Gastrointestinal symptoms in patients undergoing peritoneal dialysis

Implication for health policy/practice/research/medical education: The present study has focused on the prevalence of common gastrointestinal disorders among patients undergoing peritoneal dialysis. Our study revealed that only abdominal distention is affected by peritoneal dialysis according to the gastrointestinal symptom rating scale questionnaire. Please cite this paper as: Hasanzamani B , Naderzadeh A, Miri M, Ahadi M. Gastrointestinal symptoms in patients undergoing peritoneal dialysis. J Renal Inj Prev. 2020; 9(4): e31. doi: 10.34172/jrip.2020.31. Sh or t c om m un ic at io n


Introduction
Chronic kidney disease (CKD) is characterized by alteration in renal function and progressive decrease in glomerular filtration rate (1). This irreversible process will result in end-stage renal disease; where the accumulation of plasma toxins and electrolyte imbalance results in uremic syndrome and death if left untreated (1). CKD has great cost burden since the global prevalence of CKD has been reported to be approximately 12% (2). Unfortunately CKD patients have at least 30% lower survival rate compared to healthy individuals with the same age (1). Hemodialysis or peritoneal dialysis and kidney transplantation are the main treatment of this chronic disease. It has been reported that kidney transplantation is the treatment of choice in many aspects, including cognitive functions and mood state for CKD patients which can result in reduced mortality and increased quality of life (3,4). Approximately 280 and 65 individuals per million people are receiving dialysis and kidney transplantation. Sixty-five percent of patients who are undergoing dialysis are waiting for transplantation while only 25% receive the transplantation (1). Around 6% of patients who are candidate for transplantation will die during their awaiting period for suitable donor, too; those who receive transplantation may die if they don't receive appropriate treatment (1,5). Many of these deaths occur in developing countries like ours. These reports highlight the importance of proper dialysis and timely transplantation in patients with CKD. Whether we choose hemodialysis or peritoneal dialysis, each has its side effects. These complications vary from vascular problems in hemodialysis patients to peritonitis and local infections in peritoneal dialysis (6,7). Among those undergoing peritoneal dialysis, gastrointestinal disorders are frequent complications which are usually neglected. Gastroesophageal reflux disease (GERD), dyspepsia, nausea and vomiting as well as constipation are common gastrointestinal disorders which are both common in the general population and those who undergo peritoneal dialysis (8). By determination of the most frequent gastrointestinal disorder in patients undergoing peritoneal dialysis, management and planning lifestyle modifications for revealing such problems will become easier.

Objectives
The present study has focused on the prevalence of common gastrointestinal disorders among patients undergoing peritoneal dialysis.

Study design
The present cross-sectional study conducted between March 2017 and March 2018 in three educational hospitals in Mashhad. The study participants were chosen from patients who were referred for peritoneal dialysis. Every patient who enrolled in the present study has undergone dialysis for at least three months. The study questionnaires were filled when the peritoneal cavity was empty. All of these patients filled the Persian translated Gastrointestinal Symptom Rating Scale (GSRS). GSRS consists of 15 questions for evaluation of gastrointestinal disorders including abdominal pain, GERD, diarrhea, constipation and dyspepsia (Table 1).
Patients answer these 15 questions based on a Likert score ranging from 0 to 3 (9). It is noteworthy to mention that different languages of GSRS questionnaire have been reported to be good and provide acceptable validity and reliability (10). In the present study, dyspepsia has been considered based on having heartburn, sucking sensation in epigastrium, nausea and vomiting, as well as early fullness while taking a meal and fullness sensation after taking a meal which were graded from 0 to 3 (grade 0 as no symptoms and grade 3 as severe symptoms). The questionnaire symptoms and its scoring system have been summarized in Table 1. Those patients who had graded three of all the mentioned symptoms or a grade three in any of these symptoms considered to have dyspepsia. Additionally, in the present study addiction has been defined as using any addictive substances including tobacco and opioids. The relationship between addiction and gastrointestinal symptoms was also investigated.
After filling an informed consent, each patient received the Persian version of GSRS questionnaire and a questionnaire for demographic data. A researcher has explained the questionnaire for patients and filled the questionnaires for those patients who were not able to read or write. After peritoneal dialysis, the patients filled the same GSRS questionnaire again before discharge.

Ethical issues
Human rights were respected in accordance with the Helsinki Declaration 1975, as revised in 1983. The ethical committee of Mashhad University of Medical Sciences (Ethical code# IRMUMS.FM.REC.1395.171) approved the study. Informed consent was taken from the patients. Besides, this study was extracted from the MD thesis of Arezoo Naderzadeh (Thesis #941328) at this University.

Statistical analysis
The study data was then analyzed by SPSS 20 software. The chi-square test was used for analysis of variables between study groups. The non-parametric Kendall's tau-b test was used to assess the association of gastrointestinal symptoms with age, body mass index (BMI), and peritoneal dialysis volume. Mann-Whitney U test was applied to assess the relationship between addiction and gastrointestinal symptoms. A P < 0.05 was considered as statistical significance.

Results
During the study period, 71 patients agreed to participate in the present study. Among them, 38 patients were male (53.5%) and others were female. The mean ± SD age of patients undergoing peritoneal dialysis was 48.15±16.62 years. Most of the patients (37 patients, 52.11%) have normal body mass index (BMI) (18.5<BMI<24.9 kg/ m 2 ) and 28.16% (20 patients) were overweight (25 kg/m 2 <BMI<29.9 kg/m 2 ). The mean dialysis duration was six months since the maximum duration was 13 years (mean ± SD was 2.75 ± 2.49 years). The mean ± SD of dialysis fluid volume were 7.47 ± 1.59 L. Among abdominal pain, heartburn, acid regurgitation, sucking sensation in epigastrium, nausea and vomiting, borborygmus, abdominal distention, eructation, increased flatus, decreased passage of stool, increased passage of stool, loose  or transient pain  1 Occasional pain interfering some daily activities 2 Prolong pain which requires treatment and interfering many daily activities 3 Severe pain interfering all daily activities Heart burn 0 No or transient pain 1 Occasional and short discomfort 2 Frequent episodes which requires treatment 3 Continuous discomfort only relieved by antacid medication Acid regurgitation 0 No or transient pain 1 Occasional regurgitation 2 Regurgitation once or twice daily requiring treatment 3 Regurgitation several times with transient relief by antacid Sucking sensation in the epigastrium 0 No or transient discomfort 1 Occasional short duration discomfort 2 Frequent discomfort required taking meal or antacids between meals 3 Continuous discomfort required taking meal or antacids between meals Nausea and vomiting Somewhat difficult defecation with occasional felling of incomplete evacuation 2 Difficult defecation with often felling of incomplete evacuation 3 Extremely difficult defecation with regular felling of incomplete evacuation stool, hard stool, urgent need for defecation and feeling of incomplete evacuation, only abdominal distention was significantly different before and after dialysis (P = 0.025 for abdominal distension and P > 0.05 for the rest of symptoms; Table 2). Regarding gastrointestinal symptoms, the mean number and the mean severity of gastrointestinal symptoms in the studied patients were 4.8 ± 3.88, and 6.88 ± 6.92 respectively. The Kendall's tau b test has revealed that the prevalence of 15 mentioned gastrointestinal symptoms was not associated with patient's age, dialysis fluid volume and BMI. Among the gastrointestinal symptoms, only increased flatus was associated with patient's gender (P = 0.04). Addicted individuals were 15.5% among study population. Mann-Whitney test revealed that acid regurgitation (P = 0.005), increased flatus (P = 0.009) and some other symptoms were significantly prominent in addict patients (Table 3). Kendall's tau-b test revealed that acid regurgitation (P = 0.005), increased flatus (P = 0.009) and some other symptoms which are summarized in Table 3 were significantly prominent in addict patients. According to the definition of dyspepsia in present study, 43.66% (31 patients) of the study population has dyspepsia.

Discussion
The present study has focused on reporting the prevalence of common gastrointestinal disorders among patients undergoing peritoneal dialysis by using GSRS. According to the results, approximately half of our patients had dyspepsia and only abdominal distention was significantly changed after dialysis while other GSRS symptoms were not significantly changed after receiving dialysis. Also, addiction has great impact on gastrointestinal symptoms after dialysis. Age, dialysis fluid volume and BMI were not related to gastrointestinal symptoms in our study population.
There is growing body of evidence suggesting that gastrointestinal symptoms are prevalent among patients undergoing dialysis and researchers are focusing their attention toward determining the preventable causes as well as providing effective medications. The exact reason for the high prevalence of gastrointestinal symptoms in dialysis patients is still unclear (11). However, delayed gastric emptying, hemodynamic changes as well as inadequate dialysis has been considered as possible causes of developing gastrointestinal symptoms (12). Due to the importance of gastrointestinal disorders among dialysis patients, researchers focused on developing special tools for evaluation of this problem in such patients. Performing different types of imaging studies including endoscopy or using digital microcapsules, performing functional studies including malabsorption tests and esophageal manometry and questionnaires (8). The questionnaires are the most available and easy to perform tool for evaluation of gastrointestinal disorders in dialysis patients. Among available questionnaires, GSRS and Rome criteria's are the most frequently used tools which are available in different languages with favorable accuracy in detection of symptoms (8). In the present study we have chosen GSRS questionnaire as a questionnaire which is especially validated for the gastrointestinal symptoms of patients undergoing dialysis.
The gastrointestinal symptom of patients undergoing dialysis has been revaluated in many studies and various results have been reported according to different study protocols. Dong et al demonstrated that hemodialysis patients and peritoneal dialysis patients experience different gastrointestinal symptoms (12). They have stated that hemodialysis patients experience more gastrointestinal symptoms (12). Reflux and eating dysfunction are 2 common symptoms among peritoneal dialysis in contrast to hemodialysis (12). Lee et al reported that peritoneal dialysis patients mostly experience gastroesophageal reflux, intestinal obstruction and hernia while hemodialysis patients mostly develop peptic ulcer, diverticula and bleeding (13). Such differences can be explained in different ways. During peritoneal dialysis, the intra-abdominal pressure is increased following the entrance of dialysis solution. Back pain, hernias and dialysate leak are some of the possible complications regarding to the increased intra-abdominal pressure (14). Regarding some gastrointestinal disorders such as gastroesophageal reflux, the effect of increased intraabdominal pressure has considered as the cause of these complications (15). However, some studies such as Dejardin et al reported that increase in intra-abdominal pressure is not related to gastroesophageal reflux in peritoneal dialysis (16). Additionally, another study has suggested that peritoneal dialysis itself should not be considered as a cause of gastroesophageal reflux. Moreover, the prevalence of gastroesophageal reflux has been reported to be similar in both peritoneal and hemodialysis (17). In our study, the only symptom which was differed before and after dialysis was abdominal distension and the prevalence of acid reflux was not differed before and after dialysis. Abdominal distension after peritoneal dialysis has been reported as a complication of dialysis. Figueiredo et al reported that abdominal distension after losing appetite and constipation is frequent among dialysis patients and abdominal distension is the most frequent symptom related to therapy with peritoneal dialysis (18). Other studies reported that indigestion and eating dysfunction are common problems among peritoneal dialysis patients. Dong et al concluded that such symptoms are related to number of daily pills as well as history of corticosteroid therapy. Additionally, those who have residual renal function are less likely to develop symptoms (19). Our study has suggested a relation between addiction and gastrointestinal symptoms in peritoneal dialysis. Illicit drug dependence has been considered as an important factor causing premature mortality in end-stage renal disease patients (20). It has been reported that opioid use is associated with adverse outcomes even at lower doses in hemodialysis patients (21). Moreover, addiction to different substances such as alcohol, opioids or tobacco has been reported to have adverse effects on the gastrointestinal system (22). Alcoholic liver disease, pancreatitis or even various gastrointestinal cancers has been linked to alcohol abuse. In addition, tobacco use has been linked to development of gastroesophageal reflux and ulceration. Moreover, opioids negatively affect gastrointestinal movements and secretions, even inducing constipations (22,23). Regarding such effects of substance addiction, our study proposed that peritoneal dialysis will worsen some gastrointestinal symptoms including heartburn sensation, sucking sensation in epigastrium, abdominal flatus and abdominal distention.

Conclusion
Our study revealed that only abdominal distention is affected by peritoneal dialysis according to GSRS. Moreover, addiction will affect some gastrointestinal symptoms including heartburn sensation, acid regurgitation, sucking sensation in epigastrium, abdominal flatus and abdominal distention. The present study emphasizes the fact that managing addiction in patients undergoing peritoneal dialysis may alleviate gastrointestinal symptoms.

Limitations of the study
Lack of control group is one of the limitations of this study. A comparative study is recommended for hemodialysis and peritoneal dialysis patients.