Monique Borlace

The association between peritoneal dialysis modality and peritonitis.

BACKGROUND AND OBJECTIVES There is conflicting evidence comparing peritonitis rates among patients treated with continuous ambulatory peritoneal dialysis (CAPD) or automated peritoneal dialysis (APD). This study aims to clarify the relationship between peritoneal dialysis (PD) modality (APD versus CAPD) and the risk of developing PD-associated peritonitis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This study examined the association between PD modality (APD versus CAPD) and the risks, microbiology, and clinical outcomes of PD-associated peritonitis in 6959 incident Australian PD patients between October 1, 2003, and December 31, 2011, using data from the Australia and New Zealand Dialysis and Transplant Registry. Median follow-up time was 1.9 years. RESULTS Patients receiving APD were younger (60 versus 64 years) and had fewer comorbidities. There was no association between PD modality and time to first peritonitis episode (adjusted hazard ratio [HR] for APD versus CAPD, 0.98; 95% confidence interval [95% CI], 0.91 to 1.07; P=0.71). However, there was a lower hazard of developing Gram-positive peritonitis with APD than CAPD, which reached borderline significance (HR, 0.90; 95% CI, 0.80 to 1.00; P=0.05). No statistically significant difference was found in the risk of hospitalizations (odds ratio, 1.12; 95% CI, 0.93 to 1.35; P=0.22), but there was a nonsignificant higher likelihood of 30-day mortality (odds ratio, 1.33; 95% CI, 0.93 to 1.88; P=0.11) at the time of the first episode of peritonitis for patients receiving APD. For all peritonitis episodes (including subsequent episodes of peritonitis), APD was associated with lower rates of culture-negative peritonitis (incidence rate ratio [IRR], 0.81; 95% CI, 0.69 to 0.94; P=0.002) and higher rates of gram-negative peritonitis (IRR, 1.28; 95% CI, 1.13 to 1.46; P=0.01). CONCLUSIONS PD modality was not associated with a higher likelihood of developing peritonitis. However, APD was associated with a borderline reduction in the likelihood of a first episode of Gram-positive peritonitis compared with CAPD, and with lower rates of culture-negative peritonitis and higher rates of Gram-negative peritonitis. Peritonitis outcomes were comparable between both modalities.

Center-specific factors associated with peritonitis risk—a multi-center registry analysis

♦ Background: Previous studies have reported significant variation in peritonitis rates across dialysis centers. Limited evidence is available to explain this variability. The aim of this study was to assess center-level predictors of peritonitis and their relationship with peritonitis rate variations. ♦ Methods: All incident peritoneal dialysis (PD) patients treated in Australia between October 2003 and December 2013 were included. Data were accessed through the Australia and New Zealand Dialysis and Transplant Registry. The primary outcome was peritonitis rate, evaluated in a mixed effects negative binomial regression model. Peritonitis-free survival was assessed as a secondary outcome in a Cox proportional hazards model. ♦ Results: Overall, 8,711 incident PD patients from 51 dialysis centers were included in the study. Center-level predictors of lower peritonitis rates included smaller center size, high proportion of PD, low peritoneal equilibration test use at PD start, and low proportion of hospitalization for peritonitis. In contrast, a low proportion of automated PD exposure, high icodextrin exposure and low or high use of antifungal prophylaxis at the time of peritonitis were associated with a higher peritonitis rate. Similar results were obtained for peritonitis-free survival. Overall, accounting for center-level characteristics appreciably decreased peritonitis variability among dialysis centers (p = 0.02). ♦ Conclusion: This study identified specific center-level characteristics associated with the variation in peritonitis risk. Whether these factors are directly related to peritonitis risk or surrogate markers for other center characteristics is uncertain and should be validated in further studies.

DURATION OF HEMODIALYSIS FOLLOWING PERITONEAL DIALYSIS CESSATION IN AUSTRALIA AND NEW ZEALAND: PROPOSAL FOR A STANDARDIZED DEFINITION OF TECHNIQUE FAILURE

♦ Background: Although technique failure is a key outcome in peritoneal dialysis (PD), there is currently no agreement on a uniform definition. We explored different definitions of PD technique failure using data from the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry. ♦ Methods: We included 16,612 incident PD patients in Australia and New Zealand from January 1998 to December 2012. Different definitions of technique failure were applied according to the minimum number of days (30, 60, 90, 180, or 365) the patient received hemodialysis after cessation of PD. ♦ Results: Median technique survival varied from 2.0 years with the 30-day definition to 2.4 years with the 365-day definition. For all definitions, the most common causes of technique failure were death, followed by infectious complications. The likelihood of a patient returning to PD within 12 months of technique failure was highest in the 30-day definition (24%), and was very small when using the 180- and 365-day definitions (3% and 0.8%, respectively). Patients whose technique failed due to mechanical reasons were the most likely to return to PD (46% within 12 months using the 30-day definition). ♦ Conclusions: Both 30- and 180-day definitions have clinical relevance but offer different perspectives with very different prognostic implications for further PD. Therefore, we propose that PD technique failure be defined by a composite endpoint of death or transfer to hemodialysis using both 30-day and 180-day definitions.

Multicenter Registry Analysis of Center Characteristics Associated with Technique Failure in Patients on Incident Peritoneal Dialysis

BACKGROUND AND OBJECTIVES Technique failure is a major limitation of peritoneal dialysis. Our study aimed to identify center- and patient-level predictors of peritoneal dialysis technique failure. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS All patients on incident peritoneal dialysis in Australia from 2004 to 2014 were included in the study using data from the Australia and New Zealand Dialysis and Transplant Registry. Center- and patient-level characteristics associated with technique failure were evaluated using Cox shared frailty models. Death-censored technique failure and cause-specific technique failure were analyzed as secondary outcomes. RESULTS The study included 9362 patients from 51 centers in Australia. The technique failure rate was 0.35 (95% confidence interval, 0.34 to 0.36) episodes per patient-year, with a sevenfold variation across centers that was mainly associated with center-level characteristics. Technique failure was significantly less likely in centers with larger proportions of patients treated with peritoneal dialysis (>29%; adjusted hazard ratio, 0.83; 95% confidence interval, 0.73 to 0.94) and more likely in smaller centers (<16 new patients per year; adjusted hazard ratio, 1.10; 95% confidence interval, 1.00 to 1.21) and centers with lower proportions of patients achieving target baseline serum phosphate levels (<40%; adjusted hazard ratio, 1.15; 95% confidence interval, 1.03 to 1.29). Similar results were observed for death-censored technique failure, except that center target phosphate achievement was not significantly associated. Technique failure due to infection, social reasons, mechanical causes, or death was variably associated with center size, proportion of patients on peritoneal dialysis, and/or target phosphate achievement, automated peritoneal dialysis exposure, icodextrin use, and antifungal use. The variation of hazards of technique failure across centers was reduced by 28% after adjusting for patient-specific factors and an additional 53% after adding center-specific factors. CONCLUSIONS Technique failure varies widely across centers in Australia. A significant proportion of this variation is related to potentially modifiable center characteristics, including peritoneal dialysis center size, proportion of patients on peritoneal dialysis, and proportion of patients on peritoneal dialysis achieving target phosphate level.

Outcomes of Corynebacterium Peritonitis: A Multicenter Registry Analysis

Background: Corynebacterium is a rare cause of peritonitis that is increasingly being recognized in peritoneal dialysis (PD) patients. The aims of this study were to compare Corynebacterium peritonitis outcomes with those of peritonitis caused by other organisms and to examine the effects of type and duration of antibiotic therapy on outcomes of Corynebacterium peritonitis. Methods: Using Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) data, we included all PD patients who developed peritonitis in Australia between 2004 and 2014. The primary outcome was peritonitis cure by antibiotic therapy, defined as resolution of a peritonitis episode with antibiotics alone and without being complicated by recurrence, relapse, catheter removal, hemodialysis transfer, or death. Peritonitis outcomes were analyzed using multivariable logistic regression. Results: A total of 11,122 episodes of peritonitis in 5,367 patients were included. Of these, 162 episodes (1.5%) were due to Corynebacterium. Compared with Corynebacterium peritonitis, the odds of cure were lower in peritonitis due to Staphylococcus aureus (odds ratio [OR] 0.66, 95% confidence interval [CI] 0.45 – 0.97), Pseudomonas (OR 0.22, 95% CI 0.14 – 0.33), other gram-negative organisms (OR 0.52, 95% CI 0.35 – 0.75), fungi (OR 0.02, 95% CI 0.01 – 0.03), polymicrobial organisms (OR 0.32, 95% CI 0.22 – 0.47), and other organisms (OR 0.66, 95% CI 0.44 – 0.99) but similar for culture-negative and other gram-positive peritonitis. Similar results were observed for hemodialysis transfer and death. The outcomes of Corynebacterium peritonitis were not associated with the type of initial antibiotic selected (vancomycin vs cefazolin) or the duration of antibiotic therapy (≤ 14 days vs > 14 days). Conclusions: Outcomes for Corynebacterium peritonitis are generally favorable compared with other forms of peritonitis. Cure rates did not appear to differ if peritonitis was treated initially with vancomycin or cefazolin or if treatment duration was prolonged beyond 14 days.

Outcomes of Acinetobacter Peritonitis in Peritoneal Dialysis Patients: A Multicenter Registry Analysis

Background: Acinetobacter is a rare but important cause of peritonitis in peritoneal dialysis (PD) patients. As the complication has not been comprehensively evaluated previously, the present study examined the outcomes of Acinetobacter peritonitis in a large, national cohort of PD patients. Methods: The study included all episodes of peritonitis in Australia from January 2004 to December 2014 using Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) data. The primary outcome was peritonitis cure and secondary outcomes were catheter removal, hemodialysis transfer, recurrent/relapsing peritonitis, peritonitis-related hospitalization, and death. Outcomes were compared using multivariable logistic regression. Results: Overall, 5,367 patients experienced 11,122 episodes of peritonitis across 51 centers in Australia. Of these, 228 (4.2%) patients experienced 253 (2.3%) episodes of Acinetobacter peritonitis (176 episodes were due to Acinetobacter alone and 77 involved co-infection with other organisms). Of the 176 solitary Acinetobacter episodes, 131(74%) achieved cure with antibiotics alone. Compared with Acinetobacter, significantly lower odds of peritonitis cure were observed for Pseudomonas (adjusted odds ratio [AOR] 0.24, 95% confidence interval [CI]: 0.16 – 0.36), other gram-negative organisms (AOR 0.54, 95% CI 0.37 – 0.77), fungi (AOR 0.02, 95% CI 0.01 – 0.03), and polymicrobial organisms (AOR 0.36, 95% CI 0.25 – 0.51), whilst similar odds of cure were observed for Staphylococcus (AOR 0.73, 95% CI 0.50 – 1.06), other gram-positive organisms (AOR 1.32,95% CI 0.93 – 1.89), culture-negative (AOR 1.19, 95% CI 0.82 –1.71), and other organisms (AOR 0.72, 95% CI 0.49 – 1.07). The odds of catheter removal and hemodialysis transfer were higher with Pseudomonas, other gram-negative, fungal, and polymicrobial peritonitis than with Acinetobacter peritonitis. The odds of death were also higher with Pseudomonas and fungal peritonitis than with Acinetobacter peritonitis. Treatment of Acinetobacter peritonitis with gentamicin, ciprofloxacin, or ceftazidime achieved comparable outcomes. Conclusions: Outcomes of Acinetobacter peritonitis were favorable compared with most other forms of organism-specific peritonitis. Commonly used antibiotics covering gram-negative bacteria achieved comparable outcomes in Acinetobacter peritonitis.

EARLY PERITONITIS AND ITS OUTCOME IN INCIDENT PERITONEAL DIALYSIS PATIENTS

BACKGROUND Early-onset peritonitis is a serious complication of peritoneal dialysis (PD) and is associated with heightened risks of technique failure and death. The risk factors for early peritonitis and its outcomes are unknown. METHODS This registry study examined all incident Australian PD patients between 2003 and 2014. The primary outcome was early peritonitis, defined as onset within 12 months of starting therapy. Secondary outcomes were medical cure, relapse/recurrence, catheter removal, peritonitis-associated technique failure, and peritonitis-associated death. RESULTS Of 9,845 patients, 2,615 experienced 3,827 early-peritonitis episodes (0.50 episodes per patient-year). Early peritonitis was more common in patients who were male, obese, had a history of cigarette smoking or cerebrovascular disease, used continuous ambulatory PD, and had received prior renal replacement therapy for > 90 days. Remoteness was a risk modifier for the association between race and early peritonitis; remote Aboriginal, Torres Strait Islander, Maori and Pacific Islander patients had the highest risk. Obese patients were more likely to achieve medical cure. Older patients were less likely to achieve cure and more likely to experience peritonitis-associated death. CONCLUSIONS In summary, several factors predicted early peritonitis in incident PD patients. Modified approaches to patient selection, training techniques, and prevention strategies should be considered in high-risk individuals.

Center Effects and Peritoneal Dialysis Peritonitis Outcomes: Analysis of a National Registry

BACKGROUND Peritonitis is a common cause of technique failure in peritoneal dialysis (PD). Dialysis center-level characteristics may influence PD peritonitis outcomes independent of patient-level characteristics. STUDY DESIGN Retrospective cohort study. SETTING & PARTICIPANTS Using Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) data, all incident Australian PD patients who had peritonitis from 2004 through 2014 were included. PREDICTORS Patient- (including demographic data, causal organisms, and comorbid conditions) and center- (including center size, proportion of patients treated with PD, and summary measures related to type, cause, and outcome of peritonitis episodes) level predictors. OUTCOMES & MEASUREMENT The primary outcome was cure of peritonitis with antibiotics. Secondary outcomes were peritonitis-related catheter removal, hemodialysis therapy transfer, peritonitis relapse/recurrence, hospitalization, and mortality. Outcomes were analyzed using multilevel mixed logistic regression. RESULTS The study included 9,100 episodes of peritonitis among 4,428 patients across 51 centers. Cure with antibiotics was achieved in 6,285 (69%) peritonitis episodes and varied between 38% and 86% across centers. Centers with higher proportions of dialysis patients treated with PD (>29%) had significantly higher odds of peritonitis cure (adjusted OR, 1.21; 95% CI, 1.04-1.40) and lower odds of catheter removal (OR, 0.78; 95% CI, 0.62-0.97), hemodialysis therapy transfer (OR, 0.78; 95% CI, 0.62-0.97), and peritonitis relapse/recurrence (OR, 0.68; 95% CI, 0.48-0.98). Centers with higher proportions of peritonitis episodes receiving empirical antibiotics covering both Gram-positive and Gram-negative organisms had higher odds of cure with antibiotics (OR, 1.22; 95% CI, 1.06-1.42). Patient-level characteristics associated with higher odds of cure were younger age and less virulent causative organisms (coagulase-negative staphylococci, streptococci, and culture negative). The variation in odds of cure across centers was 9% higher after adjustment for patient-level characteristics, but 66% lower after adjustment for center-level characteristics. LIMITATIONS Retrospective study design using registry data. CONCLUSIONS These results suggest that center effects contribute substantially to the appreciable variation in PD peritonitis outcomes that exist across PD centers within Australia.

The Relationship Between Body Mass Index and Organism-Specific Peritonitis

Background: Obesity is increasingly prevalent worldwide, and a greater number of patients initiate renal replacement therapy with a high body mass index (BMI). This study aimed to evaluate the association between BMI and organism-specific peritonitis. Methods: All adult patients who initiated peritoneal dialysis (PD) in Australia between January 2004 and December 2013 were included. Data were accessed through the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry. The co-primary outcomes of this study were time to first organism-specific peritonitis episode, specifically gram-positive, gram-negative, culture-negative, and fungal. Secondary outcomes were individual rates of organism-specific peritonitis for the same 4 microbiological categories. Results: There were 7,381 peritonitis episodes among the 8,343 incident PD patients evaluated. After multivariable adjustment, obese patients (BMI 30 – 34.9 kg/m2) had an increased risk of fungal peritonitis (adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.18 – 2.42), very obese patients (BMI ≥ 35 kg/m2) had a significantly higher risk of gram-positive peritonitis (HR 1.15, 95% CI 1.02 – 1.30), while both obese and very obese patients experienced significantly higher risks of gram-negative peritonitis (HR 1.29, 95% CI 1.11 – 1.50 and HR 1.30, 95% CI 1.08 – 1.57, respectively) compared with patients with normal BMI (20 – 24.9 kg/m2). Obesity and severe obesity were independently associated with increased incidence rate ratios of all forms of organism-specific peritonitis with a non-significant trend for severe obesity and gram-negative peritonitis association. Conclusion: Among Australian patients, obesity and severe obesity are associated with significantly increased rates of gram-positive, gram-negative, fungal, and culture-negative peritonitis.

Association of Socio-Economic Position with Technique Failure and Mortality in Australian Non-Indigenous Peritoneal Dialysis Patients

Background: Few studies have examined the relationship between socio-economic position (SEP) and peritoneal dialysis (PD) outcomes, particularly at a country level. The aim of this study was to investigate the relationships between SEP, technique failure, and mortality in PD patients undertaking treatment in Australia. Methods: The study included all Australian non-indigenous incident PD patients between January 1, 1997, and December 31, 2014, using Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry data. The SEP was assessed by quartiles of postcode-based Australian Socio-Economic Indexes for Areas (SEIFA), including Index of Relative Socio-economic Advantage and Disadvantage (IRSAD – primary index), Index of Relative Socio-economic Disadvantage (IRSD), Index of Economic Resources (IER), and Index of Education and Occupation (IEO). Technique and patient survival were evaluated by multivariable Cox proportional hazards survival analyses. Results: The study included 9,766 patients (mean age 60.6 ± 15 years, 57% male, 38% diabetic). Using multivariable Cox regression, no significant association was observed between quartiles of IRSAD and technique failure (30-day definition p = 0.65, 180-day definition p = 0.68). Similar results were obtained using competing risks regression. However, higher SEP, defined by quartiles of IRSAD, was associated with better patient survival (Quartile 1 reference; Quartile 2 adjusted hazards ratio [HR] 0.96, 95% confidence interval [CI] 0.86 – 1.06; Quartile 3 HR 0.87, 95% CI 0.77 – 0.99; Quartile 4 HR 0.86, 95% CI 0.76 – 0.97). Similar results were found when IRSD was analyzed, but results were no longer statistically significant for IER and IEO. Conclusions: In Australia, where there is universal free healthcare, SEP was not associated with PD technique failure in non-indigenous PD patients. Higher SEP was generally associated with improved patient survival.