1.
Uremic toxins originating from colonic microbial metabolism.
Evenepoel, P, Meijers, BK, Bammens, BR, Verbeke, K
Kidney international. Supplement. 2009;(114):S12-9
Abstract
Numerous molecules, which are either excreted or metabolized by the kidney, accumulate in patients with chronic kidney disease (CKD). These uremic retention molecules (URMs), contributing to the syndrome of uremia, may be classified according to their site of origin, that is, endogenous metabolism, microbial metabolism, or exogenous intake. It is increasingly recognized that bacterial metabolites, such as phenols, indoles, and amines, may contribute to uremic toxicity. In vitro studies have implicated bacterial URMs in CKD progression, cardiovascular disease, and bone and mineral disorders. Furthermore, several observational studies have demonstrated a link between serum levels of bacterial URMs and clinical outcomes. Bacterial metabolism may therefore be an important therapeutic target in CKD. There is evidence that besides reduced renal clearance, increased colonic generation and absorption explain the high levels of bacterial URMs in CKD. Factors promoting URM generation and absorption include an increased ratio of dietary protein to carbohydrate due to insufficient intake of fiber and/or reduced intestinal protein assimilation, as well as prolonged colonic transit time. Two main strategies exist to reduce bacterial URM levels: interventions that modulate intestinal bacterial growth (e.g., probiotics, prebiotics, dietary modification) and adsorbent therapies that bind bacterial URMs in the intestines to reduce their absorption (e.g., AST-120, sevelamer). The efficacy and clinical benefit of these strategies are currently an active area of interest.
2.
Constipation: a physiological approach.
Thompson, WG
Canadian journal of gastroenterology = Journal canadien de gastroenterologie. 2000;:155D-162D
Abstract
The first step in managing a patient with constipation is to understand the precise nature of the complaint. Is the onset recent? What are the frequency and form of the stools, and how much effort is required to defecate? Is constipation steady or alternating as in irritable bowel syndrome? Are there structural, metabolic or pharmacological confounders? Is the patient depressed? Has dietary fibre been tried at a sufficient dose? What are the patient's understanding and beliefs about the symptoms? Has there been sufficient and appropriate investigation? Armed with the answers to these questions, physicians can help most patients through lifestyle, dietary and pharmacological adjustments, along with supplementary fibre. Some patients may require regular doses of an osmotic laxative. Those few that fail these measures should have their transit time estimated while on a high fibre diet; if it is normal, further testing is unlikely to help. The above efforts should be re-emphasized, and reassurance should be offered. Some patients may require a psychological assessment. If transit time is prolonged and the patient may benefit from surgery for colonic inertia or biofeedback for anismus, then colon and anorectal function should be assessed. The decision to perform further tests should be made carefully, and unrealistic expectations should be discouraged. Before surgery is offered, the patient should have the benefit of receiving an expert opinion. Biofeedback helps some patients with isolated anorectal dysfunction.