Pathophysiology of gastric acid secretion in patients with chronic renal failure: influence of Helicobacter pylori infection.
Watanabe H,Hiraishi H,Ishida M,Kazama J J,Terano A
Journal of internal medicine
OBJECTIVES:The incidence of gastroduodenal diseases is high in patients with chronic renal failure (CRF). However, gastric acidity in CRF has been reported to range in level from low to high. Moreover, it remains unknown whether Helicobacter pylori infection influences gastric acidity in such patients. Thus, we aimed to clarify the pathophysiological perturbation in gastric acidity and to determine the influence of H. pylori infection in CRF. DESIGN:Case-control study. SETTING:A university hospital. SUBJECTS:Twenty-seven patients with CRF and 24 control patients, presenting with either gastrointestinal symptoms, positive faecal occult blood, or anaemia (haemoglobin <10 g dL(-1)). MEASURES:The patients underwent gastroduodenal endoscopy with simultaneous determination of H. pylori infection. Gastric ammonium concentration, serum pepsinogen I and II, and basal gastrin level were measured. Thereafter, gastric acid secretion was monitored by 24-h intragastric acidity measurement with calculation of pH-3 holding time (%) (hours showing pH>3/24 h). RESULTS:In the CRF group, pH-3 holding time of H. pylori (+) subgroup was significantly greater than that of H. pylori (-) subgroup (71.2 +/- 32.4% vs. 32.8 +/- 30.0%, mean +/- SD; P=0.03). Pepsinogen I/II ratio was inversely correlated with pH-3 holding time in the control and CRF groups. Gastric ammonium concentration in CRF/H. pylori (+) subgroup (14.1 +/- 9.2 mmol L(-1)) was significantly higher than in CRF/H. pylori (-) (2.5 +/- 2.7 mmol L(-1); P=0.002) and control/H. pylori (+) subgroups (6.1 +/- 4.2 mmol L(-1); P=0.01). Serum gastrin level was significantly higher in the CRF group than in the control group (297 +/-343 pg mL(-1) vs. 116 +/- 69 pg mL(-1); P=0.02) as a whole. However, there was no significant correlation between serum creatinine and gastrin levels in the CRF group. Gastrin level in CRF/H. pylori (+) subgroup was significantly higher than in CRF/H. pylori (-), control/H. pylori (+), and control/H. pylori (-) subgroups (423 +/-398 pg mL(-1) vs. 113 +/- 79, 124 +/- 78, and 96 +/-43 pg mL(-1), respectively; P=0.01-0.03). Significant positive correlations amongst pH-3 holding time, ammonium and gastrin concentrations were found in the CRF group, but not in the control group. CONCLUSIONS:CRF without H. pylori infection primarily shows a tendency for high gastric acidity, but without hypergastrinaemia. Persistent H. pylori infection in CRF leads to decreased acidity and, consequently, to fasting hypergastrinaemia via a feedback mechanism. The hypoacidity in CRF with H. pylori infection appears to result from neutralization of acid by ammonia as well as from gastric atrophy. Thus, H. pylori infection status critically determines perturbation in gastric acidity and fasting gastrin level in CRF.
Gastric and pancreatic function in patients with end-stage renal disease.
Dinoso V P,Murthy S N,Saris A L,Clearfield H R,Lyons P,Nickey W A,Simonian S
Journal of clinical gastroenterology
Gastroduodenal disease such as peptic ulcer and duodenitis is increased in patients with end-stage renal disease. Gastric hypersecretion of acid proposed as the underlying mechanism has been disputed because peptic ulcer has occurred even in those with normal or low gastric acid secretion. We studied the pancreatic exocrine secretion of bicarbonate (HCO3) and the concentration of plasma pepsinogens in addition to gastric acid secretion in 15 patients on chronic hemodialysis, 10 patients wih previous renal transplantation and compared them with 10 subjects without gastrointestinal or renal disease. We confirmed hypersecretion of gastric acid in renal disease. We confirmed hypersecretion of gastric acid in renal patients on chronic hemodialysis but not in transplant patients. In addition, we found basal but hyposecretion of HCO3 and hyperpepsinogenemia in both renal groups. These observations suggest that the high incidence of gastroduodenal disease in end-stage renal disease might, in part, be due to the simultaneous occurrence of gastric acid hypersecretion, basal hyposecretion of HCO3 by the pancreas, and hyperpepsinogenemia.
[Influence of impaired renal function and Helicobacter pylori infection on serum pepsinogen concentrations].
Murakawa M
Nihon Jinzo Gakkai shi
It has been known that patients with chronic renal failure have elevated concentrations of serum pepsinogens, which are raised by Helicobacter pylori (H. pylori) infection of the stomach. This study was conducted to examine how renal dysfunction and H. pylori infection affect serum pepsinogen (PG) concentrations. The subjects consisted of 93 patients with renal disease (60 males and 33 females with a mean age of 55 +/- 1.3 years). Dialysis patients were not included. Twenty-four-hour urinary collection was performed, and creatinine clearance (Ccr) was calculated for all the subjects. Status of H. pylori infection was assessed by serum IgG antibody against H. pylori. Fasting serum PG I and PG II were measured by RIA. The subjects were divided into 4 groups based on Ccr: group A: Ccr > or = 71 ml/min; group B: 30-70 ml/min; group C: 11-30 ml/min; group D: Ccr < or = 10 ml/min. Regardless of the H. pylori status, serum PG I concentrations were elevated as the renal function declined; serum PG I levels of groups C and D (177.5 +/- 15.2 ng/ml and 234.0 +/- 32.2 ng/ml, respectively) were significantly higher than those of group A (66.1 +/- 9.6 ng/ml, p < 0.01); Group D also had a significantly higher concentration of PG I than group B (106.0 +/- 17.2 ng/ml, p < 0.01). The same tendency was found in serum PG II concentrations. However, the differences among the 4 groups were not statistically significant (16.2 +/- 2.3, 24.2 +/- 4.0, 28.3 +/- 3.5, 34.3 +/- 5.6 ng/ml for group A, B, C, and D, respectively). There was a negative correlation between Ccr and serum PG I concentrations (r = -0.45, p < 0.01). In comparison between H. pylori-infected patients and uninfected patients, serum levels of PG II were higher in the former patients than in the latter. This difference was significant in groups A and C. Serum PG I concentrations were the same between H. pylori-infected patients and their uninfected counterparts for the 4 groups. The present study has shown that serum PG I concentrations are raised by a loss of renal function, while PG II levels are elevated mainly by H. pylori infection of the stomach. It is concluded that renal function and H. pylori infection should be taken into account when serum PG concentrations are evaluated in patients with renal diseases.
Helicobacter pylori status and esophagogastroduodenal mucosal lesions in patients with end-stage renal failure on maintenance hemodialysis.
Moriyama Tomohiko,Matsumoto Takayuki,Hirakawa Katsuya,Ikeda Hirofumi,Tsuruya Kazuhiko,Hirakata Hideki,Iida Mitsuo
Journal of gastroenterology
OBJECTIVES:The aim of this study was to elucidate the impact of Helicobacter pylori infection on esophagogastroduodenal mucosal lesions in patients with end-stage renal failure on maintenance hemodialysis (HD). METHODS:An upper endoscopy and the (13)C-urea breath test were performed in 198 patients on maintenance HD. Clinical features, serum pepsinogen levels and esophagogastroduodenal mucosal lesions were compared between H. pylori-positive and H. pylori-negative patients. Risk factors associated with esophagogastroduodenal mucosal lesion were determined by multivariate analyses. RESULTS:The upper endoscopy revealed that gastric erosion was the most frequent (58%) type of esophagogastroduodenal mucosal lesion, followed by duodenal erosion (18%), gastric ulcer (14%), gastroesophageal reflux disease (10%), and duodenal ulcer (7%). Of the 198 patients enrolled in the study, 81 were positive and 117 patients were negative for H. pylori infection. The time duration after the introduction of HD was significantly longer and serum pepsinogen I/II ratio was significantly higher in H. pylori-negative patients than in H. pylori-positive patients. Multivariate analyses revealed that the H. pylori infection was an independent, protective factor for gastric erosion (odds ratio 0.38; 95% confidence interval 0.21-0.70), while the infection was unrelated to other mucosal lesions. CONCLUSIONS:The most common mucosal lesion observed in our study cohort, all of whom were patients on maintenance HD, was gastric erosion. The high prevalence of this type of lesion may be explained partly by the cure of H. pylori infection during the clinical course of maintenance HD.
10.1007/s00535-009-0196-6
Serum Indicators Reflecting Gastric Function May Also Correlate with Other Extragastric Diseases.
Gong Yuehua,Wang Wei,Li Yi,Yuan Yuan
Gastroenterology research and practice
Aim. Serological indicators of organ function can reveal intrinsic links between different organs. The present study aimed to determine the correlations of serum indicators for gastric and extragastric function. Methods. A total of 823 individuals were enrolled. Data on indicators reflecting blood lipids, blood glucose, indexes of stomach, kidney, liver, and thyroid function, and H. pylori IgG antibody level were collected. Results. As creatine (Cr) levels increased, PGI (pepsinogen I), PGII concentrations, and PGI/II ratio increased monotonically from 79.7 to 105.15 µg/L, 6.5 to 8.4 µg/L, and 11.97 to 12.27, respectively (P < 0.05). As thyroid peroxidase antibody (TPOAb) levels increased, PGI level decreased from 100.85 to 84 µg/L (P < 0.05) and as thyroid stimulating hormone (TSH) increased, PGI/II ratio increased monotonically from 11.54 to 12.68 (P < 0.05). As triglyceride (TG) levels increased, gastrin 17 (G17) concentrations increased monotonically from 1.73 to 2.7 pmol/L (P < 0.05). As serum glucose and glycated hemoglobin (HbA1C) increased, PGI/II concentrations increased monotonically from 11.98 to 12.67 and 9.7 to 13.54 (P < 0.05), respectively. Conclusions. Serum PG and G17 levels were associated with blood glucose and lipids, kidney function, and thyroid function but not with liver function. Serum indicators reflecting gastric function may correlate not only with primary diseases, but also with other extragastric diseases.
10.1155/2015/867495
Relation between serum group II pepsinogen concentration and the degree of Brunner's gland hyperplasia in patients with chronic renal failure.
Paimela H,Härkönen M,Karonen S L,Tallgren L G,Stenman S,Ahonen J
Gut
Serum concentrations of group I and II pepsinogens (PG I and PG II) were determined in 15 patients with chronic renal failure. Gastroduodenoscopy with biopsy and acid secretion tests were also performed. Five patients had histologically confirmed severe Brunner's gland hyperplasia manifesting as multiple polyps in the duodenal bulb. Five patients had a mild form of Brunner's gland hyperplasia which was evident only by histological analysis. Five had no signs of such alterations. The three groups of patients were comparable in age, sex, mean level of serum creatinine, mean duration of dialysis treatment, distribution of non-dialysed and dialysed patients, and gastric histology. In patients with severe Brunner's gland hyperplasia the mean serum PG II concentration was significantly higher than in the other patients. Both the serum PG I and the serum PG II concentrations decreased after receiving a well functioning renal transplant in the two patients who underwent transplantation.
10.1136/gut.26.2.198
The effects of continuous ambulatory peritoneal dialysis and hemodialysis on serum pepsinogen concentrations in patients with chronic renal failure.
Aydemir Selim,Borazan Ali,Acikgoz Serefden,Ustundag Yucel,Yilmaz Ahmet
The Tohoku journal of experimental medicine
Pepsinogen, the precursors of pepsin, is classified into two subtypes: pepsinogen I (PG I) and pepsinogen II (PG II). Patients with impaired renal function are associated with elevated concentrations of serum pepsinogen. Contradictory results have been reported about the effect of dialysis on the serum pepsinogen levels, as the previous studies were conducted only in a particular period of dialysis. We therefore investigated the effect of continuous ambulatory peritoneal dialysis (CAPD) or hemodialysis on serum pepsinogen levels in patients with chronic renal failure (CRF) before and after dialysis treatment. Thirty-four patients with CRF were enrolled in this study and were treated by CAPD (n=22) or hemodialysis (n=12). As a control group, subjects with normal renal function were included (n=20). Serum PG I and PG II levels were measured in control subjects and CRF patients before dialysis treatment and after three-month dialysis treatment. Before dialysis treatment, serum PG I levels were significantly higher in CRF patients than control subjects. In patients treated by CAPD, the serum PG I levels were significantly decreased but its levels were still higher than the values of the control subjects, whereas PG I levels remained unchanged in patients treated by hemodialysis. There were no differences in serum PG II levels between control subjects and CRF patients before or after dialysis treatment. Thus, CAPD is more effective than hemodialysis in the clearance of PG I.
The renal metabolism of pepsinogen A and C in man.
ten Kate R W,Pals G,Eriksson A W,Donker A J,Meuwissen S G
Clinical nephrology
Pepsinogen A (PGA) and pepsinogen C (PGC) are almost identical low molecular weight proteins with marked differences in renal handling. PGA is present in large amounts while PGC is almost absent in the urine of healthy subjects. Whether the amount of PGA in the urine represents the total amount of PGA that is extracted, is unknown. We, therefore, assessed the renal metabolism of PGA and PGC by measuring PGA, PGC and creatinine concentrations in the aorta and the right renal vein, and in the urine from patients undergoing elective heart catheterization. The renal extractions of PGA and PGC were not significantly different from the extraction of creatinine: 22%, 18% and 24%, respectively. Sixty-eight percent of PGA and 98% of PGC extracted from the circulation were metabolized by the kidney, and fractional metabolism was closely related to the fractional reabsorption of PGA and PGC from the glomerular filtrate. It is concluded that the kidney metabolizes PGA and PGC. The fractional metabolism of PGA and PGC can be calculated from the fractional reabsorption. Further studies on the renal handling of pepsinogens are warranted as they may provide information on factors affecting renal metabolism of low molecular weight proteins.
Elevated serum pepsinogens in chronic renal failure patients.
Nakahama H,Tanaka Y,Shirai D,Nishihara F,Takamitsu Y,Nakanishi T,Sugita M
Nephron
Human pepsinogens, the precursors of pepsin, originating from the stomach mucosa, are classified into two biochemically distinct groups, namely pepsinogen I (PG I) and pepsinogen II (PG II). We studied the serum levels of PG I and II in 51 normal volunteers, 23 chronic glomerulonephritis patients, 21 continuous ambulatory peritoneal dialysis (CAPD) patients and 40 hemodialysis patients. Serum pepsinogen levels were measured with a competitive binding double antibody radioimmunoassay. In the group of chronic glomerulonephritis patients, a positive correlation between the serum creatinine and the pepsinogen levels were found. The serum pepsinogen levels were remarkably elevated in CAPD and hemodialysis patients. The median levels of post-hemodialysis PG I (265.4 +/- 165.2 ng/ml) and PG II (41.7 +/- 38.0 ng/ml) were significantly higher than prehemodialysis values (PG I 207.4 +/- 127.5 ng/ml, PG II 29.0 +/- 16.6 ng/ml). Pepsinogen release by isolated gastric glands of guinea pigs was suppressed by guanidinosuccinic acid and was facilitated by calcium. The data suggest that both removal of guanidinosuccinic acid and infusion of calcium during hemodialysis contribute to the raised serum levels of these pepsinogens after hemodialysis.
10.1159/000188586
Serum pepsinogen I/II ratio is correlated with albuminuria in patients with type 2 diabetes.
Senmaru Takafumi,Fukui Michiaki,Kuroda Masaaki,Tanaka Muhei,Ushigome Emi,Sakabe Kazumi,Nakanishi Naoko,Mineoka Yusuke,Asano Mai,Yamazaki Masahiro,Hasegawa Goji,Nakamura Naoto
Endocrine journal
Helicobacter pylori infection, which is a common cause of atrophic gastritis, has been reported to represent a causal factor increasing the vascular damage and consequent albuminuria. On the other hand, decreased serum pepsinogen (PG) I/II ratio can be used to assess gastric mucosal atrophy. To the best of our knowledge, there are no studies investigating the correlation between PG I/II ratio and diabetic nephropathy. Therefore, we investigated a relationship between PG I/II ratio and degree of urinary albumin excretion (UAE) in patients with type 2 diabetes. We evaluated relationships between PG I/II ratio and degree of UAE or estimated glomerular filtration rate as well as various factors, including age, body mass index, blood pressure, hemoglobin A1c, serum lipid concentrations, uric acid or C-reactive protein in 333 consecutive patients with type 2 diabetes. PG I/II ratio correlated positively with logarithm of UAE in all patients (r = 0.174, P = 0.0016) and in patients without Helicobacter pylori infection (r = 0.352, P < 0.0001). Multiple regression analysis identified that PG I/II ratio correlated independently with logarithm of UAE in all patients (β = 0.264, P = 0.0005) and in patients without Helicobacter pylori infection (β = 0.295, P = 0.0022). These data suggest that serum PG I/II ratio is correlated with diabetic nephropathy.
Influences of Helicobacter pylori on serum pepsinogen concentrations in dialysis patients.
Tamura H,Tokushima H,Murakawa M,Matsumura O,Itoyama S,Mitarai T,Isoda K
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
BACKGROUND:Patients with impaired renal function have been known to have elevated concentrations of serum pepsinogens, which are raised by Helicobacter pylori infection of the stomach. The present study was performed to examine the effect of H. pylori infection on serum pepsinogen concentrations in dialysis patients. METHODS:Forty nine patients on dialysis and 48 subjects with no known kidney disease were examined for upper gastroduodenal endoscopy, H. pylori infection and serum concentrations of pepsinogen I and II. The status of H. pylori infection was evaluated from results of a urease test, histology and culture of biopsy specimens of the gastric mucosa. Serum pepsinogen levels were measured by radioimmunoassay. RESULTS:Serum concentrations of pepsinogen I and II were elevated in the dialysis patients in comparison with those in the controls (277.4+/-24.2 vs 52.6+/-4.0 pg/ml, P<0.01 for pepsinogen I, and 30.2+/-2.9 vs 14.9+/-1.3 pg/ml, P<0.01 for pepsinogen II). In both the dialysis patients and controls, those with H. pylori infection had significantly higher concentrations of serum pepsinogen I and II and a lower ratio of pepsinogen I to pepsinogen II than those without infection. Among the controls, 15 of 25 subjects with atrophic gastritis had a pepsinogen I/pepsinogen II ratio < or = 3.0, while only two out of 17 patients on dialysis fell into this range. CONCLUSIONS:We conclude that H. pylori status should be taken into account when serum pepsinogen concentrations are evaluated in dialysis patients.
10.1093/ndt/14.1.113