Intestinal-renal syndrome: mirage or reality?

The recent interest in the role of the intestine in the cardiovascular stability of uremic patients, specifically on dialysis, but potentially also in chronic kidney disease, must be seen against the background of the recent great interest in the role of the gut in chronic heart failure [Curr Opin Clin Nutr Metab Care 2008;11:632-639]. There has been a long-standing interest in the role of the intestine in renal failure, mainly concerning the role of metabolites of bacterial metabolism in the gut as potential uremic toxins. This area has recently been given a new twist by the finding that increased endotoxin concentrations in the blood of dialyzed patients are associated with hypotensive episodes and myocardial 'stunning'. Recent studies suggest that intradialytic underperfusion of myocardial areas, the so-called stunning, may be related to the entry of bacterial endotoxin and/or cytokines across the mucosal barrier into the circulation, where they have a negative impact on myocardial function (and presumably beyond the negative cardiac side effect also contribute to catabolism and malnutrition). Entry of bacterial endotoxin during dialysis sessions is presumably the result of intermittent underperfusion of the intestine if the effective blood volume is rapidly reduced causing breakdown of the mucosal barrier. Apart from the impact on myocardial perfusion, the entry of bacterial endotoxin and/or cytokines across the mucosal barrier may also contribute to malnutrition, wasting and reduced life expectancy in hemodialyzed patients. Such a causal relationship is absolutely plausible in view of an extensive literature on congestive heart failure where clinical and experimental evidence indicates that bacterial endotoxin and/or cytokines may escape from a hypoperfused edematous gut, entering the circulation, triggering an inflammatory response, upregulating circulating cytokines and interfering with the function of the heart through several pathogenic mechanisms.