A novel prediction model for peritonitis cure among PDAP patients was established and validated in this multicenter study. PD duration, serum albumin, antibiotics prior to admission, and type of causative organisms were included in the prediction model. Based on our results, the as-constructed model showed good performances in calibration and discrimination, with the C-statistic of over 0.75. Using the nomogram, it is possible to stratify individual peritonitis episodes and make reasonable treatment decisions. To our knowledge, this is the first prediction nomogram for predicting PDAP cure in patients initializing PD developed in a multicenter study.
There are few reports concerning the prediction model of peritonitis cure in PDAP population. Surapon Nochaiwong et al. developed a prediction score for the treatment failure among PD patients, which incorporated DM, systolic blood pressure (SBP), dialysate leukocyte count on day 3–4, and dialysate leukocyte count on day 515. Nevertheless, their model did not incorporate pathogenic bacteria, and no external validation was conducted. Different from this study, their outcome was treatment failure containing catheter removal, transfer to HD, or peritonitis-associated mortality. As a matter of fact, their risk factors for the outcome were inconsistent. In our study, the prediction nomogram model was more intuitive and applicable to clinical practice. The treatment decision should be made by taking into comprehensive consideration of a PDAP patient.
According to our results, a shorter PD duration was related to the possibility of peritonitis cure, which was supported by several reports. For instance, a study found that PD duration less than 2.4 years was associated with a higher resolution rate than that longer than 2.4 years 16. Another study indicated that a longer PD duration at the onset of peritonitis was related to a longer duration from PD effluent abnormalities to treatment with appropriate antibiotics, which further led to adverse outcomes17. Similar finding was also obtained from other study, which was that patients receiving long-term dialysis were prone to gram-negative bacterial infection and worse treatment outcomes compared with those undergoing short-term dialysis18. There are inconsistent results regarding the impact of PD duration on the outcome of PDAP in literature. For instance, Yang et al. did not find the relationship between PD duration and catheter loss19. The differences may be ascribed to the different definitions of study outcome. Our data confirmed that the increased PD duration reduced the probability of peritonitis cure in all the episodes of peritonitis. We infer that continuous exposure to glucose and glucose degradation products may lead to tissue toxicity in the peritoneum, resulting in peritoneal dysfunction20. This may further make it difficult to eliminate inflammation.
Another novel predictive factor for cure identified in this study was no antibiotics prior to admission. As far as we know, the relationship between antibiotics prior to admission and PDAP outcome remains unclear so far. On the one hand, the application of antibiotics at home may be related to serious patient condition, which results in the low possibility of cure. On the other hand, some patients applying antibiotics by themselves live far away from the PD center, and the remote distance from the hospital is also one of the risk factors for peritonitis and technique failure21. Moreover, in our study, the application of antibiotics was not standardized at home by PDAP patients, which delayed the optimal timing of standard treatment17 and added to the difficulty in cure.
It was observed in this dataset that a higher level of serum albumin predicted a higher probability of peritonitis cure. In contrast to our study, one article considered that serum albumin level did not affect the non-resolution of peritonitis22. Another study reported that serum albumin was not the risk factor for the poor outcomes of PDAP patients23. Such differences may be attributed to their relatively small sample sizes that are insufficient to find the association between serum albumin and the outcome of PDAP. Hypoalbuminemia is identified as a risk factor for peritonitis in PD patients24-26. As reported in one study, hypoalbuminemia, a marker of malnutrition and inflammation, also predicted the all-cause, cardiovascular, and infection-related mortality in patients receiving PD27. Moreover, a higher daily protein intake in PD patients indicates a higher serum albumin level and good nutrition status, which prevent patient death or peritonitis28. It is not hard to infer that a higher serum albumin level is related to the cure of PDAP. Theoretically, a higher serum albumin level has a good remedial effect when antibiotics are bound onto the serum albumin and the drug metabolism is reduced. We found that a high serum albumin level was good for the cure of PDAP, and it was assumed that treatment strategies to improve albumin levels should be advocated to improve the treatment outcome of peritonitis.
Noteworthily, the causative organism was included in the prediction model. As a matter of fact, the causative organism is an important factor for the outcome of PDAP. However, the specific effects on outcome between some bacteria are unclear. Our constructed nomogram allowed to intuitively observe the concrete effects of different bacteria on cure. In our study, Enterococcus showed the highest score to cure, followed by other G-positive Corynebacteria. Then, Cocoagulase-negative Staphylococcus and culture-negative organisms had the same score. In Htay's study29, causative organisms were related to the outcome of PDAP; The authors divided pathogenic bacteria into Gram-positive, Gram-negative, Culture-negative, Polymicrobial organisms and others, and found that Culture-negative bacteria had a higher cure rate than Gram-positive ones. Another study indicated that less virulent causative organisms (coagulase-negative staphylococci, and culture-negative streptococci) were associated with a higher probability of cure10. The prognosis of gram-negative bacterial peritonitis was worse than that of Gram-positive bacterial peritonitis in our study, consistent with Fung's study30. In the present work, bacterial classification was more detailed according to the ISPD peritonitis guidelines, which overcame the problem of different prognosis of different Gram-positive or Gram-negative bacteria. Pathogenic bacteria contained in our model were specific and suitable for clinical applications.
To the best of our knowledge, this is the first nomogram that provides clinicians with a predictable assessment tool for the cure of peritonitis among PDAP patients. Our research has a few strengths. First, our findings serve as the useful reference for the management of PDAP episodes by physicians, which rely on comprehensive assessment rather than a single factor. The external utility of the model is good and can be generalized. Timely ceasing PD can reduce the length of hospital stay, medical costs, and occurrence of serious complications in patients with a low probability of PDAP cure. Furthermore, the nomogram is practical because all the variables included are the easily and routinely collected clinical factors, which offers an intuitive tool for individualized prediction using a small number of risk factors.
Nonetheless, several limitations should also be noted in this study. First, given the retrospective nature of this study, there might be potential selection bias. Second, we did not take into account new biomarkers such as IL-6, COX-2, RNase 3 and RNase 731, 32. Future studies should develop or update the prediction model to include new biomarkers. Besides, a larger population size and prospective investigations are also warranted.