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      Metabolomics Evaluation of Patients With Stage 5 Chronic Kidney Disease Before Dialysis, Maintenance Hemodialysis, and Peritoneal Dialysis

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          Abstract

          Objective

          Current treatment options for patients with stage 5 chronic kidney disease before dialysis (predialysis CKD-5) are determined by individual circumstances, economic factors, and the doctor’s advice. This study aimed to explore the plasma metabolic traits of patients with predialysis CKD-5 compared with maintenance hemodialysis (HD) and peritoneal dialysis (PD) patients, to learn more about the impact of the dialysis process on the blood environment.

          Methods

          Our study enrolled 31 predialysis CKD-5 patients, 31 HD patients, and 30 PD patients. Metabolite profiling was performed using a targeted metabolomics platform by applying an ultra-high-performance liquid chromatography-tandem mass spectrometry method, and the subsequent comparisons among all three groups were made to explore metabolic alterations.

          Results

          Cysteine metabolism was significantly altered between predialysis CKD-5 patients and both groups of dialysis patients. A disturbance in purine metabolism was the most extensively changed pathway identified between the HD and PD groups. A total of 20 discriminating metabolites with large fluctuations in plasma concentrations were screened from the group comparisons, including 2-keto-D-gluconic acid, kynurenic acid, s-adenosylhomocysteine, L-glutamine, adenosine, and nicotinamide.

          Conclusion

          Our study provided a comprehensive metabolomics evaluation among predialysis CKD-5, HD, and PD patients, which described the disturbance of metabolic pathways, discriminating metabolites and their possible biological significances. The identification of specific metabolites related to dialysis therapy might provide insights for the management of advanced CKD stages and inform shared decision-making.

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          Most cited references 40

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          Prevalence of chronic kidney disease in China: a cross-sectional survey.

          The prevalence of chronic kidney disease is high in developing countries. However, no national survey of chronic kidney disease has been done incorporating both estimated glomerular filtration rate (eGFR) and albuminuria in a developing country with the economic diversity of China. We aimed to measure the prevalence of chronic kidney disease in China with such a survey. We did a cross-sectional survey of a nationally representative sample of Chinese adults. Chronic kidney disease was defined as eGFR less than 60 mL/min per 1·73 m(2) or the presence of albuminuria. Participants completed a lifestyle and medical history questionnaire and had their blood pressure measured, and blood and urine samples taken. Serum creatinine was measured and used to estimate glomerular filtration rate. Urinary albumin and creatinine were tested to assess albuminuria. The crude and adjusted prevalence of indicators of kidney damage were calculated and factors associated with the presence of chronic kidney disease analysed by logistic regression. 50,550 people were invited to participate, of whom 47,204 agreed. The adjusted prevalence of eGFR less than 60 mL/min per 1·73 m(2) was 1·7% (95% CI 1·5-1·9) and of albuminuria was 9·4% (8·9-10·0). The overall prevalence of chronic kidney disease was 10·8% (10·2-11·3); therefore the number of patients with chronic kidney disease in China is estimated to be about 119·5 million (112·9-125·0 million). In rural areas, economic development was independently associated with the presence of albuminuria. The prevalence of chronic kidney disease was high in north (16·9% [15·1-18·7]) and southwest (18·3% [16·4-20·4]) regions compared with other regions. Other factors independently associated with kidney damage were age, sex, hypertension, diabetes, history of cardiovascular disease, hyperuricaemia, area of residence, and economic status. Chronic kidney disease has become an important public health problem in China. Special attention should be paid to residents in economically improving rural areas and specific geographical regions in China. The Ministry of Science and Technology (China); the Science and Technology Commission of Shanghai; the National Natural Science Foundation of China; the Department of Health, Jiangsu Province; the Sichuan Science and Technology Department; the Ministry of Education (China); the International Society of Nephrology Research Committee; and the China Health and Medical Development Foundation. Copyright © 2012 Elsevier Ltd. All rights reserved.
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            Liquid chromatography-mass spectrometry based global metabolite profiling: a review.

            Untargeted, global metabolite profiling (often described as metabonomics or metabolomics) represents an expanding research topic and is, potentially, a major pillar for systems biology studies. To obtain holistic metabolic profiles from complex samples, such as biological fluids or tissue extracts, requires powerful, high resolution and information-rich analytical methods and for this spectroscopic technologies are generally used. Mass spectrometry, coupled to liquid chromatography (LC-MS), is increasingly being used for such investigations as a result of the significant advances in both technologies over the past decade. Here we try to critically review the topic of LC-MS-based global metabolic profiling and describe and compare the results offered by different analytical strategies and technologies. This review highlights the current challenges, limitations and opportunities of the current methodology. Copyright © 2011 Elsevier B.V. All rights reserved.
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              Hemodialysis versus peritoneal dialysis: a comparison of adjusted mortality rates.

              Although kidney transplantation is the preferred treatment method for patients with ESRD, most patients are placed on dialysis either while awaiting transplantation or as their only therapy. The question of which dialytic method provides the best patient survival remains unresolved. Survival analyses comparing hemodialysis and continuous ambulatory peritoneal dialysis/continuous cyclic peritoneal dialysis (CAPD/CCPD), a newer and less costly dialytic modality, have yielded conflicting results. Using data obtained from the Canadian Organ Replacement Register, we compared mortality rates between hemodialysis and CAPD/CCPD among 11,970 ESRD patients who initiated treatment between 1990 and 1994 and were followed-up for a maximum of 5 years. Factors controlled for include age, primary renal diagnosis, center size, and predialysis comorbid conditions. The mortality rate ratio (RR) for CAPD/CCPD relative to hemodialysis, as estimated by Poisson regression, was 0.73 (95% confidence interval: 0.68 to 0.78). No such relationship was found when an intent-to-treat Cox regression model was fit. Decreased covariable-adjusted mortality for CAPD/CCPD held within all subgroups defined by age and diabetes status, although the RRs increased with age and diabetes prevalence. The increased mortality on hemodialysis compared with CAPD/CCPD was concentrated in the first 2 years of follow-up. Although continuous peritoneal dialysis was associated with significantly lower mortality rates relative to hemodialysis after adjusting for known prognostic factors, the potential impact of unmeasured patient characteristics must be considered. Notwithstanding, we present evidence that CAPD/CCPD, a newer and less costly method of renal replacement therapy, is not associated with increased mortality rates relative to hemodialysis.
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                Author and article information

                Contributors
                Journal
                Front Physiol
                Front Physiol
                Front. Physiol.
                Frontiers in Physiology
                Frontiers Media S.A.
                1664-042X
                20 January 2021
                2020
                : 11
                Affiliations
                1Department of Pharmacy, Changzheng Hospital, Naval Medical University , Shanghai, China
                2Department of Nephrology, Changzheng Hospital, Naval Medical University , Shanghai, China
                3Department of Pharmacy, The Affiliated Wuxi Children’s Hospital of Nanjing Medical University , Wuxi, China
                Author notes

                Edited by: Vassilios Liakopoulos, Aristotle University of Thessaloniki, Greece

                Reviewed by: Panagiotis I. Georgianos, University General Hospital of Thessaloniki AHEPA, Greece; Nikoleta Printza, Aristotle University of Thessaloniki, Greece

                *Correspondence: Sheng-Qiang Yu, shengqiang.yu@ 123456smmu.edu.cn

                These authors have contributed equally to this work

                This article was submitted to Renal and Epithelial Physiology, a section of the journal Frontiers in Physiology

                Article
                10.3389/fphys.2020.630646
                7855177
                Copyright © 2021 Zhu, Zhang, Shen, Sun, Xia, Chen, Tao and Yu.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                Page count
                Figures: 4, Tables: 2, Equations: 0, References: 40, Pages: 11, Words: 0
                Categories
                Physiology
                Original Research

                Anatomy & Physiology

                hemodialysis, peritoneal dialysis, predialysis ckd-5, metabolomics, uplc-ms/ms

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