The effect of renal dysfunction and haemodialysis on circulating liver specific miR‐122

Rivoli, Laura; Vliegenthart, A. D. Bastiaan; Potter, Carmelita M. J. de; Bragt, Job J.M.H. van; Tzoumas, Nikolaos; Gallacher, Peter J.; Farrah, Tariq E.; Dhaun, Neeraj; Dear, James W.

doi:10.1111/bcp.13136

Cited by 19 publications

(17 citation statements)

References 20 publications

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“…The inverse association between miR-122-5p and poor outcome is against a causal relationship between liver failure, circulating levels of miR-122-5p, and poor outcome. Even though miR-122-5p levels were shown to be decreased in patients with renal failure 35 , the very low proportion of patients with renal failure in the present study is unable to account per se for the association between miR-122-5p and outcome after cardiac arrest. Overall, miR-122-5p levels were not associated with the different organ-specific sub-scores of the sequential organ failure assessment score (not shown).…”

Section: Discussioncontrasting

confidence: 77%

Incremental Value of Circulating MiR-122-5p to Predict Outcome after Out of Hospital Cardiac Arrest

et al. 2017

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Rationale. The value of microRNAs (miRNAs) as biomarkers has been addressed in various clinical contexts. Initial studies suggested that miRNAs, such as the brain-enriched miR-124-3p, might improve outcome prediction after out-of-hospital cardiac arrest. The aim of this study is to determine the prognostic value of miR-122-5p in a large cohort of comatose survivors of out-of-hospital cardiac arrest.Methods. We analyzed 590 patients from the Targeted Temperature Management trial (TTM-trial). Circulating levels of miR-122-5p were measured in serum samples obtained 48 hours after return of spontaneous circulation. The primary end-point was poor neurological outcome at 6 months evaluated by the cerebral performance category score. The secondary end-point was survival at the end of the trial.Results. Forty-eight percent of patients had a poor neurological outcome at 6 months and 43% were dead at the end of the trial. Levels of miR-122-5p were lower in patients with poor neurological outcome compared to patients with good neurological outcome (p<0.001), independently of targeted temperature management regimen. Levels of miR-122-5p were significant univariate predictors of neurological outcome (odds ratios (OR), 95% confidence intervals (CI): 0.71 [0.57-0.88]). In multivariable analyses, miR-122-5p was an independent predictor of neurological outcome and improved the predictive value of a clinical model including miR-124-3p (integrated discrimination improvement of 0.03 [0.02-0.04]). In Cox proportional hazards models, miR-122-5p was a significant predictor of survival at the end of the trial.Conclusion. Circulating levels of miR-122-5p improve the prediction of outcome after out-of-hospital cardiac arrest.

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Section: Discussioncontrasting

confidence: 77%

Incremental Value of Circulating MiR-122-5p to Predict Outcome after Out of Hospital Cardiac Arrest

et al. 2017

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“…Our analysis confirmed upregulation of miR-21-5p, miR-210-3p, miR-122-5p and miR-885-5p while miR-499 was not included in the panel analyzed, further supporting upregulation of miRNAs in the serum of hemodialysis patients signalized previously by Rivoli et al [15].…”

Section: Discussionsupporting

confidence: 90%

“…Earlier independent reports had shown upregulation of miR-499, miR-21-5p, miR-210, miR-122-5p and miR-885 in the serum following hemodialysis [13][14][15]. Our analysis confirmed upregulation of miR-21-5p, miR-210-3p, miR-122-5p and miR-885-5p while miR-499 was not included in the panel analyzed, further supporting upregulation of miRNAs in the serum of hemodialysis patients signalized previously by Rivoli et al [15].…”

Section: Discussionmentioning

confidence: 97%

“…Three studies to date [13][14][15] present fragmented information on selected serum miRNAs in patients undergoing hemodialysis. Therefore, to address this gap, the aim of this study was to investigate if the process of hemodialysis alters the profile of miRNAs in serum in young men and identify a potential link with development of pathologies associated with hemodialysis.…”

Section: Introductionmentioning

confidence: 99%

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Alterations in Serum MicroRNA Profile During Hemodialysis - Potential Biological Implications

Trzybulska

Eckersten

Giwercman³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Hemodialysis implies significant alterations in the profile of serum components. microRNAs (miRNAs) are present in the human serum and are considered to target distant tissues where they can regulate gene expression, thus affecting homeostasis. Whether hemodialysis alters the profile of miRNAs in the serum is not known. Methods: miRNA profiling in serum samples collected before and after hemodialysis was performed using miRNA qPCR arrays. The results were subsequently validated in an independent group of 10 hemodialyzed men. miRWalk database was used to identify mRNAs targeted by the miRNAs the levels of which changed after hemodialysis. The list of mRNAs was analyzed using the DAVID and PANTHER classification systems to identify pathways controlled by these miRNAs. Results: miRNA profiling showed that the levels of the majority of circulating miRNAs were increased at least two-fold (115 out of 179 tested) while the levels of only five miRNAs were found at least two-fold lower after hemodialysis. Validation study confirmed the majority of the array results. Bioinformatics analysis of validated and significantly upregulated miRNAs revealed that gonadotropin-releasing hormone receptor, cell cycle and cell pluripotencyrelated pathways were targeted. Conclusion: Hemodialysis alters serum miRNA expression profile and this alteration may result in disruption of pathways contributing to subfertility and increased risk for cancer development being pathologies associated with hemodialysis.

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“…Circulating miR-122 has been identified as a biomarker for ESRD, being substantially downregulated in 17 pre-haemodialysis patients compared to 22 healthy controls (19-fold lower), 30 patients with CKD (21.7-fold lower) and 15 transplanted patients [ 127 ]. Another biomarker differentially expressed in dialysis patients is miRNA-155, whose serum levels were found increased in 82 dialysis patients compared with 16 healthy subjects (P < 0.05) [ 128 ].…”

Section: Epigenetic Biomarkersmentioning

confidence: 99%

Genomic approaches in the search for molecular biomarkers in chronic kidney disease

et al. 2018

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BackgroundChronic kidney disease (CKD) is recognised as a global public health problem, more prevalent in older persons and associated with multiple co-morbidities. Diabetes mellitus and hypertension are common aetiologies for CKD, but IgA glomerulonephritis, membranous glomerulonephritis, lupus nephritis and autosomal dominant polycystic kidney disease are also common causes of CKD.Main bodyConventional biomarkers for CKD involving the use of estimated glomerular filtration rate (eGFR) derived from four variables (serum creatinine, age, gender and ethnicity) are recommended by clinical guidelines for the evaluation, classification, and stratification of CKD. However, these clinical biomarkers present some limitations, especially for early stages of CKD, elderly individuals, extreme body mass index values (serum creatinine), or are influenced by inflammation, steroid treatment and thyroid dysfunction (serum cystatin C). There is therefore a need to identify additional non-invasive biomarkers that are useful in clinical practice to help improve CKD diagnosis, inform prognosis and guide therapeutic management.ConclusionCKD is a multifactorial disease with associated genetic and environmental risk factors. Hence, many studies have employed genetic, epigenetic and transcriptomic approaches to identify biomarkers for kidney disease. In this review, we have summarised the most important studies in humans investigating genomic biomarkers for CKD in the last decade. Several genes, including UMOD, SHROOM3 and ELMO1 have been strongly associated with renal diseases, and some of their traits, such as eGFR and serum creatinine. The role of epigenetic and transcriptomic biomarkers in CKD and related diseases is still unclear. The combination of multiple biomarkers into classifiers, including genomic, and/or epigenomic, may give a more complete picture of kidney diseases.

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The effect of renal dysfunction and haemodialysis on circulating liver specific miR‐122

Cited by 19 publications

References 20 publications

Incremental Value of Circulating MiR-122-5p to Predict Outcome after Out of Hospital Cardiac Arrest

Incremental Value of Circulating MiR-122-5p to Predict Outcome after Out of Hospital Cardiac Arrest

Alterations in Serum MicroRNA Profile During Hemodialysis - Potential Biological Implications

Genomic approaches in the search for molecular biomarkers in chronic kidney disease

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