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      Mid-Regional Proadrenomedullin as a New Biomarker of Kidney and Cardiovascular Diseases—Is It the Future?

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          Abstract

          The increasing prevalence of cardiovascular disease and concomitant chronic kidney disease among the aging populations is responsible for considerable growth of mortality. Additionally, frequent, prolonged hospitalizations and long-term treatment generates progressive decline in bodily functions as well as substantial public health and economic burden. Accessibility to easy, non-invasive prognostic markers able to detect patients at risk of cardiovascular events may improve effective therapy and mitigate disease progression. Moreover, an early diagnosis allows time for implementation of prophylactic and educational programs that may result in decreased morbidity, improved quality of life and reduced public health expenditure. One of the promising candidates for a novel cardiovascular biomarker is mid-regional proadrenomedullin, a derivative of adrenomedullin. Adrenomedullin is a peptide hormone known for its vasodilatory, antioxidant, antiapoptotic and antifibrotic effects. A remarkable advantage of mid-regional proadrenomedullin is its longer half-life which is a prerequisite for plasma measurements. These review aims to discuss the importance of mid-regional proadrenomedullin with reference to its usefulness as a biomarker of increased cardiovascular risk and kidney disease progression.

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          Global Prevalence of Chronic Kidney Disease – A Systematic Review and Meta-Analysis

          Chronic kidney disease (CKD) is a global health burden with a high economic cost to health systems and is an independent risk factor for cardiovascular disease (CVD). All stages of CKD are associated with increased risks of cardiovascular morbidity, premature mortality, and/or decreased quality of life. CKD is usually asymptomatic until later stages and accurate prevalence data are lacking. Thus we sought to determine the prevalence of CKD globally, by stage, geographical location, gender and age. A systematic review and meta-analysis of observational studies estimating CKD prevalence in general populations was conducted through literature searches in 8 databases. We assessed pooled data using a random effects model. Of 5,842 potential articles, 100 studies of diverse quality were included, comprising 6,908,440 patients. Global mean(95%CI) CKD prevalence of 5 stages 13·4%(11·7–15·1%), and stages 3–5 was 10·6%(9·2–12·2%). Weighting by study quality did not affect prevalence estimates. CKD prevalence by stage was Stage-1 (eGFR>90+ACR>30): 3·5% (2·8–4·2%); Stage-2 (eGFR 60–89+ACR>30): 3·9% (2·7–5·3%); Stage-3 (eGFR 30–59): 7·6% (6·4–8·9%); Stage-4 = (eGFR 29–15): 0·4% (0·3–0·5%); and Stage-5 (eGFR<15): 0·1% (0·1–0·1%). CKD has a high global prevalence with a consistent estimated global CKD prevalence of between 11 to 13% with the majority stage 3. Future research should evaluate intervention strategies deliverable at scale to delay the progression of CKD and improve CVD outcomes.
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            Plasma brain natriuretic peptide concentration: impact of age and gender.

            We wished to examine the effects of age and gender on plasma brain natriuretic peptide (BNP) concentration in a population-based study. Measurement of BNP concentration is approved for use in the diagnosis of heart failure and may aid in the detection of left ventricular dysfunction. Although BNP is approved for clinical use, there are few data regarding the range of BNP observed in persons without cardiovascular disease or cardiac dysfunction. These data are essential for the interpretation of BNP. In 2,042 randomly selected residents of Olmsted County, Minnesota, >44 years old, BNP (Shionogi and Biosite assays), Doppler echocardiography, and medical record review were performed. A normal subset of subjects (n = 767) in sinus rhythm without cardiovascular, renal, or pulmonary disease or diabetes; on no cardiovascular medications; and with normal systolic, diastolic, and valvular function was identified. Within the normal subset, the distribution of BNP differed by age, gender, and assay system. With both assays, BNP increased significantly with age and was significantly higher in women than men, leading to age-, gender-, and assay-specific reference ranges. Receiver operating characteristic analysis for the ability of BNP to detect an ejection fraction < or = 40% was performed in each age/gender stratum in the entire cohort (n = 2,042) and confirmed that discriminatory values for BNP for detection of reduced ejection fraction were higher in women and older persons and were different between the two assays. Interpretation of BNP should include consideration of age-, gender-, and assay-specific partition values.
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              A new natriuretic peptide in porcine brain.

              Atrial natriuretic peptide (ANP), a hormone secreted from mammalian atria, regulates the homoeostatic balance of body fluid and blood pressure. ANP-like immunoreactivity is also present in the brain, suggesting that the peptide functions as a neuropeptide. We report here identification in porcine brain of a novel peptide of 26 amino-acid residues, eliciting a pharmacological spectrum very similar to that of ANP, such as natriuretic-diuretic, hypotensive and chick rectum relaxant activities. The complete amino-acid sequence determined for the peptide is remarkably similar to but definitely distinct from the known sequence of ANP, indicating that the genes for the two are distinct. Thus, we have designated the peptide 'brain natriuretic peptide' (BNP). The occurrence of BNP with ANP in mammalian brain suggests the possibility that the physiological functions so far thought to be mediated by ANP may be regulated through a dual mechanism involving both ANP and BNP.
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                Author and article information

                Contributors
                Role: Academic Editor
                Role: Academic Editor
                Role: Academic Editor
                Role: Academic Editor
                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                02 February 2021
                February 2021
                : 10
                : 3
                : 524
                Affiliations
                [1 ]2nd Department of Nephrology and Hypertension with Dialysis Unit, Medical University of Bialystok, 15-276 Bialystok, Poland; b.angelika@ 123456wp.pl (A.B.-B.); katarzynamitrosz@ 123456gmail.com (K.M.); katarzyna.kakareko@ 123456umb.edu.pl (K.K.); alicja.rosolowska@ 123456umb.edu.pl (A.R.-R.); tomasz.hryszko@ 123456umb.edu.pl (T.H.)
                [2 ]Department of Internal Medicine and Hypertension, Medical University of Bialystok, 15-540 Bialystok, Poland; edyta.zbroch@ 123456umb.edu.pl (E.Z.); mlodawska.ela@ 123456gmail.com (E.B.)
                Author notes
                Author information
                https://orcid.org/0000-0001-8046-4179
                https://orcid.org/0000-0002-8126-3085
                https://orcid.org/0000-0002-0145-3103
                Article
                jcm-10-00524
                10.3390/jcm10030524
                7867137
                33540505
                08c215d4-5c79-4907-878e-2e9e3e51addd
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 04 January 2021
                : 27 January 2021
                Categories
                Review

                cardiovascular diseases,kidney diseases,mid-regional proadrenomedullin

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