P1175INTESTINAL MICROBIOME, METABOLOME AND BACTERIALLY-DERIVED UREMIC TOXINS IN PD-PATIENTS - DISPARITIES IN CHRONIC KIDNEY DISEASE AND ACUTE KIDNEY INJURY

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Abstract Background and Aims Recent evidence suggests a bidirectional relationship between the intestinal microbiome and CKD. CKD and concomitant uremia lead to loss of integrity of the intestinal barrier, causing increased intestinal permeability and potentially contributing to systemic inflammation. Uremia itself has been speculated to cause a selection of certain microorganisms, known as dysbiosis. The alteration of the intestinal microbiome may favor the formation of specific uremic toxins. We hypothesized that the composition of the microbiome is altered between patients with CKD and AKI. The aim was to investigate the effect of CKD (with already established uremic dysbiosis) and AKI (without established uremic dysbiosis) and the exposure to PD-fluids on the intestinal microbiome and on a local (peritoneal) and systemic metabolome level of patients treated with PD. Method Patients on PD therapy with CKD and AKI were included. Stool samples were analyzed by 16S rRNA sequencing, 188 systemic (serum) and local (PD-effluent) metabolites as well as 10 uremic toxins (including p-cresyl sulfate and indoxyl sulfate) were analyzed using a mass spectrometric approach. Clinical standard parameters in serum and PD-effluent were measured by routine laboratory techniques. Results Changes in relative abundances of intestinal bacteria and differences in gut microbiome composition at the phylum level were associated with chronic disease. Patients with CKD and AKI had significantly increased levels of uremic toxins and revealed a distinct metabolomic pattern. Cross-omics correlation between bacterial phyla and metabolites was performed to obtain functional information on differentially abundant species and molecules. Conclusion Patients with CKD on PD are characterized by an altered intestinal microbiome, local and systemic metabolome changes in contrast to patients with AKI. PD-patients with CKD and AKI have increased serum levels of bacterially-derived uremic toxins. Further investigations are required to obtain deeper understanding of reciprocal influences of the uremic status and intestinal microbiome.