Abstract
Among the different types of peritonitis, those of enteric origin and, in particular, those due to gram-negative organisms show an almost constant incidence rate, in contrast to the falling incidence of cases due to gram-positive cocci, and therefore their importance has become relatively greater (3-5). Moreover, gram-negative peritonitis is known to be more likely than gram-positive peritonitis to result in catheter removal, hospital admission, and death (6). Accordingly, to improve the prognosis of peritoneal dialysis patients, it is very important to identify and control the risk factors for gram-negative peritonitis.
The known risk factors for gram-negative peritonitis include diverticulosis (7), treatment for constipation (8), interventional procedures such as colonoscopy and polypectomy (9), and use of gastric acid suppressants (10).
Among these, use of gastric acid suppressants has been thought to act as a risk factor by increasing the intestinal bacterial burden and by consequently raising the likelihood of transmigration of intestinal bacteria. The literature is inconsistent, however. In previously published studies, Caravaca et al. showed that the use of gastric acid suppressants is an independent risk factor for enteric peritonitis (10) but, on the contrary, del Peso et al. concluded that their use is not a risk factor (11). Thus, whether the use of gastric acid suppressants is a predisposing factor for enteric peritonitis is it still under debate.
Nessim et al., in this edition of Peritoneal Dialysis International, have now concluded that, consistent with the findings of del Peso et al., the use of gastric acid suppressants is not in a statistically significant correlation with the occurrence of enteric peritonitis (12). The value of this work by Nessim et al. is found in the fact that it used a larger number of patients than did previous studies addressing this issue. Although the study was conducted within a single center, the fact that it included over 100 patients enhances the reliability and importance of its results. The findings of this research are very welcome news, considering that the use of gastric acid suppressants is highly frequent in chronic renal failure patients.
However, it is too early to conclude that the use of gastric acid suppressants is not a risk factor for enteric peritonitis. While the research by Nessim et al. was conducted with many patients, it was a single-center retrospective study, and a summary of the existing literature does not allow us to conclude that gastric acid suppressants do not increase the risk of enteric peritonitis. As pointed out in the paper by Nessim et al., a prospective study has a limitation when the frequency of enteric peritonitis is not high. However, if a large number of patients are included through multicenter research, we may overcome this limitation. Such an attempt to examine the correlation between gastric acid suppressants and enteric peritonitis is essential, considering that the results of previous studies have been inconsistent, that the incidence of enteric peritonitis has changed little and that it is often clinically severe, and that many chronic renal failure patients take gastric acid suppressants for various reasons.
One of new findings in the paper by Nessim et al. is that the risk of enteric peritonitis did not increase when a proton pump inhibitor (PPI) was used but did increase with H2-blockers (H2B). Of course, each patient's gastric acid was not measured directly but, given that a PPI is generally more effective than an H2B in lowering gastric acidity, the result is somewhat unexpected. That is, it suggests the possibility that there is a mechanism other than the inhibition of gastric acid in relating the use of H2B to the increase in risk of enteric peritonitis. However, because the number of patients that used H2B was not large enough compared to the number of patients that used PPI, the possibility of bias should be considered in this interpretation. In addition, previous research that analyzed the pharmacokinetics of PPI and H2B in end-stage renal failure patients reported that the clearance of PPIs such as rabeprazole was not much affected by renal failure, while, on the contrary, the clearance of H2Bs such as ranitidine was decreased compared to that in people with normal kidney function (13,14). This suggests there is a possibility that the mechanism might still be gastric acid related. However, because Nessim et al. did not tell us the individual medications, the dosage or the duration of treatment with gastric acid suppressants, their findings may need to be reinterpreted in consideration of these facts.
The possibility of an increase in the risk of enteric peritonitis according to duration of treatment with gastric acid suppressants is another topic that needs additional study. In general, the use of gastric acid suppressants is more frequent and sometimes of longer duration in chronic renal failure patients that have a high risk of hemorrhage and a high frequency of gastric or duodenal ulcer or hemorrhagic gastritis. If the risk of enteric peritonitis differs according to duration of treatment with gastric acid suppressants, clinicians must be provided with information on the period that might not increase that risk. Such information can be used to set the therapeutic window that minimizes the risk and maximizes the benefit of administering gastric acid suppressants to peritoneal dialysis patients.
Finally, it is to be hoped that, like the work by Nessim et al., many additional studies will be conducted concerning clinicians’ problems in treating patients in the field, addressing questions that have not been adequately answered in previous research. Furthermore, opportunities for multicenter research systems should be promoted and established through the efforts of organizations such as the International Society for Peritoneal Dialysis with the aim of continuing to improve the prognosis for peritoneal dialysis patients.