The relationship between colonization of Oxalobacter formigenes serum oxalic acid and endothelial dysfunction in hemodialysis patients: From impaired colon to impaired endothelium K. Turkmen ⇑ , F.M. Erdur Department of Nephrology, School of Medicine, Konya Necmettin Erbakan University, Meram School of Medicine, Konya, Turkey article info Article history: Received 29 September 2014 Accepted 13 January 2015 abstract Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in chronic kidney dis- ease (CKD) patients receiving hemodialysis (HD). Oxalic acid is a uremic retention molecule that has been extensively studied in the pathogenesis of calcium-oxalate stones. Oxalobacter formigenes (O. formigenes), a component of the colonic microbiota, plays an important role in oxalate homeostasis. Little is known regarding the colonization of HD patients by O. formigenes and the exact role of this bacterial species in oxalic acid metabolism in these patients. We hypothesized that oxalic acid may be insufficiently degraded in HD patients due to under colonization of the colon by O. formigenes in these patients. To test this hypothesis, we sought to quantitatively measure fecal O. formigenes levels and serum oxalic acid lev- els in HD patients. We also suggest that increased oxalic acid levels may be associated with endothelial dysfunction and aortic stiffness, both of which are commonly observed in HD patients. Increased coloni- zation with O. formigenes via the ingestion of prebiotics and probiotics could potentially decrease serum oxalic acid levels and improve cardiovascular outcomes in HD patients. Ó 2015 Elsevier Ltd. All rights reserved. Introduction Despite improvements in diagnostic tools and medical applica- tions, cardiovascular diseases (CVDs) remain the most common cause of morbidity and mortality in patients with end-stage renal disease (ESRD) receiving hemodialysis (HD) [1]. Traditional and nontraditional novel risk factors including inflammation, endothe- lial dysfunction, vascular calcification and oxidative stress have been identified; however, the CVD mortality rate remains fivefold higher in HD patients than in the general population [2]. In this regard, Evenepoel and colleagues suggested that alternative ure- mic toxins originating from the degradation products of gut micro- biota may be associated with this heightened morbidity and mortality due to CVD in CKD patients [3]. Among these uremic retention molecules (URMs) or toxins, p-cresol sulfate and indoxyl sulfate are the most studied [4,5]. Oxalic acid is another exogenous URM that has been studied extensively in the pathogenesis of cal- cium-oxalate stone formation in patients with idiopathic primary hyperoxaluria [6,7]. Mounting evidence suggests that the colonic microbiota, including Oxalobacter formigenes (O. formigenes), plays important roles in oxalate homeostasis, and colonization with this bacterium has been found to be closely associated with a reduced prevalence of oxalate stones in the general population [8,9]. How- ever, little is known regarding the colonization of HD patients with O. formigenes and the exact role of this bacterial species in oxalic acid metabolism in these patients. Hypothesis We hypothesized that oxalic acid maybe insufficiently degraded due to under colonization of the colon by O. formigenes in CKD patients receiving HD, leading to increased cardiovascular mortal- ity in these patients (Fig. 1). To test this hypothesis, we sought to quantitatively measure fecal O. formigenes levels and serum oxalic acid levels in HD patients. We also suggest that increased oxalic acid levels may be associated with endothelial dysfunction and aortic stiffness, both of which are commonly observed in HD patients. Increased colonization with O. formigenes via the inges- tion of prebiotics and probiotics could potentially decrease serum oxalic acid levels and improve cardiovascular outcomes in HD patients. http://dx.doi.org/10.1016/j.mehy.2015.01.010 0306-9877/Ó 2015 Elsevier Ltd. All rights reserved. ⇑ Corresponding author at: Konya Necmettin Erbakan University, Meram School of Medicine, Department of Internal Medicine, Division of Nephrology, 42080 Konya, Turkey. Mobile: +90 5384927877. E-mail address: ucmdkt@gmail.com (K. Turkmen). Medical Hypotheses 84 (2015) 273–275 Contents lists available at ScienceDirect Medical Hypotheses journal homepage: www.elsevier.com/locate/mehy