Gene expression annalysis of peripheral blood cells in patients with chronic kidney disease
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Shinji Kitajima
PROVIDER: E-GEOD-70528 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Patients with chronic kidney disease (CKD) have significantly increased morbidity and mortality resulting from infections and cardiovascular diseases. Since monocytes play an essential role in host immunity, this study was directed to explore the gene expression profile and to identify differences in activated pathways in monocytes relevant to the pathophysiology of atherosclerosis and increased susceptibility to infections. Monocytes from CKD patients (stages 4 and 5, eGFR <20 ml/min x 1.73 m2) and healthy donors were collected from peripheral blood. Microarray gene expression profile was done and data were interpreted by Genespring software and Panther tools website. Western blot was done to validate the pathway members. The results demonstrated that 487 and 258 genes were differentially up- and down regulated respectively in the patient group. Pathways involved in the inflammatory response were highly expressed and the Wnt/β- catenin signaling pathway was the most significant pathway expressed in the patient group (P=0.02). Since this pathway has been attributed to a variety of inflammatory manifestations, the current finding may contribute to dysfunctional monocytes in CKD patients. To develop strategies to interfere with this pathway may improve host immunity and prevent cardiovascular complications in CKD patients. Six gene expression Affymetrix chip were used. Three for each group
2013-01-15 | E-GEOD-43484 | biostudies-arrayexpress
Project description:Several reports have focused on the identification of biological elements involved in the development of abnormal systemic biochemical alterations in chronic kidney disease, but this abundant literature results most of the time fragmented. To better define the cellular machinery associated to this condition, we employed an innovative high-throughput approach based on a whole transcriptomic analysis and classical biomolecular methodologies. The genomic screening of peripheral blood mononuclear cells revealed that 44 genes were up-regulated in both chronic kidney disease patients in conservative treatment (CKD, n=9) and hemodialysis (HD, n=17) compared to healthy subjects (NORM) (p<0.001, FDR=1%). Functional analysis demonstrated that 11/44 genes were involved in the oxidative phosphorylation system (OXPHOS). Western blotting for COXI and COXIV, key constituents of the complex IV of OXPHOS, performed on an independent testing-group (12 NORM, 10 CKD and 14 HD) confirmed the elevated synthesis of these subunits in CKD/HD patients. However, complex IV activity was significantly reduced in CKD/HD patients compared to NORM (p<0.01). Finally, CKD/HD patients presented higher reactive oxygen species and 8-hydroxydeoxyguanosine levels compared to NORM. Taken together these results suggest, for the first time, that CKD/HD patients may have an impaired mitochondrial respiratory system and this condition may be both the consequence and the cause of an enhanced oxidative stress. Experiment Overall Design: For microarray analysis, we studied subjects included in the training group. This population included 8 healthy subjects (NORM), 9 patients with Chronic kidney disease (CKD) on stage II-III (CKD II-III) (mean±SD of estimated GFR by MDRD formula: 41.4±4.3 ml/min) and 17 patients undergoing hemodialysis treatment (HD).All HD patients were stably treated, for at least 1 year, three times a week (4-5 hours per session), using synthetic membrane dialyzers. During the study period, no CKD patients received dialysis treatment. In addition, all patients suffering from infectious diseases, diabetes, chronic lung diseases, neoplasm, or inflammatory diseases and patients receiving antibiotics, corticosteroids, or nonsteroidal anti-inflammatory agents were excluded. No patients had symptomatic coronary artery diseases or a family history of premature cardiovascular diseases. For all subjects, 20 ml of whole blood were collected. For HD patient the biological material was obtained at the beginning of the second HD session of the week. PBMC were isolated by density separation over a Ficoll-PaqueTM (GE healthcare, Sweden) gradient (460g for 30 min). Cells were then counted and their viability was assessed by trypan blue exclusion (>90% PBMC were viable). Total RNA was isolated by RNeasy mini kit Qiagen (QIAGEN AG, Basel, Switzerland) from a minimum of 5 milion cryopreserved PBMC. RNA was, then, processed and hybridized to the GeneChip Human Genome Plus 2.0 or U133A oligonucleotide microarray (Affymetrix, Santa Clara, CA, USA)
2009-12-04 | E-GEOD-15072 | biostudies-arrayexpress
Project description:Patients with chronic kidney disease (CKD) have significantly increased morbidity and mortality resulting from infections and cardiovascular diseases. Since monocytes play an essential role in host immunity, this study was directed to explore the gene expression profile and to identify differences in activated pathways in monocytes relevant to the pathophysiology of atherosclerosis and increased susceptibility to infections. Monocytes from CKD patients (stages 4 and 5, eGFR <20 ml/min x 1.73 m2) and healthy donors were collected from peripheral blood. Microarray gene expression profile was done and data were interpreted by Genespring software and Panther tools website. Western blot was done to validate the pathway members. The results demonstrated that 487 and 258 genes were differentially up- and down regulated respectively in the patient group. Pathways involved in the inflammatory response were highly expressed and the Wnt/β- catenin signaling pathway was the most significant pathway expressed in the patient group (P=0.02). Since this pathway has been attributed to a variety of inflammatory manifestations, the current finding may contribute to dysfunctional monocytes in CKD patients. To develop strategies to interfere with this pathway may improve host immunity and prevent cardiovascular complications in CKD patients.
2013-01-15 | GSE43484 | GEO
Project description:Several reports have focused on the identification of biological elements involved in the development of abnormal systemic biochemical alterations in chronic kidney disease, but this abundant literature results most of the time fragmented. To better define the cellular machinery associated to this condition, we employed an innovative high-throughput approach based on a whole transcriptomic analysis and classical biomolecular methodologies. The genomic screening of peripheral blood mononuclear cells revealed that 44 genes were up-regulated in both chronic kidney disease patients in conservative treatment (CKD, n=9) and hemodialysis (HD, n=17) compared to healthy subjects (NORM) (p<0.001, FDR=1%). Functional analysis demonstrated that 11/44 genes were involved in the oxidative phosphorylation system (OXPHOS). Western blotting for COXI and COXIV, key constituents of the complex IV of OXPHOS, performed on an independent testing-group (12 NORM, 10 CKD and 14 HD) confirmed the elevated synthesis of these subunits in CKD/HD patients. However, complex IV activity was significantly reduced in CKD/HD patients compared to NORM (p<0.01). Finally, CKD/HD patients presented higher reactive oxygen species and 8-hydroxydeoxyguanosine levels compared to NORM. Taken together these results suggest, for the first time, that CKD/HD patients may have an impaired mitochondrial respiratory system and this condition may be both the consequence and the cause of an enhanced oxidative stress.
2009-11-30 | GSE15072 | GEO
Project description:A systems biology approach was used to comprehensively examine the impact of renal disease and hemodialysis (HD) on host response during critical illness. We examined the metabolome, proteome, and transcriptome of 150 patients with critical illness, stratified by renal function. Plasma metabolite values showed greater changes as renal function declined, with the greatest derangements in patients receiving chronic HD. Specifically, 6 uremic retention molecules, 17 other protein catabolites, 7 modified nucleosides, and 7 pentose phosphate sugars increased as renal function declined, consistent with decreased excretion or increased catabolism of amino acids and ribonucleotides. Similarly, the proteome showed increased levels of low-molecular weight proteins and acute phase reactants. The transcriptome revealed a broad-based decrease in mRNA levels among HD patients. Systems integration revealed an unrecognized association between plasma RNASE1 and several RNA catabolites and modified nucleosides. Further, allantoin, N1-methyl-4-pyridone-3-carboxamide, and n-acetylaspartate showed inverse correlations with the majority of significantly down-regulated genes. In conclusion, renal function broadly affected the plasma metabolome, proteome, and peripheral blood transcriptome during critical illness. These changes were not effectively mitigated by hemodialysis. These studies suggest several novel mechanisms whereby renal dysfunction contributes to critical illness. We sequenced peripheral blood RNA of 133 representative subjects with systemic inflammatory response syndrome that had Acute Kidney Injury (AKI) or Hemodialysis (HD). No injury (AKI0; n= 58); AKI Stage 1 (AKI1; n= 36); AKI stage 2 and 3 (AKI23; n= 17); HD (N=22).
2015-07-01 | E-GEOD-67401 | biostudies-arrayexpress
Project description:Cystinuria is the most frequent monogenic cause of renal calculi. We previously described a urinary inflammatory signature in 8 cystinuric patients through quantitative proteomic analysis. Our data suggested an association of abnormal renal function and an inflammatory protein profile. The objectives of the present study were to investigate: i) the urinary proteomic profile in cystinuric patients without chronic kidney disease (CKD), and in a control group of healthy volunteers; ii) the potential effect of urine alkalinization on the urinary proteomic profile in cystinuric patients as this is the cornerstone of the preventive medical treatment. Urinary inflammatory profile was evaluated at baseline in the control group and in cystinuric patients not yet treated or for whom the alkalizing treatment or the cysteine- binding thiols have been discontinuated for at least 3 months and with an eGFR (using the CKD-EPI formula) greater than 60 ml/min/1.73m2 (so without CKD G3-G5). In cystinuric patients, change from baseline urinary inflammatory profile was evaluated after 3 months of alkalizing treatment. Urine proteome was analyzed by Nano- liquid chromatography coupled to high resolution mass spectrometry. Twenty-one cystinuric patients (12 men, median age [IQR] 30.0 years [25.0 – 44.0]), and 7 healthy volunteers (2 men, median age 43.1 years [31.0 – 53.9]) were included. Median eGFR in these two groups was 95 ml/min/1.73m2 [87.5 – 111.5] and 116 ml/min/1.73m2 [91.0 – 120.0] respectively (p=0.38). Healthy volunteers had no inflammatory signature. The inflammatory signature was present in the cystinuric patients at different degrees. A hierarchical clustering of the cystinuric patients according to the intensity of the profile of core inflammation signature (11 proteins) was performed. The signature could clearly separate 5 cystinuric patients with a high inflammation from other cystinuric patients and healthy volunteers. The alkalizing treatment was associated with a decrease in the intensity of the urinary inflammatory profile in all 5 cystinuric patients compared to the initial high level of urinary inflammation. A panel of 11 proteins was found as elevated in some cystinuric patients without CKD G3- G5 and could work as an early inflammatory signature. The alkalizing treatment was associated with a reduction of this urinary inflammation signature, suggesting that this panel of proteins could also be a new tool to monitor the treatment of cystinuric patient.
2024-03-29 | PXD035631 | Pride
Project description:To accelerate the development of disease-modifying therapeutics for Huntington’s disease (HD), a dynamic biomarker of disease activity and treatment response is critically needed. Venous cellular whole blood from 8 patients with Huntington's disease (HD) and 6 control subjects were collected in PAXgene tubes (Wiagen, Valencia, CA). RNA was isolated from whole blood using the PAXgene blood RNA kit (Qiagene) with DNase treatment. The biotinylated complementary RNA was fragmented and hybridized to Affymetrix human genome U133A microarrays. The Affymetrix .CEL files were normalized to “all probe sets” in a standardized matter, and scaled to 100 by the MAS5 5.0 algorithm implemented in the Bioconductor package.
2011-09-01 | E-GEOD-24250 | biostudies-arrayexpress
Project description:Genes related to sleep and wakefulness were evaluated by RNA microarray in patients, including CKD,HD patients and control subjects.
2015-07-07 | GSE70528 | GEO
Project description:Background: We aimed to investigate the effects of intravenous immune globulin (IVIG) and rituximab desensitization treatment on kidney transplant rate and blood gene expression profiles by microrarrays. Methods: We enrolled patients with PRA levels >50% and on the deceased-donor waiting list for >5 years. Patients received IVIG (2.0 g/kg) on day 0 and 30; and rituximab (375 mg/m2) on day 15. The antibodies with mean fluorescence intensity (MFI) values > 5,000 were reported to UNET as unacceptable antigens. The gene expression profiles of blood samples collected in PAXGene tube were studied by Affymetrix HuGene 1.0 ST expression arrays. Results: 40 of the 415 patients (10%) on the waiting list were eligible for desensitization treatment and 11 completed the treatment. While 15 of the remaining 29 patients (52%) received a transplant without therapy, only 2 of the 11 desensitized patients (18%) received transplant during a median follow-up of 217 days. While there were no statistically significant difference in demographics, desensitized patients had higher cPRA values (97% vs. 77%, p=0.0005) and more number of unacceptable antigens (39 vs. 10, p=0.0001). There was no significant change in the mean number of unacceptable antigens (39 ± 22 versus 39 ± 23) or reduction in the mean MFI values (11,333 ± 3,133 vs 11,289 ± 3,386). Analysis of genes chosen as significantly differentially expressed revealed downregulation of genes involved in B cells and immune system (CD79a, B and T lymphocyte associated transcript, B cell scaffold protein, CD22, CXCR5, fas apoptotic inhibitory protein). Gene set enrichment analysis using Pathogenesis Based Transcripts created by Edmonton Group demonstrated significant downregulation of B cell associated (p=0.04) and immunoglobulin transcripts (p=0.03). Conclusion: Although, desensitization with IVIG and rituximab decreases the expression of B cell and immunoglobulin associated transcripts, it was not successful in increasing kidney transplant rate or in decreasing the number of unacceptable antigens. Total of 28 arrays included in this study, which corresponding to 9 individuals with paired pre/post treatment samples and an additional 10 untreated control individuals. pair_analysis_normData.txt for paired analysis of pre/post treatment; ordinary_analysis_normData.txt for non-paired analysis include all samples, except for 38 Pax V0 and 56 Pax V1, which shows technicial bias and lowest array quality, hence removed from analysis.
2011-08-29 | E-GEOD-31729 | biostudies-arrayexpress
Project description:We collected glomeruli from biopsy specimens from IgA nephropathy patients with relatively preserved kidney function (eGFR ≥ 60 mL/min/1.73 m2 and urine protein-to-creatinine ratio < 3 g/g) and from normal kidney cortices by hand microdissection and performed RNA-seq. The transcriptomic profiling of IgA nephropathy glomerulus provide insights for intraglomerular pathophysiology of IgAN before reaching profound kidney dysfunction.
2020-09-30 | GSE141295 | GEO