Objectives: Gastrointestinal complications are common in kidney transplant patients, with the most frequent being diarrhea (60%). Chronic diarrhea affects the patient’s quality of life, causes fatigue and weight loss and malabsorption, increases the number of hospitalizations, increases serum creatinine levels, and causes alterations in immunosuppressive drug levels. Diarrhea is also associated with an increased risk of graft failure and death. In this study, we aimed to determine the frequencies of common infectious organisms causing chronic diarrhea in renal transplant patients.
Materials and Methods: Our study included 124 renal transplant patients who presented with chronic diarrhea over a 6-month period at the Sindh Institute of Urology and Transplantation Department tertiary care hospital (Karachi, Pakistan). Stool analysis was performed in all transplant recipients. Upper and lower gastrointestinal endoscopy was also performed in patients with chronic diarrhea, and biopsy specimens underwent histopathologic evaluations.
Results: Of 124 renal transplant recipients, 29 were female (23.4%) and 95 were male (76.6%). Giardia was the most common organism found (n = 37 patients; 29.8%) followed by Cryptosporidium (n = 36; 29.0%), Entameba histolytica (n =29; 23.4%), tuberculosis (n =14; 11.3%), and sprue (n =8; 6.5%). The mean duration since renal transplant was 78.5 ± 63.37 months. Although not statistically significant, the frequency of diarrhea was higher in patients who had transplant procedures ≥ 2 years previously.
Conclusions: Chronic diarrhea is prevalent in renal transplant patients irrespective of age, sex, and duration since transplant. Giardiasis and Cryptosporidium species infections are important causes of chronic diarrhea, but other causative factors need to be further studied, including comorbid conditions and immunosuppressive agents.
Key words : Cryptosporidium, Gastrointestinal complications, Giardiasis, Kidney transplant recipients, Posttransplant hospitalization
Gastrointestinal complications are very common in kidney transplant patients, with the most frequent complication being diarrhea (60%).1,2 Chronic diarrhea affects a patient’s quality of life; causes fatigue, weight loss, and malabsorption; increases number of hospitalizations; increases serum creatinine levels; and causes alterations in immunosuppressive drug levels.3 Diarrhea is also associated with an increased risk of graft failure and death.4
The cause of diarrhea may include infectious and noninfectious causes but can be multifactorial.1,5,6 The incidence of infectious causes of diarrhea in transplant patient ranges from 17% to 21%.4,7 In this study, we focused on evaluation of causes of chronic diarrhea that may lead to graft failure and poor quality of life in transplant patients, which mainly included infectious causes.
Although our previous study5 involved renal transplant recipients with persistent diarrhea in Pakistan, adequate data are lacking regarding chronic causes of diarrhea in renal transplant recipients. Therefore, in this study, we aimed to determine the main causes of infectious diarrhea, as early diagnosis and appropriate treatment can improve patient and graft survival.
Materials and Methods
This cross-sectional study was conducted in the Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation (Karachi, Pakistan). Male and female patients between 18 and 60 years old who presented with chronic diarrhea at least 4 weeks after renal transplant were included in the study.
Renal transplant recipients who had normal stool detail reports, patients with history of pancreatitis, and those with previous bowel surgery were excluded. Stool specimens of included patients were sent to the microbiology department of Sindh Institute of Urology and Transplantation for physical and microscopic examination of fecal leukocytes, red blood cells, cysts, Cryptosporidium, Cyclospora, and Isospora culture. Ultrasonographic examination of the abdomen was done to rule out abdominal lymphadenopathy and bowel wall thickening, whenever it was indicated or when tissue biopsy was performed. Ultrasonography was reviewed by the consultant radiologist who had at least 3 years of post-fellowship experience, preferably by the same radiologist to avoid interobserver variations. If required, upper and/or lower gastrointestinal endoscopies with mucosal biopsies were also performed. The study received ethical approval from the institutional ethics committee.
When we considered the margin of error as 5%, confidence interval of 95%, and prevalence of chronic diarrhea of 22% in renal transplant recipients, the calculated sample size was determined to be 124.
Analyses were conducted with the consecutive sampling technique. Statistical analyses were performed with SPSS software (SPSS: An IBM Company, version 20.0, Chicago, IL, USA). Categorical variables (including patient sex and comorbid conditions of diarrhea) were expressed as frequencies (%), whereas continuous variables (like age and duration of transplant) were expressed as mean and standard deviation. Renal transplant recipients were stratified according to duration since transplant. Factors associated with causes of diarrhea were assessed using chi-square test. P < .05 was statistically significant.
Possible modifiers of effects, including age, sex, duration since transplant, and comorbid conditions (hypertension, diabetes mellitus, hepatitis B virus, and hepatitis C virus), were analyzed through stratification to determine their effects on outcomes.
Our study included 124 renal transplant recipients with chronic diarrhea. Stool analyses and upper and lower gastrointestinal endoscopies were performed to determine the cause of chronic infectious diarrhea in renal transplant recipients. Baseline demographics of the study population are shown in Table 1.
Of total patients, 95 were male (76.6%) and 29 were female (23.4%). Mean age was 33.76 ± 10.45 years. The most common comorbidity in the present study was hepatitis B virus infection; no comorbidities were found in 72 (58.1%) renal transplant recipients.
The most common cause of diarrhea in this study population was Giardia lamblia in 37 patients (29%), with the least common being tropical sprue (n = 8; 7%) (Figure 1).
In our study population, the mean duration since renal transplant was 78.5 ± 63.37 months. Patients were stratified according to duration since transplant and its association with the development of chronic diarrhea (Figure 2). The frequency of diarrhea was higher in patients with duration since transplant of ≥ 2 years (Figure 2). After stratification for duration since transplant, chi-square test was applied for each causative factor. That is, the number of patients who presented at < 2 years and ≥ 2 years since transplant was 8 and 29 for Giardia (P = .819), 8 and 28 for Cryptosporidium (P = .821), 9 and 20 for Entamoeba histolytica (P = .33), 3 and 11 for tuberculosis (P = 1.0), and 2 and 6 for and tropical sprue (P = 1.0) (Figure 2).
Renal transplant is the ultimate treatment for patients with end-stage renal disease. Microbial infections, abdominal pain, and diarrhea are common gastrointestinal adverse events in renal transplant recipients, among which diarrhea is more frequent.3,4,7 After renal transplant, chronic diarrhea can manifest as weight loss, dehydration,8 renal dysfunction,9 and fluctuations in immunosuppressive drug levels,10,11 which can in turn predispose to graft loss and can increase patient mortality.7
Most renal transplant patients with chronic diarrhea in our study were males (76.6%). This finding is consistent with another study3 in which 56% were male patients. This variability in distribution between males and females can be due to socioeconomic reasons, in which male patients undergo renal transplant much more frequently than female patients.
Onset of chronic diarrhea in renal transplant recipients is usually a delayed presentation, as mentioned in a previous study12 in which more than 50% of patients had diarrhea 2 or more years after transplant. Our study had similar results, in which mean duration of onset of chronic diarrhea since transplant was 2.16 ± 0.8 years (range, 1-4 y). The cause of diarrhea may include infectious and noninfectious causes but can be multifactorial.1,5,6 The prevalence of infectious causes of diarrhea in transplant recipients ranges from 17% to 21%.3,7 In a Belgian study of 108 renal transplant recipients by Maes and associates,3 bacterial infections were most common followed by cytomegalovirus infection as a cause of infectious diarrhea. In an Iranian study13 of 150 renal transplant patients, Entamoeba coli (10.6%) was the most prevalent parasite detected followed by Endolimax nana (8.7%) and Giardia lamblia (7.4%). In another study of 657 renal transplant recipients in Brazil, Strongyloides stercoralis was the most common parasite (11/16) followed by Giardia lamblia (3/16).12 In a Turkish study by Arslan and colleagues14 of 43 renal and liver transplant recipients, giardiasis (9/33) was the most common infectious agent followed by Cryptosporidium parvum (7/33).
In our study of 124 renal transplant recipients, the most common infection was Giardia (29.8%). Other infectious organisms included Cryptosporidium (29.0%) and Entamoeba histolytica (23.4%). Poor sanitary conditions and use of unhygienic and contaminated food and water can be contributing factors for development of giardiasis. In a subanalysis of our study, we observed that most patients who developed giardiasis and Entamoeba-associated infections were living in remote areas and belonged to poor socioeconomic status.
The aim of this study was to determine the most common organisms causing chronic diarrhea in renal transplant recipients, as diarrhea is a frequent complication after kidney transplant.15 To the best of our knowledge, such data are not available in our country. It is expected that our study could help us in taking appropriate steps in patient care, which may result in improvements in graft function and patient survival. It is also important to understand the importance of improving sanitation and using hygienic food and boiled water, which can control and prevent spread of infectious diarrhea in renal transplant patients and subsequently result in improved outcomes in terms of graft function and survival.
Chronic diarrhea is prevalent in renal transplant patients irrespective of age and sex. However, with greater duration since renal transplant, there is an increased chance of developing infectious diarrhea. Giardiasis and Cryptosporidium species infections are important causes of chronic diarrhea in renal transplant recipients, but other causative factors should also be studied. Early diagnosis and treatment of chronic infectious diarrhea can prevent long-term morbidity and mortality.
Volume : 17
Issue : 1
Pages : 212 - 215
DOI : 10.6002/ect.MESOT2018.P69
From the Department of 1Hepatogastroenterology,
3Histopathology, Sindh Institute of Urology and Transplantation, Karachi,
Acknowledgements: The authors have no sources of funding for this study and have no conflicts of interest to declare.
Corresponding author: Farina Muhammad Hanif, 48/2, Lane 15, Khayaban-e-Badban, DHA phase VII, Karachi, Pakistan
Phone: +92 3002171785
Figure 1. Frequency of Chronic Diarrhea of Infectious Organisms
Figure 2. Stratification of Chronic Diarrhea According to Duration Since Transplant
Table 1. Baseline Characteristics of Study Population (N = 124)