Identification of Gut Microbiome Signatures Associated with Indole Pathway in Tryptophan Metabolism in Patients Undergoing Hemodialysis.

Microbiota tryptophan metabolism and the biosynthesis of indole derivatives play an important role in homeostasis and pathogenesis in the human body and can be affected by the gut microbiota. However, studies on the interplay between gut microbiota and tryptophan metabolites in patients undergoing dialysis are lacking. This study aimed to identify the gut microbiota, the indole pathway in tryptophan metabolism, and significant functional differences in ESRD patients with regular hemodialysis. We performed the shotgun metagenome sequencing of stool samples from 85 hemodialysis patients. Using the linear discriminant analysis effect size (LEfSe), we examined the composition of the gut microbiota and metabolic features across varying concentrations of tryptophan and indole metabolites. Higher tryptophan levels promoted tyrosine degradation I and pectin degradation I metabolic modules; lower tryptophan levels were associated with glutamate degradation I, fructose degradation, and valine degradation modules. Higher 3-indoxyl sulfate concentrations were characterized by alanine degradation I, anaerobic fatty acid beta-oxidation, sulfate reduction, and acetyl-CoA to crotonyl-CoA. Contrarily, lower 3-indoxyl sulfate levels were related to propionate production III, arabinoxylan degradation, the Entner-Doudoroff pathway, and glutamate degradation II. The present study provides a better understanding of the interaction between tryptophan, indole metabolites, and the gut microbiota as well as their gut metabolic modules in ESRD patients with regular hemodialysis.

The Intestinal Microbiota Composition in Early and Late Stages of Diabetic Kidney Disease.

Many studies have suggested that gut microbiota dysbiosis may be one of the pathogenesis factors of diabetes mellitus (DM), while it is not clear whether it is involved in the development of diabetic kidney diseases (DKD). The objective of this study was to determine bacterial taxa biomarkers during the progression of DKD by investigating bacterial compositional changes in early and late DKD. 16S rRNA gene sequencing was performed on fecal samples, including the diabetes mellitus (DM), DNa (early DKD), and DNb (late DKD) groups. Taxonomic annotation of microbial composition was performed. Samples were sequenced on the Illumina NovaSeq platform. At the genus level, we found counts of Fusobacterium, Parabacteroides, and Ruminococcus_gnavus were significantly elevated both in the DNa group (P = 0.0001, 0.0007, and 0.0174, respectively) and the DNb group (P < 0.0001, 0.0012, and 0.0003, respectively) compared with those in the DM group. Only the level of Agathobacter was significantly decreased in the DNa group than the DM group and in the DNb group than the DNa group. Counts of Prevotella_9, Roseburia were significantly decreased in the DNa group compared with those in the DM group (P = 0.001 and 0.006, respectively) and in the DNb group compared with those in the DM group (P < 0.0001 and 0.003, respectively). Levels of Agathobacter, Prevotella_9, Lachnospira, and Roseburia were positively correlated with an estimated glomerular filtration rate (eGFR), but negatively correlated with microalbuminuria (MAU), 24 h urinary protein quantity (24hUP), and serum creatinine (Scr). Moreover, the areas under the curve (AUCs) of Agathobacter and Fusobacteria were 83.33% and 80.77%, respectively, for the DM and DNa cohorts, respectively. Notably, the largest AUC for DNa and DNb cohorts was also that of Agathobacter at 83.60%. Gut microbiota dysbiosis was found in the early and late stages of DKD, especially in the early stage. Agathobacter may be the most promising intestinal bacteria biomarker that can help distinguish different stages of DKD. IMPORTANCE It is not clear as to whether gut microbiota dysbiosis is involved in the progression of DKD. This study may be the first to explore gut microbiota compositional changes in diabetes, early-DKD, and late DKD. We identify different gut microbial characteristics during different stages of DKD. Gut microbiota dysbiosis is found in the early and late stages of DKD. Agathobacter may be the most promising intestinal bacteria biomarker that can help distinguish different stages of DKD, although further studies are warranted to illustrate these mechanisms.

Unconjugated p-cresol activates macrophage macropinocytosis leading to increased LDL uptake.

Patients with chronic kidney disease (CKD) and end-stage renal disease suffer from increased cardiovascular events and cardiac mortality. Prior studies have demonstrated that a portion of this enhanced risk can be attributed to the accumulation of microbiota-derived toxic metabolites, with most studies focusing on the sulfonated form of p-cresol (PCS). However, unconjugated p-cresol (uPC) itself was never assessed due to rapid and extensive first-pass metabolism that results in negligible serum concentrations of uPC. These reports thus failed to consider the host exposure to uPC prior to hepatic metabolism. In the current study, not only did we measure the effect of altering the intestinal microbiota on lipid accumulation in coronary arteries, but we also examined macrophage lipid uptake and handling pathways in response to uPC. We found that atherosclerosis-prone mice fed a high-fat diet exhibited significantly higher coronary artery lipid deposits upon receiving fecal material from CKD mice. Furthermore, treatment with uPC increased total cholesterol, triglycerides, and hepatic and aortic fatty deposits in non-CKD mice. Studies employing an in vitro macrophage model demonstrated that uPC exposure increased apoptosis whereas PCS did not. Additionally, uPC exhibited higher potency than PCS to stimulate LDL uptake and only uPC induced endocytosis- and pinocytosis-related genes. Pharmacological inhibition of varying cholesterol influx and efflux systems indicated that uPC increased macrophage LDL uptake by activating macropinocytosis. Overall, these findings indicate that uPC itself had a distinct effect on macrophage biology that might have contributed to increased cardiovascular risk in patients with CKD.

Treatment of Psoas abscess related coxarthrosis due to salmonella infection in a patient with chronic renal failure. A case report.

INTRODUCTION: The most common microorganisms isolated from septic arthritis are staphylococcus aureus and streptoccocci. Septic arthritis due to Salmonella spp. is extremely rare. PRESENTATION OF CASE: A 55-year-old man, chronic renal failure, is admitted hip arthtritis with newly arised symptoms. The findings were not compatible with primary arthritis. The laboratory findings which include white blood cell count, erythrocyte sedimentation rate (esr) and c-reactive protein (crp) were elevated. In magnetic resonance (mr) imaging there were psoas abscess and septic arthritis of the hip. They were treated by drainage. The culture was confirmed as Salmonella spp. Antibiotic treatment were done. DISCUSSION: Uremia in patients with chronic renal failure is associated with a state of immune dysfunction. In our case, uremia may cause immunosuppressive conditions and hematogenous dissemination of salmonella. CONCLUSION: Salmonella infection in a patient with chronic renal failure may be occured. It must be kept in mind that early diagnosis, administration of appropriate systemic antibiotics and surgical intervention play a pivotal role in successful management. KEY WORDS: Arthritis, Failure, Psoas, Salmonella Renal Abscess.

Predictive scoring models for persistent gram-negative bacteremia that reduce the need for follow-up blood cultures: a retrospective observational cohort study.

BACKGROUND: Although the risk factors for positive follow-up blood cultures (FUBCs) in gram-negative bacteremia (GNB) have not been investigated extensively, FUBC has been routinely carried out in many acute care hospitals. We attempted to identify the risk factors and develop a predictive scoring model for positive FUBC in GNB cases. METHODS: All adults with GNB in a tertiary care hospital were retrospectively identified during a 2-year period, and GNB cases were assigned to eradicable and non-eradicable groups based on whether removal of the source of infection was possible. We performed multivariate logistic analyses to identify risk factors for positive FUBC and built predictive scoring models accordingly. RESULTS: Out of 1473 GNB cases, FUBCs were carried out in 1268 cases, and the results were positive in 122 cases. In case of eradicable source of infection, we assigned points according to the coefficients from the multivariate logistic regression analysis: Extended spectrum beta-lactamase-producing microorganism (+ 1 point), catheter-related bloodstream infection (+ 1), unfavorable treatment response (+ 1), quick sequential organ failure assessment score of 2 points or more (+ 1), administration of effective antibiotics (- 1), and adequate source control (- 2). In case of non-eradicable source of infection, the assigned points were end-stage renal disease on hemodialysis (+ 1), unfavorable treatment response (+ 1), and the administration of effective antibiotics (- 2). The areas under the curves were 0.861 (95% confidence interval [95CI] 0.806-0.916) and 0.792 (95CI, 0.724-0.861), respectively. When we applied a cut-off of 0, the specificities and negative predictive values (NPVs) in the eradicable and non-eradicable sources of infection groups were 95.6/92.6% and 95.5/95.0%, respectively. CONCLUSIONS: FUBC is commonly carried out in GNB cases, but the rate of positive results is less than 10%. In our simple predictive scoring model, zero scores-which were easily achieved following the administration of effective antibiotics and/or adequate source control in both groups-had high NPVs. We expect that the model reported herein will reduce the necessity for FUBCs in GNB cases.

Effect of Different Hemodialysis Methods on Microbiota in Uremic Patients.

BACKGROUND: To investigate the effect of hemodialysis on microbiota in uremic patients. OBJECTIVE: To investigate the effect of hemodialysis on microbiota in uremic patients. METHODS: This study included 85 adult patients who have received hemodialysis since August 2014, and the treatment plan has not changed for more than 12 months. These patients were divided into hemodialysis group (group A), hemodialysis+hemodialysis filtration group (group B), and hemodialysis+hemodialysis filtration+blood perfusion group (group C). Twenty-four adult ESRD patients (CK group) were enrolled. Serum biochemical indexes were measured, glomerular filtration rate (EGFR) was estimated, dialysis adequacy (kt/V) was calculated, and fresh feces were collected. At the same time, the feces of 30 health workers were selected as the control. 16S rRNA sequence was used to determine the intestinal flora of all fecal specimens. First of all, we analyzed the difference of the whole flora distribution between dialysis and nondialysis ESRD patients; then, we selected the most representative content of bifidobacteria, Lactobacillus acidophilus, Escherichia coli, and Enterococcus faecalis to analyze the influence of different blood purification methods on the intestinal flora. RESULTS: (1) The level of C-reactive protein (CRP) in dialysis patients was lower than that in nondialysis ESRD patients, and CRP in group C was lower than that in groups A and B. There was no significant difference in kt/V between group A, group B, and group C. There was no significant difference in EGFR between the four groups. (2) The species diversity of ESRD patients without dialysis (CK group) was significantly lower than that of ESRD patients with dialysis; there was no significant difference between group A and group B; the species diversity of group C was significantly higher than that of group A and group B. (3) Compared with the control group, the levels of bifidobacteria and Lactobacillus acidophilus in ESRD patients were significantly lower, while the levels of Escherichia coli and Enterococcus faecalis were significantly higher. (4) The levels of bifidobacteria and Lactobacillus acidophilus in hemodialysis patients were significantly higher than those in nonblood purification treatment group, and the levels of Escherichia coli and Enterococcus faecalis were significantly lower than those in nonblood purification treatment group. (5) The level of Lactobacillus acidophilus in group C was significantly higher than that in groups A and B, and the level of Escherichia coli was significantly lower than that in groups A and B. CONCLUSION: ESRD patients have microbiota disorder. Hemodialysis can improve microbiota disorder in uremic patients. Compared with ordinary hemodialysis, combined hemoperfusion dialysis can further improve microbiota disorder.

Continuous ambulatory peritoneal dialysis peritonitis: Microbiology and outcomes.

Context: Continuous ambulatory peritoneal dialysis (CAPD) is now a preferred mode of the treatment in patients with end-stage renal disease, but peritonitis remains to be a shortcoming of CAPD. High-culture negativity, emerging drug resistance and peritoneal dialysis (PD)-related morbidity and mortality have been a challenge to tackle. Aims: The present study was taken up to compare the the various culture methods and to identify the spectrum of organisms causing CAPD peritonitis and their outcome. Settings and Design: A prospective, observational, cross-sectional study was conducted at a tertiary care teaching hospital in Hyderabad over a period of 1 year. Subjects and Methods: Dialysate fluid from 100 episodes of clinically suspected peritonitis in 75 patients was processed by conventional centrifuging, water lysis, direct inoculation and addition of centrifuged pellet into brain-heart infusion broth and by automated blood culture system. Identification and antibiotic susceptibility of organisms was done, and the outcome of PD-related peritonitis was analysed. Statistical Analysis Used: The categorical data and continuous data were analysed using the Chi-square test and Student's t-test, respectively. P < 0.05 was considered statistically significant. Results: Of the 100 PD fluids, 87 were culture positive. Automated blood culture systems detected 87 episodes, whereas conventional centrifuge method detected only 53 episodes (P = 0.00001). Peritonitis due to Gram-negative organisms (62.3%) was higher than that of Gram-positive peritonitis (31.1%) and fungi (6.4%). Nineteen per cent episodes were constituted by relapse (9), refractory (4), recurrent (4) and repeat (2) peritonitis. Outcomes were analysed as recovery (77%), catheter removal (15%) and death (2.6%). Conclusions: Direct inoculation of peritoneal fluid into automated blood culture bottles increases the positivity rate and also aids in the early detection of CAPD peritonitis, helping reduce morbidity and mortality of PD patients.

Changes in the Intestinal Microbiota in Patients with Stage 5 Chronic Kidney Disease on a Low-Protein Diet and the Effects of Human to Rat Fecal Microbiota Transplantation.

BACKGROUND Dietary protein restriction is recommended for patients with stage 5 chronic kidney disease (CKD), or end-stage renal disease (ESRD). This study aimed to investigate the changes in the intestinal microbiota due to different dietary regimens in patients with stage 5 CKD and the effects of human to rat fecal microbiota transplantation. MATERIAL AND METHODS Second-generation high-throughput sequencing was used to analyze the amplifiers in the 16S rRNA V4 region in the intestinal microbiota of patients with stage 5 CKD and healthy individuals. The intestinal microbiota of patients with stage 5 CKD in the low-protein group and the healthy individual group was transferred by human to rat fecal microbiota transplantation using Sprague-Dawley rats. Data underwent meta-analysis using Meta-Stat. RESULTS Patients with CKD on a very low-protein diet showed an increase in intestinal Escherichia, Shigella, and Klebsiella, a decrease in Blautia, heat map analysis showed that Christensenellaceae R-7 group rs1 were significantly increased, and MetaStat analysis showed that Bacteroides, Prevotella, and Mitsuokella were significantly increased. Following human to rat fecal microbiota transplantation from patients with stage 5 CKD, the profile of the rat intestinal microbiota became similar to the human donors. The weight of the rats fed a very low-protein diet after fecal microbiota transplantation significantly decreased after six weeks compared with normal rats and rats that received normal fecal microbiota transplantation. CONCLUSIONS Patients with stage 5 CKD on a very low-protein diet showed changes in the intestinal microbiota that could be transferred from humans to rats by fecal microbiota transplantation.

[i]Clostridioides difficile[/i] infection in patients with end stage renal disease. Is it preventable?

[i]Clostridioides difficile[/i] infection (CDI) is a leading cause of a healthcare-associated diarrhea worldwide. Recently, an increased number of new cases and growing mortality due to CDI have been observed. Patients suffering from end-stage renal disease (ESRD) are most exposed to CDI. It has been proven that CDI in patients receiving renal replacement therapy (RRT) significantly increases mortality, prolongs hospitalization and increases the cost of treatment. Important risk factors of CDI in ERSD patients include hospitalization or stay in an intensive care unit in the last 90 days, HIV infection, bacteremia, prolonged antibiotic therapy and hypoalbuminemia. Cirrhosis, age over 65 years, hypoalbuminemia, longer hospitalization time and use of antibiotics are significant risk factors of death. Effective methods of preventing CDI include hand hygiene with soap and water, isolation of infected patients in a private room with a dedicated toilet, the use of masks, gloves, disinfection of the environment and systematic education and control of medical personnel, as well as rational antibiotic policy. In addition, it is important to avoid antibiotics with a proven risk of CDI, caution use of proton pump inhibitors (PPI) and H2 receptor antagonists. It is also important in the prevention of CDI in people with ERSD, to apply a fast diagnostic since the onset of the first symptoms. The use of probiotics and bile acids in the primary prevention of CDI requires further research. It seems that knowledge of these factors and methods of prevention will significantly reduce morbidity and mortality due to CDI.

Multilevel analysis of hemodialysis-associated infection among end-stage renal disease patients: results of a retrospective cohort study utilizing the insurance claim data of Fukuoka Prefecture, Japan.

The presence of comorbid conditions along with heterogeneity in terms of healthcare practices and service delivery could have a significant impact on the patient's outcomes. With a strong interest in social epidemiology to examine the impact of health services and variations on health outcomes, the current study was conducted to analyse the incidence of hemodialysis-associated infection (HAI) as well as its associated factors, and to quantify the extent to which the contextual effects of the care facility and regional variations influence the risk of HAI.A total of 6111 patients with end-stage renal disease who received hemodialysis treatment between 1 October 2015 and 31 March 2016 were identified from the insurance claim database as a population-based, close-cohort retrospective study. Patients were followed for one year from April 1, 2016 to March 31, 2017. A total of 200 HAI cases were observed during the follow-up and 12 patients died within 90 days of the onset of HAI. Increased risks for HAI were associated with moderate (HR 1.73, 95% confidence interval [CI] 1.00-2.98) and severe (HR 1.87, 95% CI 1.11-3.14) comorbid conditions as well as malignancy (HR 1.36, 95% CI 1.00-1.85). Increased risk was also seen among patients who received hemodialysis treatment from clinics (HR 2.49, 95% CI 1.1-5.33). However, these statistics were no longer significant when variations at the level of care facilities were statistically controlled. In univariate analyses, no statistically significant association was observed between 90-day mortality and baseline patients, and the characteristics of the care facility.The results of the multivariate, multilevel analyses indicated that HAI variations were only significant at the care facility level (σ 2.07, 95% CI 1.3-3.2) and were largely explained by the heterogeneity between care facilities. The results of this study highlight the need to look beyond the influence of patient-level characteristics when developing policies that aim at improving the quality of hemodialysis healthcare and service delivery in Japan.

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?

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.

Effects of the oral adsorbent AST-120 on fecal p-cresol and indole levels and on the gut microbiota composition.

In chronic kidney disease, elevated levels of circulating uremic toxins are associated with a variety of symptoms and organ dysfunction. Indoxyl sulfate (IS) and p-cresyl sulfate (pCS) are microbiota-derived metabolites and representative uremic toxins. We have previously shown that the oral adsorbent AST-120 profoundly reduced pCS compared to IS in adenine-induced renal failure in mice. However, the mechanisms of the different attenuation effects of AST-120 between IS and pCS are unclear. To clarify the difference of AST-120 on IS and pCS, we investigated the levels of fecal indole and p-cresol, the respective precursors of IS and pCS, and examined the influence on the gut microbiota. Although fecal indole was detected in all groups analyzed, fecal p-cresol was not detected in AST-120 treatment groups. In genus level, a total of 23 organisms were significantly changed by renal failure or AST-120 treatment. Especially, AST-120 reduced the abundance of Erysipelotrichaceae uncultured and Clostridium sensu stricto 1, which have a gene involved in p-cresol production. Our findings suggest that, in addition to the adsorption of the uremic toxin precursors, AST-120 affects the abundance of some gut microbiota in normal and renal failure conditions, thereby explaining the different attenuation effects on IS and pCS.

Inulin-type fructan intervention restricts the increase in gut microbiome-generated indole in patients with peritoneal dialysis: a randomized crossover study.

BACKGROUND: Indoxyl sulfate (IS) and p-cresyl sulfate (pCS), 2 important protein-bound uremic toxins, are independent risk factors for cardiovascular disease in patients with end-stage renal disease. Indole and p-cresol are gut microbiome-generated precursors of IS and pCS. OBJECTIVE: The aim of the present study was to determine whether inulin-type fructans (ITFs) reduce the production of indole and p-cresol by altering their producing bacteria in patients with peritoneal dialysis. METHODS: Patients receiving peritoneal dialysis for >3 mo without diabetes and not using antibiotics were recruited to a randomized, double-blind, placebo-controlled, crossover trial of ITF intervention over 36 wk (12-wk washout). The primary outcomes were gut microbiome, fecal indole and p-cresol, indole-producing bacteria, p-cresol-producing bacteria, and serum IS and pCS. The secondary outcomes were fecal pH, 24-h urine, and dialysis removal of IS and pCS. RESULTS: Of 21 individuals randomly assigned, 15 completed the study. The daily nutrient intakes, including protein, tryptophan, and tyrosine, were isostatic during the prebiotic, washout, and placebo intervention. There were no baseline differences in the outcomes of interest between treatments. For fecal indole, its concentrations did not change significantly in either treatment. However, there was a trend toward the treatment-by-time effect (P = 0.052), with a quantitative reduction in the ITF treatment and an increase in the control. The difference in the changes between the 2 treatments was significant (-10.07 ± 7.48 µg/g vs +13.35 ± 7.66 µg/g; P = 0.040). Similar to Bacteroides thetaiotaomicron, there was a difference over time between the 2 treatments, with a significant treatment and time interaction effect (P = 0.047). There were no treatment, time, or interaction effects for fecal p-cresol, serum IS and pCS, 24-h urine, and dialysis removal of IS and pCS. CONCLUSIONS: Our results suggested that ITFs restricted the increase in gut microbiome-generated indole in patients with peritoneal dialysis. This trial was registered at http://www.chictr.org.cn/showproj.aspx?proj=21228 as ChiCTR-INR-17013739.

High-throughput sequencing analysis of intestinal flora changes in ESRD and CKD patients.

BACKGROUND: Chronic kidney disease (CKD) disease affects gut flora by causing dysbiosis and lead to systemic inflammatory conditions. Here, we provide intestinal flora changes of CKD patients undertook different hemodialysis therapy. METHODS: From 2017 to 2019, a total of 166 patients from Guangzhou Red Cross Hospital were recruited and divided into four groups with 17 cases in healthy control group, 47 cases in CKD non-dialysis group, 49 cases in HD group, and 53 cases in PD group. Intestinal flora genome 16S rDNA sequencing and further bio-informatic analysis were performed. RESULTS: Decreased diversity and altered communities of intestinal flora in PD patients, in which microbial diversity was positive correlated with the albumin level were observed. A total of 20 intestinal flora phyla were detected in 166 fecal samples, divided into 3 dominant intestinal types including Bacteroides-dominant gut type, Firmicutes-dominant type and Proteobacteria-dominant gut type. Further analyses found 198 genera, the abundance of 86 genera were significantly different. Butyrate-producing taxa as Faecalibacterium in genera level and Bifidobacteriaceae and Prevotellaceae in family level were dominant genus in CT, CKD, and HD groups, while urease containing-, indole- and p-cresol-forming taxa as Escherichia in genera and Enterobacteriaceae, Enterococcaceae in family level was dominated genus in PD group. Number of differential expressed genes in KEGG enrichment pathways were significantly different in PD group in carbohydrate metabolism, amino acid metabolism, energy metabolism, translation, and membrane transport. CONCLUSION: Our results suggest peritoneal dialysis therapy could result in reduced diversity and altered microbial communities, with reduced probiotic butyrate-producing taxa and increased urease containing-, indole- and p-cresol-forming taxa. The disordered intestinal flora can seriously affect the nutrition level in CKD patients with PD therapy.

The gut microbiota-inflammation-brain axis in end-stage renal disease: perspectives from default mode network.

The gut-brain axis in end-stage renal disease (ESRD) is attracting more and more attention. However, the mechanism of gut-brain axis based cognitive disorders in ESRD patients remains unclear. The purpose of this study was to investigate the linkages between the gut microbiota, inflammatory cytokines, brain default mode network (DMN) and cognitive function in ESRD patients. Methods: This prospective study enrolled 28 ESRD patients (13 males and 15 females, mean age of 44 ± 14 years) and 19 healthy controls (HCs) (12 males and 7 females, mean age of 44 ± 10 years). All subjects underwent stool microbiota analysis, blood inflammatory cytokines examination, brain MRI scans and cognitive assessments. Resting state functional MRI (rs-fMRI) data were used to construct DMN and graph theory was applied to characterize network topological properties. Two samples t-test was applied for the comparisons between ESRD and HCs. Correlation analysis and mediation analysis were conducted among factors with significant group differences. Results: ESRD patients displayed gut microbiota alterations, increased systemic inflammation and worse cognitive performance compared to HCs (all p < 0.05). Graph analysis revealed disrupted DMN topological organization, aberrant nodal centralities and functional connectivities (FCs) in ESRD patients relative to HCs (all p < 0.05, FDR corrected). Significant correlations were found between gut microbiota, inflammatory cytokines, DMN network measures and cognitive assessments. Mediation analysis found that gut microbiota alteration impaired DMN connectivity by increasing systemic inflammation. Conclusion: The present study first revealed gut microbiota alterations, systemic inflammation, DMN dissociation and cognitive dysfunction in ESRD patients simultaneously and further illuminated their inner relationship.

Chryseobacterium spp-associated bacteraemia in a haemodialysis patient: a diagnostic challenge.

Chryseobacterium species are Gram-negative bacillus widely distributed in nature. It is a rare human pathogen that has been isolated from water systems and humid surfaces of the hospital environment. We report a rare case of Chryseobacterium bacteremia in an end-stage renal disease nursing home resident, that was diagnosed using multiplex PCR and was successfully treated with intravenous piperacillin-tazobactam combination.

Nutritional Adequacy and Latent Tuberculosis Infection in End-Stage Renal Disease Patients.

BACKGROUND: Latent tuberculosis infection (LTBI) is prevalent in end-stage renal disease (ESRD) patients. The risk of tuberculosis activation is also high. The appropriate LTBI screening and treatment is required in this population. Meanwhile, whether hemodialysis adequacy is associated with LTBI in the ESRD population is unclear. In this study, we aimed to investigate the association between hemodialysis adequacy and LTBI in ESRD patients. METHODS: In the present cross-sectional study, we reviewed all outpatient-based ESRD patients in our artificial kidney room. Interferon gamma release assay (IGRA) was used for the diagnosis of LTBI. Clinical variables including nutritional adequacy (i.e., normalized protein catabolic rate, nPCR) and dialysis adequacy (i.e., Kt/V) were compared between IGRA-positive and IGRA-negative patients. RESULTS: A total of 90 patients were enrolled, of which 20 (22.2%) had positive IGRA results using the QuantiFERON-TB method. Old fibrotic changes and nPCR (g/kg/day) were significantly different between IGRA-positive and IGRA-negative patients (both p < 0.005), while serum albumin and Kt/V were comparable (p = 0.429 and p = 0.590, respectively). Normalized PCR remained to be significant in a multivariate logistic regression analysis (adjusted hazard ratio, 0.911 (0.861-0.963); p = 0.001). The cutoff nPCR value less than 0.87 g/kg/day had an adjusted hazard ratio of 7.74 (1.77-33.74) for predicting LTBI. Patients with nPCR value less than 0.87 g/kg/day were older and had lower serum hemoglobin, albumin, calcium concentration, and Kt/V levels than those with nPCR value greater than 0.87 g/kg/day. CONCLUSIONS: Nutritional adequacy, especially when assessing nPCR value, was associated with LTBI, while dialysis adequacy was not associated with LTBI.

APOL1 Kidney Risk Variants Induce Cell Death via Mitochondrial Translocation and Opening of the Mitochondrial Permeability Transition Pore.

BACKGROUND: Genetic Variants in Apolipoprotein L1 (APOL1) are associated with large increases in CKD rates among African Americans. Experiments in cell and mouse models suggest that these risk-related polymorphisms are toxic gain-of-function variants that cause kidney dysfunction, following a recessive mode of inheritance. Recent data in trypanosomes and in human cells indicate that such variants may cause toxicity through their effects on mitochondria. METHODS: To examine the molecular mechanisms underlying APOL1 risk variant-induced mitochondrial dysfunction, we generated tetracycline-inducible HEK293 T-REx cells stably expressing the APOL1 nonrisk G0 variant or APOL1 risk variants. Using these cells, we mapped the molecular pathway from mitochondrial import of APOL1 protein to APOL1-induced cell death with small interfering RNA knockdowns, pharmacologic inhibitors, blue native PAGE, mass spectrometry, and assessment of mitochondrial permeability transition pore function. RESULTS: We found that the APOL1 G0 and risk variant proteins shared the same import pathway into the mitochondrial matrix. Once inside, G0 remained monomeric, whereas risk variant proteins were prone to forming higher-order oligomers. Both nonrisk G0 and risk variant proteins bound components of the mitochondrial permeability transition pore, but only risk variant proteins activated pore opening. Blocking mitochondrial import of APOL1 risk variants largely eliminated oligomer formation and also rescued toxicity. CONCLUSIONS: Our study illuminates important differences in the molecular behavior of APOL1 nonrisk and risk variants, and our observations suggest a mechanism that may explain the very different functional effects of these variants, despite the lack of consistently observed differences in trafficking patterns, intracellular localization, or binding partners. Variant-dependent differences in oligomerization pattern may underlie APOL1's recessive, gain-of-function biology.

End-Stage Renal Disease-Associated Gut Bacterial Translocation: Evolution and Impact on Chronic Inflammation and Acute Rejection After Renal Transplantation.

Chronic inflammation in end-stage renal disease (ESRD) is partly attributed to gut bacterial translocation (GBT) due to loss of intestinal epithelium integrity. Increased levels of circulating lipopolysaccharide (LPS) -a surrogate marker of GBT- contribute to maintain a chronic inflammatory state. However, circulating LPS can be neutralized by lipoproteins and transported to the liver for elimination. While ESRD-associated GBT has been widely described, less is known about its changes and impact on clinical outcome after kidney transplantation (KT). One hundred and forty-six renal transplant recipients with serum samples obtained immediately before and 1 year after transplantation (1-Year post KT) were included. Intestinal epithelium integrity (iFABP), total LPS (by measuring 3-hydroxymyristate), LPS activity (biologically active LPS measured by the LAL assay), inflammatory biomarkers (sCD14 and cytokines), lipoproteins and LPS-binding proteins (LBP and phospholipid transfer protein [PLTP] activity) were simultaneously measured. At 1-Year post KT, iFABP decreased but remained higher than in normal volunteers. Total LPS concentration remained stable while LPS activity decreased. Inflammation biomarkers decreased 1-Year post KT. We concomitantly observed an increase in lipoproteins. Higher sCD14 levels before transplantation was associated with lower incidence of acute rejection. Although GBT remained stable after KT, the contemporary increase in lipoproteins could bind circulating LPS and contribute concomitantly to neutralization of LPS activity, as well as improvement in ESRD-associated chronic inflammation. Chronic exposure to LPS in ESRD could promote endotoxin tolerance and explain why patients with higher pre-transplant sCD14 are less prompt to develop acute rejection after transplantation.

[Acute on chronic renal failure in a 62-year-old man with ANCA-associated vasculitis]. / Neue Nierenfunktionsverschlechterung bei einem 62-jährigen Patienten mit ANCA-assoziierter Vaskulitis.

We describe a patient with ANCA (antineutrophil cytoplasmic antibodies) associated vasculitis and acute-on-chronic renal failure. He had initially presented with severe pulmonary hemorrhage and anuric renal failure and improved rapidly with immunosuppressive therapy. Repeat renal biopsy revealed candida interstitial nephritis. Candida was also detected in bronchoalveolar lavage. Kidney function improved with long-term antifungal therapy. This report adds induction therapy for ANCA vasculitis to the conditions where invasive candidal infections including nephritis need to be considered.