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      Serum metabolomics approach to monitor the changes in metabolite profiles following renal transplantation

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          Abstract

          Systemic metabolic changes after renal transplantation reflect the key processes that are related to graft accommodation. In order to describe and better understand these changes, the 1HNMR based metabolomics approach was used. The changes of 47 metabolites in the serum samples of 19 individuals were interpreted over time with respect to their levels prior to transplantation. Considering the specific repeated measures design of the experiments, data analysis was mainly focused on the multiple analyses of variance (ANOVA) methods such as ANOVA simultaneous component analysis and ANOVA-target projection. We also propose here the combined use of ANOVA and classification and regression trees (ANOVA-CART) under the assumption that a small set of metabolites the binary splits on which may better describe the graft accommodation processes over time. This assumption is very important for developing a medical protocol for evaluating a patient’s health state. The results showed that besides creatinine, which is routinely used to monitor renal activity, the changes in levels of hippurate, mannitol and alanine may be associated with the changes in renal function during the post-transplantation recovery period. Specifically, the level of hippurate (or histidine) is more sensitive to any short-term changes in renal activity than creatinine.

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          Chronic Kidney Disease.

          Angela Webster, Evi V Nagler, Rachael Morton … (2017)
          The definition and classification of chronic kidney disease (CKD) have evolved over time, but current international guidelines define this condition as decreased kidney function shown by glomerular filtration rate (GFR) of less than 60 mL/min per 1·73 m(2), or markers of kidney damage, or both, of at least 3 months duration, regardless of the underlying cause. Diabetes and hypertension are the main causes of CKD in all high-income and middle-income countries, and also in many low-income countries. Incidence, prevalence, and progression of CKD also vary within countries by ethnicity and social determinants of health, possibly through epigenetic influence. Many people are asymptomatic or have non-specific symptoms such as lethargy, itch, or loss of appetite. Diagnosis is commonly made after chance findings from screening tests (urinary dipstick or blood tests), or when symptoms become severe. The best available indicator of overall kidney function is GFR, which is measured either via exogenous markers (eg, DTPA, iohexol), or estimated using equations. Presence of proteinuria is associated with increased risk of progression of CKD and death. Kidney biopsy samples can show definitive evidence of CKD, through common changes such as glomerular sclerosis, tubular atrophy, and interstitial fibrosis. Complications include anaemia due to reduced production of erythropoietin by the kidney; reduced red blood cell survival and iron deficiency; and mineral bone disease caused by disturbed vitamin D, calcium, and phosphate metabolism. People with CKD are five to ten times more likely to die prematurely than they are to progress to end stage kidney disease. This increased risk of death rises exponentially as kidney function worsens and is largely attributable to death from cardiovascular disease, although cancer incidence and mortality are also increased. Health-related quality of life is substantially lower for people with CKD than for the general population, and falls as GFR declines. Interventions targeting specific symptoms, or aimed at supporting educational or lifestyle considerations, make a positive difference to people living with CKD. Inequity in access to services for this disease disproportionally affects disadvantaged populations, and health service provision to incentivise early intervention over provision of care only for advanced CKD is still evolving in many countries.
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            Global Prevalence of Chronic Kidney Disease – A Systematic Review and Meta-Analysis

            Nathan Hill, Samuel T Fatoba, Jason L. Oke … (2016)
            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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              Chronic kidney disease: global dimension and perspectives.

              Vivekanand Jha, Guillermo Garcia-Garcia, Kunitoshi Iseki … (2013)
              Chronic kidney disease is defined as a reduced glomerular filtration rate, increased urinary albumin excretion, or both, and is an increasing public health issue. Prevalence is estimated to be 8-16% worldwide. Complications include increased all-cause and cardiovascular mortality, kidney-disease progression, acute kidney injury, cognitive decline, anaemia, mineral and bone disorders, and fractures. Worldwide, diabetes mellitus is the most common cause of chronic kidney disease, but in some regions other causes, such as herbal and environmental toxins, are more common. The poorest populations are at the highest risk. Screening and intervention can prevent chronic kidney disease, and where management strategies have been implemented the incidence of end-stage kidney disease has been reduced. Awareness of the disorder, however, remains low in many communities and among many physicians. Strategies to reduce burden and costs related to chronic kidney disease need to be included in national programmes for non-communicable diseases. Copyright © 2013 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                Ivana Stanimirova: istanimi@us.edu.pl
                Piotr Młynarz: piotr.mlynarz@pwr.edu.pl
                Journal
                Journal ID (nlm-ta): Sci Rep
                Journal ID (iso-abbrev): Sci Rep
                Title: Scientific Reports
                Publisher: Nature Publishing Group UK (London )
                ISSN (Electronic): 2045-2322
                Publication date (Electronic): 14 October 2020
                Publication date PMC-release: 14 October 2020
                Publication date Collection: 2020
                Volume: 10
                Electronic Location Identifier: 17223
                Affiliations
                [1 ]GRID grid.11866.38, ISNI 0000 0001 2259 4135, Institute of Chemistry, , The University of Silesia, ; 9 Szkolna Street, 40-006 Katowice, Poland
                [2 ]GRID grid.4495.c, ISNI 0000 0001 1090 049X, Department of Nephrology and Transplantation Medicine, , Wroclaw Medical University, ; 213 Borowska Street, 50-556 Wroclaw, Poland
                [3 ]PORT Polish Center for Technology Development, 147 Stablowicka Street, 54-066 Wroclaw, Poland
                [4 ]GRID grid.4495.c, ISNI 0000 0001 1090 049X, Department of Vascular, General and Transplantation Surgery, , Wroclaw Medical University, ; 213 Borowska Street, 50-556 Wroclaw, Poland
                [5 ]GRID grid.7005.2, ISNI 0000 0000 9805 3178, Department of Bioorganic Chemistry, , Wrocław University of Technology, ; 27 Wybrzeze Wyspianskiego Street, 50-370 Wroclaw, Poland
                Article
                Publisher ID: 74245
                DOI: 10.1038/s41598-020-74245-z
                PMC ID: 7560840
                PubMed ID: 33057167
                SO-VID: efc2ad61-22a3-479d-9df8-fc7956ef32da
                Copyright © © The Author(s) 2020
                License:

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                Date received : 16 January 2020
                Date accepted : 23 September 2020
                Funding
                Funded by: Wroclaw University of Technology
                Award ID: 2018/Z0303
                Award Recipient :
                Funded by: The National Centre for Research and Development, Poland
                Award ID: NanoMat Project EIT POIG.01.01.02-02-002/08
                Award Recipient :
                Categories
                Subject: Article
                Custom metadata
                issue-copyright-statement © The Author(s) 2020

                ScienceOpen disciplines: Uncategorized
                Keywords: chronic kidney disease,metabolomics
                Data availability:
                ScienceOpen disciplines: Uncategorized
                Keywords: chronic kidney disease, metabolomics

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