scholarly journals Rhubarb Enema Decreases Circulating Trimethylamine N-Oxide Level and Improves Renal Fibrosis Accompanied With Gut Microbiota Change in Chronic Kidney Disease Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Chunlan Ji ◽  
Yin Li ◽  
Yenan Mo ◽  
Zhaoyu Lu ◽  
Fuhua Lu ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Intestinal Microbiota ◽  
Renal Fibrosis ◽  
Interstitial Fibrosis ◽  
Underlying Mechanism ◽  
Uremic Toxins ◽  
16S Rrna Sequence ◽  
Tubular Atrophy ◽  
The Impact

Objectives: Trimethylamine N-oxide (TMAO), a metabolic product of gut flora, is increased in chronic kidney disease (CKD) subjects and is recognized as one type of uremic toxins which is associated with poor cardiovascular outcomes and kidney function loss. Previous studies have suggested that rhubarb enema could reduce circulating uremic toxins such as urea, creatinine, and indoxyl sulfate and also regulate the intestinal microbiota. However, whether rhubarb enema retards kidney dysfunction by reducing circulating TMAO and its underlying mechanism, are still unclear. The present study aims to investigate the impact of rhubarb enema on TMAO and its precursors, as well as on the intestinal microbiota in 5/6 nephrectomized (5/6Nx) CKD rats.Design: Rats in the treatment groups were given rhubarb enema after modeling. At the end of the study, blood, feces, and kidney tissues were collected and processed for biochemical analyses, histological and western blot analyses, 16S rRNA sequence and untargeted metabolomic analyses.Results: Rhubarb enema reduced serum TMAO and trimethylamine (TMA) levels, inhibited the expression of inflammatory markers (interleukin-6, tumor necrosis factor α and Interferon-γ) and alleviated tubular atrophy, monocyte infiltration and interstitial fibrosis in 5/6Nx CKD rats. Moreover, rhubarb enema significantly increased the abundance of some symbiotic bacteria and probiotics, while reduced the abundance of some potential pathogens at the genus level. In addition, Spearman’s correlation analysis revealed that lachnospiraceae and romboutsia were positively correlated with TMAO.Conclusion: Rhubarb enema decreases circulating TMAO level and improves renal fibrosis in 5/6Nx CKD rats, which may be related to the regulation of intestinal microbial community.

scholarly journals Microbiome-Metabolomics Analysis Reveals the Protection Mechanism of α-Ketoacid on Adenine-Induced Chronic Kidney Disease in Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Yenan Mo ◽  
Huang Sun ◽  
Lei Zhang ◽  
Wenjia Geng ◽  
Lixin Wang ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Intestinal Microbiota ◽  
Interstitial Fibrosis ◽  
Intestinal Barrier ◽  
Indoxyl Sulfate ◽  
16S Rrna Sequence ◽  
Tubular Atrophy ◽  
Protection Mechanism ◽  
The Impact

Objectives: As nitrogen-free precursors of corresponding essential amino, α-ketoacid have been widely prescribed to end-stage renal disease patients together with a low protein diet However, the impact of α-ketoacid on intestinal microbiota in chronic kidney disease (CKD) individuals is unknown. The study aims at investigating the variation in the intestinal microbiota and metabolic profile in response to α-ketoacid treatment in an adenine-induced CKD rat model.Design: Rats in the treatment groups were given solution of compound α-ketoacid tablets. At the end of the study, blood, feces, colon tissues and kidney tissues were collected and processed for biochemical analyses, histological and western blot analyses, 16S rRNA sequence and untargeted metabolomic analyses.Results:α-Ketoacid treatment reduced serum creatinine, blood urea nitrogen and 24 h urine protein, and alleviated tubular atrophy, glomerulosclerosis and interstitial fibrosis in adenine-induced CKD rats. Moreover, α-ketoacid significantly improved intestinal barrier and increased the abundance of Methanobrevibacter, Akkermansia, Blautia and Anaerositipes while reduced the abundance of Anaerovorax and Coprococcus_3 at the genus level. In addition, our results also demonstrated that α-ketoacid significantly reduced the concentrations of indoxyl sulfate, betaine, choline and cholesterol. Spearman’s correlation analysis revealed that the abundance of Coprococcus_3 was positively correlated with serum level of betaine, trimethylamine N-oxide, indoxyl sulfate, cholic acid and deoxycholic acid.Conclusion:α-Ketoacid has a reno-protective effect against adenine-induced CKD, which may be mediated regulation of serum metabolic profiles via affecting intestinal microbial community.

scholarly journals AB0646 COMPARATIVE ANALYSIS OF ASYMPTOMATIC HYPERURICEMIA AND GOUT - AN IMPACT ON KIDNEY STRUCTURE AND FUNCTION

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1356.1-1356
Author(s):  
M. Hristova ◽  
A. Kundurdzhiev ◽  
T. Kundurzhiev ◽  
R. Gancheva
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Urine Analysis ◽  
Interstitial Fibrosis ◽  
Structural Parameters ◽  
Population Level ◽  
Oxidase Inhibitor ◽  
Tubular Atrophy ◽  
Xanthine Oxidase Inhibitor ◽  
The Impact

Background:The significance of asymptomatic hyperuricemia (AH) continues to be debated. At the population level, asymptomatic hyperuricemia is associated with multiple comorbidities, including hypertension, coronary artery disease, diabetes and chronic kidney disease.1Objectives:To investigate the impact of asymptomatic hyperuricemia on renal functional and structural parameters in comparison with symptomatic gout.Methods:The subjects included in the study were divided into two groups - 46 patients with asymptomatic hyperuricemia and 18 diagnosed with gout according to ACR/EULAR 2015 criteria.2 For renal function assessment urine analysis, albuminuria, estimated glomerular filtration rate (eGFR) based on Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation were used. Diagnostic ultrasound as well as renal biopsy were performed to evaluate structural and histological kidney changes. Statistical analysis was performed using SPSS 22.0 software (SPSS Inc, Chicago, USA).Results:There were no significant differences between the two groups on serum uric acid levels, albuminuria, and eGFR. However, erythrocyturia (p=0.047) and nephrolithiasis (p<0.001) prevailed significantly in patients with gout, 66.7% and 61.1% respectively. We did not find any histological differences between the two groups regarding the number of affected glomeruli, tubular atrophy and percentage of interstitial fibrosis based on light microscopy scans.Conclusion:Our results indicate that patients with AH need renal screening since both AH and gout show similar kidney changes. Further research is needed to elucidate the role of early treatment with xanthine oxidase inhibitor for asymptomatic hyperuricemia as prevention of complications such as erythrocyturia and nephrolithiasis.References:[1]Yip K, Cohen RE, Pillinger MH. Asymptomatic hyperuricemia: is it really asymptomatic? CurrOpin Rheumatology 2020; 32(1):71-79 doi: 10.1097/BOR.0000000000000679.[2]Neogi T, Jansen TL, Dalbeth N et al. 2015 Gout classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheumatogy 2015;67(10):2557-68. doi: 10.1002/art.39254.Disclosure of Interests:None declared.

scholarly journals Cellular Mechanisms of Tissue Fibrosis. 3. Novel mechanisms of kidney fibrosis

2013 ◽  
Vol 304 (7) ◽  
pp. C591-C603 ◽  
Author(s):  
Gabriela Campanholle ◽  
Giovanni Ligresti ◽  
Sina A. Gharib ◽  
Jeremy S. Duffield
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Interstitial Fibrosis ◽  
Kidney Injury ◽  
Innate Immune ◽  
Cellular Mechanisms ◽  
Tubular Atrophy ◽  
Kidney Fibrosis ◽  
Capillary Rarefaction ◽  
Peritubular Capillaries

Chronic kidney disease, defined as loss of kidney function for more than three months, is characterized pathologically by glomerulosclerosis, interstitial fibrosis, tubular atrophy, peritubular capillary rarefaction, and inflammation. Recent studies have identified a previously poorly appreciated, yet extensive population of mesenchymal cells, called either pericytes when attached to peritubular capillaries or resident fibroblasts when embedded in matrix, as the progenitors of scar-forming cells known as myofibroblasts. In response to sustained kidney injury, pericytes detach from the vasculature and differentiate into myofibroblasts, a process not only causing fibrosis, but also directly contributing to capillary rarefaction and inflammation. The interrelationship of these three detrimental processes makes myofibroblasts and their pericyte progenitors an attractive target in chronic kidney disease. In this review, we describe current understanding of the mechanisms of pericyte-to-myofibroblast differentiation during chronic kidney disease, draw parallels with disease processes in the glomerulus, and highlight promising new therapeutic strategies that target pericytes or myofibroblasts. In addition, we describe the critical paracrine roles of epithelial, endothelial, and innate immune cells in the fibrogenic process.

scholarly journals Impacts of Indoxyl Sulfate and p-Cresol Sulfate on Chronic Kidney Disease and Mitigating Effects of AST-120

Toxins ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 367 ◽  
Author(s):  
Wen-Chih Liu ◽  
Yasuhiko Tomino ◽  
Kuo-Cheng Lu
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Large Scale ◽  
Interstitial Fibrosis ◽  
Uremic Toxins ◽  
Indoxyl Sulfate ◽  
Renal Diseases ◽  
Glomerular Sclerosis ◽  
Inflammatory Reactions

Uremic toxins, such as indoxyl sulfate (IS) and p-cresol, or p-cresyl sulfate (PCS), are markedly accumulated in the organs of chronic kidney disease (CKD) patients. These toxins can induce inflammatory reactions and enhance oxidative stress, prompting glomerular sclerosis and interstitial fibrosis, to aggravate the decline of renal function. Consequently, uremic toxins play an important role in the worsening of renal and cardiovascular functions. Furthermore, they destroy the quantity and quality of bone. Oral sorbent AST-120 reduces serum levels of uremic toxins in CKD patients by adsorbing the precursors of IS and PCS generated by amino acid metabolism in the intestine. Accordingly, AST-120 decreases the serum IS levels and reduces the production of reactive oxygen species by endothelial cells, to impede the subsequent oxidative stress. This slows the progression of cardiovascular and renal diseases and improves bone metabolism in CKD patients. Although large-scale studies showed no obvious benefits from adding AST-120 to the standard therapy for CKD patients, subsequent sporadic studies may support its use. This article summarizes the mechanisms of the uremic toxins, IS, and PCS, and discusses the multiple effects of AST-120 in CKD patients.

scholarly journals Kidneys and microbiota

2019 ◽  
pp. 48-57
Author(s):  
Zh. Semydotska ◽  
I. Chernyakova ◽  
O. Avdeyeva
Keyword(s):  
Chronic Kidney Disease ◽  
Fatty Acids ◽  
Kidney Disease ◽  
Intestinal Microbiota ◽  
General Circulation ◽  
Short Chain Fatty Acids ◽  
Uremic Toxins ◽  
Short Chain ◽  
Intestinal Lumen ◽  
Chain Fatty Acids

 The review article analyzes the results of studies of the bi-directional relationship of the intestinal microbiota and kidneys, the so-called colorenal interactive axis of interaction.  The intestinal microbiota is considered as a kind of organ that influences the brain, cardiovascular and immune systems, as well as the kidneys of the "host".  Short-chain fatty acids (SCFA) formed in the colon as the result of microbial metabolism from plant components of dietary fiber and acting as ligands for the olfactory receptor, paired G-proteins in the kidneys are recognized as the markers of this symbiosis.  With the help of modern omix technologies, the development of dysbiosis taking into account patients with chronic kidney disease (CKD) has been proved, which leads to the accumulation of precursors of uremic toxins, a decrease in the production of SCFA, which have nephroprotective properties and play a key role in energy homeostasis.  Changes in the composition of the intestinal microbiota in CKD, an increase in the content of uremic toxins in the intestinal lumen contribute to the appearance of the “leaky” intestinal barrier syndrome, the movement of bacteria from the intestine into the general circulation, the development of systemic inflammation, oxidative stress, comorbidity, the progression of CKD, and an increase in mortality. Diets with restriction of protein and potassium quotas, violation of nutritional status lead to the development of dysbiosis in CKD.  A decrease in the diet of vegetables and fruit causes the expansion of bacteria producing uricase and urease, which are enzymes in the formation of uremic toxins and reduce the number and variety of bacteria producing short-chain fatty acids.  Potential targeted effects on the axis of “intestinal microbiota - chronic kidney disease” are being discussed: the use of a diet enriched in plant fibers, heat-treated, then chilled potatoes and rice as prebiotics (sources of resistant starch), nuts, plant seeds, and pro-, pre-, synbiotics, fecal transplantation.  Most of the proposed interventions in the structure and functions of the microbiota are not dangerous, side effects are minimal.

scholarly journals Ketoacid Analogues Supplementation in Chronic Kidney Disease and Future Perspectives

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2071 ◽  
Author(s):  
Laetitia Koppe ◽  
Mariana Cassani de Oliveira ◽  
Denis Fouque
Keyword(s):  
Chronic Kidney Disease ◽  
Glomerular Filtration Rate ◽  
Kidney Disease ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Uremic Toxins ◽  
Protein Diet ◽  
Current Evidence ◽  
Low Protein ◽  
The Impact

Diet is a key component of care during chronic kidney disease (CKD). Nutritional interventions, and, specifically, a restricted protein diet has been under debate for decades. In order to reduce the risk of nutritional disorders in very-low protein diets (VLDP), supplementation by nitrogen-free ketoacid analogues (KAs) have been proposed. The aim of this review is to summarize the potential effects of this dietary therapy on renal function, uremic toxins levels, and nutritional and metabolic parameters and propose future directions. The purpose of this paper is also to select all experimental and randomized clinical studies (RCTs) that have compared VLDP + KA to normal diet or/and low protein diet (LPD). We reviewed the SCOPUS, WEB of SCIENCES, CENTRAL, and PUBMED databases from their inception to 1 January, 2019. Following duplicate removal and application of exclusion criteria, 23 RCTs and 12 experimental studies were included. LPD/VLPD + KAs appear nutritionally safe even if how muscle protein metabolism adapts to an LPD/VLPD + KAs is still largely unknown. VLPD + KAs seem to reduce uremic toxins production but the impact on intestinal microbiota remains unexplored. All studies observed a reduction of acidosis, phosphorus, and possibly sodium intake, while still providing adequate calcium intake. The impact of this diet on carbohydrate and bone parameters are only preliminary and need to be confirmed with RCTs. The Modification of Diet in Renal Disease study, the largest RCTs, failed to demonstrate a benefit in the primary outcome of the decline rate for the glomerular filtration rate. However, the design of this study was challenged and data were subsequently reanalyzed. However, when adherent patients were selected, with a rapid rate of progression and a long-term follow up, more recent meta-analysis and RCTs suggest that these diets can reduce the loss of the glomerular filtration rate in addition to the beneficial effects of renin-angiotensin-aldosterone system (RAAS) inhibitors. The current evidence suggests that KAs supplemented LPD diets should be included as part of the clinical recommendations for both the nutritional prevention and metabolic management of CKD. More research is needed to examine the effectiveness of KAs especially on uremic toxins. A reflection about the dose and composition of the KAs supplement, the cost-effective features, and their indication to reduce the frequency of dialysis needs to be completed.

scholarly journals The Impact of CKD on Uremic Toxins and Gut Microbiota

Toxins ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 252
Author(s):  
Jacek Rysz ◽  
Beata Franczyk ◽  
Janusz Ławiński ◽  
Robert Olszewski ◽  
Aleksanda Ciałkowska-Rysz ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Microbial Community ◽  
Kidney Disease ◽  
Gut Microbiota ◽  
Intestinal Inflammation ◽  
Adverse Outcomes ◽  
Uremic Toxins ◽  
Dietary Interventions ◽  
Stress Injury ◽  
The Impact

Numerous studies have indicated that the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD) is strictly associated with the accumulation of toxic metabolites in blood and other metabolic compartments. This accumulation was suggested to be related to enhanced generation of toxins from the dysbiotic microbiome accompanied by their reduced elimination by impaired kidneys. Intestinal microbiota play a key role in the accumulation of uremic toxins due to the fact that numerous uremic solutes are generated in the process of protein fermentation by colonic microbiota. Some disease states, including CKD, are associated with the presence of dysbiosis, which can be defined as an “imbalanced intestinal microbial community with quantitative and qualitative changes in the composition and metabolic activities of the gut microbiota”. The results of studies have confirmed the altered composition and functions of gut microbial community in chronic kidney disease. In the course of CKD protein-bound uremic toxins, including indoxyl sulfate, p-cresyl glucuronide, p-cresyl sulfate and indole-3-acetic acid are progressively accumulated. The presence of chronic kidney disease may be accompanied by the development of intestinal inflammation and epithelial barrier impairment leading to hastened systemic translocation of bacterial-derived uremic toxins and consequent oxidative stress injury to the kidney, cardiovascular and endocrine systems. These findings offer new therapeutic possibilities for the management of uremia, inflammation and kidney disease progression and the prevention of adverse outcomes in CKD patients. It seems that dietary interventions comprising prebiotics, probiotics, and synbiotics could pose a promising strategy in the management of uremic toxins in CKD.

Semicarbazide-sensitive amine oxidase and kidney disease

2013 ◽  
Vol 305 (12) ◽  
pp. F1637-F1644 ◽  
Author(s):  
May Y. W. Wong ◽  
Sonia Saad ◽  
Carol Pollock ◽  
Muh Geot Wong
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Fibrosis ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Amine Oxidase ◽  
Tubular Atrophy ◽  
Progression Of Renal Disease ◽  
Protein Enzyme

With better understanding of the molecular mechanisms underpinning chronic kidney disease, the roles of inflammation and fibrosis are becoming increasingly inseparable. The progression of renal disease is characterized by pathomorphological changes that consist of early inflammatory responses followed by tubulointerstitial fibrosis, tubular atrophy, and glomerular and vascular sclerosis. Currently available therapies that reduce hypertension, proteinuria, hyperglycemia, and interruption of the renin-angiotensin-aldosterone system are at best only partially effective. Hence, there remains a need to explore agents targeting nonrenin-angiotensin-aldosterone system pathways. In this review, we discuss mechanistic aspects in the physiological and pathological role of semicarbazide-sensitive amine oxidase, a protein enzyme involved in cellular trafficking and inflammation, with respect to the kidney. We explore the evidence for the use of semicarbazide-sensitive amine oxidase inhibitors as potential agents in renal fibrosis to delay the onset and progression of chronic kidney disease.

Colchicine attenuates renal injury in a model of hypertensive chronic kidney disease

2013 ◽  
Vol 305 (10) ◽  
pp. F1466-F1476 ◽  
Author(s):  
Tianxiu Guan ◽  
Bo Gao ◽  
Guang Chen ◽  
Xing Chen ◽  
Melissa Janssen ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Fibrosis ◽  
Interstitial Fibrosis ◽  
Mechanical Strain ◽  
Tissue Growth ◽  
Glomerular Sclerosis ◽  
Glomerular Mesangial Cells ◽  
Rhoa Activation ◽  
Microtubule Disruption

Hypertension is a risk factor for chronic kidney disease, particularly when associated with impaired renal autoregulation and thereby increased intraglomerular pressure (Pgc). Elevated Pgc can be modeled in vitro by exposing glomerular mesangial cells to mechanical strain. We previously showed that RhoA mediates strain-induced matrix production. Here, we show that RhoA activation is dependent on an intact microtubule network. Upregulation of the profibrotic cytokine connective tissue growth factor (CTGF) by mechanical strain is dependent on RhoA activation and inhibited by microtubule disruption. We tested the effects of the microtubule depolymerizing agent colchicine in 5/6 nephrectomized rats, a model of chronic kidney disease driven by elevated Pgc. Colchicine inhibited glomerular RhoA activation and attenuated both glomerular sclerosis and interstitial fibrosis without affecting systemic blood pressure. Upregulation of the matrix proteins collagen I and fibronectin, as well as CTGF, was attenuated by colchicine. Activity of the profibrotic cytokine TGF-β, as assessed by Smad3 phosphorylation, was also inhibited by colchicine. Microtubule disruption significantly decreased renal infiltration of lymphocytes and macrophages. Our studies thus indicate that colchicine modifies hypertensive renal fibrosis. Its protective effects are likely mediated by inhibition of RhoA signaling and renal infiltration of inflammatory cells. Already well-established in clinical practice for other indications, prevention of hypertension-associated renal fibrosis may represent a new potential use for colchicine.

scholarly journals Lithium-Associated Kidney Microcysts

2008 ◽  
Vol 8 ◽  
pp. 828-829 ◽  
Author(s):  
Jennifer Tuazon ◽  
David Casalino ◽  
Ehteshamuddin Syed ◽  
Daniel Batlle
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Mr Imaging ◽  
Interstitial Fibrosis ◽  
Renal Cysts ◽  
Lithium Therapy ◽  
Tubular Atrophy ◽  
Advanced Chronic Kidney Disease ◽  
Tubulointerstitial Nephropathy

Long-term lithium therapy is associated with impairment in concentrating ability and, occasionally, progression to advanced chronic kidney disease from tubulointerstitial nephropathy. Biopsy findings in patients with lithium-induced chronic tubulointerstitial nephropathy include tubular atrophy and interstitial fibrosis interspersed with tubular cysts and dilatations. Recent studies have shown that cysts are seen in 33––62.5% of the patients undergoing lithium therapy. MR imaging is highly capable of defining renal morphological features and has been demonstrated to be superior to US and CT scan for the visualization of small renal cysts. The microcysts are found in both cortex and medulla, particularly in the regions with extensive atrophy and fibrosis, and can be multiple and bilateral. They tend to be sparse and do not normally exceed 1–2 mm in diameter. The renal microcysts in the image here reported are subtle, but consistent with lithium-induced chronic nephropathy. An MRI of the kidneys provides noninvasive evidence that strengthens the diagnosis of lithium-induced nephropathy.

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