MO137DIFFERENCES IN GUT MICROBIOTA PROFILES AND FUNCTIONS BETWEEN END-STAGE KIDNEY DISEASE AND HEALTHY POPULATIONS

Abstract Background and Aims Patients with end-stage kidney disease (ESKD) are characterized by altered gut microbiota, impaired intestinal barrier function, and experienced gut microbiota-derived metabolites related to systemic complications. However, limited studies evaluated the microbial diversity and function in ESKD patients previously. Method Compared to age- and gender-matched subjects without kidney disease, 82 ESKD patients in the discovery cohort and 58 ESKD patients in the validation cohort were investigated for the microbial richness, biodiversity, gut dysbiosis, microbial composition differences, and the functional changes by gut metabolic module analysis. Bacterial derived free form protein-bound uremic toxins were analyzed by mass spectrometry and their association with microbial richness in ESKD patients was determined. Results Compared to controls, an increased α-diversity and distinct β-diversity were found in ESKD (Figure). The increase in α-diversity was correlated with protein-bound uremic toxins, particularly hippuric acid. A higher microbial dysbiosis index (MDI) was found in ESKD patients with the following enriched genera: Facealibacterium, Ruminococcus, Fusobacterium, Dorea, Anaerovorax, Sarcina, Akkermansia, Streptococcus, and Dysgonomonas. MDI at the genus level successfully differentiated between ESKD and controls in the discovery cohort (area under the curve [AUC] of 81.9%) and the validation cohort (AUC of 83.2%). Regarding functional enrichment analysis with gut metabolic modules, ESKD subjects presented with gut microbial function of increased saccharide and amino acid metabolism compared with matched controls. Conclusion An enriched but dysbiotic gut microbiota was presented in ESKD patients, in which the bacteria that were present increase amino acid metabolism linked to the production of protein-bound uremic toxins.

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Differences in Gut Microbiota Profiles and Functions Between End-stage Renal Disease and Healthy Populations

10.21203/rs.3.rs-82652/v1 ◽

2020 ◽

Author(s):

Ping-Hsun Wu ◽

Ting-Yun Lin ◽

Hsiu J. Ho ◽

Ching-Hung Tseng ◽

Yi-Ting Lin ◽

...

Keyword(s):

Amino Acid ◽

Gut Microbiota ◽

End Stage Renal Disease ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Α Diversity ◽

Stage Renal Disease ◽

End Stage ◽

And Control ◽

Esrd Patients

Abstract Background: Patients with end-stage renal disease (ESRD) have extremely high risks of mortality and morbidity, as well as altered gut microbiota and impaired intestinal barrier function. The translocation of gut-derived molecules in ESRD contributes to systemic complications. In this study, we evaluated the gut microbiome difference in ESRD patients compared to age- and gender-matched subjects without kidney disease in discovery and validation cohorts.Results: Compared to controls with normal renal function, an increased α-diversity and distinct β-diversity were found in ESRD subjects. The increase in α-diversity was correlated with protein-bound uremic toxins, particularly hippuric acid. A higher microbial dysbiosis index (MDI) was found in ESRD patients with the following enriched genera: Facealibacterium, Ruminococcus, Fusobacterium, Dorea, Anaerovorax, Sarcina, Akkemansia, Streptococcus, and Dysgonomonas. MDI at the genus level demonstrated highly differentiated accuracies between ESRD and control subjects in the discovery cohort (area under the curve [AUC] of 81.9%) and between ESRD and control subjects in the validation cohort (AUC of 83.2%). On functional enrichment analysis with gut metabolic modules, ESRD subjects presented with increased saccharide and amino acid metabolism when compared with matched controls.Conclusions: An enriched but dysbiotic gut microbiota was presented in ESRD patients, in which the bacteria that were present increase amino acid metabolism linked to the production of protein-bound uremic toxins.

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Contribution of Gut Microbiota-Derived Uremic Toxins to the Cardiovascular System Mineralization

Toxins ◽

10.3390/toxins13040274 ◽

2021 ◽

Vol 13 (4) ◽

pp. 274

Author(s):

Iwona Filipska ◽

Agata Winiarska ◽

Monika Knysak ◽

Tomasz Stompór

Keyword(s):

Kidney Disease ◽

Gut Microbiota ◽

Mineral Content ◽

Uremic Toxins ◽

World Population ◽

Uremic Toxin ◽

Excess Morbidity ◽

The Media ◽

Cardio Vascular ◽

End Stage

Chronic kidney disease (CKD) affects more than 10% of the world population and leads to excess morbidity and mortality (with cardiovascular disease as a leading cause of death). Vascular calcification (VC) is a phenomenon of disseminated deposition of mineral content within the media layer of arteries preceded by phenotypic changes in vascular smooth muscle cells (VSMC) and/or accumulation of mineral content within the atherosclerotic lesions. Medial VC results in vascular stiffness and significantly contributes to increased cardio-vascular (CV) morbidity, whereas VC of plaques may rather increase their stability. Mineral and bone disorders of CKD (CKD-MBD) contribute to VC, which is further aggravated by accumulation of uremic toxins. Both CKD-MBD and uremic toxin accumulation affect not only patients with advanced CKD (glomerular filtration rate (GFR) less than 15 mL/min./1.72 m2, end-stage kidney disease) but also those on earlier stages of a disease. The key uremic toxins that contribute to VC, i.e., p-cresyl sulphate (PCS), indoxyl sulphate (IS) and trimethylamine-N-oxide (TMAO) originate from bacterial metabolism of gut microbiota. All mentioned toxins promote VC by several mechanisms, including: Transdifferentiation and apoptosis of VSMC, dysfunction of endothelial cells, oxidative stress, interaction with local renin–angiotensin–aldosterone system or miRNA profile modification. Several attractive methods of gut microbiota manipulations have been proposed in order to modify their metabolism and to limit vascular damage (and VC) triggered by uremic toxins. Unfortunately, to date no such method was demonstrated to be effective at the level of “hard” patient-oriented or even clinically relevant surrogate endpoints.

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Protection of Residual Renal Function and Nutritional Treatment: First Step Strategy for Reduction of Uremic Toxins in End-Stage Kidney Disease Patients

Toxins ◽

10.3390/toxins13040289 ◽

2021 ◽

Vol 13 (4) ◽

pp. 289

Author(s):

Adamasco Cupisti ◽

Piergiorgio Bolasco ◽

Claudia D’Alessandro ◽

Domenico Giannese ◽

Alice Sabatino ◽

...

Keyword(s):

Kidney Disease ◽

Residual Renal Function ◽

The Body ◽

Uremic Toxins ◽

End Stage Kidney Disease ◽

Waste Products ◽

Hemodialysis Treatment ◽

Life Saving ◽

Kidney Replacement Therapy ◽

End Stage

The retention of uremic toxins and their pathological effects occurs in the advanced phases of chronic kidney disease (CKD), mainly in stage 5, when the implementation of conventional thrice-weekly hemodialysis is the prevalent and life-saving treatment. However, the start of hemodialysis is associated with both an acceleration of the loss of residual kidney function (RKF) and the shift to an increased intake of proteins, which are precursors of uremic toxins. In this phase, hemodialysis treatment is the only way to remove toxins from the body, but it can be largely inefficient in the case of high molecular weight and/or protein-bound molecules. Instead, even very low levels of RKF are crucial for uremic toxins excretion, which in most cases are protein-derived waste products generated by the intestinal microbiota. Protection of RKF can be obtained even in patients with end-stage kidney disease (ESKD) by a gradual and soft shift to kidney replacement therapy (KRT), for example by combining a once-a-week hemodialysis program with a low or very low-protein diet on the extra-dialysis days. This approach could represent a tailored strategy aimed at limiting the retention of both inorganic and organic toxins. In this paper, we discuss the combination of upstream (i.e., reduced production) and downstream (i.e., increased removal) strategies to reduce the concentration of uremic toxins in patients with ESKD during the transition phase from pure conservative management to full hemodialysis treatment.

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Alteration of the gut microbiota by vinegar is associated with amelioration of hyperoxaluria-induced kidney injury

Food & Function ◽

10.1039/c9fo02172h ◽

2020 ◽

Vol 11 (3) ◽

pp. 2639-2653

Author(s):

Wei Zhu ◽

Yang Liu ◽

Xiaolu Duan ◽

Chenglin Xiao ◽

Yu Lan ◽

...

Keyword(s):

Kidney Disease ◽

Gut Microbiota ◽

Renal Injury ◽

Kidney Injury ◽

End Stage Kidney Disease ◽

End Stage

Hyperoxaluria is well known to cause renal injury and end-stage kidney disease.

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Sevelamer Use in End-Stage Kidney Disease (ESKD) Patients Associates with Poor Vitamin K Status and High Levels of Gut-Derived Uremic Toxins: A Drug–Bug Interaction?

Toxins ◽

10.3390/toxins12060351 ◽

2020 ◽

Vol 12 (6) ◽

pp. 351

Author(s):

Lu Dai ◽

Björn K. Meijers ◽

Bert Bammens ◽

Henriette de Loor ◽

Leon J. Schurgers ◽

...

Keyword(s):

Kidney Disease ◽

Vitamin K ◽

Phosphate Binder ◽

Microbial Metabolism ◽

Uremic Toxins ◽

Matrix Gla Protein ◽

Vitamin K Deficiency ◽

End Stage Kidney Disease ◽

K Deficiency ◽

End Stage

Gut microbial metabolism is not only an important source of uremic toxins but may also help to maintain the vitamin K stores of the host. We hypothesized that sevelamer therapy, a commonly used phosphate binder in patients with end-stage kidney disease (ESKD), associates with a disturbed gut microbial metabolism. Important representatives of gut-derived uremic toxins, including indoxyl sulfate (IndS), p-Cresyl sulfate (pCS), trimethylamine N-oxide (TMAO), phenylacetylglutamine (PAG) and non-phosphorylated, uncarboxylated matrix-Gla protein (dp-ucMGP; a marker of vitamin K status), were analyzed in blood samples from 423 patients (65% males, median age 54 years) with ESKD. Demographics and laboratory data were extracted from electronic files. Sevelamer users (n = 172, 41%) were characterized by higher phosphate, IndS, TMAO, PAG and dp-ucMGP levels compared to non-users. Sevelamer was significantly associated with increased IndS, PAG and dp-ucMGP levels, independent of age, sex, calcium-containing phosphate binder, cohort, phosphate, creatinine and dialysis vintage. High dp-ucMGP levels, reflecting vitamin K deficiency, were independently and positively associated with PAG and TMAO levels. Sevelamer therapy associates with an unfavorable gut microbial metabolism pattern. Although the observational design precludes causal inference, present findings implicate a disturbed microbial metabolism and vitamin K deficiency as potential trade-offs of sevelamer therapy.

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Effect of Oral Administration of Freeze-Dried Lactobacillus acidophilus on Small Bowel Bacterial Overgrowth in Patients with End Stage Kidney Disease: Reducing Uremic Toxins and Improving Nutrition

International Dairy Journal ◽

10.1016/s0958-6946(98)00081-8 ◽

1998 ◽

Vol 8 (5-6) ◽

pp. 545-553 ◽

Cited By ~ 32

Author(s):

Stephen R. Dunn ◽

Michael L. Simenhoff ◽

Kamal E. Ahmed ◽

William J. Gaughan ◽

Babikar O. Eltayeb ◽

...

Keyword(s):

Small Bowel ◽

Kidney Disease ◽

Oral Administration ◽

Lactobacillus Acidophilus ◽

Bacterial Overgrowth ◽

Uremic Toxins ◽

End Stage Kidney Disease ◽

Small Bowel Bacterial Overgrowth ◽

Freeze Dried ◽

End Stage

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Role of GDF-15, YKL-40 and MMP 9 in patients with end-stage kidney disease: focus on sex-specific associations with vascular outcomes and all-cause mortality

Biology of Sex Differences ◽

10.1186/s13293-021-00393-0 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Agne Laucyte-Cibulskiene ◽

Liam J. Ward ◽

Thomas Ebert ◽

Giulia Tosti ◽

Claudia Tucci ◽

...

Keyword(s):

Oxidative Stress ◽

Kidney Disease ◽

Gut Microbiota ◽

Vascular Calcification ◽

Cardiovascular Complications ◽

Enzyme Linked Immunosorbent Assay ◽

End Stage Kidney Disease ◽

All Cause Mortality ◽

Novel Biomarkers ◽

End Stage

Abstract Background Sex differences are underappreciated in the current understanding of cardiovascular disease (CVD) in association with chronic kidney disease (CKD). A hallmark of CKD is vascular aging that is characterised, amongst others, by; systemic inflammation, microbiota disbalance, oxidative stress, and vascular calcification—features linked to atherosclerosis/arteriosclerosis development. Thus, it is the necessary to introduce novel biomarkers related to athero-/arteriosclerotic damage for better assessment of vascular ageing in patients CKD. However, little is known about the relationship between uraemia and novel CVD biomarkers, such as growth differentiation factor-15 (GDF-15), cartilage glycoprotein-39 (YKL-40) and matrix metalloproteinase-9 (MMP-9). Therefore, we hypothesise that there are sex-specific relationships between GDF-15, YKL-40, MMP-9 levels in end-stage kidney disease (ESKD) patients in relation to gut microbiota, vascular calcification, inflammation, comorbidities, and all-cause mortality. Methods ESKD patients, males (n = 151) and females (n = 79), not receiving renal replacement therapy were selected from two ongoing prospective ESKD cohorts. GDF-15, YKL-40 and MMP9 were analysed using enzyme-linked immunosorbent assay kits. Biomarker levels were analysed in the context of gut microbiota-derived trimethylamine N-oxide (TMAO), vascular calcification, inflammatory response, oxidative stress, comorbidities, and all-cause mortality. Results Increased GDF-15 correlated with higher TMAO in females only, and with higher coronary artery calcification and IL-6. In females, diabetes was associated with elevated GDF-15 and MMP-9, whilst males with diabetes only had elevated GDF-15. No associations were found between biomarkers and CVD comorbidity. Deceased males and females had higher GDF-15 concentrations (p = 0.01 and p < 0.001, respectively), meanwhile only YKL-40 was increased in deceased males (p = 0.02). Conclusions In conclusion, in males GDF-15 and YKL-40 were related to vascular calcification, inflammation, and oxidative stress, whilst in females GDF-15 was related to TMAO. Increased levels of YKL-40 and GDF-15 in males, and only GDF-15 in females, were associated with all-cause mortality. Our findings suggest that sex-specific associations of novel CVD biomarkers have a potential to affect development of cardiovascular complications in patients with ESKD.

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