment of neutrophils. In the case of IP injection, neutrophil recruitment and complement activation were inhibited by LMWH. In both models, LMWH inhibited thrombin formation, reduced complement-dependent chemotactic activity, and increased the IP fluid volume, indicating an improved ultrafiltration.

The acute inflammatory reaction to PD fluid involves the complement and coagulation cascades. Addition of LMWH to the PD fluid improves ultrafiltration, inhibits formation of thrombin, and potentially blocks C5a activity. The present results motivate further investigations of the IP cascade systems in PD.