Effects of a Statewide Protocol for the Management of Peritoneal Dialysis-Related Peritonitis on Microbial Profiles and Antimicrobial Susceptibilities: A Retrospective Five-Year Review

♦ Background:

Peritonitis is a major complication of peritoneal dialysis (PD) and is associated with significant morbidity and mortality. Early empirical antibiotic therapy is recommended, with the choice of agents guided by local resistance patterns. As routine use of specific antimicrobial agents can drive resistance, regular assessment of causative organisms and their susceptibility to empirical therapy is essential.

♦ Methods:

We conducted a retrospective review of all PD peritonitis cases and positive PD fluid cultures obtained over a 5-year period in Western Australia following the introduction of a statewide protocol for the initial management of PD peritonitis with intraperitoneal vancomycin and gentamicin.

♦ Results:

The incidence of PD peritonitis decreased from 1 in 16 patient months (0.75/year at risk) to 1 in 29 patient months (0.41/year at risk) over the 5 years. There were 1,319 culture-positive samples and 1,069 unique isolates identified. Gram-positive bacteria accounted for 69.9% of positive cultures, with vancomycin resistance averaging 2% over the study period. Gram-negative bacteria accounted for 25.4% of positive cultures, with gentamicin resistance identified in an average of 8% of organisms. No increase in antimicrobial resistance to vancomycin or gentamicin occurred over the 5 years and there was no change in the proportion of gram-positive (69.9%), gram-negative (25.4%) or fungal (4.4%) organisms causing PD peritonitis.

♦ Conclusions:

Over time, the peritonitis rates have dramatically improved although the profile of causative organisms remains similar. Empirical treatment of PD peritonitis with intraperitoneal vancomycin and gentamicin remains efficacious, with high levels of susceptibility and no evidence that the introduction of this statewide empirical PD peritonitis treatment protocol is driving resistance to these agents.     

Can Dialysis Patients Be Accurately Identified Using Healthcare Claims Data?

♦ Background: While health insurance claims data are often used to estimate the costs of renal replacement therapy in patients with end-stage renal disease (ESRD), the accuracy of methods used to identify patients receiving dialysis — especially peritoneal dialysis (PD) and hemodialysis (HD) — in these data is unknown.♦ Methods: The study population consisted of all persons aged 18 - 63 years in a large US integrated health plan with ESRD and dialysis-related billing codes (i.e., diagnosis, procedures) on healthcare encounters between January 1, 2005, and December 31, 2008. Using billing codes for all healthcare encounters within 30 days of each patient’s first dialysis-related claim (“index encounter”), we attempted to designate each study subject as either a “PD patient” or “HD patient.” Using alternative windows of ± 30 days, ± 90 days, and ± 180 days around the index encounter, we reviewed patients’ medical records to determine the dialysis modality actually received. We calculated the positive predictive value (PPV) for each dialysis-related billing code, using information in patients’ medical records as the “gold standard.”♦ Results: We identified a total of 233 patients with evidence of ESRD and receipt of dialysis in healthcare claims data. Based on examination of billing codes, 43 and 173 study subjects were designated PD patients and HD patients, respectively (14 patients had evidence of PD and HD, and modality could not be ascertained for 31 patients). The PPV of codes used to identify PD patients was low based on a ± 30-day medical record review window (34.9%), and increased with use of ± 90-day and ± 180-day windows (both 67.4%). The PPV for codes used to identify HD patients was uniformly high — 86.7% based on ± 30-day review, 90.8% based on ± 90-day review, and 93.1% based on ± 180-day review.♦ Conclusions: While HD patients could be accurately identified using billing codes in healthcare claims data, case identification was much more problematic for patients receiving PD.     

Persistent Sterile Peritoneal Inflammation After Catheter Removal for Refractory Bacterial Peritonitis Predicts Full-Blown Encapsulating Peritoneal Sclerosis

♦ Background: Encapsulating peritoneal sclerosis (EPS) is the most serious complication of peritoneal dialysis, having high morbidity and mortality. To improve outcomes, early diagnosis is needed to direct treatment during the early inflammatory phase. However, in the early inflammatory phase, clinical features are nonspecific, and no reliable diagnostic criteria have been established. Because bacterial peritonitis and termination of dialysis are two important risk factors triggering the progression of EPS, patients with refractory bacterial peritonitis necessitating dialysis catheter removal are at particularly high risk of developing EPS. Many of these patients might indeed experience non-resolving sterile peritonitis (probably the inflammatory phase of EPS) before progression to full-blown disease (that is, the presence of intestinal obstruction). We undertook a retrospective study to compare, in this particular situation, the clinical characteristics of patients with or without sterile peritoneal inflammation, assessing their clinical outcomes in terms of short-term mortality and the chance of developing full-blown EPS.♦ Methods: Our retrospective review included 62 patients whose dialysis catheter was removed because of refractory peritonitis between January 2005 and December 2010.♦ Results: Of the 62 patients identified, 39 (63%) had persistent sterile peritoneal inflammation (“high-risk” group, n = 39), and 23 (37%) had resolution of inflammation without significant intra-abdominal collection after catheter withdrawal (“control” group, n = 23). Compared with the control group, the high-risk group had a significantly longer PD duration (71.6 ± 43.3 months vs 42.3 ± 29.9 months, p = 0.003), a higher dialysate-to-plasma ratio (D/P) of creatinine (0.768 ± 0.141 vs 0.616 ± 0.091, p = 0.004), and a higher computed tomography score for EPS (7.69 ± 2.98 vs 1.00 ± 1.00, p < 0.001). During the 6-month study period, the high-risk group had a higher chance of developing full-blown EPS (31% vs 0%, p = 0.002) and a higher 6-month all-cause mortality (36% vs 4.3%, p = 0.004).♦ Conclusions: Persistent sterile peritoneal inflammation was common after dialysis catheter removal for refractory bacterial peritonitis, and the patients with such inflammation were at high risk of progression to full-blown EPS.     

The Role of Monitoring Vancomycin Levels in Patients with Peritoneal Dialysis-Associated Peritonitis

♦ Background: There is limited available evidence regarding the role of monitoring serum vancomycin concentrations during treatment of peritoneal dialysis (PD)-associated peritonitis.♦ Methods: A total of 150 PD patients experiencing 256 episodes of either gram-positive or culture-negative peritonitis were included to investigate the relationship between measured serum vancomycin within the first week and clinical outcomes of cure, relapse, repeat or recurrence of peritonitis, catheter removal, temporary or permanent transfer to hemodialysis, hospitalization and death.♦ Results: Vancomycin was used as an initial empiric antibiotic in 54 gram-positive or culture-negative peritonitis episodes among 34 patients. The median number of serum vancomycin level measurements in the first week was 3 (interquartile range; IQR 1 – 4). The mean day-2 vancomycin level, measured in 34 (63%) episodes, was 17.5 ± 5.2 mg/L. Hospitalized patients were more likely to have serum vancomycin levels measured on day 2 and ≥ 3 measurements in the first week. The peritonitis cure rates were similar between patients with < 3 and ≥ 3 measurements in the first week (77% vs 57%, p = 0.12) and if day-2 vancomycin levels were measured or not (68% vs 65%, p = 0.84). The average day-2 (18.0 ± 5.9 vs 16.6 ± 3.2, p = 0.5), first-week average (18.6 ± 5.1 vs 18.6 ± 4.3, p = 0.9) and nadir (14.5 ± 4.1 vs 13.6 ± 4.2, p = 0.5) vancomycin levels were comparable in patients who did or did not achieve peritonitis cure. Similar results were observed for all other clinical outcomes.♦ Conclusion: The clinical outcomes of gram-positive and culture-negative peritonitis episodes are not associated with either the frequency or levels of serum vancomycin measurements in the first week of treatment when vancomycin is dosed according to International Society for Peritoneal Dialysis (ISPD) Guidelines.     

Novel Predictors of Peritonitis-Related Outcomes in the BRAZPD Cohort

♦ Introduction: Peritonitis remains the main cause of peritoneal dialysis (PD) technique failure worldwide, despite significant reductions in infection rates observed over the past decades. Several studies have described risk factors for peritonitis, technique failure and mortality. However, there are scarce data regarding predictors of complications during and after a peritonitis episode. The aim of our study was to analyze predictors of peritonitis-related outcome in the Brazilian Peritoneal Dialysis study (BRAZPD) cohort.♦ Methods: All adult incident patients recruited in the BRAZPD Study between December 2004 and October 2007, who remained at least 90 days on PD and presented their first peritonitis episode (n = 474 patients) were included in the study. The endpoints analyzed were non-resolution, death due to a peritonitis episode and long-term technique survival after a peritonitis episode.♦ Results: In the multivariable regression, non-resolution was independently associated with older age (odds ratio (OR) 1.02; p < 0.01), collagenosis as the primary renal disease (OR 4.6; p < 0.05) and Pseudomonas spp as etiological agent (OR 2.9; p < 0.05). Patients who were transferred from APD to CAPD during peritonitis therapy presented a higher risk of non-response (OR 2.5; p < 0.05). The only factor associated with death during a peritonitis episode was older age (OR 1.04; p < 0.05). Exposure to vancomycin and male gender were the independent predictors of long-term technique failure (OR 2.2; p < 0.01).♦ Conclusion: Apart from confirming previous observations of the negative impact of older age and Pseudomonas spp peritonitis on outcomes, we observed that collagenosis may negatively impact response to treatment and exposure to vancomycin may possibly reduce long-term technique survival. It is important to emphasize that the association of vancomycin with technique failure does not prove causality. These findings shed light on new factors predicting outcome when peritonitis is diagnosed.     

Predictors of Peritonitis and the Impact of Peritonitis on Clinical Outcomes of Continuous Ambulatory Peritoneal Dialysis Patients in Taiwan—10 Years’ Experience in a Single Center

♦ Objective: Peritoneal dialysis (PD) has become more prevalent as a treatment modality for end-stage renal disease, and peritonitis remains one of its most devastating complications. The aim of the present investigation was to examine the frequency and predictors of peritonitis and the impact of peritonitis on clinical outcomes.♦ Methods: Our retrospective observational cohort study enrolled 391 patients who had been treated with continuous ambulatory PD (CAPD) for at least 90 days. Relevant demographic, biochemical, and clinical data were collected for an analysis of CAPD-associated peritonitis, technique failure, drop-out from PD, and patient mortality.♦ Results: The peritonitis rate was 0.196 episodes per patient-year. Older age (>65 years) was the only identified risk factor associated with peritonitis. A multivariate Cox regression model demonstrated that technique failure occurred more often in patients experiencing peritonitis than in those free of peritonitis (p < 0.001). Kaplan-Meier analysis revealed that the group experiencing peritonitis tended to survive longer than the group that was peritonitis-free (p = 0.11). After multivariate adjustment, the survival advantage reached significance (hazard ratio: 0.64; 95% confidence interval: 0.46 to 0.89; p = 0.006). Compared with the peritonitis-free group, the group experiencing peritonitis also had more drop-out from PD (p = 0.03).♦ Conclusions: The peritonitis rate was relatively low in the present investigation. Elderly patients were at higher risk of peritonitis episodes. Peritonitis independently predicted technique failure, in agreement with other reports. However, contrary to previous studies, all-cause mortality was better in patients experiencing peritonitis than in those free of peritonitis. The underlying mechanisms of this presumptive “peritonitis paradox” remain to be clarified.     

Clinical Characteristics and Outcomes of “Silent” and “Non-Silent” Peritonitis in Patients on Peritoneal Dialysis

♦ Objectives: We compared the clinical characteristics and outcomes of “silent” peritonitis (meaning episodes without fever and abdominal pain) and “non-silent” peritonitis in patients on peritoneal dialysis (PD).♦ Methods: Our cohort study collected data about all peritonitis episodes occurring between January 2008 and April 2010. Disease severity score, demographics, and biochemistry and nutrition data were recorded at baseline. Effluent cell counts were examined at regular intervals, and the organisms cultured were examined. Treatment failure was defined as peritonitis-associated death or transfer to hemodialysis.♦ Results: Of 248 episodes of peritonitis occurring in 161 PD patients, 20.9% led to treatment failure. Of the 248 episodes, 51 (20.6%) were not accompanied by fever and abdominal pain. Patients with these silent peritonitis episodes tended to be older (p = 0.003). The baseline values for body mass index, triglycerides, and daily energy intake were significantly lower before silent peritonitis episodes than before non-silent episodes (p = 0.01, 0.003, and 0.001 respectively). Although silent peritonitis episodes were more often culture-negative and less often caused by gram-negative organisms, and although they presented with low effluent white cell counts on days 1 and 3, the risk for treatment failure in those episodes was not lower (adjusted odds ratio: 1.33; 95% confidence interval: 0.75 to 2.36; p = 0.33).♦ Conclusions: Silent peritonitis is not a rare phenomenon, especially in older patients on PD. Although these episodes were more often culture-negative, silent presentation was not associated with a better outcome.Key words: Peritonitis, outcomesPeritonitis, a common complication of peritoneal dialysis (PD), contributes to treatment failure, hospitalization, and death. It is important to diagnose PD-associated peritonitis and to initiate empiric antibiotic therapy as early as possible to prevent those serious consequences (1). Peritonitis is defined based on the presentation of symptoms, peritoneal effluent cell count, and culture of micro-organisms. Patients have to recognize their symptoms—including cloudy effluent, fever, and abdominal pain—early in the onset of peritonitis. Awareness of the symptoms of peritonitis is a key precondition for obtaining an effluent cell count and culture to promptly make the diagnosis, especially for patients who live far from the hospital and who cannot easily send dialysate samples to a lab.In fact, the symptoms of peritonitis vary in severity across the PD population. In pediatric PD patients, disease severity scores (DSSs) at the onset of peritonitis are calculated as a points total for pain and fever (2-5). The range shows that some patients might present with cloudy effluent alone, and some might complain of severe abdominal pain or high fever, or both.In most PD centers, DSS is not a routine measurement tool for PD-related peritonitis in adults. The DSS range for the adult PD population is not known, but we recognized that abdominal pain and fever might be absent at the onset of some peritonitis episodes. Here, we refer to those peritonitis episodes as “silent” peritonitis episodes. We coined the term silent peritonitis for this phenomenon because patients do not complain of fever or abdominal pain, and yet they have peritonitis. By contrast, we refer to peritonitis episodes with varying extents of fever and abdominal pain as “non-silent”peritonitis.Because previous studies reported that an absence of fever in bacteremic community-acquired pneumonia predicts a worse outcome in elderly individuals (6,7), comparisons of the clinical characteristics and outcomes in silent and non-silent peritonitis in the PD population are of interest. In the present study, we addressed that issue in a single-center cohort of patients presenting with incident episodes of peritonitis. Specifically, we set out to determine the clinical characteristics (including demographics, biochemical and nutrition indices, effluent cell counts, and causative organisms) and final outcomes associated with these two types of peritonitis.     

The Negative Impact of Early Peritonitis on Continuous Ambulatory Peritoneal Dialysis Patients

♦ Background: Peritonitis rate has been reported to be associated with technique failure and overall mortality in previous literatures. However, information on the impact of the timing of the first peritonitis episode on continuous ambulatory peritoneal dialysis (CAPD) patients is sparse. The aim of this research is to study the influence of time to first peritonitis on clinical outcomes, including technique failure, patient mortality and dropout from peritoneal dialysis (PD).♦ Methods: A retrospective observational cohort study was conducted over 10 years at a single PD unit in Taiwan. A total of 124 patients on CAPD with at least one peritonitis episode comprised the study subjects, which were dichotomized by the median of time to first peritonitis into either early peritonitis patients or late peritonitis patients. Cox proportional hazard model was used to analyze the correlation of the timing of first peritonitis with clinical outcomes.♦ Results: Early peritonitis patients were older, more diabetic and had lower serum levels of creatinine than the late peritonitis patients. Early peritonitis patients were associated with worse technique survival, patient survival and stay on PD than late peritonitis patients, as indicated by Kaplan-Meier analysis (log-rank test, p = 0.04, p < 0.001, p < 0.001, respectively). In the multivariate Cox regression model, early peritonitis was still a significant predictor for technique failure (hazard ratio (HR), 0.54; 95% confidence interval (CI), 0.30 - 0.98), patient mortality (HR, 0.34; 95% CI, 0.13 - 0.92) and dropout from PD (HR, 0.50; 95% CI, 0.30 - 0.82). In continuous analyses, a 1-month increase in the time to the first peritonitis episode was associated with a 2% decreased risk of technique failure (HR, 0.98; 95% CI, 0.97 - 0.99), a 3% decreased risk of patient mortality (HR, 0.97; 95% CI, 0.95 - 0.99), and a 2% decreased risk of dropout from PD (HR, 98%; 95% CI, 0.97 - 0.99). Peritonitis rate was inversely correlated with time to first peritonitis according to the Spearman analysis (r = -0.64, p < 0.001).♦ Conclusions: Time to first peritonitis is significantly correlated with clinical outcomes of peritonitis patients with early peritonitis patients having poor prognosis. Patients with shorter time to first peritonitis were prone to having a higher peritonitis rate.     

Intraperitoneal vancomycin concentrations during peritoneal dialysis-associated peritonitis: correlation with serum levels

♦ Background: For the treatment of peritoneal dialysis–associated peritonitis (PDP), it has been suggested that serum concentrations of vancomycin be kept above 12 mg/L – 15 mg/L. However, studies correlating vancomycin concentrations in serum and peritoneal dialysate effluent (PDE) during active infection are sparse. We undertook the present study to investigate this issue and to determine whether achieving the recommended serum level of vancomycin results in therapeutic levels intraperitoneally.♦ Methods: We studied patients treated with intraperitoneal (IP) vancomycin for non-gram-negative PDP. We gave a single dose (approximately 30 mg/kg) at presentation, and we subsequently measured vancomycin levels in PDE on day 5; we wanted to determine if efflux of vancomycin from serum to PDE during a 4-hour dwell was consistent and resulted in therapeutic levels.♦ Results: Of the 48 episodes of PDP studied, serum vancomycin concentrations exceeding 12 mg/L were achieved in 98% of patients, but in 11 patients (23%), a PDE vancomycin level below 4 mg/L—the minimal inhibitory concentration (MIC) of many gram-positive organisms—was observed at the end of a 4-hour dwell on day 5. The correlation between the concentrations of vancomycin in serum and PDE (from efflux of antibiotic over 4 hours) was statistically significant, but poor (R² = 0.18).♦ Conclusions: Our data support the International Society for Peritoneal Dialysis statement that adequate serum vancomycin concentrations can be achieved with intermittent dosing (single dose every 5 days), but cannot guarantee therapeutic PDE levels in the treatment of PDP. Intermittent dosing of vancomycin may not consistently result in PDE concentrations markedly greater than MIC of many important pathogens. Although the clinical significance of this finding remains to be determined, it may be preferable to give smaller but more frequent doses of PDE vancomycin (continuous dosing) for adults with PDP (as is currently recommended for children).     

Advanced Nursing Experience Is Beneficial for Lowering the Peritonitis Rate in Patients on Peritoneal Dialysis

♦ Objectives: We explored the relationship between the experience level of nurses and the peritonitis risk in peritoneal dialysis (PD) patients.♦ Methods: Our observational cohort study followed 305 incident PD patients until a first episode of peritonitis, death, or censoring. Patients were divided into 3 groups according to the work experience in general medicine of their nurses—that is, least experience (<10 years), moderate experience (10 to <15 years), and advanced experience (≥15 years). Demographic characteristics, baseline biochemistry, and residual renal function were also recorded. Multivariate Cox regression was used to analyze the association of risks for all-cause and gram-positive peritonitis with patient training provided by nurses at different experience levels.♦ Results: Of the 305 patients, 91 were trained at the initiation of PD by nurses with advanced experience, 100 by nurses with moderate experience, and 114 by nurses with the least experience. Demographic and clinical variables did not vary significantly between the groups. During 13 582 patient–months of follow-up, 129 first episodes of peritonitis were observed, with 48 episodes being attributed to gram-positive organisms. Kaplan–Meier analysis showed that training by nurses with advanced experience predicted the longest period free of first-episode gram-positive peritonitis. After adjustment for some recognized confounders, the advanced experience group was still associated with the lowest risk for first-episode gram-positive peritonitis. The level of nursing experience was not significantly correlated with all-cause peritonitis risk.♦ Conclusions: The experience in general medicine of nurses might help to lower the risk of gram-positive peritonitis among PD patients. These data are the first to indicate that nursing experience in areas other than PD practice can be vital in the training of PD patients.     

Comparison of the Impact of “Fast Decline” in Residual Renal Function and “Initial Anuria” on Long-Term Outcomes in CAPD Patients

♦ Background: Residual renal function (RRF) is pivotal to long-term outcomes, while rapid RRF decline (RRFD) is associated with mortality risk for continuous ambulatory peritoneal dialysis (CAPD) patients. This study was conducted to compare the impact of “initial anuria” and rapid RRFD on the long-term prognosis of CAPD patients.♦ Method: According to the timing of anuria and the slope of RRFD, a total of 255 incident CAPD patients were divided into 3 groups. For the “anuria” group, anuria was detected from CAPD initiation and persisted for > 6 months (n = 27). Based on the median of the RRFD slope, the other 228 non-anuric patients were divided into a “slow decliner” group (n = 114), and a “rapid decliner” group (n = 114). The maximal observation period was 120 months.♦ Results: Logistic regression tests indicated that the “anuria” group was associated with previous hemodialysis > 3 months (odds ratio [OR]: 8.52, 95% confidence interval [CI]: 3.12 – 23.28), and female (OR: 0.29, 95% CI: 0.09 – 0.90), while the “fast decliner” group with higher Davies co-morbidity scores (DCS) (OR: 1.52; 95% CI: 1.08 – 2.14), body mass index (BMI) (OR: 1.12; 95% CI: 1.04 – 1.21), and male (OR: 1.12; 95% CI: 1.04 – 1.21). After adjusting for DCS, the “fast decliner” group (hazard ratio [HR]: 0.37; 95% CI: 0.17 – 0.80) showed a better outcome than that of the “anuria” group (reference = 1). Both baseline RRF (β = -0.24; p < 0.001) and DCS (β = -3.76; p < 0.001) showed inverse linear correlations to the slope of RRFD. From the Cox proportional analyses, higher baseline RRF (HR: 0.92; 95% CI: 0.88 –.97) and higher slope of RRFD (slower decline in RRF) (HR: 0.90; 95% CI: 0.85 – 0.96) were independent factors for less mortality risk in patients with DCS = 0. However, only a higher slope of RRFD (HR: 0.97; 95% CI: 0.94 – 0.99) was significant for better survival in CAPD patients with DCS > 0.♦ Conclusion: Compared to the baseline RRF, CAPD patients with co-morbidities that rapidly deteriorate RRFD are more crucially associated with long-term mortality risk.     

The Role of NGAL in Peritoneal Dialysis Effluent in Early Diagnosis of Peritonitis: Case-Control Study in Peritoneal Dialysis Patients

♦ Background:

Peritoneal dialysis (PD) is frequently complicated by high rates of peritonitis, which result in hospitalization, technique failure, transfer to hemodialysis, and increased mortality. Early diagnosis, and identification of contributing factors are essential components to increasing effectiveness of care. In previous reports, neutrophil gelatinase-associated lipocalin (NGAL), a lipocalin which is a key player in innate immunity and rapidly detectable in peritoneal dialysis effluent (PDE), has been demonstrated to be a useful tool in the early diagnosis of peritonitis. This study investigates predictive value of PDE NGAL concentration as a prognostic indicator for PD-related peritonitis.

♦ Methods:

A case-control study with 182 PD patients was conducted. Plasma and PDE were analyzed for the following biomarkers: C-reactive protein (CRP), blood procalcitonin (PCT), leucocytes and NGAL in PDE. The cases consisted of patients with suspected peritonitis, while controls were the patients who came to our ambulatory clinic for routine visits without any sign of peritonitis. The episodes of peritonitis were defined in agreement with International Society for Peritoneal Dialysis guidelines. Continuous variables were presented as the median values and interquartile range (IQR). Mann-Whitney U test was used to compare continuous variables. Univariate and multivariate logistic regression were used to evaluate the association of biomarkers with peritonitis. Receiver operating characteristic (ROC) curve analysis was used to calculate area under curve (AUC) for biomarkers. Finally we evaluated sensitivity, and specificity for each biomarker. All statistical analyses were performed with SPSS version 17.0 (SPSS Inc., Chicago, IL, USA).

♦ Results:

During the 19-month study, of the 182 patients, 80 had a clinical diagnosis of peritonitis. C-reactive protein levels (p < 0.001), PCT (p < 0.001), NGAL in PDE (p < 0.001), and white blood cells (WBC) in PDE (p < 0.001) were all significantly different in patients with and without peritonitis. In univariate analysis, CRP (odds ratio [OR] 1,339; p = 0.001), PCT (OR 2,473; p < 0,001), WBC in PDE (OR 3,986; p < 0,001), and NGAL in PDE (OR 36.75 p < 0.001) were significantly associated with episodes of peritonitis. In multivariate regression analysis, only WBC (OR 24.84; p = 0,012), and peritoneal NGAL levels (OR 136.6; p = 0,01) were independent predictors of peritonitis events. Moreover, AUC for NGAL in peritoneal effluent was 0,936 (p < 0.001) while AUC for CRP, PCT, and WBC count in peritoneal effluent were 0,704 (p = 0.001), 0.762 (p = 0.039), 0,975 (p < 0.001), respectively. Finally, combined WBC and peritoneal NGAL test increased the specificity (= 96%) of the single test.

♦ Conclusions:

These results identify NGAL in peritoneal effluent as a reliable marker of peritonitis episodes in PD patients. Collectively, our findings demonstrate that the use of peritoneal NGAL cooperatively with current clinical diagnostic tools as a prognostic indicator, presents a valuable diagnostic tool in PD-associated peritonitis.     

Outcomes of a Peritoneal Dialysis Program in Remote Communities Within Colombia

♦ Background and Objective: Colombia is a country of diverse geographic regions, some with mountainous terrain that can make access to urban areas difficult for individuals who live in remote areas. In 2005, a program was initiated to establish remote peritoneal dialysis (PD) centers in Colombia to improve access to PD for patients with end-stage renal disease who face geographic or financial access barriers.♦ Patients and Methods: The present study was a multi-center cohort observational study of prevalent home PD patients who were at least 18 years of age and were being managed by one of nine established remote PD centers in Colombia over a 2-year period. Data were collected from clinical records, databases, and patient interviews. Patient survival, incidence of peritonitis, and rate of withdrawal from PD therapy were assessed.♦ Results: A total of 345 patients were eligible for the study. The majority (87.8%) of patients lived on one to two times a minimum monthly salary (equivalent to US$243 – US$486). On average, patients traveled 1.2 hours and 4.3 hours from their home to their remote PD center or an urban reference renal clinic, respectively. The incidence rate of peritonitis was 2.54 episodes per 100 patient-months of therapy. A bivariate analysis showed a significantly higher risk of peritonitis in patients who were living on less than one times a monthly minimum salary (p < 0.05) or who had a dirt, cement, or unfinished wood floor (p < 0.05). The 1-year and 2-year patient survival rates were 92.44% and 81.55%, respectively. The 1-year and 2-year technique survival rates were 97.27% and 89.78%, respectively.♦ Conclusions: With the support of remote PD centers that mitigate geographic and financial barriers to healthcare, home PD therapy is a safe and appropriate treatment option for patients who live in remote areas in Colombia.     

Can EPS Development Be Avoided with Early Interventions? The Potential Role of Tamoxifen—A Single-Center Study

♦ Background: Encapsulating peritoneal sclerosis (EPS) is a severe complication of peritoneal dialysis (PD). Identification of patients at high risk for EPS (“EPS-prone”) and delivery of appropriate interventions might prevent its development. Our aim was to evaluate the clinical characteristics and outcomes of all EPS and EPS-prone patients diagnosed at our PD unit.♦ Methods: For a 30-year period representing our entire PD experience, we retrospectively identified all patients with EPS (diagnosed according to International Society for Peritoneal Dialysis criteria) and all patients defined as EPS-prone because they met at least 2 established criteria (severe peritonitis, PD vintage greater than 3 years, severe hemoperitoneum, overexposure to glucose, and acquired ultrafiltration failure).♦ Results: Of 679 PD patients, we identified 20 with EPS, for an overall prevalence of 2.9%. Mean age at diagnosis was 50.2 ± 16.4 years, with a median PD time of 77.96 months (range: 44.36 - 102.7 months) and a median follow-up of 30.91 months (range: 4.6 - 68.75 months). Of patients with EPS, 10 (50%) received tamoxifen, 10 (50%) received parenteral nutrition, and 2 (10%) underwent adhesiolysis, with 25% mortality related to EPS. Another 14 patients were identified as EPS-prone. Median follow-up was 54.05 months (range: 11.9 - 87.04 months). All received tamoxifen, and 5 (36%) received corticosteroids; none progressed to full EPS. We observed no differences in baseline data between the groups, but the group with EPS had been on PD longer (84 ± 53 months vs 39 ± 20 months, p = 0.002) and had a higher cumulative number of days of peritoneal inflammation from peritonitis (17.2 ± 11.1 days vs 9.8 ± 7.9 days, p = 0.015). Overall mortality was similar in the groups. The incidence of EPS declined during our three decades of experience (5.6%, 3.9%, and 0.3%).♦ Conclusions: Being a serious, life-threatening complication of PD, EPS requires high suspicion to allow for prompt diagnosis and treatment. Early detection of EPS-prone states and delivery of appropriate intervention might prevent EPS development. Tamoxifen seems to be a key strategy in prevention, but caution should be used in interpreting our results. Additional randomized controlled studies are needed.     

Streptococcus bovis Peritonitis Complicating Peritoneal Dialysis—A Review of 10 Years’ Experience

♦ Objective: An association of Streptococcus bovis bacteremia with carcinoma of colon has been reported, but data regarding peritoneal dialysis (PD) peritonitis caused by S. bovis is scarce. In this study, we examined the clinical characteristics, associations, and outcomes of this disease entity.♦ Methods: The case records of patients with S. bovis PD peritonitis presenting to 2 renal centers between January 2000 and September 2010 were reviewed. Clinical features and outcomes were identified and analyzed.♦ Results: Of cultures from 23 episodes of S. bovis peritonitis in 20 patients (1.28% of all peritonitis episodes at our center), 19 (82.6%) showed S. bovis alone, and 4 (17.4%) showed mixed growth. In 7 episodes, the S. bovis was moderately resistant to penicillin G. Rates of resistance to clindamycin and erythromycin were 43.5% and 47.8% respectively. In 18 episodes (78.3%), a primary response was achieved with a first-generation cephalosporin and an aminoglycoside. In 4 episodes, a secondary response was achieved after a switch from cephalosporin to vancomycin, and in 1 episode with mixed growth, the Tenckhoff catheter had to be removed. Repeat peritonitis occurred in 3 patients at a mean of 50.0 months (range: 24.2 – 83.1 months). Of the 20 patients of S. bovis peritonitis, 10 (50%) underwent either a barium enema or a colonoscopy. One patient had history of colonic carcinoma 2 years before the peritonitis, and a subsequent work-up revealed no recurrence. Three patients had diverticulosis, and one had a concomitant sigmoid polyp. Findings in the other 6 patients were normal. No colorectal malignancy had developed in the remaining 10 patients after a mean follow-up of 76.6 months (range: 0.8 – 125.1 months).♦ Conclusions: Outcomes in S. bovis PD peritonitis were favorable, and an association with colorectal cancer was not found in our patients. Routine colonoscopy in these patients remains controversial and should be individualized.     

A Qualitative Systematic Review of the Literature Supporting a Causal Relationship Between Exit-Site Infection and Subsequent Peritonitis in Patients with End-Stage Renal Disease Treated with Peritoneal Dialysis

♦ Objective: The objective of our research was to summarize and review evidence supporting a causal relationship between exit-site infection and peritonitis in peritoneal dialysis (PD) patients.♦ Data Sources: We undertook a qualitative review of studies retrieved from MEDLINE, EMBASE, and PubMed, and supplemented that process with a hand search of references and abstracts in the literature.♦ Study Selection: Our quality criteria were based on the Paediatric Risk of Mortality guidelines, definitions, and recommendations from the International Society for Peritoneal Dialysis (ISPD), and the Bradford Hill criteria for causality. All identified abstracts were reviewed for content. Of 776 abstracts, 59 were selected for full-text evaluation, and 22 of those met the ISPD criteria for good-quality research in PD-related infections. Of the 22 eligible studies, 9 met the study’s quality criteria and were included in the summative analysis. No articles reported sufficient data for a quantitative analysis.♦ Data Extraction: Information on study design, study population characteristics, definitions, peritonitis rates, exit-site care protocol, exit-site treatment protocol, follow-up period, potential bias, and outcomes was extracted. Criteria for including data in the final study were determined using ISPD guidelines.♦ Data Synthesis: Of the 9 included studies, 8 suggested that a history of exit-site infection increased the risk for subsequent peritonitis. Of those studies, 3 met 5 causality criteria, 4 met 4 causality criteria, and 1 met 3 causality criteria.♦ Conclusions: The literature provides weak evidence to support a causal relationship between exit-site infection and subsequent peritonitis. Few criteria for causation were met. We were unable to attribute causation and could assume an association only. The exclusion of studies focusing on PD-related tunnel infections may be viewed as both a strength and a limitation of the present work.     

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.     

Long-Term Clinical Outcomes of Peritoneal Dialysis Patients: 9-Year Experience of a Single Center from North India

♦ Objective: There is a paucity of published data on the outcome of maintenance peritoneal dialysis (PD) since the initiation of continuous ambulatory PD (CAPD) in India in 1991. The purpose of this study is to report long-term clinical outcomes of PD patients at a single center.♦ Design: Retrospective study.♦ Setting: A government-owned tertiary-care hospital in North India.♦ Patients: Patients who were initiated on CAPD between October 2002 and June 2011, and who survived and/or had more than 6 months’ follow-up on this treatment with last follow-up till December 31, 2011, were studied.♦ Results: A total of 60 patients were included in the analysis. The mean age of the patients was 60.2 ± 9.2 years. The majority (65%) of the patients lived in rural areas. A high proportion (47%) were diabetic and 62% had ≥ 2 comorbidities. Total duration on peritoneal dialysis treatment was 1,773 patient-months (148 patient-years) with a mean duration of 29.6 ± 23 patient-months and median duration of 25 patient-months (range 6 - 110 patient-months). Overall patient and technique survival at 1, 2, 3, 4 and 5 years was 77%, 53%, 25%, 15%, and 10% respectively. Patient survival of diabetics vs non-diabetics at 1, 2, 3, 4, and 5 years was 68% vs 84%, 54% vs 53%, 14% vs 34%, 11% vs 19%, and 11% vs 13%, respectively. The mortality in non-diabetics (16/32) was less than that in diabetic (18/28) patients (p = not significant). The main cause of mortality in these patients was cardiac followed by sepsis. There were 58 episodes of peritonitis. The rate of peritonitis was 1 episode per 30.6 patient-months or 0.39 episodes per patient-year. Furthermore, the total number of episodes of peritonitis and number of episodes of peritonitis per patient were higher in the non-survival group (p < 0.05). The incidence of tuberculosis (TB), herpes zoster (HZ) and hernias was 15%, 10% and 5% respectively.♦ Conclusion: The study reports long-term outcomes of the PD patients, the majority of whom were elderly with a high burden of comorbidities. There was a high proportion of diabetics. The survival of diabetic vs non-diabetic and elderly vs non-elderly PD patients was similar in our study. The mortality in non-diabetics was less than that in diabetic patients. TB and HZ were common causes of morbidity. Peritonitis was associated with mortality in these 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.     

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.