The Association between Peritoneal Dialysis Modality and Peritonitis

Discussion

This large multicenter registry study demonstrated that PD modality was not associated with a patient’s overall risk of developing peritonitis. However, we found that APD was associated with a lower risk of culture-negative peritonitis, which was balanced by an increased risk of Gram-negative peritonitis compared with CAPD. When only the first peritonitis episodes were analyzed, APD was not associated with overall peritonitis risk but was associated with a lower risk of Gram-positive peritonitis. At the same time, the clinical outcomes of peritonitis were comparable between both patient groups.

The overall finding of our analysis is in agreement with a number of other observational studies (7,9–12) and one randomized control trial (8), which reported comparable peritonitis rates between CAPD and APD. Two of the observational studies were also registry-based analyses from Canada (11) and Scotland (12). Each consisted of a smaller cohort of patients compared with our analysis, and each was performed almost a decade ago. The randomized trial reporting no association between PD modality and peritonitis was performed in three Danish dialysis units >10 years ago, and was limited by its small sample size (8). The study involved only 13 CAPD and 12 APD patients, and was limited by a low event rate (only three peritonitis events in total) (8).

By contrast, two other observational studies showed higher rates of peritonitis in APD (13,14). Golper et al. compared 866 CAPD patients with 213 APD patients, and found that the peritonitis-free interval was inferior in the APD patients (14.9 versus 20.2 months), such that the relative risk for peritonitis was 28% higher in APD patients (13). Similarly, in a retrospective study of the US Renal Data System, Oo et al. found that CAPD patients had a lower risk of peritonitis (relative risk, 0.94; 95% CI, 0.88 to 0.99) compared with APD patients (14). Unfortunately, this study only examined the time to first peritonitis after 9 months of PD had been completed. This is a clear limitation of the analysis and would have resulted in significant survivor bias. This study was also performed over a decade ago, limiting its applicability to current practice.

Several other studies have demonstrated lower peritonitis rates in association with APD therapy. A randomized controlled trial by de Fijter et al. found that APD was associated with lower rates of peritonitis than CAPD (0.51 versus 0.94 episodes per patient-year; P=0.03) (3). However, this trial was limited by its small sample size and short duration. A meta-analysis performed by Rabindranath et al. concluded that APD reduced peritonitis rates compared with CAPD (rate ratio, 0.54; 95% CI, 0.35 to 0.83) (15). However, this analysis was limited by both the number of available trials and patients (139 patients from three randomized controlled trials). Several other single-center, observational cohort studies have demonstrated reduced peritonitis rates with APD (4–6).

The apparent disparity in peritonitis rates according to PD modality between the previously mentioned studies and our study may be explained by the fact that many of the previously mentioned studies involved small patient numbers, had low peritonitis event rates, were conducted at different time periods, and utilized different cycler connection methodologies from study to study. As a result, the majority of these studies would have been confounded by both center-specific factors (e.g., patient training, center size, and regular auditing of infection rates) and patient-specific factors (e.g., compliance, age, diabetic status, connection systems used, and previous peritonitis episodes). Our study overcomes these limitations by including all PD patients within Australia, resulting in both a large patient population and a large number of events. However, we did find that in our patient cohort, patients receiving APD were younger (60 versus 64 years) and had slightly fewer comorbidities (Table 1). It is also important to note that the majority of the above-discussed studies were performed over a decade ago. By contrast, our study was restricted to 2003–2011, meaning that our results remain relevant to current clinical practice.

The decision for choosing a PD modality for individual patients in Australia is currently based on the Caring for Australasians with Renal Insufficiency guidelines and is dominated by lifestyle considerations. Although there may have initially been a preference for commencing patients more prone to infections on APD, the International Society of Peritoneal Dialysis (ISPD) Peritonitis Guidelines have acknowledged that there is conflicting evidence as to the rates of peritonitis in APD and CAPD (17). The available evidence, updated with our findings, indicates that the PD modality does not affect the overall risk of peritonitis. However, the risk of developing peritonitis due to a Gram-positive organism appears to be higher with CAPD, whereas the risk of developing Gram-negative peritonitis is lower in these patients. The higher likelihood of Gram-positive peritonitis has also been reported by other investigators (4,7,10) and may be related to the greater number of daily connections required in CAPD versus APD, thereby increasing the likelihood of contamination with Gram-positive skin micro-organisms. Because ANZDATA does not collect any data on PD exit-site care, exit-site management may have differed between treating units in our study, potentially altering the risk of infections secondary to skin-based bacteria. However, exit-site care of patients on APD and CAPD within the same unit are not likely to have been different. The explanation for the observed lower risk of Gram-negative peritonitis in patients receiving CAPD compared with those receiving APD is uncertain. Although indigenous racial origin was more common in patients receiving APD and was previously identified by our group as a key independent risk factor for Pseudomonas peritonitis (18), race was adjusted for in the multivariable analysis.

With regard to other risk factors identified for the development of peritonitis, our study findings were consistent with a number of previous studies. For instance, our study confirmed the previous finding that the Australian indigenous population was at a higher risk of developing peritonitis (19). This study also confirmed the findings that an increased BMI at the time of PD commencement (20,21), the requirement for hemodialysis before commencing PD (11), diabetes mellitus (14,22,23), and cigarette smoking (24) all increase the likelihood of developing peritonitis. The fact that patients who transferred to PD from hemodialysis do poorly was also evident in a study performed by McDonald et al., who found that patients who changed from PD to hemodialysis had a higher mortality rate compared with those who commenced PD from the start (25). Additional risk factors that were identified but were not able to be measured in our model included socioeconomic status (26) and level of education (27).

The other important finding of this study is that there was a nonsignificant higher likelihood of both hospitalization and mortality in patients undergoing APD, a finding that may be of clinical significance. There was no statistical difference found in regard to hospitalization, and all other outcomes, including catheter removal and temporary or permanent transfer to hemodialysis, were comparable between the two modalities. These results can be compared with a single-center study performed by Rüger et al., which found no difference between CAPD and APD patients during treatment of 508 episodes of PD-related peritonitis in 205 patients with respect to the outcomes of relapse, mortality, or the combined end point of mortality plus catheter removal (28). There are a number of possible explanations for our findings. First, APD patients are less likely to observe the initial changes in their PD fluid at the time of peritonitis, because the majority of these patients are exchanging at night. Second, we found that APD patients were more likely to develop a Gram-negative infection as opposed to a Gram-positive infection. Previous studies demonstrated that Gram-negative peritonitis is associated with worse outcomes compared with Gram-positive infections, including higher rates of mortality (29) and technique failure (29,30). Another explanation may be related to a concern raised in the ISPD guidelines that the rapid exchanges in APD may lead to inadequate time to achieve satisfactory intraperitoneal levels of antibiotics, resulting in suboptimal peritonitis outcomes (31). Anecdotally, it appears to be common practice for patients to change modality to CAPD while being treated for peritonitis, although there is no means of assessing how commonly this occurs with our data.

The strengths of this study include its large sample size and inclusiveness. We included all incident PD patients during the study period, such that all centers providing PD service in Australia were included. Because there are substantial variations in the prevention, diagnosis, treatment, and auditing of peritonitis in Australian PD centers (32), the multicenter design of this study greatly enhanced the external validity of our results. In addition to center-specific factors, we corrected for several patient-specific risk factors in the multivariable analysis. These strengths should be balanced against the study’s limitations, which included limited depth of data collection. ANZDATA does not collect information such as the presence of concomitant exit-site and tunnel infections, patient compliance, socioeconomic status, severity of comorbidities, dialysate collection techniques or culture methods, and antibiotic dosages or routes of administration. Although we adjusted for a large number of patient characteristics, the possibility of residual confounding could not be excluded. Similar to other registries, ANZDATA is a voluntary registry and there is no external audit of data accuracy, including the diagnosis of peritonitis. Consequently, the possibility of coding/classification bias cannot be excluded. Finally, because this is an observational study, we are only able to demonstrate association and not causation.

In conclusion, this is the largest and most definitive study to examine the relationship between PD modality and peritonitis; in doing so, we found that PD modality was not associated with overall peritonitis risk. Future research should focus on other aspects of PD technique in order to improve peritonitis rates.