EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Objectives: We investigated the incidence of gastrointestinal disorders requiring endoscopic and histopathologic diagnoses in renal transplant recipients.

Materials and Methods: In this retrospective analysis, we examined records of patients seen at the Department of Hepato-Gastroenterology and Transplantation Sciences, Sindh Institute of Urology and Transplantation (Karachi, Pakistan) from January 2010 to December 2014. Renal transplant recipients with gastrointestinal disorders who required endoscopy, including proctoscopy and upper and lower gastrointestinal endoscopy as per indication, were included.

Results: Of 1770 patients included in this study, most were male patients (n = 1517; 85.7%). In this patient group, 1957 endoscopies, including proctoscopies, were performed, which included 1033 esophagogastroduodenoscopies (52.8%), 571 sigmoidoscopies (29.2%), and 107 colonoscopies (5.5%). The most common indications were diarrhea (n = 697; 31.2%) and weight loss (n = 690; 31%). Findings showed esophageal candidiasis in 127 patients (12%); however, biopsy revealed Candida species in 33 patients (34%). Cytomegalovirus and herpes esophagitis were observed in 8 (8.3%) and 5 patients (5.2%). Helicobacter pylori gastritis was seen in 119 patients (15.4%), cytomegalovirus gastritis in 9 patients (1.2%), and gastric lymphoma in 1 patient (0.1%). Duodenal fissuring was the most common pathology observed during endoscopy (396 patients; 33.9%), followed by decreased height of duodenal folds in 157 patients (13.4%), with biopsy showing sprue in 325 patients (37.6%) and giardiasis in 118 patients (13.7%). Lower gastrointestinal endoscopy showed ulcers in 198 patients (24.6%) and polyps in 31 patients (3.9%). Histopathologic examination showed cytomegalovirus colitis in 89 patients (15.5%), amebic colitis in 21 (3.7%), and tuberculosis in 11 (1.9%).

Conclusions: We observed a wide spectrum of pathologic lesions, including opportunistic infections, in endoscopic biopsies from our renal transplant patients. Cytomegalovirus colitis was the most common infection in the lower gastrointestinal tract, whereas giardiasis was the most common in the duodenum.

Key words : Cytomegalovirus, Endoscopy, Renal transplantation

Renal transplant is the treatment of choice for end-stage renal disease patients. After transplant, there is increased risk of various gastrointestinal tract (GI) disorders. Incidence of GI problems varies in renal transplant recipients (RTRs) from 20% to 55%.^1-4 These complications can range from mild to severe in intensity and can include oral ulcers, diarrhea, peptic ulcer disease (PUD), lower GI bleed, bowel obstruction, perforation, peritonitis, pancreatitis, and malignancy.^1,5 Infections and drugs are the common culprits for GI problems in RTRs.^6-9Renal transplant recipients are at increased risk of malignancy compared with the general population. For example, anal cancer is about 100 times more common and GI lymphoproliferative disorders are reported in about 10% of patients.^1,10

After transplant, cytomegalovirus (CMV), giardia, and cryptosporidial infections are the common pathogens implicated in infectious diarrheal illness. Other causes include tuberculosis, tropical sprue, and immunoproliferative small intestinal disease.¹¹ Helicobacter pylori gastritis is the most common cause of infective gastritis; other causes of gastritis include CMV gastritis, drug-induced gastritis, and PUD.^3,12,13 Local data regarding GI complications in RTRs are limited. This study was conducted to highlight the importance of endoscopy and biopsy findings for the management of GI complications in RTRs, which helps to reduce the morbidity and mortality rates associated with these disorders.

Materials and Methods

We conducted a retrospective survey of patients seen at the Department of Hepato-Gastroenterology and Transplantation Sciences, Sindh Institute of Urology and Transplantation (Karachi, Pakistan) from January 2010 to December 2014. The study was approved by the ethical review committee of our center. All protocols conformed to the ethical guidelines of the 1975 Helsinki Declaration.

During the study period, 1770 patients underwent upper GI endoscopy, lower GI endoscopy, proctoscopy, and proctoscopic band ligation, with 1950 procedures performed. Diarrhea was defined as at least 3 soft stools of unformed consistency in 24 hours. Weight loss was considered to be significant when more than 5% weight was reduced unintentionally over 3 months. Dyspepsia was characterized according to the Leeds questionnaire.¹⁴Varices were shown as prominent tortuous veins in distal esophagus, candida was shown as whitish exudates that were not washable, hiatal hernia was shown when Z-line and hiatus were more than 3 cm apart, and Barrett's esophagus was shown as salmon pink tongue-like projection of mucosa. Erosions were defined as breach in mucosa. Erythema was labeled as increased redness of mucosa, ulcer as breach of mucosa with overlying whitish exudates, and gastropathy as mosaic pattern of mucosa with or without red marks. Fissuring was scalloping of duodenal folds. Biopsy specimens obtained from esophagus, stomach, duodenum, and colon were sent to the histopathology department to determine pathology (infective, inflammatory, or malignancy).

Statistical analyses were performed with SPSS software (SPSS: An IBM Company, version 20.0, IBM Corporation, Armonk, NY, USA). Results are presented as means and SD for quantitative variables and frequency with percentages for categorical variables.

Of the 1770 RTRs evaluated in our study, 1517 (85.7%) were male patients. Mean age of patients was 33.4 ± 10.1 years. Patients had upper and lower GI endoscopy, proctoscopy, and proctoscopic band ligation procedures according to their symptoms. The most common indication was diarrhea, which was seen in 697 patients (31.2%), followed by weight loss in 690 patients (31%), lower GI bleed in 347 (15.5%), dyspepsia in 209 (9.4%), and screening esophagogastroduodenoscopy for varices in 90 patients (4.1%). There were also 74 procedures (3.3%) for sprue and 22 procedures (1%) for CMV surveillance (Table 1).

Of 1957 endoscopic procedures, 1033 (52.7%) were esophagogastroduodenoscopy, 551 (29.2%) were sigmoidoscopies, 107 (5.4%) were colonoscopies, and 221 (11.3%) were proctoscopies (Table 1). Hemorrhoids were found in 216 patients (97.7%), and proctoscopic band ligations were performed in 195 patients (88.2%).

Upper GI endoscopic examination showed normal esophageal mucosa in 683 patients (64.3%), Candida species in 127 patients (12.0%), hiatal hernia in 53 patients (5.0%), varices in 50 patients (4.7%), and reflux esophagitis in 50 patients (4.7%) (Table 2). Endoscopic findings of Barrett's esophagus were seen in 7 RTRs (0.7%) (Table 2). A esophageal biopsy was performed in 97 cases, with reflux esophagitis as the most common finding in 39 (40.2%) followed by esophageal candidiasis in 33 (34%), CMV in 8 (8.3%), herpes virus in 5 (5.2%), and necrotizing esophagitis in 1 patient (1%) (Table 3). Normal mucosa of stomach was seen in 298 patients (28%), erythema in 561 (52.8%), erosions in 132 (12.4%), congestive gastropathy in 45 (4.2%), ulcer in 17 (1.6%), and oozing vessel in 2 patients (0.2%) (Table 2). Of 774 biopsies of the antrum or body of the stomach, 419 (54.1%) showed nonspecific active gastritis, 211 (27.2%) showed reflux gastropathy, 119 (15.4%) showed H. pylori gastritis, 9 (1.1%) showed CMV gastritis, and 1 (0.1%) showed lymphoma (Table 3). Normal duodenal mucosa was seen in 444 RTRs (38%), fissuring in 396 (33.9%), decreased height of duodenal folds in 157 (13.4%), erosions in 73 (6.2%), erythema in 35 (3%), nodularity in 29 (2.4%), and ulcer in 19 (1.6%) (Table 2). Of 864 RTRs who had duodenal mucosal biopsies, nonspecific duodenitis was seen in 338 (39.1%), sprue in 325 (37.6%), giardiasis in 118 (13.7%), cryptosporidial infection in 15 (1.7%), immunoproliferative small intestinal disease in 12 (1.4%), CMV duodenitis in 9 (1.1%), and duodenal candidiasis in 2 (0.2%) (Table 3).

Lower GI endoscopy was performed in 698 patients, which included sigmoidoscopy, left-sided colonoscopy, right-sided colonoscopy, and complete colonoscopy (up to terminal ileum). Most patients, that is, 288 (35.8%), showed normal mucosa on endoscopy, whereas the most common pathology was ulcers over the mucosa in 198 patients (24. 6%), erythema in 167 patients (20. 7%), and erosions in 94 patients (11.7%) (Table 2). Polyps were seen in 31 patients (3.9%), whereas growth was seen in 3 patients (0.4%). Endoscopic mucosal biopsies were conducted in 572 patients, with nonspecific colitis (the most frequent finding) seen in 416 patients (72.7%). This finding was followed by infectious colitis, with CMV colitis observed in 89 patients (15.5%) (Figure 1, A and B), amebic colitis observed in 21 patients (3.7%), and tuberculous observed in 11 patients (1.9%) (Table 3).

Large bowel malignancy was seen in 2 cases, with 1 patient having adenocarcinoma and the other having T-cell lymphoma. Most polyps had benign histology: 10 findings (1.7%) were hyperplastic and 5 (0.9%) showed malignant potential (adenomyomatous polyps with dysplastic transformation).

Gastrointestinal complications in RTRs are quite common. Its prevalence varies from 8% to 37%.¹⁵ These complications range from minor to severe and are often associated with increased morbidity, mortality, and disease burden. Frequently encountered problems are diarrhea, PUD, nausea, vomiting, oral ulcers, lower GI bleeding, and malignancy.^1,9

Our study included 1770 RTRs of 4500 patients who presented with GI symptoms. The most common indication of endoscopy was diarrhea, which was followed by weight loss. This is the most common adverse event experienced by solid-organ transplant recipients.^16-19 The mean age of our patients at presentation was around 33 years, which is considerably less than shown in other studies.^5,20 In our study, male-to-female ratio was 5.9:1, which is in contrast to reports from Gil-Vernet and associates and Singh and associates.^5,20

Diarrhea in solid-organ transplant recipients can result in severe dehydration, weight loss, and increased risk of graft loss.²¹ Dyspepsia can also commonly occur in solid-organ transplant patients, with about 35% of patients having these symptoms up to 6 months after transplant.²² Although infections are important and common causes of diarrhea in patients after transplant, in our study, duodenal villous atrophy was the most common cause of posttransplant diarrhea and weight loss, followed by giardia and cryptococcal infection. Hanif and associates showed similar results, reporting that giardiasis was a common cause of duodenal villous atrophy.²³ Immunoproliferative small intestinal disease has been reported to occur in 3.7% to 6.8%^11,23 of RTRs in various studies done in Pakistan; however, only 1.4% of the patients in our study had this lymphoproliferative disorder.

Esophageal disorders are also common in RTRs. In our study, the most common infection was esophageal candidiasis, CMV infection, and herpes esophagitis (Figure 1C). In mucosal biopsy, reflux esophagitis was the most common finding. Our results were consistent with the other studies.^1,24 Cytomegalovirus esophagitis is also common in immunosuppressed patients, and it can present as dysphagia or odynophagia. In a case reported by Veroux and associates, CMV esophagitis resulted in a giant ulcer in the esophagus, causing odynophagia.²⁵ Only one case of necrotizing esophagitis was seen in our study. Barrett's esophagitis was only shown in 0.7% of the observed specimens, which is similar to results observed by Kim and associates.²⁶

Regarding endoscopic findings, erythema was the most frequently observed pathology followed by erosions, with PUD seen in only 1.7% of patients. However, Benoit and associates²⁷ reported 9.6% of patients with PUD. In our study, H. pylori gastritis and reflux gastropathy were the most common causes of gastritis, but CMV gastritis and lymphoma were uncommon, observed in 1% and 0.1% of cases, respectively. H. pylori gastritis is a common cause of gastritis in the general population, with a reported incidence in endoscopic biopsies of about 88%.²⁸ Another study showed that patients with chronic renal failure and RTRs had prevalence of 66% and 40%, respectively.²⁹ Our low incidence of H. pylori can be attributed to several reasons. First and most important was the inadequate biopsy sampling (2 biopsies from body and 4 from antrum, with biopsies not conducted for each case). Second, proton pump inhibitors were not stopped before esophagogastroduodenoscopy in patients with dyspeptic symptoms. Finally, our center aimed to maintain proper sanitary conditions and provided dietary counseling sessions. As a result, most patients had hygienic food.

Lower GI bleed was the most common indication for endoscopic procedures in our study, followed by diarrhea. Most patients showed hemorrhoidal bleed, and other causes included ulceration and erosions of colonic mucosa. Cytomegalovirus colitis was the most common infective pathology followed by amebic colitis and tuberculosis. Polyps and malignancies were uncommon observations, noticed in 3.8% and 0.1%, respectively. Malignancy was seen in only 2 patients (T-cell lymphoma and adenocarcinoma). Dysplasia was present in 16% of the polyps. In their study of reasons for GI bleeding in RTRs, Rencuzogullari and associates concluded that angiodysplasia and colitis were the most common reasons; however, polyps were seen in around 10% of patients.³⁰ A multicenter study showed incidence of colonic cancer in RTRs of approximately 13%.³¹ Collagenous colitis and Candida species and spirochetosis infections were not common in our study.

Our study has some limitations, including its retrospective design. We also did not record information about types of immunosuppressants used and posttransplant duration. Endoscopies were not performed in patients before renal transplant. However, our study provides valuable information about GI complications in RTRs, with no such study done so far in this geographic region. Health services for renal transplant patients in this region of the world are limited, and this study can help practicing gastroenterologists and renal physicians to improve health care facilities.

We observed a wide spectrum of pathologic lesions, including opportunistic infections, in the GI endoscopic biopsies from renal transplant patients. Cytomegalovirus colitis was the most common infection in the lower GI system, whereas giardiasis was frequently seen in the duodenum.

Volume: 16 Issue: 5 October 2018

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