Proteome-Wide Changes in Blood Biomarkers During Hemodialysis.
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ABSTRACT:
SUBMITTER: Lanktree MB
PROVIDER: S-EPMC10831367 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
Publications
Proteome-Wide Changes in Blood Biomarkers During Hemodialysis.
Lanktree Matthew B MB Collister David D Pigyere Marie M Mazzetti Andrea A Paré Guillaume G Walsh Michael M
Kidney international reports 20231102 1
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Project description:To investigate the predictive value of the central arterial waveform for intradialytic blood pressure (BP) change, a total of 152 hemodialysis patients (mean age 68 years) on a thrice-weekly hemodialysis schedule were enrolled, and at both the first and second session of the week, BP and central arterial waveform were measured every 30 min during hemodialysis. In both sessions, a 1-standard deviation increase in baseline subendocardial viability ratio (SEVR), an index of subendocardial perfusion, as well as in baseline systolic BP (SBP) was an independent predictor of maximum SBP decrease ≥ 30 mmHg during hemodialysis. When divided into four groups based on the respective median level of SEVR in the SBP ≥ median and SBP < median groups, intradialytic SBP change was different among the subgroups. Multiple logistic regression analysis revealed that, compared with the SBP < median; low SEVR group, the SBP < median; high SEVR group had lower risk, and the SBP ≥ median; low SEVR group had higher risk of SBP decrease ≥ 30 mmHg, but the risk did not differ from that in the SBP ≥ median; high SEVR group. Predialysis subendocardial perfusion evaluated by SEVR was associated with the maximum intradialytic BP decrease, and evaluation of the central arterial waveform could be used as complementary screening for intradialytic BP change.
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Project description:BackgroundRelative blood volume (RBV) monitoring is widely used in hemodialysis (HD) patients, yet the association between intradialytic RBV and mortality is unknown.MethodsIntradialytic RBV was recorded once/min during a 6-month baseline period; all-cause mortality was noted during follow-up. RBV at 1, 2 and 3 h into HD served as a predictor of all-cause mortality during follow-up. We employed Kaplan-Meier analysis, univariate and adjusted Cox proportional hazards models for survival analysis.ResultsWe studied 842 patients. During follow-up (median 30.8 months), 249 patients (29.6%) died. The following hourly RBV ranges were associated with improved survival: first hour, 93-96% [hazard ratio (HR) 0.58 (95% confidence interval (CI) 0.42-0.79)]; second hour, 89-94% [HR 0.54 (95% CI 0.39-0.75)]; third hour, 86-92% [HR 0.46 (95% CI 0.33-0.65)]. In about one-third of patients the RBV was within these ranges and in two-thirds it was above. Subgroup analysis by median age (≤/> 61 years), sex, race (white/nonwhite), predialysis systolic blood pressure (SBP; ≤/> 130 mmHg) and median interdialytic weight gain (≤/> 2.3 kg) showed comparable favorable RBV ranges. Patients with a 3-h RBV between 86 and 92% were younger, had higher ultrafiltration volumes and rates, similar intradialytic average and nadir SBPs and hypotension rates, lower postdialysis SBP and a lower prevalence of congestive heart failure when compared with patients with an RBV >92%. In the multivariate Cox analysis, RBV ranges remained independent and significant outcome predictors.ConclusionSpecific hourly intradialytic RBV ranges are associated with lower all-cause mortality in chronic HD patients.
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Project description:Pregnancy involves a significant number of physiological changes. A normal pregnancy is essential to ensure healthy maternal and fetal development. We sought to explore whether the urinary proteome could reflect the pregnancy process. Urine samples were collected from pregnant and control rats on various gestational days. The urinary proteome was profiled by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), and differential proteins were obtained by comparing to the gestational day 1 of the same group at each time point. Many pathways related to embryo implantation and trophoblast differentiation were enriched in the early days in urine. Liver, kidney, and bone development started early to be enriched in the pregnant group, but not in the control group. Interestingly, the developmental processes of the fetal heart such as heart looping and endocardial cushion formation could be seen in urine of pregnant rats. Moreover, the timings were consistent with those of embryological studies. The timing of the surfactant appearance in urine was right before birth. The differential proteins related to pancreas development appeared in urine at the time during reported time of pancreatic cell proliferation and differentiation. These processes were enriched only in the pregnant group and not in the control group. Furthermore, coagulation-associated pathways were found to be increasingly prominent before labor. Our results indicated that the urine proteome of pregnant rats can reflect the process of pregnancy, even fetal embryonic development. Maternal urinary proteome detection was earlier than the developmental time point of tissue sections observed by microscopy.
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Project description:BackgroundAccumulating evidence indicates importance of RNA regulation in cancer. This includes events such as splicing, translation, and regulation of noncoding RNAs, functions which are governed by RNA binding proteins (RBPs).AimsTo find which RBPs could be relevant for prostate cancer, we performed systematic screening of RBP expression in clinical prostate cancer.Methods and resultsWe interrogated four proteome-wide proteomics datasets including tumor samples of primary, castration resistant, and metastatic prostate cancer. We found that, while the majority of RBPs are expressed but not significantly altered during prostate cancer development and progression, expression of several RBPs increases in advanced disease. Interestingly, most of the differentially expressed RBPs are not targets of differential posttranscriptional phosphorylation during disease progression. The RBPs undergoing expression changes have functions in, especially, poly(A)-RNA binding, nucleocytoplasmic transport, and cellular stress responses, suggesting that these may play a role in formation of castration resistance. Pathway analyzes indicate that increased ribosome production and chromatin-related functions of RBPs are also linked to castration resistant and metastatic prostate cancers. We selected a group of differentially expressed RBPs and studied their role in cultured prostate cancer cells. With siRNA screens, several of these were indicated in survival (DDX6, EIF4A3, PABPN1), growth (e.g., EIF5A, HNRNPH2, LRRC47, and NVL), and migration (e.g., NOL3 and SLTM) of prostate cancer cells. Our analyzes further show that RRP9, a U3 small nucleolar protein essential for ribosome formation, undergoes changes at protein level during metastasis in prostate cancer.ConclusionIn this work, we recognized significant molecular alterations in RBP profiles during development and evolution of prostate cancer. Our study further indicates several functionally significant RBPs warranting further investigation for their functions and possible targetability in prostate cancer.
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Project description:Long-chain fatty acids (LCFAs) serve as energy sources, components of cell membranes, and precursors for signaling molecules. Uremia alters LCFA metabolism so that the risk of cardiovascular events in chronic kidney disease (CKD) is increased. End-stage renal disease (ESRD) patients undergoing dialysis are particularly affected and their hemodialysis (HD) treatment could influence blood LCFA bioaccumulation and transformation. We investigated blood LCFA in HD patients and studied LCFA profiles in vivo by analyzing arterio-venous (A-V) LFCA differences in upper limbs. We collected arterial and venous blood samples from 12 ESRD patients, before and after HD, and analyzed total LCFA levels in red blood cells (RBCs) and plasma by LC-MS/MS tandem mass spectrometry. We observed that differences in arterial and venous LFCA contents within RBCs (RBC LCFA A-V differences) were affected by HD treatment. Numerous saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA) n-6 showed negative A-V differences, accumulated during peripheral tissue perfusion of the upper limbs, in RBCs before HD. HD reduced these differences. The omega-3 quotient in the erythrocyte membranes was not affected by HD in either arterial or venous blood. Our data demonstrate that A-V differences in fatty acids status of LCFA are present and active in mature erythrocytes and their bioaccumulation is sensitive to single HD treatment.
| S-EPMC8949028 | biostudies-literature
Project description:Used hemodialysis membranes (HD-M) are a valuable reservoir of biological information. Proteins bind to HD-M, but whether this process depends on the type of membrane or patient factors or selectively affects specific protein classes has not been adequately elucidated. State-of-the-art proteomics techniques are capable of identifying and quantifying this therapy-specific subproteome to enable the analysis of disease- or membrane-induced pathophysiologies. We demonstrate the feasibility of the deep proteomic characterization of the extracorporeal proteome adsorbed to HD-M. A shotgun proteomics approach using nano-flow liquid chromatography coupled to mass-spectrometry identified 1648 unique proteins eluted by a chaotropic buffer from the HD-M of eight patients. In total, 995 proteins were present in all eluates; a more stringent approach showed that a core proteome of 310 proteins could be identified independently in all samples. Stability of the dialyzer proteome was demonstrated by a >90% re-identification rate on longitudinal samples of a single patient. The core proteome showed an overrepresentation of pathways of hemostasis and the immune system, and showed differences in membrane materials (polysulfone vs. helixone). This study demonstrates that optimized conditions combined with high-performance proteomics enable the in-depth exploration of the subproteome bound to HD-M, yielding a stable core proteome that can be exploited to study patient-specific factors and improve hemodialysis therapy.
| S-EPMC9695746 | biostudies-literature
Project description:Blood lipid traits are treatable and heritable risk factors for heart disease, a leading cause of mortality worldwide. Although genome-wide association studies (GWAS) have discovered hundreds of variants associated with lipids in humans, most of the causal mechanisms of lipids remain unknown. To better understand the biological processes underlying lipid metabolism, we investigated the associations of plasma protein levels with total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL), and low-density lipoprotein cholesterol (LDL) in blood. We trained protein prediction models based on samples in the Multi-Ethnic Study of Atherosclerosis (MESA) and applied them to conduct proteome-wide association studies (PWAS) for lipids using the Global Lipids Genetics Consortium (GLGC) data. Of the 749 proteins tested, 42 were significantly associated with at least one lipid trait. Furthermore, we performed transcriptome-wide association studies (TWAS) for lipids using 9,714 gene expression prediction models trained on samples from peripheral blood mononuclear cells (PBMCs) in MESA and 49 tissues in the Genotype-Tissue Expression (GTEx) project. We found that although PWAS and TWAS can show different directions of associations in an individual gene, 40 out of 49 tissues showed a positive correlation between PWAS and TWAS signed p-values across all the genes, which suggests a high-level consistency between proteome-lipid associations and transcriptome-lipid associations.
| S-EPMC10473643 | biostudies-literature
Project description:Blood lipid traits are treatable and heritable risk factors for heart disease, a leading cause of mortality worldwide. Although genome-wide association studies (GWASs) have discovered hundreds of variants associated with lipids in humans, most of the causal mechanisms of lipids remain unknown. To better understand the biological processes underlying lipid metabolism, we investigated the associations of plasma protein levels with total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol in blood. We trained protein prediction models based on samples in the Multi-Ethnic Study of Atherosclerosis (MESA) and applied them to conduct proteome-wide association studies (PWASs) for lipids using the Global Lipids Genetics Consortium (GLGC) data. Of the 749 proteins tested, 42 were significantly associated with at least one lipid trait. Furthermore, we performed transcriptome-wide association studies (TWASs) for lipids using 9,714 gene expression prediction models trained on samples from peripheral blood mononuclear cells (PBMCs) in MESA and 49 tissues in the Genotype-Tissue Expression (GTEx) project. We found that although PWASs and TWASs can show different directions of associations in an individual gene, 40 out of 49 tissues showed a positive correlation between PWAS and TWAS signed p values across all the genes, which suggests high-level consistency between proteome-lipid associations and transcriptome-lipid associations.
| S-EPMC11650301 | biostudies-literature
Project description:ObjectivesPlasma levels of copeptin, a surrogate marker for the vasoconstrictor hormone arginine vasopressin (AVP), are increased in hemodialysis patients. Presently, it is unknown what drives copeptin levels in hemodialysis patients. We investigated whether the established physiological stimuli for copeptin release, i.e. plasma osmolality, blood volume and mean arterial pressure (MAP), are operational in hemodialysis patients.MethodsOne hundred and eight prevalent, stable hemodialysis patients on a thrice-weekly dialysis schedule were studied during hemodialysis with constant ultrafiltration rate and dialysate conductivity in this observational study. Plasma levels of copeptin, sodium, MAP, and blood volume were measured before, during and after hemodialysis. Multivariate analysis was used to determine the association between copeptin (dependent variable) and the physiological stimuli plasma sodium, MAP, excess weight as well as NT-pro-BNP immediately prior to dialysis and between copeptin and changes of plasma sodium, MAP and blood volume with correction for age, sex and diabetes during dialysis treatment.ResultsPatients were 63 ± 15.6 years old and 65% were male. Median dialysis vintage was 1.6 years (IQR 0.7-4.0). Twenty-three percent of the patients had diabetes and 82% had hypertension. Median predialysis copeptin levels were 141.5 pmol/L (IQR 91.0-244.8 pmol/L). Neither predialysis plasma sodium levels, nor NT-proBNP levels, nor MAP were associated with predialysis copeptin levels. During hemodialysis, copeptin levels rose significantly (p<0.01) to 163.0 pmol/L (96.0-296.0 pmol/L). Decreases in blood volume and MAP were associated with increases in copeptin levels during dialysis, whereas there was no significant association between the change in plasma sodium levels and the change in copeptin levels.ConclusionsPlasma copeptin levels are elevated predialysis and increase further during hemodialysis. Volume stimuli, i.e. decreases in MAP and blood volume, rather than osmotic stimuli, are associated with change in copeptin levels during hemodialysis.
| S-EPMC4431805 | biostudies-literature
Project description:PurposeTo investigate the aqueous humor proteome in patients with glaucoma and a control group.MethodAqueous humor was obtained from five human donors diagnosed with primary open angle glaucoma (POAG) and five age- and sex-matched controls undergoing cataract surgery. Quantitative proteome analysis of the aqueous humor by hyper reaction monitoring mass spectrometry (HRM-MS) based on SWATH technology was performed.ResultsExpression levels of 87 proteins were found to be different between glaucomatous and control aqueous humor. Of the 87 proteins, 34 were significantly upregulated, whereas 53 proteins were downregulated in the aqueous humor from glaucoma patients compared to controls. Differentially expressed proteins were found to be involved in cholesterol-related, inflammatory, metabolic, antioxidant as well as proteolysis-related processes.ConclusionGlaucoma leads to profound changes to the aqueous humor proteome consistent with an altered metabolic state, an inflammatory response and impaired antioxidant defense.
| S-EPMC5082887 | biostudies-literature