Constipation in Patients With Chronic Kidney Disease

Constipation is a frequent symptom in patients with chronic kidney disease (CKD). This review outlines the mechanisms and management of constipation in patients with CKD from a physician’s perspective. Common causes of constipation in patients with CKD include concomitant medications, low dietary fiber intake, water-restricted diet, lack of physical activity, altered gut microbiota, and reduced gastrointestinal motility. Constipation has a negative impact on overall health, and, in particular, the presence of constipation has been associated with worsening kidney function and increased risk of developing advanced stages of CKD. Although lifestyle and dietary modifications may not always be practical for patients with CKD, they are recommended because they are beneficial as they lower mortality in patients with CKD. The use of laxatives containing magnesium salts, bulking agents, and osmotic laxatives may have insufficient efficacy and may be associated with adverse effects. In contrast, lactulose and lubiprostone have been shown to exhibit reno-protective effects. Linaclotide and plecanatide have very limited systemic absorption and appear safe in patients with CKD. Tenapanor reduces paracellular intestinal phosphate absorption in addition to blocking sodium uptake by enterocytes, and provides additional benefit in patients patients with CKD who have hyperphosphatemia and constipation. Prucalopride leads to improvements in bowel function and constipation-related symptoms in cases in which response to conventional laxatives are inadequate. However, the dose of prucalopride should be reduced to 1 mg once daily for patients with CKD. In conclusion, there are important advances on the impact and treatment of constipation in patients with CKD.

Regional Colonic Transit Pattern Does Not Conclusively Identify Evacuation Disorders in Constipated Patients with Delayed Colonic Transit

BACKGROUND/AIMS: After exclusion of structural diseases, chronic constipation may be associated with normal or slow transit or rectal evacuation disorders. We evaluated: (1) clinical features and anorectal function, (2) difference of regional colonic transit according to the presence or absence of evacuation disorders, and (3) association of colonic transit with gender in patients with objectively slow colonic transit. METHODS: We reviewed electronic medical records of 1553 patients with constipation seen by one gastroenterologist from 1994–2015 at a tertiary medical center. We identified patients with slow colonic transit using scintigraphy. Evacuation disorders were identified on clinical examination or anorectal manometry. Colonic compliance and tone were measured in 29 patients. Statistical analysis was by the Mann-Whitney rank sum test. RESULTS: Of the 207 patients (155 females, mean age 41.3 ± 15.3 [SD] years), 113 had evacuation disorders (ED+ve) and 94 did not (ED−ve). There were no significant differences in colonic transit or gastric emptying between ED+ve or ED−ve; similarly, colonic compliance, tone and responses to neostigmine were not different in ED+ve and ED−ve. Conversely, there were significant differences by gender in patients with slow colonic transit: colonic transit, small bowel transit, and gastric emptying (all P < 0.005). CONCLUSIONS: Delayed colonic transit does not exclude evacuation disorders in chronic constipation. In chronic constipation and objectively slow colonic transit, females had slower gastric, small bowel, and colonic transit than males.

A Pilot Study of the Effect of Daikenchuto on Rectal Sensation in Patients with Irritable Bowel Syndrome

BACKGROUND/AIMS: Daikenchuto (TU 100), a botanical agent that modulates gastrointestinal nerves, is used in the treatment of motility and functional disorders. Our aim was to study the effects of TU-100 on rectal compliance and sensation in patients with irritable bowel syndrome (IBS). METHODS: In 20 patients per treatment arm, we conducted a single-center, randomized, parallel-group, double-blind, placebo-controlled, single-dose pharmacodynamics study evaluating the effects of TU-100, 15 g (5 g t.i.d. [means 3 times a day]), for 14-16 consecutive days on rectal compliance and rectal sensation (thresholds and sensation ratings), all measured at baseline and on the last day of medication treatment. The primary endpoint was rectal sensation thresholds and sensation ratings in response to balloon distension at 32 mmHg. Secondary endpoints were rectal compliance, sensation thresholds, ratings and tone (fasting and postprandial), bowel pattern, abdominal pain (average and worst severity) and bloating scores, IBS quality of life and safety profile. RESULTS: Rectal sensation ratings post-treatment were significantly associated with baseline (pre-treatment) ratings and with level of anxiety or stress recorded at the time of the sensation testing. There were no effects of TU-100 treatment on rectal sensation ratings, sensation thresholds, rectal fasting or postprandial tone, rectal compliance, bowel function, abdominal pain or bloating scores, or IBS quality of life. CONCLUSIONS: TU-100 did not significantly affect rectal compliance and sensation in patients with IBS in this study.

Bile Acid Diarrhea: Prevalence, Pathogenesis, and Therapy

Bile acid diarrhea (BAD) is usually seen in patients with ileal Crohn's disease or ileal resection. However, 25% to 50% of patients with functional diarrhea or diarrhea-predominant irritable bowel syndrome (IBS-D) also have evidence of BAD. It is estimated that 1% of the population may have BAD. The causes of BAD include a deficiency in fibroblast growth factor 19 (FGF-19), a hormone produced in enterocytes that regulates hepatic bile acid (BA) synthesis. Other potential causes include genetic variations that affect the proteins involved in BA enterohepatic circulation and synthesis or in the TGR5 receptor that mediates the actions of BA in colonic secretion and motility. BAs enhance mucosal permeability, induce water and electrolyte secretion, and accelerate colonic transit partly by stimulating propulsive high-amplitude colonic contractions. There is an increased proportion of primary BAs in the stool of patients with IBS-D, and some changes in the fecal microbiome have been described. There are several methods of diagnosing BAD, such as 75selenium homotaurocholic acid test retention, serum C4, FGF-19, and fecal BA measurement; presently, therapeutic trials with BA sequestrants are most commonly used for diagnosis. Management involves the use of BA sequestrants including cholestyramine, colestipol, and colesevelam. FXR agonists such as obeticholic acid constitute a promising new approach to treating BAD.

Noninvasive Measurement of Gastric Accommodation by SPECT

No abstract available.