Project description:We investigated the endogenous peptidomes of spent hemodialysate, urine, and plasma, to shed light on peptide handling in the kidney. Our study was based on the hypothesis that hemodialysis replaces glomerular filtration and aims at gaining first insight into the comparative distribution of the peptidome/proteome in these body fluids. These data are expected to support insight into the underlying biological and physiological processes that take place in the kidney, which may help to advance treatment in advanced-stage chronic kidney disease and detoxification in renal replacement therapies.
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).
Project description:Understanding gut bacterial composition and proteome changes in patients with early-stage chronic kidney disease (CKD) could lead to better methods of controlling the disease progression. Here, we investigated the gut microbiome and microbial functions in patients with S. stercoralis infection (strongyloidiasis) and early-stage CKD.
Project description:Chronic kidney disease is associated with an increased cardiovascular morbidity/mortality and the altered biological properties of HDL particles have been pointed out in this burden. We aimed to describe the proteome of HDL from non-diabetic hemodialysis patients and proteins which were up and down represented in HDL particles of HD patients compared to heathy controls. HDL were sampled from the plasma of 9 non-diabetic HD and 9 potential kidney-donors patients with a sequential potassium bromide stepwise density gradient ultracentrifugation. Samples were analyzed using an nano-RSLC coupled on line with a Q-Orbitrap.
2020-05-26 | PXD013301 | Pride
Project description:Oral microbiome in chronic kidney disease patients Raw sequence reads
| PRJNA422651 | ENA
Project description:Oral microbiome analysis of young patients with chronic kidney disease
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)
Project description:End-stage renal disease patients experience uremia-driven immune compromise characterized by complex alterations of both innate and adaptive immunity, and results in higher susceptibility to infection and lower response to vaccination. This immune compromise, coupled with greater risk of exposure to infectious disease at hemodialysis (HD) centers, motivates an examination of immune response to the COVID-19 mRNA-based BTN162b2 vaccine. We performed gene expression profiling by RNA-seq across 6 time points to assess vaccine response in healthy controls and hemodialysis patients over time.