#2377 Association of uremic toxins with morbidity and mortality in patients on hemodialysis

Abstract Background and Aims Morbidity and mortality are increased in patients on hemodialysis (HD), and the possible impact of protein bound uremic toxins (PBUT) is of great interest. We assessed the association between PBUT serum levels and clinical events including cardiovascular (CVE), severe infections (hospitalization due to infection, respiratory infection) and all-cause mortality. Method In this prospective observational study, PBUT plasma levels hippuric acid (HA), indoxyl sulfate (IxS), p-cresyl sulfate (pCS), p-cresyl glycuronide (pCG), indole-3-acetic acid (IAA), 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF) were quantified by ultra-performance liquid chromatography in 54 patients on HD (Age 51.3±16.91 years) and the association with future clinical events (CVE, hospitalization due to severe infection, respiratory infection and all-cause mortality) during 24 months follow up (FU), was assessed. Results In patients who died during FU (n=6), increased levels of total HA 6.42 (4.54) vs 2.75 (3.03)mg/dl (p=0.007), free HA 4.79 (3.93) vs 1.363 (1.85)mg/dl (p=0.004); free IxS 0.29 (0.29) vs 0.13 (0.17)mg/dl (p=0.045); total pCG 0.36 (0.5) vs 0.19 (0.28)mg/dl (p=0.045), free pCG 0.33 (0.43) vs 0.18 (0.26)mg/dl (p=0.042) were found. Moreover, in patients who experienced a CVE (n=11), a higher concentration of CMPF 0.39 (0.67) vs 0.15 (0.19)mg/dl (p=0.015) was observed. No significant correlations were found between pCS and IAA levels with morbidity and mortality in this study. A logistic regression model, describing the effect of each PBUT on death probability could explain 44% (Nagelkerke R2) of the variance in death and correctly classified 90.7% of cases. Patients with increased levels of free IxS, total and free HA were more likely to die within a 2-year FU period (p=0.047, p=0.013, p=0.003, respectively). PBUT levels were not different among HD patients with and without severe infections. Conclusion Increased levels of PBUT (HA and free IxS) in patients on HD, associate with increased risk of death and CMPF with cardiovascular events.