| Abstract|| |
Ammonia generated by the action of urease producing organism(s) on urea is generally held responsible for the gastrointestinal symptoms of uremia, however, little information is available on the exact organism(s) responsible. We have studied prospectively 70 consecutive patients with moderate or severe degree of chronic renal failure for the presence of Helicobacter pylori (H. pylori) infection of the gastric and duodenal mucosa using bacteriological and histological methods. All patients were endoscoped for presence of gastroduodenal mucosal lesions and graded for the severity of uremia related gastrointestinal symptoms. Uremic symptoms of varying severity were present in all the patients, while H. pylori was present in 81.4% and gastroduodenal erosions and/or ulcers were in 53% of them. No direct correlation was demonstrated between H. pylori infection of the gastroduodenal mucosa, endoscopic findings and presence or severity of uremia related gastrointestinal symptoms. It is concluded that H. pylori is present in the gastroduodenal mucosa of a large number of patients with advanced renal failure however, it does not appear to play a causative role in gastritis or dyspeptic symptoms associated with uremia. Histological examination provided a higher yield over microbiological methods in demonstrating H. pylori infection of gastroduodenal mucosa.
Keywords: Chronic renal failure, Helicobacter pylori, Uremia.
|How to cite this article:|
Gupta RK, Johny K V, Sobki N, Johny M, Madda JP, Narayanan Nampoory M R. Helicobacter Pylori in Patients with Advanced Chronic Renal Failure. Saudi J Kidney Dis Transpl 1997;8:414-8
|How to cite this URL:|
Gupta RK, Johny K V, Sobki N, Johny M, Madda JP, Narayanan Nampoory M R. Helicobacter Pylori in Patients with Advanced Chronic Renal Failure. Saudi J Kidney Dis Transpl [serial online] 1997 [cited 2020 Dec 4];8:414-8. Available from: https://www.sjkdt.org/text.asp?1997/8/4/414/39340
| Introduction|| |
Gastrointestinal symptoms of uremia are generally attributed to the direct injurious action of ammonia. A high content of ammonia has been demonstrated in the gastroduodenal environment of uremic patients  . This seems to be the consequence of urea decomposition by urease producing bacteria  . Little information, if any, is available on which particular organism(s) is responsible for the urease production in the gastrointestinal tract of uremic patients. Helicobacter pylori ori), a well recognized urease producer, is found in the stomach and duodenum of 20 percent of healthy persons  . H. pylori can be isolated from the gastric mucosa in 60 percent of patients with non-ulcer dyspepsia, 90 percent of patients with duodenal ulcer and almost always from those with chronic gastritis  . Patients in end-stage renal failure on maintenance dialysis have also been shown to harbour this bacteria and it has been suggested that the erosive, antral gastritis found in uremia might be associated with H. pylori infection  .
The purpose of the present study was to examine the prevalence of H. pylori in stomach and duodenum of patients in advanced renal failure, not yet on dialysis, and to assess its possible relationship to gastritis and gastrointestinal symptoms encountered in uremia.
| Subjects and Methods|| |
Seventy consecutive patients in advanced chronic renal failure (serum creatinine above 500 umol/L) attending the nephrology service of Mubarak Al-Kabeer University hospital during a period of six months were selected for this prospective study.
The severity of renal failure was arbitrarily classified as moderate (serum creatinine ranging from 500 to 800 umol/L) or severe (serum creatinine ranging above 800 umol/L) according to the serum creatinine values. The purpose of the study was explained to all patients and the collected data from each patient were recorded in a preplanned form. The study consisted of a detailed enquiry into the presence of gastrointestinal symptoms possibly related to uremia, upper gastrointestinal endoscopy and histopathological and microbiological examination of gastric biopsy tissue for presence of H. pylori. After an initial clinical examination and base-line renal work up all patients were questioned by one of us in a standardized manner for 10 predefined gastrointestinal related symptoms frequently encountered in patients with uremia. Those symptoms were loss of appetite, nausea/ vomiting, epigastric discomfort/pain, abdominal fullness/bloating, early satiety, loss of mouth taste, abnormal taste in mouth, ammoniacal mouth smell, oral ulceration and weight loss. The presence of each symptom was scored as: 0 absent; 1 re-called on direct questioning; 2 present, but not impairing activities; 3 interfering with daily work and life. The symptoms scores were added for each patient giving a possible score ranging from 0 to 30. If a patient had less than 10 scores he was graded to have mild, 11-20 moderate and more than 20 severe, dyspesia.
Upper gastrointestinal endoscopy and endoscopic gastric biopsy was performed in all the study patients. The endoscopist was blinded for any clinical data on the study patients. Endoscopic findings were recorded as per the protocol. Two biopsy specimens were routinely taken from the antral mucosa using cidex disinfected biopsy forceps (Olympus GIF QID, Olympus Corp Tokyo). Two extra specimens were taken from any detected focal lesion such as an ulcer or erosion. Two specimens were fixed in 10 percent formalin for histopathological examination. The pathologist was also blinded for any clinical or microbiological information on the study patients. Additional biopsy specimens were placed in separate sterile containers, one containing 0.5 ml sterile saline and another with 1 ml urea broth (DIFCO). The specimen placed in saline was inoculated within two hours of collection on the surfaces of blood agar with trypticase soy agar base (BBL) and chocolate agar plates with G.C. agar base (OXOID). After the inoculation of the plates, the tissue was placed in the same urea broth containing the other piece of tissue. The urea broth was incubated aerobically at 37 degrees centigrade and examined after two hours and twenty four hours of incubation for positive direct urease results. Culture plates were incubated in microaerophilic atmosphere (in anaerobic gas pack jar without catalyst -Oxoid gas generating kit - anaerobic system) at 37 degree centigrade and examined after four days and seven days of incubation. Small transparent colonies of 0.5 to 1 mm in diameter with faint hemolysis on blood agar were considered typical of H. pylori. Colonies were identified on the basis of gram stain morphology, positive oxidase test and rapid urease production (within 15 minutes). The microbiologist was also blinded for any additional data on the study patients.
Specimens for histopathological examination were processed by a standard procedure and blocked in paraffin wax. Three 5 uM serial sections at three levels were stained with hematoxylin and eosin. Two further sections from each level were stained with modified half-gram  and combined Alcian Blue - Periodic Acid Schiff (PAS) stains  . Helicobacter status was assessed on the slides stained by half-gram method. The positive slides were those that had bacilli with characteristic shape and size of the helicobacter. No attempt was made to quantify the density of bacillary colonization as it has been, in our experience, variable from section to section even from the same level of the block.
Helicobacter pylori was considered to be present in the gastric mucosa of the patient when they were detected either on histopathological examination, direct urease test or culture.
| Data Analysis|| |
Data were analyzed by using SPSSX - statistical package. The difference among proportions and the association between two variables (categorical nature) were tested by using chi-square test. Value of 'p' less than or equal to 0.05 was regarded as statistically significant.
| Results|| |
The study patients were 50 males (71.4%) and 20 females (28.6%), with age 45.8 ± 14.3 years (ranging from 13 to 80 years). These patients were, 26 Kuwaiti (37.1%), 38 non-Kuwaiti Arabs (54.6%) and six non-Arab Asians (8.6%). The underlying renal diseases leading to renal insufficiency are summarized in [Table - 1]. Chronic tubulointer-stitial disease was the most common disease. Twenty three patients had moderate and 47 patients had severe degree of renal failure.
The mean serum creatinine level was (623.3 umol/L). H. pylori infection was demonstrated in the gastric mucosa of 57 (81.4%) patients by histology, direct urease test and/ or culture. H. pylori infection occurred with nearly equal frequencies in patients having moderate or severe degrees of renal failure and the level of blood urea did not influence it [Table - 2].
Upper gastrointestinal endoscopy was normal in appearance in 33 (47.1%) patients. Abnormal findings included erosions and ulcers in the antrum and/or duodenum. Erosions alone were seen in 27 (38.6%) patients and both erosions and ulcers were present in 10 (14.3%) patients. Gastrointestinal symptoms attributable to uremia were present in all patients. However, their severity varied in individual patients. The symptoms were graded as mild in 17, moderate in 33 and severe in 20 patients. The presence of H. pylori infection in the gastric mucosa and its relation to endoscopic findings and gastrointestinal symptoms is shown in [Table - 3].
There was no direct correlation between H. pylori infection, endoscopic gastritis or dyspeptic symptoms. Of interest are  46 percent of H. pylori positive patients had normal endoscopic findings  an equal percentage of H. pylori negative patients had endoscopic gastritis and  moderate to severe dyspeptic symptoms were present with nearly equal frequencies (75% and 78%) in H. pylori positive and negative patients. The endoscopic findings did not correlate with the presence or severity of dyspeptic symptoms. Of interest again, are the following observations:  82 percent of patients with normal endoscopic findings had moderate to severe dyspeptic symptoms and  30 percent of patients with endoscopic gastritis had only mild dyspeptic symptoms, [Table - 4]. Histological examination of tissue for H. pylori was positive in 53 patients (75%). Direct urease test and culture gave positive results in 45 patients (64%) each. Histological examination succeded in detecting 93 percent of H. pylori positive patients whereas the other two techniques detected only 79 percent, [Table - 5].
| Discussion|| |
There are few reports about the prevalence of H. pylori infection in gastric mucosa of patients with chronic renal insufficiency (810). Twenty four to 42 percent of patients on chronic dialysis therapy have been reported to harbour H. pylori (1,5.11-13). Urea, a known growth factor for H. pylori  reaches high levels in the gastric mucosa of uremics by transcellular diffusion. Thus, it is probable to find high prevalence of H. pylori infection in patients with advanced renal failure.
The role of ammonia in causing uremic dyspeptic symptoms has been postulated, since its formation in uremia may be enhanced in the presence of urease in the gastric environment  . Since there is no normal internal source for urease in the gastric mucosa, it is possible that H. pylori infection may be a urease provider. H. pylori negative uremics have high concentrations of ammonia in gastric juice, possibly from the presence of other urease producing bacteria  , but to a lesser extent than H. pylori positive uremics  .
Based on animal studies it has been suggested that high concentration of ammonia at the epithelial surface could cause mucosal damage , .
It has been claimed that ammonia production plays a pathogenetic role in the development of H. pylori related gastritis in man  . However, recently the role of ammonia in the pathogenesis of gastritis in patients with and without renal failure has been challenged  . No direct correlation between gastric juice ammonia concentration and severity of antral gastritis in H. pylori positive uremics on dialysis or controls has been found.
Our study has also failed to demonstrate a direct correlation between the presence of H. pylori infection, presence of endoscopic gastritis and severity of dyspeptic symptoms in patients with advanced chronic renal failure. Noticeably, even H. pylori negative uremics had an equal incidence of endoscopic gastritis and dyspeptic symptoms as the H. pylori positive ones. Furthermore, almost half of our H. pylori positive uremics had normal endoscopic findings. It may be speculated that the high ammonia concentration in the gastric environment may directly contribute to dyspeptic symptoms in uremics and not necessarily because of ammonia related gastritis.
The prevalence of H. pylori infection in our normal population is not known. However, the prevalence of H. pylori infection in adults (20-75 years) in Kuwait, endoscoped and biopsied for dyspeptic symptoms in patients without renal failure was 84 percent which is very similar to that in our study population. This would further suggest that H. pylori may not have a causative role in the generation of dyspeptic symptoms in uremia. Our study did not include patients with mild renal failure (serum creatinine less than 500 umol/L) and therefore, all patients had some form of dyspeptic symptom(s). Such a group would have provided a valid control group to the prevalence of H. pylori infection in patients with mildly elevated blood urea levels. The questionnaire used in this study to evaluate the severity of dyspeptic symptoms in uremia has not been previously validated, therefore, we cannot claim a high degree of specificity of our findings.
In our hands direct histopathological examination of biopsy tissue yielded 93 percent success rate, which was improved very little by additional tests such as the direct urease test and bacterial culture. Radiolabelled urea breath test was not tested for improving accuracy of our results.
In conclusion, H. pylori infection seems to be as prevalent in patients with advanced renal failure as the general population. However, H. pylori infection did not appear to play a causative role in gastritis or dyspeptic symptoms associated with uremia.
| Acknowledgements|| |
The authors wish to thank Dr. T.N. Sugathan for performing statistical analysis, Miss Lubna N. Al-Sherif for technical assistance and Mr. George Varughese for secretarial assistance.
| References|| |
|1.||Rowe PA, El Nujumi A, Williams C, et al. Diagnosis of Helicobacter pylori infection in chronic renal failure. 29th congress of the Eur Dialysis and Trans Assoc. Paris, France 1992;87. |
|2.||Simenhoff ML, Saukoncn JJ, Burke JF, Wesson LG Jr, Schaedlcr RW, Gordon SJ. Bacterial populations of the small intestine in uremia. Nephron 1978;22:63-8. |
|3.||Marshall BJ, Whisson M, Francis G, McGechie D. Correlation between symptoms of dyspesia and Campylobacter pyloridis serology in Western Australia blood donors. In: Campylobacter III Proceeding of the Third International Workshop on Campylobacter Infection. Public Health Laboratory Service London 1985;188-89. |
|4.||Marshall BJ, McGechie DB, Rogers PA, Glancy RJ. Pyloric campylobacter infection and gastroduodenal disease. Med J Aust 1985;143:439- 44. |
|5.||Conz P, Chiaramonte S, Ronco C, Feriani M, La Greca G. Campylobacter pyloric in uremic dialyzed patients. Nephron 1989;53:90. [PUBMED] |
|6.||Gray SF, Wyatt JI, Rhathbone BJ. Simplified techniques for identifying Campylobacter pyloridis. J Clin Path 1986;39:1279. |
|7.||Cook HC. Combined Alcian Blue-P.A.S. technique for acid and neutral mucins. In: Bancroft JD and Stevens A. Eds. Theory and practice of histological techniques. Churchill Livingstone 1982:197. |
|8.||Jaspersen D, Fassbinder W, Heinkele P, et al. Significantly lower prevalence of Helicobacter pylori in uremic patients than in patients with normal renal function. J Gastroenterol 1995;30(5):585-8. |
|9.||Gladziwa U, Haase G, Handt S, et al. Prevalence of Helicobacter pylori in patients with chronic renal failure. Nephrol Dial Transplant 1993;8(4):301-6. |
|10.||Neithercut WD, Rowe PA, EI-Nujumi AM, et al. Effect of Helicobacter pylori infection on intra-gastric urea and ammonium concentrations in patients with chronic renal failure. J Clin Pathol 1993;46(6):544-7. |
|11.||Loffeld RJ, Peltenburg HG, v.d. Oever H, Stobberingh E. Prevalence of Helicobacter pylori antibodies in patients on chronic intermittent haemodialysis. Nephron 1991;59:250-3. |
|12.||Shousha S, Arnaout AH, Abbas SH, Parkins RA. Antral Helicobacter pylori in patients with chronic renal failure. J Clin Pathol 1990;43:397-9. [PUBMED] [FULLTEXT]|
|13.||Wee A, Kang JY, Ho MS, Choong HL, Wu Ay, Sutherland IH. Gastroduodenal mucosa in uremia: endoscopic and histological correlation and prevalence of helicobacter-like organisms. Gut 1990;31:1093-6. [PUBMED] [FULLTEXT]|
|14.||Hazell SL, Lee A, Brady L, Hennessy W. Campylobacter pyloridis and gastritis: association with intercellular spaces and adaptation to an environment of mucus as important factors in colonization of the gastric epithelium. J Infect Dis 1986;153:658-63. [PUBMED] |
|15.||Marshall BJ. Campylobacter pyloridis and gastritis. J Infect Dis 1986;153(4):650-7. |
|16.||Bliss S. Site of ammonia formation and the prominent role of vomiting in ammonia elimination. J Biol Chem 1926;67:109-40. |
K V Johny
Dept. of Medicine, Kuwait university, P.O. Box 24923, Safar 13110
[Table - 1], [Table - 2], [Table - 3], [Table - 4], [Table - 5]