Metagenomic profiling of gut microbiome in early chronic kidney disease

2020 ◽  
Author(s):  
Noriaki Sato ◽  
Masanori Kakuta ◽  
Takanori Hasegawa ◽  
Rui Yamaguchi ◽  
Eiichiro Uchino ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Gut Microbiome ◽  
Short Chain Fatty Acids ◽  
Toxin Production ◽  
Metagenomic Sequencing ◽  
Stool Samples ◽  
The Mean ◽  
Estimated Glomerular Filtration Rates ◽  
The Relationship

Abstract Background The relationship between chronic kidney disease (CKD) and the gut microbiome, which interact through chronic inflammation, uraemic toxin production and immune response regulation, has gained interest in the development of CKD therapies. However, reports using shotgun metagenomic analysis of the gut microbiome are scarce, especially for early CKD. Here we characterized gut microbiome differences between non-CKD participants and ones with early CKD using metagenomic sequencing. Methods In total, 74 non-CKD participants and 37 participants with early CKD were included based on propensity score matching, controlling for various factors including dietary intake. Stool samples were collected from participants and subjected to shotgun sequencing. Bacterial and pathway abundances were profiled at the species level with MetaPhlAn2 and HUMAnN2, respectively, and overall microbiome differences were determined using Bray–Curtis dissimilarities. Diabetic and non-diabetic populations were analysed separately. Results For diabetic and non-diabetic participants, the mean estimated glomerular filtration rates of the CKD group were 53.71 [standard deviation (SD) 3.87] and 53.72 (SD 4.44), whereas those of the non-CKD group were 72.63 (SD 7.72) and 76.10 (SD 9.84), respectively. Alpha and beta diversities were not significantly different between groups. Based on taxonomic analysis, butyrate-producing species Roseburia inulinivorans, Ruminococcus torques and Ruminococcus lactaris were more abundant in the non-CKD group, whereas Bacteroides caccae and Bacteroides coprocora were more abundant in the non-diabetic CKD group. Conclusions Although gut microbiome changes in individuals with early CKD were subtle, the results suggest that changes related to producing short-chain fatty acids can already be observed in early CKD.

scholarly journals Bacterial metabolites and cardiovascular risk in children with chronic kidney disease

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Julia Schlender ◽  
Felix Behrens ◽  
Victoria McParland ◽  
Dominik Müller ◽  
Nicola Wilck ◽  
...  
Keyword(s):  
Risk Factors ◽  
Chronic Kidney Disease ◽  
Cardiovascular Risk ◽  
Kidney Disease ◽  
Gut Microbiome ◽  
Short Chain Fatty Acids ◽  
Underlying Disease ◽  
Human Gut ◽  
Endogenous Factors ◽  
Human Gut Microbiome

AbstractCardiovascular complications are the major cause of the marked morbidity and mortality associated with chronic kidney disease (CKD). The classical cardiovascular risk factors such as diabetes and hypertension undoubtedly play a role in the development of cardiovascular disease (CVD) in adult CKD patients; however, CVD is just as prominent in children with CKD who do not have these risk factors. Hence, the CKD-specific pathophysiology of CVD remains incompletely understood. In light of this, studying children with CKD presents a unique opportunity to analyze CKD-associated mechanisms of CVD more specifically and could help to unveil novel therapeutic targets.Here, we comprehensively review the interaction of the human gut microbiome and the microbial metabolism of nutrients with host immunity and cardiovascular end-organ damage. The human gut microbiome is evolutionary conditioned and modified throughout life by endogenous factors as well as environmental factors. Chronic diseases, such as CKD, cause significant disruption to the composition and function of the gut microbiome and lead to disease-associated dysbiosis. This dysbiosis and the accompanying loss of biochemical homeostasis in the epithelial cells of the colon can be the result of poor diet (e.g., low-fiber intake), medications, and underlying disease. As a result of dysbiosis, bacteria promoting proteolytic fermentation increase and those for saccharolytic fermentation decrease and the integrity of the gut barrier is perturbed (leaky gut). These changes disrupt local metabolite homeostasis in the gut and decrease productions of the beneficial short-chain fatty acids (SCFAs). Moreover, the enhanced proteolytic fermentation generates unhealthy levels of microbially derived toxic metabolites, which further accumulate in the systemic circulation as a consequence of impaired kidney function. We describe possible mechanisms involved in the increased systemic inflammation in CKD that is associated with the combined effect of SCFA deficiency and accumulation of uremic toxins. In the future, a more comprehensive and mechanistic understanding of the gut–kidney–heart interaction, mediated largely by immune dysregulation and inflammation, might allow us to target the gut microbiome more specifically in order to attenuate CKD-associated comorbidities.

P0930SERUM LEVELS OF OSTEOPROTEGERIN ARE ASSOCIATED WITH OBESITY IN CHRONIC KIDNEY DISEASE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Yooju Nam ◽  
Seonyeong Lee ◽  
Hyung Woo Kim ◽  
Jae Hyun Chang ◽  
Tae-Hyun Yoo
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Large Scale ◽  
Multivariate Logistic Regression Model ◽  
Cox Models ◽  
Prevalence Of Obesity ◽  
The Mean ◽  
Artery Disease ◽  
The Relationship

Abstract Background and Aims Osteoprotegerin (OPG), which is an osteoclastic inhibitory factor, is associated with type 2 diabetes mellitus, severity of vascular calcification, coronary artery disease, and chronic kidney disease. Obesity is a risk factor for diabetes, and cardiovascular disease, however there are few studies about the relationship between OPG and obesity, especially in patients with CKD. This study aimed to investigate association between OPG level and obesity in a large-scale prospective cohort. Method Among 2,238 patients with non-dialysis CKD enrolled in the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD), 1,970 patients who measured body mass index (BMI), waist circumference (WC) and OPG level were included in the analysis. Obesity were defined as having a BMI >25 kg/m2 and WC > 90 cm in male, > 85 cm in female. Results The mean age was 53.6 ± 12.2 years and 1,196 (60.7%) patients were males. At baseline, obesity by BMI, WC, and composite of BMI and WC were found in 814 (41.3%), 208 (26.9%) and 1,137 (57.7%) patients. A multivariate logistic regression model showed that log transformed OPG level was independently associated with the prevalence of obesity by BMI, WC, composite of BMI and WC (odds ratio [OR], 0.33; 95% confidence interval [CI], 0.16-0.65, P<0.001 and OR, 0.37; 95% CI, 0.18-0.75, P=0.006, and OR, 0.33, 95% CI, 0.16-0.69, P=0.003, respectively). Among patients without baseline obesity, 207 (19.3%) patients developed obesity by BMI, 202 (21.7%) by WC, and 194 (23.3%) by composite of BMI and WC. In the fully adjusted multivariable Cox models, risks of developing obesity by BMI, WC and composite of BMI and WC were significantly higher with increased level of OPG (hazard ratio [HR], 0.59; 95% CI, 0.38-0.92; P=0.019, HR, 0.63; 95% CI, 0.41-0.98; P=0.001). Conclusion We showed that serum OPG levels are associated with obesity in patients with non-dialysis CKD.

scholarly journals Can body shape index indicate obesity-associated inflammation and cardiovascular diseases in stage 3-4 chronic kidney disease patients?

2021 ◽  
pp. 60-66
Author(s):  
Gulsah Sasak ◽  
Banu Isbilen Basok ◽  
Semih Basci ◽  
Abdulkadir Kocanoglu ◽  
Ali Bakan ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Cardiovascular Diseases ◽  
Kidney Disease ◽  
Body Shape ◽  
Shape Index ◽  
Group I ◽  
The Mean ◽  
Group Ii ◽  
The Relationship

The incidence and prevalence of obesity are increasing rapidly throughout the world. Various methods have been developed to evaluate obesity. A body shape index (aBSI) is based on waist circumference adjusted for height and weight. High BSI values have been found to be associated with early mortality. It is known that obesity is associated with inflammation and cardiovascular diseases. In this study, we examined the relationship between aBSI, inflammatory markers such as C-reactive protein and interleukin-6 and cardiovascular disease in patients with stage 3-4 chronic kidney disease. Methods. One hundred twenty patients were enrolled in this cross-sectional observational study. The mean aBSI value was 0.0870. Patients were divided into 2 groups according to the mean value of aBSI as there is no currently defined cut-off value for BSI. Those with aBSI ≤ 0.087 were allocated to group I, and those with aBSI> 0.0870 to group II. Results. Patients in group II had more cardiovascular disease than in group I. In partial Spearman correlation analysis, the presence of cardiovascular disease was correlated with aBSI (r = 0.36, p = 0.0001). aBSI higher than 0.0986 predicted cardiovascular disease in our cohort: the area under the curve (CI 95%) for aBSI was 0.715 (0.602-0.829). Conclusions. The relationship between aBSI and inflammation could not be shown. But we found that high aBSI is associated with increased cardiovascular disease. Further studies are needed to recommend the routine clinical use of aBSI as a cardiovascular disease marker.

scholarly journals The Effects of Gum Acacia on the Composition of the Gut Microbiome and Plasma Levels of Short-Chain Fatty Acids in a Rat Model of Chronic Kidney Disease

2020 ◽  
Vol 11 ◽  
Author(s):  
Maha Al-Asmakh ◽  
Muhammad Umar Sohail ◽  
Ola Al-Jamal ◽  
Banan Mosaad Shoair ◽  
Asmaa Yousef Al-Baniali ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Fatty Acids ◽  
Renal Function ◽  
Kidney Disease ◽  
Gut Microbiome ◽  
Plasma Levels ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Biochemical Indicators ◽  
Chain Fatty Acids

Chronic kidney disease (CKD) may be fatal for its victims and is an important long-term public health problem. The complicated medical procedures and diet restrictions to which patients with CKD are subjected alter the gut microbiome in an adverse manner, favoring over-accumulation of proteolytic bacteria that produce ammonia and other toxic substances. The present study aimed to investigate the effect of GA on 1) the composition of the gut microbiome and 2) on plasma levels of short-chain fatty acids. Male Wister rats were divided into four groups (six each) and treated for 4 weeks based on the following: control, dietary adenine (0.75%, w/w) to induce CKD, GA in the drinking water (15%, w/v), and both adenine and GA. At the end of the treatment period, plasma, urine, and fecal samples were collected for determination of several biochemical indicators of renal function and plasma levels of short-chain fatty acids (SCFAs) as well as characterization of the gut microbiome. Dietary adenine induced the typical signs of CKD, i.e., loss of body weight and impairment of renal function, while GA alleviated these effects. The intestine of the rats with CKD contained an elevated abundance of pathogenic Proteobacteria, Actinobacteria, and Verrucomicrobia but lowered proportions of Lactobacillaceae belonging to the Firmicutes phylum. Plasma levels of propionate and butyrate were lowered by dietary adenine and restored by GA. A negative association (Spearman’s p-value ≤ 0.01, r ≤ 0.5) was observed between Firmicutes and plasma creatinine, urea, urine N-acetyl-beta-D-glucosaminidase (NAG) and albumin. Phylum Proteobacteria on the other hand was positively associated with these markers while Phylum Bacteroidetes was positively associated with plasma SCFAs. In conclusion, the adverse changes in the composition of the gut microbiome, plasma levels of SCFAs, and biochemical indicators of renal function observed in the rats with CKD induced by dietary adenine were mitigated by GA. These findings are indicative of a link between uremia and the composition of the microbiome in connection with this disease. Dietary administration of GA to patients with CKD may improve their renal function via modulating the composition of their microbiome—a finding that certainly warrants further investigation.

scholarly journals Altered microbiome in chronic kidney disease: systemic effects of gut-derived uremic toxins

2018 ◽  
Vol 132 (5) ◽  
pp. 509-522 ◽  
Author(s):  
Wei Ling Lau ◽  
Javad Savoj ◽  
Michael B. Nakata ◽  
Nosratola D. Vaziri
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Gut Microbiome ◽  
Short Chain Fatty Acids ◽  
Intestinal Wall ◽  
Uremic Toxins ◽  
Blood Levels ◽  
Systemic Effects ◽  
Kidney Fibrosis ◽  
Microbial Dysbiosis

In chronic kidney disease (CKD), influx of urea and other retained toxins exerts a change in the gut microbiome. There is decreased number of beneficial bacteria that produce short-chain fatty acids, an essential nutrient for the colonic epithelium, concurrent with an increase in bacteria that produce uremic toxins such as indoxyl sulphate, p-cresyl sulphate, and trimethylamine-N-oxide (TMAO). Due to intestinal wall inflammation and degradation of intercellular tight junctions, gut-derived uremic toxins translocate into the bloodstream and exert systemic effects. In this review, we discuss the evidence supporting a role for gut-derived uremic toxins in promoting multiorgan dysfunction via inflammatory, oxidative stress, and apoptosis pathways. End-organ effects include vascular calcification, kidney fibrosis, anemia, impaired immune system, adipocyte dysfunction with insulin resistance, and low turnover bone disease. Higher blood levels of gut-derived uremic toxins are associated with increased cardiovascular events and mortality in the CKD population. Clinical trials that have examined interventions to trap toxic products or reverse gut microbial dysbiosis via oral activated charcoal AST-120, prebiotics and probiotics have not shown impact on cardiovascular or survival outcomes but were limited by sample size and short trials. In summary, the gut microbiome is a major contributor to adverse cardiovascular outcomes and progression of CKD.

Correlation of Serum Sclerostin Levels with Carotid Intima Media Thickness in Chronic Kidney Disease Hemodialysis

2020 ◽  
Vol 6 (1) ◽  
pp. 18-26
Author(s):  
Adhi Permana ◽  
Ian Effendi ◽  
Taufik Indrajaya
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Vascular Calcification ◽  
Ultrasound Examination ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Media Thickness ◽  
The Mean ◽  
Sclerostin Level ◽  
Hemodialysis Duration

Chronic kidney disease is associated with a high mortality rate, especially cardiovascular disease associated with mineral and bone disorders. Sclerostin is an inhibitor of Wnt signaling which has the effect of increasing the occurrence of vascular calcification in patients with chronic kidney disease. There are several studies that show different results. Carotid intima media thickness ultrasound examination is a tool to identify atherosclerosis which is part of vascular calcification. The aim of this study is to look at the correlation of sclerostin with carotid intima media thickness (CIMT) in patients with chronic kidney disease undergoing hemodialysis. In this cross section, the concentration of sclerostin was measured by examination of enzymed linked immunosorbent assay. CIMT measurement by ultrasound mode B examination. There were 40 patients in this study. The mean sclerostin level was 256.68 ± 127.76 pg / ml. Sclerostin levels are declared high if above 162 pg / ml there are 30 people. CIMT thickening was present in 11 patients. There was no significant correlation of serum sclerostin with CIMT in patients with chronic kidney disease undergoing hemodialysis (r-0.32 p0,847). In multivariate linear regression, hemodialysis duration is an independent factor that is significantly significant with CIMT. There was no significant correlation of serum sclerostin with CIMT in patients with chronic kidney disease undergoing hemodialysis.

scholarly journals Association between albuminuria and thyroid function in patients with chronic kidney disease

Endocrine ◽  
2021 ◽  
Author(s):  
Walter Reinhardt ◽  
Nils Mülling ◽  
Stefan Behrendt ◽  
Sven Benson ◽  
Sebastian Dolff ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Thyroid Function ◽  
Filtration Rate ◽  
Creatinine Ratio ◽  
Protein Loss ◽  
Reverse T3 ◽  
Thyroid Antibody ◽  
Hormone Status ◽  
The Relationship

Abstract Purpose The relationship between proteinuria and thyroid function remains controversial in patients with chronic kidney disease (CKD). We prospectively investigated the association between kidney and thyroid function in thyroid antibody-negative patients through all CKD stages. Methods We enrolled 184 nondialysis patients (mean age: 63.1 ± 16.9 years) without previous thyroid disease or thyroid-specific antibodies. Kidney function was assessed by estimating the glomerular filtration rate (eGFR) classified according KDIGO (CKD G1–5). Kidney damage was assessed by albuminuria (albumin-to-creatinine ratio, ACR) and classified as mild, moderate, or severe (ACR1: <300, ACR2: 300–3000, and ACR3: 3000 mg/g). To evaluate thyroid function, TSH, T4, fT4, T3, fT3, reverse T3 (rT3), and thyroxine-binding globulin (TBG) were measured. Results rT3 concentrations correlated negatively with albuminuria (r = −0.286, p < 0.001) and were significantly lower in patients with severe albuminuria than in those with mild or moderate albuminuria (ACR3: 0.28 vs. ACR2: 0.32 vs. ACR1: 0.36 nmol/l, p < 0.001). The severity of albuminuria revealed no impact on TSH, fT4, T3, fT3, and TBG. EGFR correlated with increasing T4, fT4, T3, fT3, and TBG (T4: r = 0.289, p < 0.01; fT4: r = 0.196, p < 0.01; T3: r = 0.408, p < 0.01; fT3: r = 0.390, p < 0.01) but not with rT3. Conclusions In thyroid antibody-negative patients presenting advanced CKD (stages 4 and 5), even severe kidney protein loss failed to influence thyroid hormone status. However, albuminuria severity correlated negatively with rT3, which was significantly lower in patients with albuminuria in the nephrotic range.

scholarly journals Plasma natriuretic peptide level is an independent determinant of major clinical outcomes in atrial fibrillation patients without heart failure: the Fushimi AF Registry

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
Y Hamatani ◽  
M Iguchi ◽  
Y Aono ◽  
K Ishigami ◽  
S Ikeda ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Clinical Outcomes ◽  
Prognostic Marker ◽  
Oral Anticoagulants ◽  
Systemic Embolism ◽  
The Mean

Abstract Background Atrial fibrillation (AF) increases the risk of death, stroke/systemic embolism and heart failure (HF). Plasma natriuretic peptide (NP) level is an important prognostic marker in HF patients. However, little is known regarding the prognostic significance of plasma NP level in AF patients without HF. Purpose The aim of this study is to investigate the relationship between plasma NP level and clinical outcomes such as all-cause death, stroke/systemic embolism and HF hospitalization during follow-up period in AF patients without HF. Methods The Fushimi AF Registry is a community-based prospective survey of AF patients in our city. The inclusion criterion of the registry is the documentation of AF at 12-lead electrocardiogram or Holter monitoring at any time, and there are no exclusion criteria. We started to enroll patients from March 2011, and follow-up data were available for 4,466 patients by the end of November 2019. From the registry, we excluded 1,220 patients without a pre-existing HF (defined as having one of the following; prior hospitalization for HF, New York Heart Association class ≥2, or left ventricular ejection fraction &lt;40%). Among 3,246 AF patients without HF, we investigated 1,189 patients with the data of plasma BNP (n=401) or N-terminal pro-BNP (n=788) level at the enrollment. We divided the patients according to the quartile of each plasma BNP or NT-pro BNP level and compared the backgrounds and outcomes between these 4 groups stratified by plasma NP level. Results Of 1,189 patients, the mean age was 72.1±10.2 years, 454 (38%) were female and 684 (58%) were paroxysmal AF. The mean CHADS2 and CHA2DS2-VASc score were 1.6±1.1 and 2.9±1.5, respectively. Oral anticoagulants were prescribed in 671 (56%) at baseline. The median (interquartile range) BNP and N-terminal pro-BNP level were 84 (38, 176) and 500 (155, 984) pg/ml, respectively. Patients with high plasma NP level were older, and demonstrated lower prevalence of paroxysmal AF, higher CHADS2 and CHA2DS2-VASc scores and higher prevalence of chronic kidney disease and oral anticoagulants prescription (all P&lt;0.01). A total of 165 all-cause death, 114 stroke/systemic embolism and 103 HF hospitalization occurred during the median follow-up period of 5.0 years. Kaplan-Meier curves demonstrated that higher plasma NP level was significantly associated with the incidences of all-cause death, stroke/systemic embolism and HF hospitalization in AF patients without HF (Figure 1A). Multivariable Cox regression analysis revealed that plasma NP level could stratify the risk of clinical outcomes even after adjustment by type of AF, CHA2DS2-VASc score, chronic kidney disease and oral anticoagulant prescription (Figure 1B). Conclusion Plasma NP level is a significant prognostic marker for all-cause death, stroke/systemic embolism and HF hospitalization in AF patients without HF, suggesting the importance of measuring plasma NP level in AF patients even without HF. Figure 1 Funding Acknowledgement Type of funding source: None

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