scholarly journals Resistant starch alters gut microbiome and metabolomic profiles concurrent with amelioration of chronic kidney disease in rats

2016 ◽  
Vol 310 (9) ◽  
pp. F857-F871 ◽  
Author(s):  
Dorothy A. Kieffer ◽  
Brian D. Piccolo ◽  
Nosratola D. Vaziri ◽  
Shuman Liu ◽  
Wei L. Lau ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kidney Function ◽  
Resistant Starch ◽  
Blood Levels ◽  
Microbial Composition ◽  
Urine Metabolites ◽  
Fiber Diet ◽  
Gut Microbe ◽  
Serum And Urine

Patients and animals with chronic kidney disease (CKD) exhibit profound alterations in the gut environment including shifts in microbial composition, increased fecal pH, and increased blood levels of gut microbe-derived metabolites (xenometabolites). The fermentable dietary fiber high amylose maize-resistant starch type 2 (HAMRS2) has been shown to alter the gut milieu and in CKD rat models leads to markedly improved kidney function. The aim of the present study was to identify specific cecal bacteria and cecal, blood, and urinary metabolites that associate with changes in kidney function to identify potential mechanisms involved with CKD amelioration in response to dietary resistant starch. Male Sprague-Dawley rats with adenine-induced CKD were fed a semipurified low-fiber diet or a high-fiber diet [59% (wt/wt) HAMRS2] for 3 wk ( n = 9 rats/group). The cecal microbiome was characterized, and cecal contents, serum, and urine metabolites were analyzed. HAMRS2-fed rats displayed decreased cecal pH, decreased microbial diversity, and an increased Bacteroidetes-to-Firmicutes ratio. Several uremic retention solutes were altered in the cecal contents, serum, and urine, many of which had strong correlations with specific gut bacteria abundances, i.e., serum and urine indoxyl sulfate were reduced by 36% and 66%, respectively, in HAMRS2-fed rats and urine p-cresol was reduced by 47% in HAMRS2-fed rats. Outcomes from this study were coincident with improvements in kidney function indexes and amelioration of CKD outcomes previously reported for these rats, suggesting an important role for microbial-derived factors and gut microbe metabolism in regulating host kidney function.

scholarly journals Isolation and Quantification of Uremic Toxin Precursor-Generating Gut Bacteria in Chronic Kidney Disease Patients

2020 ◽  
Vol 21 (6) ◽  
pp. 1986 ◽  
Author(s):  
Tessa Gryp ◽  
Geert R.B. Huys ◽  
Marie Joossens ◽  
Wim Van Biesen ◽  
Griet Glorieux ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kidney Function ◽  
Bacterial Species ◽  
Uremic Toxins ◽  
Bacterial Number ◽  
Uremic Toxin ◽  
Microbial Composition ◽  
Indolic Compounds ◽  
Cardiovascular Morbidity And Mortality

In chronic kidney disease (CKD), impaired kidney function results in accumulation of uremic toxins, which exert deleterious biological effects and contribute to inflammation and cardiovascular morbidity and mortality. Protein-bound uremic toxins (PBUTs), such as p-cresyl sulfate, indoxyl sulfate and indole-3-acetic acid, originate from phenolic and indolic compounds, which are end products of gut bacterial metabolization of aromatic amino acids (AAA). This study investigates gut microbial composition at different CKD stages by isolating, identifying and quantifying PBUT precursor-generating bacteria. Fecal DNA extracts from 14 controls and 138 CKD patients were used to quantify total bacterial number and 11 bacterial taxa with qPCR. Moreover, isolated bacteria from CKD 1 and CKD 5 fecal samples were cultured in broth medium supplemented with AAA under aerobic and anaerobic conditions, and classified as PBUT precursor-generators based on their generation capacity of phenolic and indolic compounds, measured with U(H)PLC. In total, 148 different fecal bacterial species were isolated, of which 92 were PBUT precursor-generators. These bacterial species can be a potential target for reducing PBUT plasma levels in CKD. qPCR indicated lower abundance of short chain fatty acid-generating bacteria, Bifidobacterium spp. and Streptococcus spp., and higher Enterobacteriaceae and E. coli with impaired kidney function, confirming an altered gut microbial composition in CKD.

scholarly journals Comparison of Surface-Enhanced Raman Scattering Properties of Serum and Urine for the Detection of Chronic Kidney Disease in Patients

2020 ◽  
pp. 000370282096632
Author(s):  
Ming Zong ◽  
Lan Zhou ◽  
Qiunong Guan ◽  
Duo Lin ◽  
Jianhua Zhao ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Raman Scattering ◽  
Kidney Function ◽  
Urine Samples ◽  
Surface Enhanced ◽  
Surface Enhanced Raman ◽  
Enhanced Raman Scattering ◽  
Serum And Urine ◽  
Serum And Urine Samples

Chronic kidney disease (CKD) affects more than 10% of the global population and is associated with significant morbidity and mortality. In most cases, this disease is developed silently, and it can progress to the end-stage renal failure. Therefore, early detection becomes critical for initiating effective interventions. Routine diagnosis of CKD requires both blood test and urinalyses in a clinical laboratory, which are time-consuming and have low sensitivity and specificity. Surface-enhanced Raman scattering (SERS) is an emerging method for rapidly assessing kidney function or injury. This study was designed to compare the differences between the SERS properties of the serum and urine for easy and simple detection of CKD. Enrolled for this study were 126 CKD patients (Stages 2–5) and 97 healthy individuals. SERS spectra of both the serum and urine samples were acquired using a Raman spectrometer (785 nm excitation). The correlation of chemical parameters of kidney function with the spectra was examined using prinicpal component analysis (PCA) combined with linear discriminant analysis (LDA) and partial least squares (PLS) analysis. Here, we showed that CKD was discriminated from non-CKD controls using PCA–LDA with a sensitivity of 74.6% and a specificity of 93.8% for the serum spectra, and 78.0% and 86.0 % for the urine spectra. The integration area under the receiver operating characteristic curve was 0.937 ± 0.015 ( p < 0.0001) for the serum and 0.886 ± 0.025 ( p < 0.0001) for the urine. The different stages of CKD were separated with the accuracy of 78.0% and 75.4% by the serum and urine spectra, respectively. PLS prediction (R2) of the serum spectra was 0.8540 for the serum urea ( p < 0.001), 0.8536 for the serum creatinine ( p < 0.001), 0.7500 for the estimated glomerular filtration rate (eGFR) ( p < 0.001), whereas the prediction (R2) of urine spectra was 0.7335 for the urine urea ( p < 0.001), 0.7901 for the urine creatinine ( p < 0.001), 0.4644 for the eGFR ( p < 0.001) and 0.6579 for the urine microalbumin ( p < 0.001). In conclusion, the accuracy of associations between SERS findings of the serum and urine samples with clinical conclusions of CKD diagnosis in this limited number of patients is similar, suggesting that SERS may be used as a rapid and easy-to-use method for early screening of CKD, which however needs further evaluation in a large cohort study.

scholarly journals P0703IDENTIFICATION AND QUANTIFICATION OF UREMIC TOXIN PRECURSORS-GENERATING GUT BACTERIA IN CHRONIC KIDNEY DISEASE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Tessa Gryp ◽  
Mario Vaneechoutte ◽  
Marie Joossens ◽  
Wim Van Biesen ◽  
Griet Glorieux
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kidney Function ◽  
Bacterial Species ◽  
Uremic Toxins ◽  
Anaerobic Conditions ◽  
Microbial Composition ◽  
Fecal Samples ◽  
Indolic Compounds ◽  
Ckd Stage

Abstract Background and Aims In chronic kidney disease (CKD), impaired kidney function results in the accumulation of uremic toxins, which exert deleterious biological effects, contributing to cardiovascular morbidity and mortality. Protein-bound uremic toxins (PBUTs), such as p-cresyl sulfate, indoxyl sulfate and indole-3-acetic acid (IAA), originate from phenolic and indolic compounds, which are end products of the gut bacterial metabolization of aromatic amino acids (AAA). This study investigated the microbial composition in different stages of CKD by isolating, identifying and quantifying PBUT precursor-generating bacteria from fecal samples. Method Using fecal samples from patients in CKD stage 1 (n=6) and stage 5 (n=6), bacteria were cultured in a yeast casitone fatty acid glucose broth medium supplemented with AAA under aerobic (2d at 37°C) and anaerobic conditions (7d at 37°C), and confirmed as PBUT precursor-generating bacteria based on their generation capacity of phenolic and indolic compounds, measured with (U)HPLC. Next, fecal DNA from 14 controls, 111 non-dialyzed and 27 dialyzed CKD patients was used to quantify the total bacterial number but also of 11 of the identified PBUT precursor-generating bacteria with qPCR. Using a Kruskal-Wallis test, bacterial loads were compared between the different CKD stages and control. Correlations between disease stages (control and CKD 1-5) and the abundance of bacterial species were assessed with the Spearman’s rank test. Results In total, 150 different bacterial species were isolated from the CKD fecal samples, of which 101 were identified and 92 classified as PBUT precursor-generating bacteria. In general, p-cresol and phenol were mainly generated under anaerobic conditions, while indole and IAA were generated under both aerobic and anaerobic conditions. Phenolic compounds and IAA were predominantly generated by bacterial species belonging to the Bacteroidaceae, Clostridiaceae, Enterococcaceae and Tannerellaceae, while indolic compounds were mainly generated by Bifidobacteriaceae and Enterobacteriaceae. Quantitative analysis of 11 confirmed PBUT precursor-generating bacteria revealed a higher abundance of Streptococcus spp. and Enterobacteriaceae in fecal samples from HD patients compared to controls and early CKD stages, and for Roseburia spp. compared to CKD 5. Moreover, in HD, the abundance of Clostridioides difficile and Lactobacillus spp. was increased compared to CKD 1-5, and of Escherichia coli compared to control (all p&gt;0.05). The abundance of Bacteroides spp., Faecalibacterium prausnitzii, Akkermansia muciniphila and Bifidobacterium spp. as well as the total number of bacteria was comparable among the different CKD stages and controls. Finally, decrease in kidney function (ranging from control to CKD 5) positively correlated with the abundance of Enterobacteriaceae (rs=0.210), and E. coli (rs=0.286), while an inverse correlation was found with Streptococcus spp. (rs=-0.255), Butyricoccus spp. (rs=-0.326), F. prausnitzii (rs=-0.250), Roseburia spp. (rs=-0.342) and Bifidobacterium spp. (rs=-0.303) (all p&gt;0.05). Conclusion The identified PBUT precursor-generating bacteria are potential targets to reduce the plasma PBUT levels in CKD. In addition, in this CKD cohort, based on qPCR, an altered gut microbial composition with the progression of CKD could be established/confirmed.

scholarly journals Lipocalin 2 stimulates bone fibroblast growth factor 23 production in chronic kidney disease

Bone Research ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Guillaume Courbon ◽  
Connor Francis ◽  
Claire Gerber ◽  
Samantha Neuburg ◽  
Xueyan Wang ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Growth Factor ◽  
Kidney Disease ◽  
Iron Deficiency ◽  
Fibroblast Growth Factor ◽  
Kidney Function ◽  
Fibroblast Growth Factor 23 ◽  
Left Ventricular ◽  
Fibroblast Growth ◽  
Lipocalin 2

AbstractBone-produced fibroblast growth factor 23 (FGF23) increases in response to inflammation and iron deficiency and contributes to cardiovascular mortality in chronic kidney disease (CKD). Neutrophil gelatinase-associated lipocalin (NGAL or lipocalin 2; LCN2 the murine homolog) is a pro-inflammatory and iron-shuttling molecule that is secreted in response to kidney injury and may promote CKD progression. We investigated bone FGF23 regulation by circulating LCN2. At 23 weeks, Col4a3KO mice showed impaired kidney function, increased levels of kidney and serum LCN2, increased bone and serum FGF23, anemia, and left ventricular hypertrophy (LVH). Deletion of Lcn2 in CKD mice did not improve kidney function or anemia but prevented the development of LVH and improved survival in association with marked reductions in serum FGF23. Lcn2 deletion specifically prevented FGF23 elevations in response to inflammation, but not iron deficiency or phosphate, and administration of LCN2 increased serum FGF23 in healthy and CKD mice by stimulating Fgf23 transcription via activation of cAMP-mediated signaling in bone cells. These results show that kidney-produced LCN2 is an important mediator of increased FGF23 production by bone in response to inflammation and in CKD. LCN2 inhibition might represent a potential therapeutic approach to lower FGF23 and improve outcomes in CKD.

scholarly journals Enteropeptidase inhibitor SCO-792 effectively prevents kidney function decline and fibrosis in a rat model of chronic kidney disease

2020 ◽  
Author(s):  
Yuko Katayama ◽  
Jun Sugama ◽  
Tomohisa Suzuki ◽  
Yoshimasa Ishimura ◽  
Akihiro Kobayashi ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kidney Function ◽  
Therapeutic Potential ◽  
Renal Plasma Flow ◽  
Production Capacity ◽  
Therapeutic Effects ◽  
Kidney Fibrosis ◽  
Obesity And Diabetes ◽  
Gfr Decline

Abstract Background Inhibiting enteropeptidase, a gut serine protease regulating protein digestion, suppresses food intake and ameliorates obesity and diabetes in mice. However, the effects of enteropeptidase inhibition on the kidney parameters are largely unknown. Here, we evaluated the chronic effects of an enteropeptidase inhibitor, SCO-792, on kidney function, albuminuria, and kidney pathology in spontaneously hypercholesterolaemic (SHC) rats, a rat chronic kidney disease (CKD) model. Methods SCO-792, an orally available enteropeptidase inhibitor, was administered (0.03% and 0.06% (w/w) in the diet) for five weeks to 20-week-old SHC rats showing albuminuria and progressive decline in glomerular filtration rate (GFR). The effects of SCO-792 and the contribution of amino acids to these effects were evaluated. Results SCO-792 increased the faecal protein content, indicating that SCO-792 inhibited enteropeptidase in SHC rats. Chronic treatment with SCO-792 prevented GFR decline and suppressed albuminuria. Moreover, SCO-792 improved glomerulosclerosis and kidney fibrosis. Pair feeding with SCO-792 (0.06%) was less effective in preventing GFR decline, albuminuria, and renal histological damage than SCO-792 treatment, indicating the enteropeptidase-inhibition-dependent therapeutic effects of SCO-792. SCO-792 did not affect the renal plasma flow, suggesting that its effect on GFR was mediated by an improvement in filtration fraction. Moreover, SCO-792 increased hydrogen sulphide production capacity, which has a role in tissue protection. Finally, methionine and cysteine supplementation to the diet abrogated SCO-792-induced therapeutic effects on albuminuria. Conclusions SCO-792-mediated inhibition of enteropeptidase potently prevented GFR decline, albuminuria, and kidney fibrosis; hence, it may have therapeutic potential against CKD.

scholarly journals Everyday Discrimination and Kidney Function Among Older Adults: Evidence From the Health and Retirement Study

2019 ◽  
Vol 75 (3) ◽  
pp. 517-521
Author(s):  
Ryon J Cobb ◽  
Roland J Thorpe ◽  
Keith C Norris
Keyword(s):  
Older Adults ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kidney Function ◽  
The United States ◽  
Health And Retirement Study ◽  
Disease Epidemiology ◽  
Lower Egfr ◽  
Everyday Discrimination ◽  
Retirement Study

Abstract Background With advancing age, there is an increase in the time of and number of experiences with psychosocial stressors that may lead to the initiation and/or progression of chronic kidney disease (CKD). Our study tests whether one type of experience, everyday discrimination, predicts kidney function among middle and older adults. Methods The data were from 10 973 respondents (ages 52–100) in the 2006/2008 Health and Retirement Study, an ongoing biennial nationally representative survey of older adults in the United States. Estimated glomerular filtration rate (eGFR) derives from the Chronic Kidney Disease Epidemiology Collaboration equation. Our indicator of everyday discrimination is drawn from self-reports from respondents. Ordinary Least Squared regression (OLS) models with robust standard errors are applied to test hypotheses regarding the link between everyday discrimination and kidney function. Results Everyday discrimination was associated with poorer kidney function among respondents in our study. Respondents with higher everyday discrimination scores had lower eGFR after adjusting for demographic characteristics (B = −1.35, p &lt; .05), and while attenuated, remained significant (B = −0.79, p &lt; .05) after further adjustments for clinical, health behavior, and socioeconomic covariates. Conclusions Our study suggests everyday discrimination is independently associated with lower eGFR. These findings highlight the importance of psychosocial factors in predicting insufficiency in kidney function among middle-aged and older adults.

scholarly journals Carotid Intima-Media Thickness and Visit-to-Visit HbA1c Variability Predict Progression of Chronic Kidney Disease in Type 2 Diabetic Patients with Preserved Kidney Function

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Akiko Takenouchi ◽  
Ayaka Tsuboi ◽  
Miki Kurata ◽  
Keisuke Fukuo ◽  
Tsutomu Kazumi
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kidney Function ◽  
Subclinical Atherosclerosis ◽  
Intima Media Thickness ◽  
Glycemic Variability ◽  
Carotid Intima Media Thickness ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients

Background/Aims. Subclinical atherosclerosis and long-term glycemic variability have been reported to predict incident chronic kidney disease (CKD) in the general population. However, these associations have not been investigated in patients with type 2 diabetes with preserved kidney function.Methods. We prospectively followed up 162 patients with type 2 diabetes (mean age, 62.3 years; 53.6% men) and assessed whether carotid intima-media thickness (IMT) measured by B-mode ultrasound and visit-to-visit HbA1c variability are associated with deterioration of CKD (incident CKD defined as estimated GFR [eGFR] < 60 mL/min/1.73 m2and progression of CKD stages) over a median follow-up of 6.0 years. At baseline, 25 patients (15.4%) had CKD. Cox proportional hazards regression models were used for identifying associated factors of CKD deterioration.Results.Estimated GFR decreased from75.8±16.3to67.4±18.2 mL/min/1.73 m2(p<0.01). Of 162 patients, 32 developed CKD and 8 made a progression of CKD stages. Multivariate Cox regression analysis revealed that carotid IMT (HR: 4.0, 95% CI: 1.1–14.226.7, andp=0.03) and coefficient of variation of HbA1c (HR: 1.12, 95%: 1.04–1.21, andp=0.003) were predictors of deterioration of CKD independently of age, mean HbA1c, urinary albumin/creatinine ratio, baseline eGFR, uric acid, and leucocyte count.Conclusions.Subclinical atherosclerosis and long-term glycemic variability predict deterioration of chronic kidney disease (as defined by incident or worsening CKD) in type 2 diabetic patients with preserved kidney function.

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