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

Encapsulating peritoneal sclerosis (EPS) is a serious complication of peritoneal dialysis (PD) with a multifactorial pathophysiology and possible increasing incidence. The aim of the present study was to evaluate the independent associations of PD duration, age, dialysis fluids, and kidney transplantation with EPS.

A multicenter case–control study was performed in the Netherlands from 1 January 1996 until 1 July 2007. The population comprised 63 patients with EPS and 126 control patients. Control patients were selected from the national registry and were matched for date of PD start. Associations were analyzed using a log linear regression model. Primary outcome was appearance of EPS.

Compared with control patients, patients with EPS were younger at the start of PD (34.7 ± 15.4 years vs. 51.5 ± 14.7 years, p < 0.0001). The cumulative period on PD was longer in EPS patients than in control patients (78.7 ± 37.8 months vs. 32.8 ± 24 months, p < 0.0001), and the cumulative period on icodextrin was also longer in EPS patients (32.7 ± 23.3 months vs. 18.1 ± 15.7 months, p = 0.006). Compared with control patients, more EPS patients underwent kidney transplantation (47 vs. 59, p < 0.0001). With regard to the period after transplantation, the yearly probability of EPS increased in the year after transplantation to 7.5% from 1.75%. In multivariate regression analysis, cumulative PD duration, age at PD start, transplantation, time from last transplantation to EPS, calendar time, time on icodextrin, and ultrafiltration failure were independently associated with EPS. Transfer from PD to hemodialysis for reasons other than suspected EPS could not be identified as a risk factor for EPS.

Duration of PD, age at PD start, kidney transplantation, time since last transplantation, ultrafiltration failure, and time on icodextrin were associated with a higher risk of EPS.

Encapsulating peritoneal sclerosis (EPS) is a rare but life-threatening complication of peritoneal dialysis (PD). The optimal management of patients with EPS is uncertain. In the present study, we investigated differences in the expression of nuclear receptors [progesterone (PR), androgen (AR), vitamin D (VDR), and glucocorticoid (GCR)] in the human peritoneum. We also investigated estrogen receptor (ER), matrix metalloproteinase 9 (MMP9), and transforming growth factor β1 (TGFβ1) in the context of their potential role in tamoxifen therapy.

We analyzed clinical and histologic characteristics of 72 peritoneal biopsy specimens (22 from EPS patients, 11 from PD patients, 15 from uremic patients, and 24 from control subjects undergoing hernia repair). For immunophenotyping, we used antibodies against VDR, GCR, ER, PR, AR, MMP9, and TGFβ1.

In human peritoneum, VDR and GCR are highly expressed (98.6% and 87.3% respectively). Except in the case of VDR (p = 0.0012), we observed no significant difference in receptor expression between the groups. Expression of ER and PR was sparse (11.4% and 31% respectively), with higher expression in women, and AR was absent. Minimal MMP9 expression and moderate TGFβ1 expression were observed in all groups. The differences between the groups were nonsignificant.

Nuclear receptors are present in human peritoneum. Except in the case of VDR, the pattern for any one group is nonspecific. Glucocorticoids, vitamin D, and angiotensin converting-enzyme inhibitors or angiotensin II receptor blockers (via the vitamin D/angiotensin II pathway) might be suitable interventions for preservation of the integrity of the peritoneal membrane. The mechanism of action of tamoxifen is still not elucidated, ER expression in the peritoneum is sparse, and data about the studied pathways (MMP9, TGFβ) are inconsistent.

In the U.S. Renal Data System registry, technique and patient survival are similar with automated peritoneal dialysis (APD) and continuous ambulatory peritoneal dialysis (CAPD). The clinical outcomes of APD and CAPD in various age groups have not been clarified.

We investigated whether patient and technique survival are different for incident dialysis patients treated with APD or CAPD in two age groups.

Our retrospective study of prospectively collected data included 282 incident peritoneal dialysis (PD) patients (161 on APD, 121 on CAPD). Patients on PD for less than 3 months were excluded. The patients were divided into those less than 65 years of age and those 65 years of age or older. Overall mortality and technique failure were the primary endpoints of the study. Hazard ratios (HRs) for mortality and technique failure were calculated by the Cox proportional hazards model and were adjusted for age, sex, diabetes mellitus, initial peritoneal equilibration test (PET), weekly peritoneal and renal creatinine clearances, and PD caregiver (self or other).

The characteristics and clinical data were not significantly different between patients on APD and CAPD, except for age and sex. The adjusted risk for overall mortality was not different between patients on APD and CAPD (HR: 0.72; 95% CI: 0.44 to 1.20; p = 0.207). The adjusted risk for technique failure was lower in APD patients than in CAPD patients (HR: 0.58; 95% CI: 0.34 to 0.98; p = 0.041). In patients less than 65 years of age, those on APD had a significantly lower risk of mortality (HR: 0.35; 95% CI: 0.16 to 0.75; p = 0.007) and technique failure (HR: 0.52; 95% CI: 0.28 to 0.95; p = 0.034) than did those on CAPD. In patients 65 years of age and older, those on APD had risks for mortality (HR: 1.14; 95% CI: 0.53 to 2.46; p = 0.730) and technique failure (HR: 0.51; 95% CI: 0.17 to 1.50; p = 0.220) that were similar to those of patients on CAPD. Nutrition status, including serum albumin and protein catabolic rate, was not significantly different between patients on APD and on CAPD, in either younger or older patients.

Younger Chinese patients on APD have better patient and technique survival than do those on CAPD. However, there is a strong possibility that this benefit may be confounded or accounted for by baseline differences between the APD and CAPD populations.

Our prospective randomized double-blind study enrolled 60 adult patients with chronic renal failure who were scheduled for laparoscopic implantation of a PD catheter. Patients were randomly assigned to one of two groups: one receiving IV ketamine, and the other receiving SC ketamine. In both groups, patients were premedicated with IV midazolam 0.015 mg/kg, fentanyl 1–2 μg/kg, and lidocaine 1.5 mg/kg. Patients then received 0.6 mg/kg ketamine either intravenously (IV group) or by subcutaneous injection at the anterior aspect of the forearm (SC group). If systolic blood pressure (BP) increased more than 20% from baseline or exceeded 170 mmHg, IV nitroglycerine (TNG) 50 μg was administered incrementally (repeated 50-μg doses). After a desirable level of conscious sedation was achieved, local anesthesia and nitrous oxide pneumoperitoneum were applied, and the PD catheter was implanted under laparoscopic guidance. Heart rate and BP were measured throughout the procedure. Adverse effects and recovery events were recorded.

All patients tolerated the procedure well. Administration of TNG was significantly more frequent in the IV ketamine group. Pain intensity during the surgery was similar in both groups. Both groups were comparable with regard to heart rate, but patients in the SC ketamine group had a significantly lower systolic BP at the 2nd measurement and a lower rate–pressure product at the 2nd, 4th, and 5th measurements. All patients in the SC ketamine group were cooperative during surgery and experienced uneventful recoveries; mild hallucinations were observed in 5 patients in the IV ketamine group. In the IV ketamine group, 3 patients lost the ability to cooperate during surgery. All catheters were successfully placed.

Dissociative conscious sedation is an acceptable alternative to general anesthesia in laparoscopic implantation of the PD catheter. Ketamine by the SC route is as effective as, but safer than, IV ketamine.

In peritoneal dialysis (PD), a standard therapy for patients with end-stage renal disease (ESRD), the effects of using the peritoneum as an exchange membrane and of dialysate dwelling within the peritoneal cavity creates some mechanical changes, including an increase in intraperitoneal pressure (IPP) that might lead to intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS). The diagnosis of IAH and ACS depend on intra-abdominal measurement of IAP by an indirect technique. There is no clear distinction between IPP and intra-abdominal pressure (IAP). Our objective in this study was to find if there is real difference between IPP and IAP.

This study was conducted at the PD unit of King Fahd Hospital of the University, Al-Khobar, between July 2008 and January 2009. To be included, patients had to have known ESRD for at least 5 years, to be 18 years of age or older at enrollment, with stable body weight and blood pressure, and with no clinical signs of overhydration. Patients with congestive heart failure III and IV (New York Heart Association criteria) and severe pulmonary disease, psychiatric illnesses, neurogenic bladder, known history of peritonitis, or medical or surgical abdominal intervention in the preceding 3 months were excluded. We measured IAP by the direct technique through the peritoneal catheter and by an indirect technique using an intravesical catheter.

The 25 patients who met the inclusion criteria included 13 men and 12 women, with a mean age of 53 ± 2 years (range: 18 – 76 years). The predominant causes of ESRD were diabetes mellitus and glomerulonephritis. Mean IPP in the dry state (supine) was 9.49 ± 5 mmHg, and mean IAP was 9.4 ± 5.4 mmHg (p = 0.9). In the dry state (erect), the mean IPP increased to 16.9 ± 7.2 mmHg, and the mean IAP, to 16.4 ± 6.9 mmHg (p = 0.8). In the filled state (supine), mean IPP was 12.6 ± 4.7 mmHg, and mean IAP, 12.8 ± 4.8 mmHg (p = 0.88); the erect pressures were 21.4 ± 7 mmHg and 21.6 ± 6.9 mmHg respectively (p = 0.9).

Our findings indicate that there is no statistical difference between IPP and IAP in either the erect or the supine position.

Human herpesvirus 6 (HHV-6) infection occurs worldwide and can be reactivated from latency during periods of immunosuppression, especially after organ transplantation. No previous study has evaluated the influence of dialysis type on HHV-6 infection. The aim of the present study was to determine the prevalence of HHV-6 antibodies in hemodialysis (HD) and peritoneal dialysis (PD) patients.

We studied 36 PD patients, 35 HD patients, and 20 healthy subjects, all with no history of organ transplantation. After systematic inquiries and a physical examination, blood was drawn for determination of biochemical parameters, cytomegalovirus immunoglobulin M (IgM) and immunoglobulin G (IgG), hepatitis B surface antigen, and the hepatitis C and human immunodeficiency virus antibodies. Titers of HHV-6 IgM and IgG antibodies were determined by ELISA.

Titers for HHV-6 IgM antibody were positive in 9 HD patients (25.7%), 8 PD patients (22.2%), and 2 control subjects (10.0%, p > 0.05). More HD patients (20.0%) than PD patients (5.6%, p = 0.07) or control subjects (0.0%, p =0.03) were positive for HHV-6 IgG antibody. In HD patients, HHV-6 IgG seropositivity and duration of dialysis were positively correlated (R = 0.33, p = 0.05).

Infection with HHV-6 is not rare in PD and HD patients. In addition, HHV-6 IgG seropositivity was significantly higher in H D patients than in control subjects and approached significance when compared with seropositivity in PD patients. Moreover, in HD patients, HHV-6 IgG seropositivity correlated with duration on HD. These preliminary findings provide insight into the pre-transplantation period for patients and may aid our understanding of how to best protect patients against HHV-6 after transplantation.

Continuous exposure of the peritoneal membrane to high glucose dialysis solutions can produce functional alterations in this membrane. We studied the toxic effects of high glucose (50 mmol/L and 83 mmol/L) and its reversal by atorvastatin (0.5 – 5 μmol/L) on cultures of rat peritoneal mesothelial cells (PMCs).

Rat PMCs were harvested from the peritonea of male Sprague–Dawley rats and grown in M199 medium supplemented with 10% fetal bovine serum. The effects of high glucose (50 mmol/L and 83 mmol/L) on levels of reactive oxygen species (ROS), on caspase 3 activity, and on phospho-p38 mitogen-activated protein kinase (MAPK) in the cultures were evaluated.

Exposure to high glucose (for 4, 8, and 24 hours) increased intracellular levels of ROS and phospho-p38 MAPK (indices of cellular toxicity). Atorvastatin blocked these toxic effects of high glucose, being more effective against 50 mmol/L glucose (protective effects were observed above 0.5 μmol/L) than against 83 mmol/L (protective effects were observed above 2.5 μmol/L). Atorvastatin was also able to prevent glucose-induced increase in caspase 3 activity.

The present study shows that high glucose may promote oxidative stress and may activate apoptotic pathways in rat PMCs. These toxic effects could be reversed by atorvastatin.

Noninfectious upregulation of proinflammatory pathways in mesothelial cells may represent an integral part of their stress response upon exposure to peritoneal dialysis fluids (PDF).

The aim of this study was to evaluate the role of the stress-inducible mitogen-activated protein kinase (MAPK) p38 in regulation of inflammatory and stress responses in mesothelial cells following in vitro exposure to PDF.

Human peritoneal mesothelial cells were exposed to Dianeal PD4 or Physioneal (Baxter AG, Vienna, Austria) containing 1.36% glucose and then allowed to recover. Phosphorylation of p38, induction of heat shock protein-70 (HSP70), release of lactate dehydrogenase (LDH), secretion of interleukin (IL)-8, gene transcription, and mRNA stability were assessed with and without the MAPK p38 inhibitor SB203580.

Exposure to Dianeal resulted in phosphorylation of p38 within 30 minutes (309% of control, p < 0.05) and increased IL-8 release (370% of control, p < 0.05), HSP70 expression (151% of control, p < 0.05), and LDH release (180% of control, p < 0.05). Exposure to Physioneal resulted in attenuated changes in IL-8, HSP70, and LDH. Addition of the p38 inhibitor SB203580 to Dianeal resulted in dampened IL-8 release (-55%; p < 0.05) and basal HSP70 expression, and unchanged LDH release. Effects of p38 on IL-8 were at transcriptional, posttranscriptional, and translational levels.

These data confirm concordant p38-dependent upregulation of IL-8 and HSP70 following exposure to bioincompatible PDF. The MAPK p38 pathway therefore links proinflammatory processes and the cellular stress response in human peritoneal mesothelial cells.

Coagulase-negative staphylococcus (CoNS) is the most common pathogen in continuous ambulatory peritoneal dialysis (CAPD)–associated peritonitis. There is no well-organized, standardized database for CoNS, and few studies have used gene sequencing in reporting species distribution in CAPD peritonitis. In the present study, we used 3 housekeeping genes to evaluate the prevalence of CoNS isolated from CAPD peritonitis episodes and to estimate the accuracy of, and the characteristic differences between, these genes for species identification.

All 51 non-duplicated CoNS isolates obtained from CAPD peritonitis between April 2006 and May 2008 were used. The strains were identified by polymerase chain reaction and by direct sequencing using the 16S ribosomal RNA (rRNA), tuf, and sodA genes. We determined species distribution, and using selected databases, we analyzed the characteristics and diagnostic utility of the individual genes for species identification.

In GenBank (National Institutes of Health, Bethesda, MD, USA), we found 49 type or reference strains for CoNS 16S rRNA, 17 for tuf, and 46 for sodA, and we used those data for sequence-similarity comparisons with CAPD isolates. Among our 51 strains, S. epidermidis (66.7%) was the most common, followed by S. haemolyticus (11.8%), S. warneri (7.8%), S. caprae (5.9%), S. capitis (3.9%), and S. pasteuri (2.0%). For 1 strain, different species results were obtained with each gene. The identification rates with 16S rRNA, sodA, and tuf gene sequencing were 84.0%, 96.0%, and 92.2% respectively. The discrimination capability of 16S rRNA gene was lower in a few individual species, and for the sodA gene, the percentage similarity to sequences from reference strains was also lower. The tuf gene had excellent identification capacity, but relatively few type strains are available in public databases. The 16S rRNA gene did not discriminate between S. caprae and S. capitis. The sodA gene showed a similarity rate that was lower than that for sequences of the 16S rRNA gene. The tuf type strain sequences for S. caprae and S. pasteuri are not available in public databases.

The sodA, tuf, and 16S rRNA genes were very useful for CoNS identification. Each has its own characteristics of similarity, discriminative power, and inclusion in databases.