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      MicroRNA‐497/fibroblast growth factor‐23 axis, a predictive indictor for decreased major adverse cardiac and cerebral event risk in end‐stage renal disease patients who underwent continuous ambulatory peritoneal dialysis

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          Abstract

          Objective

          This study aimed at exploring the correlation of microRNA (miR)‐497/fibroblast growth factor‐23 (FGF‐23) axis with major adverse cardiac and cerebral event (MACCE) occurrence in end‐stage renal disease (ESRD) patients who underwent continuous ambulatory peritoneal dialysis (CAPD).

          Methods

          Totally, 360 ESRD patients who underwent CAPD were enrolled. Their plasma samples were collected to detect miR‐497 expression by real‐time quantitative polymerase chain reaction, and FGF‐23 level by enzyme‐linked immunosorbent assay. All patients were followed up for 36 months, and the occurrence of MACCE during the follow‐up was documented.

          Results

          MiR‐497 expression negatively correlated with FGF‐23 level in ESRD patients who underwent CAPD ( P < .001). The MACCE occurrence rate at 1, 2, and 3‐year was 5.6%, 11.9%, and 15.0%, respectively. Furthermore, miR‐497/FGF‐23 axis high level ( P < .001) and miR‐497 high expression ( P = .034) correlated with reduced accumulating MACCE occurrence, whereas FGF‐23 high level ( P = .008) correlated with increased accumulating MACCE occurrence. Forward stepwise multivariate Cox's regression disclosed that miR‐497/FGF‐23 axis high level ( P = .008) was an independent predictive factor for lower accumulating MACCE occurrence, whereas age (≥55 years) ( P < .001), body mass index (≥21.7 kg/m 2) ( P = .006), peritoneal dialysis duration (≥61.0 months) ( P < .001), C‐reactive protein (≥4.7 mg/L) ( P = .001), serum uric acid (≥409.4 μmol/L) ( P = .009), β‐fibrinogen (≥5.8 mmol/L) ( P < .001), and low‐density lipoprotein cholesterol (≥2.7 mmol/L) ( P = .003) were independent factors for predicting higher accumulating MACCE occurrence.

          Conclusion

          MiR‐497/FGF‐23 axis holds clinical significance for predicting attenuated MACCE risk in ESRD patients who underwent CAPD.

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          Most cited references 19

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          miR-497 regulates neuronal death in mouse brain after transient focal cerebral ischemia.

          Dysfunction of the microRNA (miR) network has been emerging as a major regulator in neurological diseases. However, little is known about the functional significance of unique miRs in ischemic brain damage. Here, we found that miR-497 is induced in mouse brain after transient middle cerebral artery occlusion (MCAO) and mouse N2A neuroblastoma (N2A) cells after oxygen-glucose deprivation (OGD). Loss-of-miR-497 function significantly suppresses OGD-induced N2A cell death, whereas gain-of-miR-497 function aggravates OGD-induced neuronal loss. Moreover, miR-497 directly binds to the predicted 3'-UTR target sites of bcl-2/-w genes. Furthermore, knockdown of cerebral miR-497 effectively enhances bcl-2/-w protein levels in the ischemic region, attenuates ischemic brain infarction, and improves neurological outcomes in mice after focal cerebral ischemia. Taken together, our data suggest that miR-497 promotes ischemic neuronal death by negatively regulating antiapoptotic proteins, bcl-2 and bcl-w. We raise the possibility that this pathway may contribute to the pathogenesis of the ischemic brain injury in stroke. Copyright 2009 Elsevier Inc. All rights reserved.
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            Factors influencing patient choice of dialysis versus conservative care to treat end-stage kidney disease.

            For every patient with chronic kidney disease who undergoes renal-replacement therapy, there is one patient who undergoes conservative management of their disease. We aimed to determine the most important characteristics of dialysis and the trade-offs patients were willing to make in choosing dialysis instead of conservative care. We conducted a discrete choice experiment involving adults with stage 3-5 chronic kidney disease from eight renal clinics in Australia. We assessed the influence of treatment characteristics (life expectancy, number of visits to the hospital per week, ability to travel, time spent undergoing dialysis [i.e., time spent attached to a dialysis machine per treatment, measured in hours], time of day at which treatment occurred, availability of subsidized transport and flexibility of the treatment schedule) on patients' preferences for dialysis versus conservative care. Of 151 patients invited to participate, 105 completed our survey. Patients were more likely to choose dialysis than conservative care if dialysis involved an increased average life expectancy (odds ratio [OR] 1.84, 95% confidence interval [CI] 1.57-2.15), if they were able to dialyse during the day or evening rather than during the day only (OR 8.95, 95% CI 4.46-17.97), and if subsidized transport was available (OR 1.55, 95% CI 1.24-1.95). Patients were less likely to choose dialysis over conservative care if an increase in the number of visits to hospital was required (OR 0.70, 95% CI 0.56-0.88) and if there were more restrictions on their ability to travel (OR=0.47, 95%CI 0.36-0.61). Patients were willing to forgo 7 months of life expectancy to reduce the number of required visits to hospital and 15 months of life expectancy to increase their ability to travel. Patients approaching end-stage kidney disease are willing to trade considerable life expectancy to reduce the burden and restrictions imposed by dialysis.
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              The role of FGF23 in CKD--with or without Klotho.

              During the past few years, fibroblast growth factor 23 (FGF23) has emerged as a central player of disordered mineral metabolism in patients with chronic kidney disease (CKD). The physiological actions of FGF23 are to promote phosphaturia, decrease production of 1,25-dihydroxyvitamin D and suppress secretion of parathyroid hormone mediated through FGF receptors and the co-receptor Klotho. Recent epidemiological studies demonstrate strong associations between elevated FGF23 levels in patients with CKD and poor clinical outcomes. In patients with end-stage renal disease, markedly increased levels of FGF23 fail to exert Klotho-dependent effects owing to the absence of a functioning kidney and downregulation of the parathyroid complex of Klotho and FGF receptor 1. In this setting, FGF23 may exert a toxic effect on the cardiovascular system in a Klotho-independent manner. Future research should examine whether treatment to attenuate the pathogenic action of FGF23 provides survival benefits in patients with CKD.
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                Author and article information

                Contributors
                mu43328528@163.com
                Journal
                J Clin Lab Anal
                J. Clin. Lab. Anal
                10.1002/(ISSN)1098-2825
                JCLA
                Journal of Clinical Laboratory Analysis
                John Wiley and Sons Inc. (Hoboken )
                0887-8013
                1098-2825
                20 February 2020
                June 2020
                : 34
                : 6 ( doiID: 10.1002/jcla.v34.6 )
                Affiliations
                [ 1 ] Department of Nephrology The Central Hospital of Wuhan Tongji Medical College Huazhong University of Science and Technology Wuhan China
                [ 2 ] Emergency Department The Central Hospital of Wuhan Tongji Medical College Huazhong University of Science and Technology Wuhan China
                Author notes
                [* ] Correspondence

                Huihui Mao, Department of Nephrology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, 26 Shengli Street, Jiang'an District, Wuhan 430014, China.

                Email: mu43328528@ 123456163.com

                Article
                JCLA23220
                10.1002/jcla.23220
                7307374
                32077150
                © 2020 The Authors. Journal of Clinical Laboratory Analysis Published by Wiley Periodicals, Inc.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                Page count
                Figures: 4, Tables: 3, Pages: 8, Words: 5019
                Product
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                June 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.4 mode:remove_FC converted:22.06.2020

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