scholarly journals Dietary Fermented Soy Extract and Active Lactic Acid Alleviate Chronic Kidney Disease in Mice via Inhibition of Inflammation and Modulation of Gut Microbiota (FS15-07-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Lixia He
Keyword(s):  
Chronic Kidney Disease ◽  
Lactic Acid ◽  
Kidney Disease ◽  
Gut Microbiota ◽  
Kidney Injury ◽  
Serum Levels ◽  
Negative Control ◽  
Mrna Levels ◽  
Blood Cytokines ◽  
Model Control

Abstract Objectives Chronic kidney disease (CKD) is a global epidemic and posing serious health problems with an increasing prevalence worldwide. Effective preventive strategies are urgently needed. This study was conducted to investigate the effect of a fermented soybean product (ImmunBalance, IMB) and active lactic acid (ALA) on adenine-induced CKD in mice. Methods Female C57BL/6 mice were randomly assigned into one of the following experimental groups: negative control (NC), model control (MC), models with oral gavage of IMB at 250 (IMB-L) or 1000 mg/kg BW (IMB-H), ALA at 1000 (ALA-L) or 2000 mg/kg BW (ALA-H). The CKD model was established by ip. injection of adenine daily for 4 weeks, and treatments started the same day as adenine injection till for 8 weeks. The kidney histopathology was evaluated by H&E staining. Blood cytokines and kidney injury biomarkers were measured by Multiplex sandwich immunoassays. Expression of cytokines and stem cells-related genes in kidney was analyzed by quantitative real-time PCR. The levels of major phyla of gut microbiota were quantified by quantitative PCR. Results The CKD mice showed obvious tubular dilation, tubulointerstitium degeneration or atrophy, interstitial chronic and acute inflammation. The administration of IMB and ALA significantly improved histopathological damages. Both of IMB and ALA decreased serum levels of cytokines and kidney toxicity biomarkers MCP-1, IL-6, IP-10, TIMP-1, Cystatin C and Clusterin, and the mRNA levels of inflammatory biomarkers IL-6, IL-1β, TGF-β1, TLR-4, F4/80 and TNF-α in kidney samples. CKD increased gene expression levels of stem cell biomarkers in kidney, which were reduced by IMB or ALA treatment. CKD reduced gut Clostridium leptumb level that was significantly increased by IMB or ALA treatment. Conclusions Our results suggest that dietary supplementation of IMB or ALA may significantly delay the development and progression of CKD. Funding Sources Nichimo Biotics Co., Ltd and Lifetrade Co. Ltd, Japan.

scholarly journals Dietary Fermented Soy Extract and Oligo-Lactic Acid Alleviate Chronic Kidney Disease in Mice via Inhibition of Inflammation and Modulation of Gut Microbiota

Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2376
Author(s):  
Li-Xia He ◽  
Hamid M. Abdolmaleky ◽  
Sheng Yin ◽  
Yihong Wang ◽  
Jin-Rong Zhou
Keyword(s):  
Chronic Kidney Disease ◽  
Body Weight ◽  
Lactic Acid ◽  
Kidney Disease ◽  
Kidney Injury ◽  
Negative Control ◽  
The Body ◽  
Serum Cystatin C ◽  
Acid Product ◽  
Model Control

Chronic kidney disease (CKD) is a global epidemic with an increasing prevalence worldwide. Effective preventive strategies are urgently needed. This study aimed to investigate the effect of nutraceutical components, a fermented soybean product (ImmuBalance, IMB) and an oligo-lactic acid product (LAP), on the prevention of adenine-induced CKD in mice. Female C57BL/6 mice were randomly assigned into following experimental groups: negative control; model control; and models treated with IMB at 250 or 1000 mg/kg body weight (BW), LAP at 1000 or 2000 mg/kg BW, and IMB/LAP combinations. The CKD model was established by intraperitoneal injection of adenine daily for 4 weeks, and treatments started 2 weeks before adenine injection and ended after 10 weeks. Compared with the model control, the treatments did not significantly alter the body weight or food intake. Both IMB and LAP, especially their combination, significantly inhibited tubular dilation, tubulointerstitial degeneration or atrophy, interstitial chronic inflammation and acute inflammation in the kidneys of CKD mice, and significantly decreased serum cystatin C levels. IMB or LAP significantly reversed CKD-associated increases of circulating and kidney levels of inflammatory cytokines, circulating levels of kidney injury biomarkers, and kidney levels of stem cell biomarkers, and significantly reversed CKD-associated reduction of cecum Clostridium leptum group. Our results suggest that dietary supplementation of IMB or LAP may significantly delay the development and/or progression of CKD.

scholarly journals Augmented transcripts of kidney injury markers and renin angiotensin system in urine samples of overweight young adults

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Patricia Rivera ◽  
Catalina Miranda ◽  
Nicole Roldán ◽  
Aaron Guerrero ◽  
Javier Olave ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Young Adults ◽  
Body Weight ◽  
Kidney Disease ◽  
Kidney Injury ◽  
Tissue Growth ◽  
Mrna Levels ◽  
Simple Method ◽  
Renin Angiotensin

AbstractObesity has been firmly established as a major risk factor for common disease states including hypertension, type 2 diabetes mellitus, and chronic kidney disease. Increased body mass index (BMI) contributes to the activation of both the systemic and intra-tubular renin angiotensin systems (RAS), which are in turn associated with increased blood pressure (BP) and kidney damage. In this cross-sectional study, 43 subjects of normal or increased body weight were examined in order to determine the correlation of BMI or body fat mass (BFM) with blood pressure, fasting blood glucose (FBG), and urinary kidney injury markers such as interleukin-18 (IL-18), connective tissue growth factor (CTGF), neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1 (KIM-1). Our results showed that: (1) subjects with increased body weight showed significantly higher BP, BFM, total body water and metabolic age; (2) BMI was positively correlated to both systolic (R2 = 0.1384, P = 0.01) and diastolic BP (R2 = 0.2437, P = 0.0008); (3) BFM was positively correlated to DBP (R2 = 0.1232, P = 0.02) and partially correlated to urine protein (R2 = 0.047, P = 0.12) and FBG (R2 = 0.07, P = 0.06); (4) overweight young adults had higher urinary mRNA levels of renin, angiotensinogen, IL-18 and CTGF. These suggest that BMI directly affects BP, kidney injury markers, and the activation of the intra-tubular RAS even in normotensive young adults. Given that BMI measurements and urine analyses are non-invasive, our findings may pave the way to developing a new and simple method of screening for the risk of chronic kidney disease in adults.

scholarly journals Increased Expression of the Leptin Gene in Adipose Tissue of Patients with Chronic Kidney Disease–The Possible Role of an Abnormal Serum Fatty Acid Profile

Metabolites ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 98
Author(s):  
Justyna Korczyńska ◽  
Aleksandra Czumaj ◽  
Michał Chmielewski ◽  
Maciej Śledziński ◽  
Adriana Mika ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chronic Kidney Disease ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Kidney Disease ◽  
Elevated Serum ◽  
Serum Levels ◽  
Mrna Levels ◽  
Serum Fatty Acid ◽  
Serum Leptin

Chronic kidney disease (CKD) is associated with an increased level of leptin and an abnormal fatty acid (FA) profile in the serum. However, there are no data on the associations between them, and the reason for increased serum levels in patients with CKD is not well elucidated. Recently, we found that a CKD-related abnormal FA profile caused significant changes in the expression of genes involved in lipid metabolism in hepatocytes. The aim of this study was to examine whether leptin gene expression in subcutaneous adipose tissue (SAT) of patients with CKD may contribute to increased serum levels of this adipokine and whether the abnormal serum FA profile observed in CKD patients has an impact on leptin gene expression in adipocytes. The FA profile was measured in serum samples from patients with CKD and controls by GC–MS. The relative mRNA levels of leptin were measured in SAT by Real-Time PCR. Moreover, the effect of the CKD-related abnormal FA profile on leptin gene expression was studied in in vitro cultured 3T3-L1 adipocytes. Patients with CKD had higher concentrations of serum leptin than controls and higher expression level of the leptin gene in SAT. They also had increased serum monounsaturated FAs and decreased polyunsaturated FAs. The incubation of adipocytes with FAs isolated from CKD patients resulted in an increase of the levels of leptin mRNA. Increased leptin gene expression in SAT may contribute to elevated concentrations of these adipokine in patients with CKD. CKD-related alterations of the FA profile may contribute to elevated serum leptin concentrations in patients with CKD by increasing the gene expression of this adipokine in SAT.

scholarly journals Nutritional Therapy Modulates Intestinal Microbiota and Reduces Serum Levels of Total and Free Indoxyl Sulfate and P-Cresyl Sulfate in Chronic Kidney Disease (Medika Study)

2019 ◽  
Vol 8 (9) ◽  
pp. 1424 ◽  
Author(s):  
Biagio Raffaele Di Iorio ◽  
Maria Teresa Rocchetti ◽  
Maria De Angelis ◽  
Carmela Cosola ◽  
Stefania Marzocco ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Gut Microbiota ◽  
Binding Capacity ◽  
Controlled Trial ◽  
Serum Levels ◽  
Nutritional Therapy ◽  
Indoxyl Sulfate ◽  
Lower Amount ◽  
Dietary Intakes

In chronic kidney disease (CKD), the gut-microbiota metabolites indoxyl sulfate (IS) and p-cresyl sulfate (PCS) progressively accumulate due to their high albumin-binding capacity, leading to clinical complications. In a prospective crossover controlled trial, 60 patients with CKD grades 3B–4 (GFR = 21.6 ± 13.2 mL/min) were randomly assigned to two dietary regimens: (i) 3 months of free diet (FD) (FD is the diet usually used by the patient before being enrolled in the Medika study), 6 months of very low protein diet (VLPD), 3 months of FD and 6 months of Mediterranean diet (MD); (ii) 3 months of FD, 6 months of MD, 3 months of FD, and 6 months of VLPD. VLPD reduced inflammatory Proteobacteria and increased Actinobacteria phyla. MD and VLPD increased some butyrate-forming species of Lachnospiraceae, Ruminococcaceae, Prevotellaceae, Bifidobacteriaceae, and decrease the pathobionts Enterobacteriaceae. The increased level of potential anti-inflammatory Blautia and Faecalibacterium, as well as butyrate-forming Coprococcus and Roseburia species in VLPD was positively associated with dietary intakes and it was negatively correlated with IS and PCS. Compared to FD and MD, VLPD showed a lower amount of some Lactobacillus, Akkermansia, Streptococcus, and Escherichia species. MD and VLPD reduced both the total and free serum IS (MD −36%, −40% and VLPD −69%, −73%, respectively) and PCS (MD −38%, −44% and VLPD −58%, −71%, respectively) compared to FD. VLPD reduced serum D-lactate compared to MD and FD. MD and, to a greater extent, VLPD are effective in the beneficial modulation of gut microbiota, reducing IS and PCS serum levels, and restoring intestinal permeability in CKD patients.

scholarly journals Significance of the Gut Microbiota in Acute Kidney Injury

Toxins ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 369
Author(s):  
Taku Kobayashi ◽  
Yasunori Iwata ◽  
Yusuke Nakade ◽  
Takashi Wada
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Gut Microbiota ◽  
Kidney Injury ◽  
Protective Effects ◽  
Diseased Condition ◽  
New Treatments ◽  
Established Treatment

Recent studies have revealed that the gut microbiota plays a crucial role in maintaining a healthy, as well as diseased condition. Various organs and systems, including the kidney, are affected by the gut microbiota. While the impacts of the gut microbiota have been reported mainly on chronic kidney disease, acute kidney injury (AKI) is also affected by the intestinal environment. In this review, we discussed the pathogenesis of AKI, highlighting the relation to the gut microbiota. Since there is no established treatment for AKI, new treatments for AKI are highly desired. Some kinds of gut bacteria and their metabolites reportedly have protective effects against AKI. Current studies provide new insights into the role of the gut microbiota in the pathogenesis of AKI.

scholarly journals A Link between Chronic Kidney Disease and Gut Microbiota in Immunological and Nutritional Aspects

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3637
Author(s):  
Paulina Mertowska ◽  
Sebastian Mertowski ◽  
Julia Wojnicka ◽  
Izabela Korona-Głowniak ◽  
Ewelina Grywalska ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Immune System ◽  
Kidney Disease ◽  
Gut Microbiota ◽  
Intestinal Microbiota ◽  
Kidney Diseases ◽  
Disease Onset ◽  
Kidney Injury ◽  
Dietary Factors

Chronic kidney disease (CKD) is generally progressive and irreversible, structural or functional renal impairment for 3 or more months affecting multiple metabolic pathways. Recently, the composition, dynamics, and stability of a patient’s microbiota has been noted to play a significant role during disease onset or progression. Increasing urea concentration during CKD can lead to an acceleration of the process of kidney injury leading to alterations in the intestinal microbiota that can increase the production of gut-derived toxins and alter the intestinal epithelial barrier. A detailed analysis of the relationship between the role of intestinal microbiota and the development of inflammation within the symbiotic and dysbiotic intestinal microbiota showed significant changes in kidney dysfunction. Several recent studies have determined that dietary factors can significantly influence the activation of immune cells and their mediators. Moreover, dietary changes can profoundly affect the balance of gut microbiota. The aim of this review is to present the importance and factors influencing the differentiation of the human microbiota in the progression of kidney diseases, such as CKD, IgA nephropathy, idiopatic nephropathy, and diabetic kidney disease, with particular emphasis on the role of the immune system. Moreover, the effects of nutrients, bioactive compounds on the immune system in development of chronic kidney disease were reviewed.

Does Low-Protein Diet Influence the Uremic Toxin Serum Levels From the Gut Microbiota in Nondialysis Chronic Kidney Disease Patients?

2018 ◽  
Vol 28 (3) ◽  
pp. 208-214 ◽  
Author(s):  
Ana Paula Black ◽  
Juliana S. Anjos ◽  
Ludmila Cardozo ◽  
Flávia L. Carmo ◽  
Carla J. Dolenga ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Gut Microbiota ◽  
Serum Levels ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Uremic Toxin ◽  
Low Protein

scholarly journals Melatonin Prevents Chronic Kidney Disease-Induced Hypertension in Young Rat Treated with Adenine: Implications of Gut Microbiota-Derived Metabolites

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1211
Author(s):  
Chien-Ning Hsu ◽  
Hung-Wei Yang ◽  
Chih-Yao Hou ◽  
Guo-Ping Chang-Chien ◽  
Sufan Lin ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Gut Microbiota ◽  
Kidney Injury ◽  
Male Rats ◽  
Uremic Toxin ◽  
Protective Effects ◽  
Renal Hypertrophy ◽  
Α Diversity ◽  
Young Rat

Melatonin, a signaling hormone with pleiotropic biofunctions, has shown health benefits. Trimethylamine-N-oxide (TMAO) and asymmetric dimethylarginine (ADMA) are uremic toxins involved in the development of hypertension. TMAO originates from trimethylamine (TMA), a gut microbial product. ADMA is an endogenous nitric oxide (NO) synthase inhibitor. We examined whether melatonin therapy could prevent hypertension and kidney disease by mediating gut microbiota-derived metabolites and the NO pathway using an adenine-induced chronic kidney disease (CKD) young rat model. Six-week-old young Sprague Dawley rats of both sexes were fed a regular diet (C group), a diet supplemented with 0.5% adenine (CKD group), or adenine plus 0.01% melatonin in their drinking water (CKD + M group) for three weeks (N = 8/group). Adenine-fed rats developed renal dysfunction, hypertension, renal hypertrophy and increased uremic toxin levels of TMAO and ADMA. Melatonin therapy prevented hypertension in both sexes and attenuated kidney injury in males. Melatonin reversed the changes to the plasma TMAO-to-TMA ratio induced by CKD in both sexes. Besides, the protective effects of melatonin were associated with restoration of gut microbiota alterations, including increased α-diversity, and enhancement of the abundance of the phylum Proteobacteria and the genus Roseburia in male rats. Melatonin therapy also partially prevented the increases in ADMA in male CKD rats. Melatonin sex-specifically protected young rats against hypertension and kidney injury induced by CKD. The results of this study contribute toward a greater understanding of the interaction between melatonin, gut microbiota-derived metabolites, and the NO pathway that is behind CKD, which will help to prevent CKD-related disorders in children.

scholarly journals Ketoanalogs’ Effects on Intestinal Microbiota Modulation and Uremic Toxins Serum Levels in Chronic Kidney Disease (Medika2 Study)

2021 ◽  
Vol 10 (4) ◽  
pp. 840
Author(s):  
Maria Teresa Rocchetti ◽  
Biagio Raffaele Di Iorio ◽  
Mirco Vacca ◽  
Carmela Cosola ◽  
Stefania Marzocco ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Gut Microbiota ◽  
Therapeutic Option ◽  
Specific Effect ◽  
Serum Levels ◽  
Nutritional Therapy ◽  
Low Protein ◽  
Diet Regimen

Nutritional therapy (NT) is a therapeutic option in the conservative treatment of chronic kidney disease (CKD) patients to delay the start of dialysis. The aim of this study was to evaluate the specific effect of ketoanalogs (KA)-supplemented diets for gut microbiota modulation. In a previous study we observed that the Mediterranean diet (MD) and a KA-supplemented very-low-protein diet (VLPD) modulated beneficially gut microbiota, reducing indoxyl- and p-cresyl-sulfate (IS, PCS) serum levels, and ameliorating the intestinal permeability in CKD patients. In the current study, we added a third diet regimen consisting of KA-supplemented MD. Forty-three patients with CKD grades 3B–4 continuing the crossover clinical trial were assigned to six months of KA-supplemented MD (MD + KA). Compared to MD, KA-supplementation in MD + KA determined (i) a decrease of Clostridiaceae, Methanobacteriaceae, Prevotellaceae, and Lactobacillaceae while Bacteroidaceae and Lachnospiraceae increased; (ii) a reduction of total and free IS and PCS compared to a free diet (FD)—more than the MD, but not as effectively as the VLPD. These results further clarify the driving role of urea levels in regulating gut integrity status and demonstrating that the reduction of azotemia produced by KA-supplemented VLPD was more effective than KA-supplemented MD in gut microbiota modulation mainly due to the effect of the drastic reduction of protein intake rather than the effect of KA.

scholarly journals Assessment of the Diagnostic Validities of Serum NGAL, KIM-1, and L-FABP in Patients With Chronic Kidney Disease

2020 ◽  
Vol 5 (2) ◽  
pp. 48-53
Author(s):  
Tahmineh Ostovar ◽  
Hosein Rezaei ◽  
Javad Zavar Reza
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Area Under The Curve ◽  
Kidney Injury ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Fatty Acid Binding ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Kidney Injury Molecule 1

Introduction: Chronic kidney disease (CKD) is one of the most threatening and important disorders worldwide in both industrial and developing nations. In addition, neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty acid-binding protein (L-FABP), and kidney injury molecule-1 (KIM-1) are three factors suggested as diagnostic and prognostic biomarkers in CKDs. Considering the lack of enough efficiency of the creatinine in the prognosis of the CKD, the present study aimed to assess the relationship between these three factors and CKD occurrence and determine if they could be considered valid biomarkers in this regard. Materials and Methods: The present case-control study was designed enrolling 42 patients with confirmed CKD referring to the Imam Khomeini hospital of Kangan. The participants were 42 years old and gender-matched healthy counterparts. Blood samples were obtained, and then NGAL, KIM-1, and L-FABP were determined by the enzyme-linked immunosorbent assay using commercial kits (Bioassay Technology Laboratory). Finally, the serum creatinine was detected by applying Jaffe’s method. Results: Based on the results, significant differences were found in the serum levels of all four factors between CKD patients and the control group. More precisely, the serum levels of NGAL (P < 0.0001, specificity: 87.6%, sensitivity: 79.3%, and the area under the curve, AUC: 0.89), L-FABP (P < 0.0001, specificity: 83.3%, sensitivity: 78.3%, and AUC: 0.86), KIM-1 (P < 0.0001, specificity: 85.7%, sensitivity: 78.6%, and AUC: 0.88), and creatinine (P < 0.0001) were significantly higher in individuals with CKDs in comparison with controls. Eventually, the serum levels of NGAL, L-FABP, and KIM-1 were significantly correlated with each other in both patient and control groups (P < 0.0001). Conclusion: In general, NGAL, L-FABP, KIM-1, and creatinine could be used as independent biomarkers for the diagnosis of CKD. Moreover, the measurement of NGAL, L-FABP, and KIM-1 altogether could be a valid assessment for the diagnosis of CKD.

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