Intestinal-Renal Syndrome: Mirage or Reality?

Abstract

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.

Linking gut microbiota to cardiovascular disease and hypertension: Lessons from chronic kidney disease

“…Dysfunction of the intestinal barrier in CKD is associated with bacterial translocation and endotoxinemia, which is related to systemic inflammation, malnutrition, cardiovascular disease, and possibly reduced survival [28,72,73,9].…”

Plasma p-Cresol Lowering Effect of Sevelamer in Peritoneal Dialysis Patients: Evidence from a Cross-Sectional Observational Study

“…The reason of the differences between these results and ours are unclear but they could be related to the different dialysis procedure that was used. Recent evidence suggests, indeed, that the underperfusion that can take place during extracorporeal hemodialysis could alter the permeability of the intestinal barrier favoring the passage of intestinal bacterial products (Intestinal-Renal Syndrome) [34]. Supporting this hypothesis, McIntyre et al recently reported [35] that measurable levels of endotoxins coming from intestinal bacteria can be detected in the plasma of hemodialysis patients and, importantly, that they increase at the time of dialysis.…”

“…These important results have been interpreted assuming that dialysis-induced hemodynamic stress could damage the intestinal mucosa finally leading to an increase of its permeability to endotoxins [35]. Although a formal demonstration of this hypothesis by quantitative measurement of intestinal blood flow is still lacking [34], it is tempting to speculate that Sev could be less effective in preventing p-cresol absorption in hemodialysis patients because this dialysis procedure increases the permeability of the intestinal mucosa to the point that too much p-cresol can escape from Sev and enter the blood.…”

“…If confirmed in larger randomized double blinded clinical trials, this observation could have important implications for planning the best pharmacological treatment in PD patients. The concept that lowering p-cresol concentrations is a priority in CKD patients strongly emerged, indeed, during the last years because of compelling experimental evidence showing that this uremic toxin negatively influences the prognosis of this disease by significantly increasing the cardiovascular risk [34], [36]. Unfortunately, no pharmacological treatment effective in lowering p-cresol is available with the only exception of AST-120, a non-absorbable carbon adsorbent approved in Japan that adsorbs both indoxyl-sulphate and p-cresol in the gut [37]–[38].…”

B type natriuretic peptide and troponin T as independent predictors of cardiovascular mortality in predialysis patients with chronic kidney disease

“…U jednom od pionirskih radova, Mallamaci i saradnici su pokazali da je nivo TnT kod bolesnika na hemodijalizi bez akutnog koronarnog sindroma i bez srčane insuficijencije nezavisno povezan sa masom LV i da predviđa ukupni i KV mortalitet [26]. Nakon toga, Wood i saradnici su saopštili da je već blago povišeni nivo TnT kod bolesnika sa HBS pre započinjanja dijaliznog lečenja povezan sa lošim preživljavanjem [27]. U metaanalizi koja je obuhvatila 28 studija, Khan i saradnici su potvrdili da povišeni nivo TnT u grupi asimptomatskih dijaliznih bolesnika identifikuje podgrupu bolesnika sa lošim preživljavanjem i visokim rizikom srčane smrti [13].…”