Post-Market Clinical Evaluation for the Safety of Peritoneal Dialysis
The safety of peritoneal dialysis was evaluated for the potential infectious complications, mainly the peritonitis, in reference to some medical devices reports at the National Center of Medical Devices Reporting (NCMDR). Further analyses at the US FDA database revealed the availability of 2601 reports, through which 52 reports caused fatal incidents and 182 were reported to result in serious injuries. In addition, data provided by the Saudi Center for Organ Transplantation illustrate a mortality rate of about 6% of the PD population in Saudi Arabia, in 2019 .
The aim of this study is to evaluate the safety of peritoneal dialysis in general, and to test, in particular, whether the current local rate of peritonitis is within the acceptable rate, as indicated by reliable global societies, or otherwise, to recommend certain actions to ensure the safety of the device.
Peritoneal dialysis refers to the treatment used to compensate some lost kidney functions, which use the lining of the abdominal cavity, peritoneum, to serve as a filter for the dialysis process to be completed inside the body. Before starting the peritoneal dialysis, a catheter must be implanted permanently into the belly or the chest to allow the flow of a solution called dialysate in and out of the abdominal cavity.  The dialysate is a solution that contains electrolytes to help maintain blood composition, an osmotic agent and a pH buffer.  Long-term catheters are usually made of silicon with a strip of radiopaque to be visualized on x-ray. The catheter is divided into three sections: an intraperitoneal section, a subcutaneous section and an external section to be connected to the dialysis system. Two cuffs are implanted for catheter stabilization, movement limitation, leaks prevention, and microorganisms’ entry control, as illustrated in figure 1. 
FIGURE 1. (A) AN IMPLANTED PERITONEAL CATHETER. (B) A CLOSE-UP SHOWING THE STABILIZING CUFFS. 
The process of filling and draining the dialysate is called an exchange. Patients do exchanges in accordance to two types of peritoneal dialysis, which are Continuous Ambulatory Peritoneal Dialysis (CAPD), or Automated Peritoneal Dialysis (APD), as illustrated in figure 2. These types are almost similar, except for the exchanges schedule, which is done automatically with APD . In CAPD, patients usually are prescribed to do four exchanges a day, with each exchange the dialysate will sit in the abdomen for a dwell time while maintaining their daily activities. On the other hand, APD is usually done at night while the patient is asleep, using a machine called cycler.
FIGURE 2: MODE OF OPERATION OF PERITONEAL DIALYSIS. A: CONTINUOUS AMBULATORY PERITONEAL DIALYSIS (CAPD), B: AUTOMATED PERITONEAL DIALYSIS (APD) 
Risks and complications
Given that peritoneal dialysis is a home-use system, the most common complication is infections. Peritoneal dialysis is potentially associate with two types of infections, which are catheter related infections and peritonitis. Peritonitis is the inflammation of the peritoneum, which is reported to contribute to death in 16% of PD patients . Catheter related infections, on the other hand, are divided into tunnel and exit-site infections, both of them are susceptible to lead to serious consequences including peritonitis. The International Society of Peritoneal Dialysis (ISPD) recommended monitoring PD programs to maintain an overall peritonitis rate that does not exceed 0.5 episodes per patient-year .
Peritoneum inflammation is usually caused by contamination, in which microorganisms find their ways inside the abdominal cavity through the catheter tube. Peritonitis is mostly caused by the touch contamination , beside other sources of contaminations as indicated in table 1.
TABLE 1. CAUSES OF PERITONITIS AND THEIR POSSIBILITIES.
Part 1: Clinical Paper Review for the Safety of Peritoneal Dialysis
1.1 Search criteria
The search criteria followed some measures to define the research question, relative databases, inclusion criteria, and quality measures. A total of 86 articles were acquired for the period of 2012-2020. The screening process resulted in obtaining 22 articles to be included in the clinical evaluation, as shown in figure 3.
FIGURE 3. SCHEMATIC REPRESENTATION OF THE SEARCH FINDINGS ON EVALUATING THE SAFETY OF PD IN REGARDS TO THE PERITONITIS RATE.
1.2 Summary of the literature findings:
The ultimate aim of the review was to discover the range of the peritonitis rate as revealed by the published literature. This is an issue of interest in Saudi Arabia, since it triggered a safety concern that threatens patients’ lives. Table 6 illustrates the data obtained from 22 articles, which reported peritonitis rates ranging from 0.13 to 0.87 episode per patient-year with an average of 0.3 episode per patient-year.
TABLE 2. SUMMARY OF THE PAPER REVIEW FINDINGS THAT REVEAL THE PERITONITIS RATE IN DIFFERENT STUDIES.
Part 2: Clinical Experience Review for the Safety of Peritoneal Dialysis
The international society for peritoneal dialysis (ISPD) is a society built to promote quality practice, and achieve optimal outcomes of peritoneal dialysis through enhanced advocacy, research, and education, in order to improve the health and well-being of people living with end-stage kidney disease or suffering from acute kidney injury. In 2016, the ISPD published a guideline to clarify the correct practices of the treatment and prevention of peritonitis. This section aims to state the ISPD recommendations regarding the peritonitis rate in PD units and the best practices to prevent peritonitis from occurring , and to reflect the Saudi users' opinion in the topic.
2.1 ISPD peritonitis-related recommendations:
• All PD units should monitor the peritonitis incidence within their facility on regular basis. Episodes of peritonitis should be counted starting from the beginning of PD training, whereas all relapsing episodes should be counted as one. The monitored parameters should include the following: overall peritonitis rate, peritonitis rates of specific organisms, peritonitis-free patients' percentage, and the antimicrobial susceptibilities of the infecting organisms.
• The overall peritonitis rate is recommended to be reported as episode per patient-year and should not exceed 0.5 episodes per patient-year at risk.
2.2 Saudi Users' Experience Review
In order to reflect the local situation of PD in Saudi Arabia, local experts were consulted to give opinion regarding the current situation of the safety of PD. The advisory panel were represented by nephrologists from different healthcare facilities in Saudi Arabia.
The consulted experts highlighted that peritonitis and infectious complications have been an issue since the inception of PD modalities as a kidney failure treatment. However, wrong practices could be the cause of infections rather than the PD modality itself. Therefore, manufacturers should focus on the internal training at the hospitals, in addition to the home visits. In addition, it is also highlighted that the currently available data related to PD complications at the national level are known through the voluntary efforts of some organizations, but there is no reliable source to have clear and precise rates of such complications. Thus, manufacturers shall monitor the overall peritonitis rate among PD patients by keeping records of every peritonitis case.
In order to maintain the PD patient safety, and to reduce the potential risk of peritonitis, SFDA has established several meetings with the PD-related manufacturers in the Saudi market, and end-up with some actions that should be fulfilled, which are:
• Manufacturers of PD shall provide a plan to collect clinical data from the Saudi healthcare facilities, in regards to monitoring the peritonitis cases and rates.
• Manufacturers of PD shall implement the plan to monitor the peritonitis cases and rates as part of their post-market surveillance plan, and to submit to SFDA a monthly report that shows maintaining the peritonitis rate within the accepted international standards.
• Manufacturers of PD shall report to SFDA all PD-related incidents whenever received from PD users.
Grateful thanks to Eng. Danah Alotaibi for designing, reviewing the up to date articles, and writing up the context of this study. Eng. Bader Aloufi verified the study methodology and supervised the study progress. With the appreciation to the post-market clinical evaluation team for their efforts in conducting this work.
We also acknowledge the following members for sharing valuable inputs in evaluating the safety of peritoneal dialysis:
- Talal Alfadhel, the head of the nephrology unit and his team from King Saud University Medical City
- Dr. Wael Habhab, the section head of nephrology at King Faisal Specialist Hospital & Research Center in Jeddah
For inquiries related to this study, you may reach us through this email: firstname.lastname@example.org
 Bader Aloufi, "Clinical Evaluation for the Infections Associated with Peritoneal Dialysis," Saudi Food and Drug Authority, 2015.
 S. G. A. f. Statistics, "Kidney Haemodialysis Patients by Sector, Gender, and Nationality," 2017.
 "King Abdullah Foundation," [Online]. Available: https://kingabdullahfoundation.org/. [Accessed May 2020].
 "Your Kidneys & How They Work," National Institute of Diabetes and Digestive and Kidney Diseases, June 2018. [Online]. Available: https://www.niddk.nih.gov/health-information/kidney-disease/kidneys-how-they-work. [Accessed May 2020].
 "Hemodialysis," National Institute of Diabetes and Digestive and Kidney Diseases , January 2018. [Online]. Available: https://www.niddk.nih.gov/health-information/kidney-disease/kidney-failure/hemodialysis. [Accessed May 2020].
 M. C. Staff, "Hemodialysis," Mayo Clinic, July 2019. [Online]. Available: https://www.mayoclinic.org/tests-procedures/hemodialysis/about/pac-20384824. [Accessed May 2020].
 "Peritoneal Diyalsis," National Institute of Diabetes and Digestive and Kidney Diseases, January 2018. [Online]. [Accessed May 2020].
 A. Alamri, "Risk Analysis Report (Peritoneal Dialysis)," Saudi Food and Drug Authority, 2020.
 "Peritoneal Dialysis," Mayo Clinic, April 2019. [Online]. Available: https://www.mayoclinic.org/tests-procedures/peritoneal-dialysis/about/pac-20384725. [Accessed May 2020].
 Herlihy SE, Starke HE, Lopez-Anton M, et al., "Peritoneal Dialysis Fluid and Some of Its Components Potentiate Fibrocyte Differentiation.," International Society of Peritoneal Dialysis, pp. 367-373, 2016.
 Suzanne C. O'Connell Smeltzer، Brenda G. Bare، Janice L. Hinkle، Kerry H. Cheever, Brunner & Suddarth's Textbook of Medical-Surgical Nursing, 2010.
 R. K. 2. Madhukar Misra, "Mechanisms of Solute Clearance and Ultrafiltration in Peritoneal Dialysis," UpToDate, 2011.
 Philip Kam-Tao Li, Cheuk Chun Szeto, Beth Piraino, Javier de Arteaga, Stanley Fan, Ana E. Figueiredo,, "ISPD PERITONITIS RECOMMENDATIONS: 2016 UPDATE ON PREVENTION AND TREATMENT," International Society for Peritoneal Dialysis, vol. 36, p. 481–508, 2016.
 "Peritoneal Dialysis Market Size, Share and Industry Growth By Product Type (CAPD, APD), Product (Cyclers, Fluids), End User (Home health care and Hospitals) and Regional Forecast, 2018 - 2025," Fortune Business Insights, April 2019. [Online]. Available: https://www.fortunebusinessinsights.com/industry-reports/peritoneal-dialysis-market-100089. [Accessed June 2020].
 SCOT staff, "Saudi Center for Organ Transplantation," 2017. [Online]. Available: http://www.scot.gov.sa/webb/Reports/1040?lang=En. [Accessed 06 2020].
 Michael S Balzer, Robert Claus, Hermann Haller, Marcus Hiss, "Are ISPD Guidelines on Peritonitis Diagnosis Too Narrow? A 15-Year Retrospective Single-Center Cohort Study on PD-Associated Peritonitis Accounting for Untrained Patients," journal of the International Society for Peritoneal Dialysis, vol. 39, no. 3, pp. 220-228, 2019.
 Hsiao-Ling Chen, Der-Cherng Tarng, Lian-Hua Huang, "Risk factors associated with outcomes of peritoneal dialysis in Taiwan: An analysis using a competing risk model," Medicine (Baltimore), Baltimore, 2019.
 Yixin Luo, Yanlin Huang, Xiuyu Chen, Gang Meng, Yongsheng Zhang, "Effects of Multidisciplinary Team Care Based on 5E's Renal Rehabilitation for Peritoneal Dialysis Patients in Guangxi Zhuang Autonomous Region of China: A Randomized Controlled Trial," Blood Purif , 2019.
 Shouci Hu, Pei Ming, Abdul Rashid Qureshi, Bengt Lindholm, Yang Bo, Hongtao Yang, "Peritonitis: Episode Sequence, Microbiological Variation, Risk Factors and Clinical Outcomes in a North China Peritoneal Dialysis Center," Kidney Blood Press Res., 2018.
 Cheng-Kai Hsu, Chin-Chan Lee, Yih-Ting Chen, Ming-Kuo Ting, Chiao-Yin Sun, Chun-Yu Chen, Heng-Jung Hsu, Yung-Chang Chen, I-Wen Wu, "Multidisciplinary predialysis education reduces incidence of peritonitis and subsequent death in peritoneal dialysis patients: 5-year cohort study," PLoS One., 2018.
 Dev Jegatheesan, David W Johnson, Yeoungjee Cho, Elaine M Pascoe, Darsy Darssan, Htay Htay, Carmel Hawley, Philip A Clayton, Monique Borlace, Sunil V Badve, Kamal, "The Relationship Between Body Mass Index and Organism-Specific Peritonitis," Perit Dial Int. , vol. 38, no. 3, pp. 206-214., 2018.
 Davidson B, Crombie K, Manning K, Rayner B, Wearne N. , "Outcomes and Challenges of a PD-First Program, a South-African Perspective," Perit Dial Int. , vol. 38, no. 3, pp. 179-186., 2018.
 Al Wakeel JS, Al Ghonaim MA, Aldohayan A, Usama S, Al Obaili S, Tarakji AR, Alkhowaiter M. , "Appraising the outcome and complications of peritoneal dialysis patients in self-care peritoneal dialysis and assisted peritoneal dialysis: A 5-year review of a single Saudi center.," Saudi J Kidney Dis Transpl., vol. 29, no. 1, pp. 71-80, 2018.
 Nataatmadja M, Cho Y, Pascoe EM, Darssan D, Hawley CM, Johnson DW, "Association Between Peritoneal Glucose Exposure and Peritonitis in Peritoneal Dialysis Patients: The balANZ Trial.," Perit Dial Int., vol. 37, no. 4, pp. 407-413, 2017.
 Yan H, Fang W, Lin A, Cao L, Ni Z, Qian J. , "Three Versus 4 Daily Exchanges and Residual Kidney Function Decline in Incident CAPD Patients: A Randomized Controlled Trial," Am J Kidney Dis., vol. 69, no. 4, pp. 506-513, 2017.
 Wael El-Reshaid, Hanan Al-Disawy, Hossameldeen Nassef, Usama Alhelaly, "Comparison of peritonitis rates and patient survival in automated and continuous ambulatory peritoneal dialysis: a 10-year single center experience," Ren Fail., vol. 38, no. (8), pp. 1187-92, 2016.
 Alicia M Neu, Troy Richardson, John Lawlor, Jayne Stuart, Jason Newland, Nancy McAfee, Bradley A Warady, SCOPE Collaborative Participants, "Implementation of standardized follow-up care significantly reduces peritonitis in children on chronic peritoneal dialysis," Kidney Int., vol. 89, no. (6), pp. 1346-54, 2016 .
 Haishan Wu, Rong Huang, Chunyan Yi, Juan Wu, Qunying Guo, Qian Zhou, Xueqing Yu, Xiao Yang, "Risk Factors for Early-Onset Peritonitis in Southern Chinese Peritoneal Dialysis Patients," Perit Dial Int., vol. 36, no. (6), pp. 640-646, 2016.
 Loke Meng Ong, Chin Chin Ch'ng, Hong Chin Wee, Premaa Supramaniam, Hadzlinda Zainal, Bak Leong Goh, Sunita Bavanandan, Lily Mushahar, Lai Seong Hooi, Ghazali Ahmad, "Risk of Peritoneal Dialysis-Related Peritonitis in a Multi-Racial Asian Population," Perit Dial Int., vol. 37, no. (1), pp. 35-43, 2017.
 Mei-Fen Pai, Ju-Yeh Yang, Hung-Yuan Chen, Shih-Ping Hsu, Yen-Ling Chiu, Hon-Yen Wu, Wan-Chuan Tsai, Yu-Seng Peng, "Comparing long-term outcomes between early and delayed initiation of peritoneal dialysis following catheter implantation," Ren Fail., vol. 38, no. (6), pp. 875-81, 2016.
 Xiaoguang Fan, Rong Huang, Juan Wang, Hongjian Ye, Qunying Guo, Chunyan Yi, Jianxiong Lin, Qian Zhou, Fengmin Shao, Xueqing Yu, Xiao Yang, "Risk factors for the first episode of peritonitis in Southern Chinese continuous ambulatory peritoneal dialysis patients," PLoS One., 2014.
 Narayan Prasad, Archana Sinha, Amit Gupta, Raj Kumar Sharma, Dharmendra Bhadauria, Abhilash Chandra, Kashi Nath Prasad, Anupama Kaul, "Effect of body mass index on outcomes of peritoneal dialysis patients in India," Perit Dial Int., vol. 34, no. (4), pp. 399-408, 2014 .
 Mauricio Sanabria, Martha Devia, Gilma Hernández, Kindar Astudillo, Carlos Trillos, Mauricio Uribe, Catalina Latorre, Astrid Bernal, Angela Rivera, Local investigators in study, "Outcomes of a peritoneal dialysis program in remote communities within Colombia," Perit Dial Int., pp. 52-61, 2014.
 Yao-Peng Hsieh, Chia-Chu Chang, Yao-Ko Wen, Ping-Fang Chiu, Yu Yang, "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," Perit Dial Int., vol. 34(1), pp. 85-94, 2014.
 Yahn-Bor Chern, Pei-Shan Ho, Li-Chueh Kuo, Jin-Bor Chen, "Lower education level is a major risk factor for peritonitis incidence in chronic peritoneal dialysis patients: a retrospective cohort study with 12-year follow-up," Perit Dial Int., vol. 33(5), pp. 552-8, 2013.
 Chun-Yan Su, Juan Pei, Xin-Hong Lu, Wen Tang, Tao Wang, "Gastrointestinal symptoms predict peritonitis rates in CAPD patients," Clin Nephrol., vol. 77(4), pp. 267-74, 2012.
 Rong Xu, Min Zhuo, Zhikai Yang, Jie Dong, "Experiences with assisted peritoneal dialysis in China.," Perit Dial Int., vol. 32(1), pp. 94-101, 2012.
Post-Market Clinical Evaluation for the Safety of Peritoneal Dialysis