Search

Background: Quantitative proteomics is an invaluable tool in biomedicine for the massive comparative analysis of protein component of complex biological samples. In the last two decades, this technique has been used to describe proteins potentially involved in the pathophysiological mechanisms of preeclampsia as well as to identify protein biomarkers that could be used with diagnostic/prognostic purposes in pre-eclampsia. Results: We have done a systematic review of all proteomics-based papers describing differentially expressed proteins in this disease. Searching Pubmed with the terms pre-eclampsia and proteomics, restricted to the Title/Abstract and to MeSH fields, and following manual curation of the original list, retrieved 69 original articles corresponding to the 2004–2020 period. We have only considered those results based on quantitative, unbiased proteomics studies conducted in a controlled manner on a cohort of control and pre-eclamptic individuals. The sources of biological material used were serum/plasma (n = 32), placenta (n = 23), urine (n = 9), cerebrospinal fluid (n = 2), amniotic fluid (n = 2) and decidual tissue (n = 1). Overall results were filtered based on two complementary criteria. First, we have only accounted all those proteins described in at least two (urine), three (placenta) and four (serum/plasma) independent studies. Secondly, we considered the consistency of the quantitative data, that is, inter-study agreement in the protein abundance control/pre-eclamptic ratio. The total number of differential proteins in serum/plasma (n = 559), placenta (n = 912), urine (n = 132) and other sources of biological material (n = 26), reached 1631 proteins. Data were highly complementary among studies, resulting from differences on biological sources, sampling strategies, patient stratification, quantitative proteomic analysis methods and statistical data analysis. Therefore, stringent filtering was applied to end up with a cluster of 18, 29 and 16 proteins consistently regulated in pre-eclampsia in placenta, serum/plasma and urine, respectively. The systematic collection, standardization and evaluation of the results, using diverse filtering criteria, provided a panel of 63 proteins whose levels are consistently modified in the context of pre-eclampsia. [ABSTRACT FROM AUTHOR]

Background: Reproductive function in women with end stage renal disease generally improves after kidney transplant. However, pregnancy remains challenging due to the risk of adverse clinical outcomes.Methods: We searched PubMed/MEDLINE, Elsevier EMBASE, Scopus, BIOSIS Previews, ISI Science Citation Index Expanded, and the Cochrane Central Register of Controlled Trials from date of inception through August 2017 for studies reporting pregnancy with kidney transplant.Results: Of 1343 unique studies, 87 met inclusion criteria, representing 6712 pregnancies in 4174 kidney transplant recipients. Mean maternal age was 29.6 ± 2.4 years. The live-birth rate was 72.9% (95% CI, 70.0-75.6). The rate of other pregnancy outcomes was as follows: induced abortions (12.4%; 95% CI, 10.4-14.7), miscarriages (15.4%; 95% CI, 13.8-17.2), stillbirths (5.1%; 95% CI, 4.0-6.5), ectopic pregnancies (2.4%; 95% CI, 1.5-3.7), preeclampsia (21.5%; 95% CI, 18.5-24.9), gestational diabetes (5.7%; 95% CI, 3.7-8.9), pregnancy induced hypertension (24.1%; 95% CI, 18.1-31.5), cesarean section (62.6, 95% CI 57.6-67.3), and preterm delivery was 43.1% (95% CI, 38.7-47.6). Mean gestational age was 34.9 weeks, and mean birth weight was 2470 g. The 2-3-year interval following kidney transplant had higher neonatal mortality, and lower rates of live births as compared to > 3 year, and < 2-year interval. The rate of spontaneous abortion was higher in women with mean maternal age < 25 years and > 35 years as compared to women aged 25-34 years.Conclusion: Although the outcome of live births is favorable, the risks of maternal and fetal complications are high in kidney transplant recipients and should be considered in patient counseling and clinical decision making. [ABSTRACT FROM AUTHOR]

Background: Nonclinical studies indicate that the hormone relaxin is a good candidate for a safe cervical ripening agent that does not cause uterine contractions.Methods: This Phase II study (conducted November 2, 2005-October 20, 2006) was a randomised, double blind, placebo controlled trial testing 24-h intravenous infusion of serelaxin (recombinant human relaxin) or placebo for cervical ripening in 72 healthy, primiparous women. Eligible subjects had a singleton pregnancy ≥40 weeks, were planned for elective induction, had vertex presentation of the fetus, intact membranes and a Bishop score at screening ≤4. In Part A of the study, safety evaluation of three escalating doses of serelaxin (7.5, 25 or 75 μg/kg/day) or placebo was performed in 22 subjects admitted to the hospital 24 h prior to scheduled induction (n = 7, 4, 4, and 7 subjects, respectively). The highest safe dose from Part A and placebo were then tested in Part B for safety and cervical ripening (n = 25 subjects/arm). Planned randomisation ratio was of 4:2 (serelaxin:placebo) for each dose group in Part A and 1:1 for Part B. For analysis, subjects in Part B were pooled with those receiving the same dose in Part A and all subjects receiving placebo were pooled. The primary efficacy endpoint was change from baseline in Bishop score at 6, 12 and 24 h or end of study drug administration. Maternal safety evaluations included adverse events and vital signs through 4 weeks. Fetal assessments included serial heart rate monitoring and nonstress testing. Neonatal assessments included Apgar scores, NICU admissions, and adverse events through 4 weeks.Results: Overall, 74 subjects were randomized and 72 were treated. There were no significant differences between the groups receiving the highest safe dose of serelaxin (75 μg/kg/day) and placebo in the primary or secondary efficacy endpoints. Changes from baseline in Bishop score at 24 h were 4.19 ± 1.9 and 3.26 ± 2.26 in the pooled placebo and serelaxin groups, respectively (p = 0.2507). Serelaxin was well tolerated and no anti-serelaxin antibodies were detected in either subjects or neonates.Conclusion: Serelaxin infusion at the end of pregnancy was well tolerated but did not advance cervical ripening.Trial Registration: Clinicaltrials.gov identifier NCT00259103 (15 November 2005). [ABSTRACT FROM AUTHOR]

Background: Preeclampsia (PE) is a pregnancy-related vascular disorder which is the leading cause of maternal morbidity and mortality. We sought to identify novel serological protein markers to diagnose PE with a multi-’omics’ based discovery approach. Methods: Seven previous placental expression studies were combined for a multiplex analysis, and in parallel, two-dimensional gel electrophoresis was performed to compare serum proteomes in PE and control subjects. The combined biomarker candidates were validated with available ELISA assays using gestational age-matched PE (n=32) and control (n=32) samples. With the validated biomarkers, a genetic algorithm was then used to construct and optimize biomarker panels in PE assessment. Results: In addition to the previously identified biomarkers, the angiogenic and antiangiogenic factors (soluble fms-like tyrosine kinase (sFlt-1) and placental growth factor (PIGF)), we found 3 up-regulated and 6 down-regulated biomakers in PE sera. Two optimal biomarker panels were developed for early and late onset PE assessment, respectively. Conclusions: Both early and late onset PE diagnostic panels, constructed with our PE biomarkers, were superior over sFlt-1/PIGF ratio in PE discrimination. The functional significance of these PE biomarkers and their associated pathways were analyzed which may provide new insights into the pathogenesis of PE. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) and coronary artery disease (CAD) are independently associated with increased vascular stiffness. We examined whether renal function contributes to vascular stiffness independently of CAD status. Methods: We studied 160 patients with CAD and 169 subjects without CAD. The 4-variable MDRD formula was used to estimate glomerular filtration rate (eGFR); impaired renal function was defined as eGFR <60 mL/min. Carotid-femoral pulse wave velocity (PWV) was measured with the SphygmoCor® device. Circulating biomarkers were assessed in plasma using xMAP® multiplexing technology. Results: Patients with CAD and impaired renal function had greater PWV compared to those with CAD and normal renal function (10.2 [9.1;11.2] vs 7.3 [6.9;7.7] m/s; P < 0.001). In all patients, PWV was a function of eGFR (β = -0.293; P < 0.001) even after adjustment for age, sex, systolic blood pressure, body mass index and presence or absence of CAD. Patients with CAD and impaired renal function had higher levels of adhesion and inflammatory molecules including E-selectin and osteopontin (all P < 0.05) compared to those with CAD alone, but had similar levels of markers of oxidative stress. Conclusions: Renal function is a determinant of vascular stiffness even in patients with severe atherosclerotic disease. This was paralleled by differences in markers of cell adhesion and inflammation. Increased vascular stiffness may therefore be linked to inflammatory remodeling of the vasculature in people with impaired renal function, irrespective of concomitant atherosclerotic disease. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is a prominent problem in hospitalized patients and associated with increased morbidity and mortality. Clinical medicine is currently hampered by the lack of accurate and early biomarkers for diagnosis of AKI and the evaluation of the severity of the disease. In 2010, we established a multivariate peptide marker pattern consisting of 20 naturally occurring urinary peptides to screen patients for early signs of renal failure. The current study now aims to evaluate if, in a different study population and potentially various AKI causes, AKI can be detected early and accurately by proteome analysis.Methods: Urine samples from 60 patients who developed AKI after cardiac surgery were analyzed by capillary electrophoresis-mass spectrometry (CE-MS). The obtained peptide profiles were screened by the AKI peptide marker panel for early signs of AKI. Accuracy of the proteomic model in this patient collective was compared to that based on urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) ELISA levels. Sixty patients who did not develop AKI served as negative controls.Results: From the 120 patients, 110 were successfully analyzed by CE-MS (59 with AKI, 51 controls). Application of the AKI panel demonstrated an AUC in receiver operating characteristics (ROC) analysis of 0.81 (95 % confidence interval: 0.72-0.88). Compared to the proteomic model, ROC analysis revealed poorer classification accuracy of NGAL and KIM-1 with the respective AUC values being outside the statistical significant range (0.63 for NGAL and 0.57 for KIM-1).Conclusions: This study gives further proof for the general applicability of our proteomic multimarker model for early and accurate prediction of AKI irrespective of its underlying disease cause. [ABSTRACT FROM AUTHOR]