scholarly journals RNA-Seq analysis reveals critical transcriptome changes caused by sodium butyrate in DN mouse models

2021 ◽  
Vol 41 (4) ◽  
Author(s):  
Hansen Yang ◽  
Zheng Zhang ◽  
Rui Peng ◽  
Luyu Zhang ◽  
Handeng Liu ◽  
...  
Keyword(s):  
Renal Dysfunction ◽  
Sodium Butyrate ◽  
Mesangial Cells ◽  
Underlying Mechanism ◽  
Intestinal Bacterium ◽  
Messenger Rnas ◽  
Rna Seq ◽  
Chain Reactions ◽  
Stage Renal Disease ◽  
End Stage

Abstract Diabetic nephropathy (DN)—a common complication of diabetes—is the primary cause of end-stage renal disease. Sodium butyrate (NaB) is a short-chain fatty acid (SCFA) that is a metabolic product of intestinal bacterium, and its protective effect on the kidney has been reported in cases of DN. However, its underlying mechanism remains unclear. The aim of the present study was to investigate the effect of NaB on globe transcriptome changes in DN. In our study, 8-week-old male db/db mice suffering from DN were randomly divided into two groups: the DN+NaB group (DN mice treated with NaB, 5 g/kg/day) and the DN group (DN mice treated with saline). Further, normal db/m mice were used as the normal control (NC) group. The blood glucose, body weight, urinary microalbumin and urinary creatinine of mice were measured for all three groups. Whole-transcriptome analysis was performed by RNA sequencing (RNA-Seq) to evaluate the profiling of long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs). Bioinformatics analysis was performed to predict the potential NaB-related lncRNAs and genes in DN. The expressions of lncRNAs and mRNAs were tested using the quantitative real-time polymerase chain reactions (qRT-PCRs) in renal tissues and mesangial cells treated with NaB. The results of the present study demonstrated that NaB ameliorated renal dysfunction in DN mice. Moreover, RNA-Seq results identified that some lncRNAs and mRNAs were reversely changed in the DN+NaB group in comparison to those in the DN group. Additionally, the integrated co-expression networks of NaB-related lncRNAs revealed that these lncRNAs interacted with 155 key mRNAs. Furthermore, the co-expression network of inflammation-related lncRNAs and mRNAs demonstrated that those reversed lncRNAs and mRNAs also play essential roles in the inflammatory response. In summary, the present study suggests that NaB ameliorates diabetes-induced renal dysfunction and regulates transcriptome changes in DN.

scholarly journals Inhibition of Kirsten-Ras reduces fibrosis and protects against renal dysfunction in a mouse model of chronic folic acid nephropathy

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Lucy J. Newbury ◽  
Jui-Hui Wang ◽  
Gene Hung ◽  
Bruce M. Hendry ◽  
Claire C. Sharpe
Keyword(s):  
Folic Acid ◽  
Kidney Disease ◽  
Mouse Model ◽  
Renal Dysfunction ◽  
Antisense Oligonucleotides ◽  
Underlying Mechanism ◽  
Therapeutic Benefit ◽  
End Stage

Abstract Chronic Kidney Disease is a growing problem across the world and can lead to end-stage kidney disease and cardiovascular disease. Fibrosis is the underlying mechanism that leads to organ dysfunction, but as yet we have no therapeutics that can influence this process. Ras monomeric GTPases are master regulators that direct many of the cytokines known to drive fibrosis to downstream effector cascades. We have previously shown that K-Ras is a key isoform that drives fibrosis in the kidney. Here we demonstrate that K-Ras expression and activation are increased in rodent models of CKD. By knocking down expression of K-Ras using antisense oligonucleotides in a mouse model of chronic folic acid nephropathy we can reduce fibrosis by 50% and prevent the loss of renal function over 3 months. In addition, we have demonstrated in vitro and in vivo that reduction of K-Ras expression is associated with a reduction in Jag1 expression; we hypothesise this is the mechanism by which targeting K-Ras has therapeutic benefit. In conclusion, targeting K-Ras expression with antisense oligonucleotides in a mouse model of CKD prevents fibrosis and protects against renal dysfunction.

scholarly journals Comprehensive genomic profiling in diabetic nephropathy reveals the predominance of proinflammatory pathways

2013 ◽  
Vol 45 (16) ◽  
pp. 710-719 ◽  
Author(s):  
K. J. Kelly ◽  
Yunlong Liu ◽  
Jizhong Zhang ◽  
Chirayu Goswami ◽  
Hai Lin ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Systems Biology ◽  
Gene Networks ◽  
Inflammatory Cells ◽  
Rna Seq ◽  
Cycle Arrest ◽  
Comprehensive Genomic Profiling ◽  
Novel Therapeutic Strategies ◽  
Stage Renal Disease ◽  
End Stage

Despite advances in the treatment of diabetic nephropathy (DN), currently available therapies have not prevented the epidemic of progressive chronic kidney disease (CKD). The morbidity of CKD, and the inexorable increase in the prevalence of end-stage renal disease, demands more effective approaches to prevent and treat progressive CKD. We undertook next-generation sequencing in a rat model of diabetic nephropathy to study in depth the pathogenic alterations involved in DN with progressive CKD. We employed the obese, diabetic ZS rat, a model that develops diabetic nephropathy, characterized by progressive CKD, inflammation, and fibrosis, the hallmarks of human disease. We then used RNA-seq to examine the combined effects of renal cells and infiltrating inflammatory cells acting as a pathophysiological unit. The comprehensive systems biology analysis of progressive CKD revealed multiple interactions of altered genes that were integrated into morbid networks. These pathological gene assemblies lead to renal inflammation and promote apoptosis and cell cycle arrest in progressive CKD. Moreover, in what is clearly a major therapeutic challenge, multiple and redundant pathways were found to be linked to renal fibrosis, a major cause of kidney loss. We conclude that systems biology applied to progressive CKD in DN can be used to develop novel therapeutic strategies directed to restore critical anomalies in affected gene networks.

scholarly journals In-hospital mortality of acute myocardial infarction in patients with and without renal dysfunction

2016 ◽  
Vol 11 (3) ◽  
Author(s):  
Abdul Rehman Abid ◽  
Muhammad Tahir Mohyuddin ◽  
Liaqat Ali ◽  
Muhammad Shahid Naveed ◽  
Nadeem Hayat Mallick
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Renal Insufficiency ◽  
Renal Disease ◽  
Hospital Mortality ◽  
Renal Dysfunction ◽  
End Stage Renal Disease ◽  
Study Population ◽  
Stage Renal Disease ◽  
End Stage

Objective: To compare in-hospital mortality of acute myocardial Infarction in patients having normal renal functions with renal dysfunction patients. Setting: Emergency ward, Coronary care units and cardiology wards of the Punjab Institute of Cardiology Lahore. Study design: It was a comparative study. Sample size: 1000 consecutive patients presenting with acute myocardial infarction admitted to the Punjab Institute of cardiology Lahore were studied from 1st March 2004 to 15th August 2004. Results: After fulfilling the inclusion criteria 1000 patients were studied. The mean age of the study population was 60.8+9.38 years. Total number of males in the study population was 642(64.2%) while female patients were 358(35.8%). Patients with any degree of renal dysfunction, except those with end-stage renal disease were more likely to present with anterior MI than were patients without renal dysfunction. Patients with end-stage renal disease and more severe renal dysfunction were more likely to develop heart failure during hospitalization, to experience atrial fibrillation, and to have mechanical complications. Streptokinase therapy was used less frequently in patients with any degree of renal dysfunction than in patients without renal dysfunction, despite a similar incidence of MI. In-hospital mortality was 51(12%) in Group I patients, 46(16.6%) in Group II patients, 36(22%) in Group III patients, 35(27.7%) in Group IV patients and 5(35.7%) in Group V patients with a p value of <0.0001. Severe renal insufficiency had the maximum in-hospital mortality with OR of 5.4 and 95% confidence interval of 2.9-10.3 followed by end stage renal disease OR 5.1 (CI 2.2-12.1), moderate renal insufficiency OR 4.1 (CI 2.3-7.2) and mild renal insufficiency OR 1.9(CI 1.1-3.1) with a p value of <0.0001. Similarly congestive heart failure during hospital stay was observed in 20(4.7%) patients in Group I, 17(6.1%) patients in Group II, 15(9.4%) patients in Group III, 16(12.6%) patients in Group IV and 4(28.6%) patients in Group V. Similar trends were observed in mechanical complications and post myocardial arrhythmias in the study population, Conclusion: Patients with renal dysfunction who have acute MI are a high-risk population and suffer from increased mortality once they are admitted to the hospital. This is because of presence of more risk factors in this sub set of patients.

scholarly journals Determination of the Optimal Procalcitonin Threshold for Infection in Patients With Impaired Renal Function at a Community Hospital

2020 ◽  
Vol 36 (4) ◽  
pp. 157-163
Author(s):  
Caitlin Bowman ◽  
Elizabeth W. Covington
Keyword(s):  
Renal Dysfunction ◽  
Bacterial Infections ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Kidney Injury ◽  
Future Studies ◽  
Institutional Review ◽  
Stage Renal Disease ◽  
End Stage

Background: Procalcitonin (PCT) is a biomarker that can help identify bacterial infections but can be difficult to interpret in the presence of renal dysfunction, which can elevate PCT even in the absence of infection. Objective: To determine the optimal PCT threshold to identify infection in patients with renal dysfunction and pneumonia or sepsis. Methods: A retrospective analysis was performed for inpatients with creatinine clearance of ≤60 mL/min and PCT level from 2018 to 2019. A pharmacist blinded to study outcomes classified patients as infected or noninfected based on predetermined criteria. Receiver operating characteristic curve analysis was performed to establish the optimal PCT threshold overall, as well as in subgroups of patients with chronic kidney disease (CKD), acute kidney injury (AKI), and end-stage renal disease (ESRD). Institutional review board approval was obtained. Results: A total of 198 patients were included in the study (99 infected, 99 noninfected). The optimal threshold in the AKI, CKD, and ESRD subgroups was determined to be 1.5 ng/mL, 0.1 ng/mL, and 1.75 ng/mL, respectively. Conclusion: The results of this study show that PCT thresholds were specific to type of renal dysfunction. These results differ from the traditionally accepted PCT threshold of 0.5 ng/mL for sepsis and 0.25 mg/mL for pneumonia. Future studies should confirm the appropriate PCT threshold in ESRD and CKD patient populations.

scholarly journals Pharmacokinetics of Linezolid in Subjects with Renal Dysfunction

2003 ◽  
Vol 47 (9) ◽  
pp. 2775-2780 ◽  
Author(s):  
Michael E. Brier ◽  
Dennis J. Stalker ◽  
George R. Aronoff ◽  
Donald H. Batts ◽  
Kristi K. Ryan ◽  
...  
Keyword(s):  
Renal Function ◽  
Renal Disease ◽  
Renal Dysfunction ◽  
End Stage Renal Disease ◽  
Oral Clearance ◽  
Apparent Oral Clearance ◽  
Severe Renal Insufficiency ◽  
Plasma And Urine Samples ◽  
Stage Renal Disease ◽  
End Stage

ABSTRACT Linezolid is a member of a new, unique class of synthetic antibacterial agents called oxazolidinones that are effective against gram-positive bacteria, including vancomycin-resistant organisms. We tested the hypothesis that the linezolid clearance would not be altered in subjects with renal dysfunction. Twenty-four subjects with renal function that ranged from normal to severe chronic impairment were enrolled, including patients with end-stage renal disease who were maintained on hemodialysis. Hemodialysis subjects were studied while they were both on and off dialysis. Linezolid was administered as a single oral 600-mg dose, and plasma and urine samples were assayed for linezolid and metabolites for 48 h for all subjects and for up to 96 h for those subjects with impaired renal function not on dialysis. The total apparent oral clearance of linezolid did not change with renal function and ranged from 92.5 to 109.6 ml/min for subjects not requiring dialysis. For subjects on dialysis, the total apparent oral clearance increased from 76.6 ml/min on their off-dialysis day to 130.0 ml/min on their on-dialysis day. Approximately one-third of the dose was removed by dialysis. However, those subjects with severe renal insufficiency (creatinine clearance, <40 ml/min) and those with end-stage renal disease maintained on hemodialysis had higher concentrations of both metabolites. We conclude that no adjustment of the linezolid dosage is needed in subjects with renal dysfunction or subjects on hemodialysis.

scholarly journals Risk of bloodstream infection in patients with renal dysfunction: a population-based cohort study

2020 ◽  
Vol 148 ◽  
Author(s):  
Gabrielle Dagasso ◽  
Joslyn Conley ◽  
Lisa Steele ◽  
Elizabeth E. C. Parfitt ◽  
Kelsey Pasquill ◽  
...  
Keyword(s):  
Cohort Study ◽  
Renal Dysfunction ◽  
Bloodstream Infections ◽  
Population Based ◽  
Increased Risk ◽  
Rate Ratios ◽  
Stage Renal Disease ◽  
End Stage ◽  
Estimated Glomerular Filtration Rates ◽  
Community Onset

Abstract Although patients with end-stage renal disease (ESRD) are known to be at high risk for developing bloodstream infections (BSI), the risk associated with lesser degrees of renal dysfunction is not well defined. We sought to determine the risk for acquiring and dying from community-onset BSIs among patients with renal dysfunction. A retrospective, population-based cohort study was conducted among adult residents without ESRD in the western interior of British Columbia. Estimated glomerular filtration rates (eGFR) were determined for cases and incidence rate ratios (IRR) were calculated using prevalence estimates. Overall, 1553 episodes of community-onset BSI were included of which 39%, 32%, 17%, 9%, 2% and 1% had preceding eGFRs of ≥90, 60–89, 45–59, 30–44, 15–29 and <15 ml/min/m2, respectively. As compared to those with eGFR ≥60 ml/min/m2, patients with eGFR 30–59 ml/min/m2 (IRR 4.4; 95% confidence interval (CI) 3.9–4.9) and eGFR <30 ml/min/m2 (IRR 7.0; 95% CI 5.0–9.5) were at significantly increased risk for the development of community-onset BSI. An eGFR <30 ml/min/m2 was an independent risk factor for death (odds ratio 2.3; 95% CI 1.01–5.15). Patients with renal dysfunction are at increased risk for developing and dying from community-onset BSI that is related to the degree of dysfunction.

Effect of high glucose on gene expression in mesangial cells: upregulation of the thiol pathway is an adaptational response

2004 ◽  
Vol 17 (3) ◽  
pp. 271-282 ◽  
Author(s):  
Jolean Morrison ◽  
Kristen Knoll ◽  
Martin J. Hessner ◽  
Mingyu Liang
Keyword(s):  
Lipid Peroxidation ◽  
Mrna Expression ◽  
High Glucose ◽  
Molecular Mechanisms ◽  
Mesangial Cells ◽  
Critical Role ◽  
Glomerular Mesangial Cells ◽  
Human Mesangial Cells ◽  
Stage Renal Disease ◽  
End Stage

Pathological alterations in glomerular mesangial cells play a critical role in the development of diabetic nephropathy, the leading cause of end-stage renal disease. Molecular mechanisms mediating such alterations, however, remain to be fully understood. The present study first examined the effect of high glucose on the mRNA expression profile in rat mesangial cells using cDNA microarray. Based on variation-weighted criteria and with a false discovery rate of 4.3%, 459 of 17,664 cDNA elements examined were found to be upregulated and 151 downregulated by exposure to 25 mM d-glucose for 5 days. A large number of differentially expressed genes belonged to several functional categories, indicating high glucose had a profound effect on mesangial cell proliferation, protein synthesis, energy metabolism, and, somewhat unexpectedly, protein sorting and the cytoskeleton. Interestingly, several thiol antioxidative genes (glutathione peroxidase 1, peroxiredoxin 6, and thioredoxin 2) were found by microarray and confirmed by real-time PCR to be upregulated by high glucose. These changes suggested that the oxidative stress known to be induced in mesangial cells by high glucose might be buffered by upregulation of the thiol antioxidative pathway. Upregulation of thiol antioxidative genes also occurred in high-glucose-treated human mesangial cells and in glomeruli isolated from rats after 1 wk of streptozotocin-induced diabetes, but not in human proximal tubule cells. High glucose slightly increased lipid peroxidation and decreased the amount of reduced thiols in rat and human mesangial cells. Disruption of the thiol antioxidative pathway by two different thiol-oxidizing agents resulted in a three- to fivefold increase in high-glucose-induced lipid peroxidation. In summary, the present study provided a global view of the short-term effect of high glucose on mesangial cells at the level of mRNA expression and identified the upregulation of the thiol antioxidative pathway as an adaptational response of mesangial cells to high glucose.

A Case Report of Neurotoxicity After Prolonged Doses of Acyclovir in a Patient With Renal Dysfunction

2019 ◽  
Vol 33 (2) ◽  
pp. 217-221 ◽  
Author(s):  
Godsfavour O. Umoru ◽  
Punit J. Shah ◽  
Farheen Tariq
Keyword(s):  
Renal Dysfunction ◽  
Viral Infections ◽  
Clinical Symptoms ◽  
Plasma Concentrations ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Serum Levels ◽  
Drug Induced ◽  
Stage Renal Disease ◽  
End Stage

Renal dysfunction is a significant risk factor for acyclovir-induced neurotoxicity and altered mentation and myoclonic movements are the most common clinical symptoms observed. In majority of reported cases, neurological sequelae associated with acyclovir-induced neurotoxicity often mimic viral infections of the central nervous system and makes diagnosis of the former challenging. Although plasma concentrations of the drug may not always correlate with neurotoxic symptoms, obtaining serum levels of acyclovir may be helpful in confirming drug-induced neurotoxicity. Hemodialysis has been shown to significantly improve altered mentation in patients with suspected or confirmed acyclovir-induced neurotoxicity. Here, we report a definite case of acyclovir-induced neurotoxicity in a patient with end-stage renal disease. Clinical improvements in neurologic symptoms were observed following discontinuation of the drug and hemodialysis.

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