Part One Helicobacter Pylori Eradication in Renal Transplant Candidates

Abstract

1. Introduction

Treatment for Helicobacter pylori (H. pylori) infection is recommended in transplant candidates due to the association between this infection and gastrointestinal disorders, which could significantly increase morbidity after renal transplantation with the use of immunosuppression. The objective of this study was to analyze the rate of eradication of H. pylori after antimicrobial treatment in chronic kidney disease patients who are candidates for kidney transplantation.

2. Methods

A multicenter prospective cohort study was conducted. All adult chronic kidney disease patients seen at our institution were included. In the pretransplantation evaluation, 83 patients underwent upper gastrointestinal endoscopy with 2 diagnostic methods to detect H. pylori: histology and the rapid urease test. In total, 33 patients with H. pylori infection received treatment with 20 mg omeprazole, 500 mg amoxicillin, and 500 mg clarithromycin once daily for 14 days. Another upper gastrointestinal endoscopy was performed 8 to 12 weeks after the end of treatment to check for healing.

3. Results

The study showed a prevalence of H. pylori in 51 (61.4%) patients. Histology was positive in 50 (98%) patients and the rapid urease test was positive in 31 (60.8%). The infection eradication rate was 48.5% (16 patients).

4. Conclusions

There was a high prevalence rate of H. pylori and a low eradication rate after the long-term antimicrobial triple scheme was used. The association of the rapid urease test with gastric mucosa histology did not increase the detection rate of H. pylori.

Keywords

Renal Insufficiency, Chronic; Helicobacter pylori; Kidney Transplantation.

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Introduction

Helicobacter pylori (H. pylori) is a human pathogen with worldwide distribution, responsible for the most prevalent bacterial infection currently known2. It is an etiologic agent of gastrointestinal tract comorbidities varying from mild to severe3,4. The prevalence of H. pylori ranges from 30 to 80% in several countries. Despite the high prevalence, clinical manifestations are rare in most patients who carry H. pylori in their gastrointestinal tracts, and only a minority of patients develop symptoms5.

The study of Home and collaborators6 showed that 100% of these patients present some form of high endoscopic alteration, many of which are potentially severe, including peptic ulcers, gastritis, erosive duodenitis, and gastric intestinal metaplasia7. H. pylori causes chronic gastric inflammation, which can progress into precancerous alterations such as atrophic gastritis and intestinal metaplasia8.

There are currently several methods to diagnose H. pylori. Some methods require a prior upper gastrointestinal endoscopy for access to the necessary material2. A biopsy of the gastric mucosa is required for some diagnostic methods such as histology, culture, polymerase chain reaction, and the rapid urease test2. Histology is considered the gold standard method for diagnosis of infection by H. pylori. It also provides relevant information for the detection of numerous diseases of the esophagus and gastric mucosa2. The rapid urease test uses the ability of H. pylori to synthesize large amounts of urea as the basis for diagnosis and presents advantages such as low cost, availability, and high specificity, making it widely used in clinical practice.

Treatment for H. Pylori infection has been recommended in transplant candidates because of the association between this infection and gastrointestinal disorders such as peptic ulcers, gastric hyperplastic polyps, gastric adenomas, gastric cancers, and mucosa associated-lymphoid-type (MALT) lymphomas9,10,11. With the use of immunosuppression, these disorders could become serious, significantly increasing morbidity after renal transplant. The American College of Gastroenterology Guideline12 recommends that clarithromycin triple therapy and bismuth quadruple therapy for H. pylori be administered for 14 days, similar to the current recommendations for prolonged treatments (10 to 14 days)13,14.

The goal of this study was to analyze the efficacy of an antimicrobial regime on the eradication of H. pylori infection in patients with chronic renal disease, who were candidates for renal transplant.

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Methods

A multicenter prospective cohort study was conducted from May 20th, 2016 to November 23rd, 2017.

All patients over 18 years of age with chronic kidney disease enrolled in the renal transplant service of the Evangelical Hospital of Londrina and treated in the 6 dialysis clinics in the North of Parana were included in the study. The clinics and locations were as follows: Histocom, Londrina, which treats approximately 200 dialysis patients a month; the Kidney Institute, Londrina, with approximately 65 dialysis patients a month; the Kidney Institute, Cornelio Procopio, with approximately 145 dialysis patients a month; Nefronor, Cornelio Procopio, with approximately 120 dialysis patients a month; and Kidney Institute, Santo Antônio da Platina, with approximately 180 dialysis patients a month. All these units treat patients from the Public or Private Health System who are enrolled in the renal transplant service at the Evangelical Hospital of Londrina.

Patients with the following characteristics were excluded: pregnant, those with a recent history (less than three months) of H. pylori infection, abdominal surgery, or high digestive hemorrhage, use of any antibiotic in the past 30 days, and history of allergies to any of the compounds of the therapeutic plan (omeprazole, amoxicillin, or clarithromycin) to be used in the treatment of H. pylori infection.

On the day of the procedure, the patients were interviewed regarding medications of continuous use and gastrointestinal tract symptoms. Upper gastrointestinal endoscopies were performed in the ambulatory service by a member of the Gastroenterology/Endoscopy service of the Evangelical Hospital of Londrina. Patients on continuous use of gastric protectors were advised to suspend the medication for 7 days before the endoscopy. Patients with H. pylori infections were treated daily with 20 mg omeprazole in the morning, in a fasting state, and 500 mg amoxicillin plus 500 mg clarithromycin at night, for 14 days. On hemodialysis days, patients were instructed to take the antibiotic after the sessions.

Data on general characteristics of the studied population were obtained: age, sex, ethnicity, origin, place of residence, and hemodialysis clinic. The following clinical data were collected through an interview: underlying disease, duration of hemodialysis before upper gastrointestinal endoscopy, associated comorbidities, previous and/or current smoking history, use of anti-hypertensives, use of gastric protectors, and presence of gastrointestinal tract symptoms in the three months before endoscopy. The data sources were registered in the patients’ charts in the 6 dialysis units.

The first upper gastrointestinal endoscopy was performed at the time of pre-renal transplantation assessment at the clinic. The rapid urease test and histology, performed through gastric biopsy, were used to confirm H. pylori infection. A positive finding in one of these tests was indicative of H. pylori infection.

The biopsy was performed in two gastric regions: the antrum and the body. A third region was assessed in case of inflammation, a suggestive aspect of intestinal metaplasia or neoplasia. The fragments were fixed in 10% formalin and processed for histology and staining with Giemsa. Evaluations were performed by a single pathology laboratory.

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Gastritis was classified by the Sidney System (topography: pangastritis, gastritis of body and antrum; category: exanthematous, plane erosive and elevated, atrophic, hemorrhagic, reflux, hyperplastic gastric folds; and level of intensity: mild, moderate, severe).

The rapid urease test consisted of immersion of a gastric mucosa fragment of the antrum region into a vial containing urea and phenol red, an indicator of pH (H. pylori produces a urease enzyme that turns urea into carbon dioxide and ammonia, leading to an elevation in pH and color alteration to a shade of pink). The test was considered positive when the alteration occurred within two to sixty minutes.

Patients positive for H. pylori infection by at least one of the above methods received treatment according to the American College of Gastroenterology Guideline12. After one week of treatment, the patients were contacted by telephone to verify adherence to the treatment plan. At this point, the importance of completing treatment was reinforced. After completion of treatment, full compliance was confirmed when patients returned to see a nephrologist.

Eight to 12 weeks after the completion of treatment, a control upper gastrointestinal endoscopy was performed as the criterion for eradication. The patient was considered negative when both tests were negative. Patients with a negative H. pylori test in the first upper gastrointestinal endoscopy did not undergo the second endoscopy.

Ethical aspects

This research was approved by the National Research Ethics Committee through the Presentation for Ethical Appreciation Certificate no 54971916.3.0000.5231 and by the Ethics Committee on Research on Human Beings of the State University of Londrina/ North of Parana University Hospital according to report no 1.565.003281 on the 20th of May 2016. All patients were aware of the nature and goals of the study, agreed to participate, and signed the informed consent term.

Statistical analysis

The data were analyzed with the Windows’ Medcalc program, version 18.0 (Medcalc Software, Ostend, Belgium).

The data are descriptively presented using simple frequencies (relative and absolute), means and deviation rates, or medians and interquartile range (IQR) depending on the variable distribution. The data distribution was tested with the Shapiro-Wilk test. The frequencies were described as raw numbers or percentages, represented in contingency tables, and compared with Fisher’s exact test.

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References

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Mariana E. Maioli1 Raquel F. N. Frange2 Cintia M. C. Grion2 Vinicius D. A. Delfino2

1 Universidade Estadual de Londrina, Departamento de Clínica Médica, Londrina, PR, Brasil.

2 Pontifícia Universidade Católica, Departamento de Clínica Médica, Londrina, PR, Brasil.