Estimation of homeostatic dysregulation and frailty using biomarker variability: a principal component analysis of hemodialysis patients

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Abstract

Increased intraindividual variability in several biological parameters is associated with aspects of frailty and may reflect impaired physiological regulation. As frailty involves a cumulative decline in multiple physiological systems, we aimed to estimate the overall regulatory capacity by applying a principal component analysis to such variability. The variability of 20 blood-based parameters was evaluated as the log-transformed coefficient of variation (LCV) for one year’s worth of data from 580 hemodialysis patients. All the LCVs were positively correlated with each other and shared common characteristics. In a principal component analysis of 19 LCVs, the first principal component (PC1) explained 27.7% of the total variance, and the PC1 score exhibited consistent correlations with diverse negative health indicators, including diabetes, hypoalbuminemia, hyponatremia, and relative hypocreatininemia. The relationship between the PC1 score and frailty was subsequently examined in a subset of the subjects. The PC1 score was associated with the prevalence of frailty and was an independent predictor for frailty (odds ratio per SD: 2.31, P = 0.01) using a multivariate logistic regression model, which showed good discrimination (c-statistic: 0.85). Therefore, the PC1 score represents principal information shared by biomarker variabilities and is a reasonable measure of homeostatic dysregulation and frailty.

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Network physiology reveals relations between network topology and physiological function

Amir Bashan, Ronny P. Bartsch, Jan Kantelhardt … (2012)

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A1C Variability and the Risk of Microvascular Complications in Type 1 Diabetes

Eric Kilpatrick, Alan Rigby, Stephen L Atkin (2008)

OBJECTIVE—Debate remains as to whether short- or long-term glycemic instability confers a risk of microvascular complications in addition to that predicted by mean glycemia alone. In this study, we analyzed data from the Diabetes Control and Complications Trial (DCCT) to assess the effect of A1C variability on the risk of retinopathy and nephropathy in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS—A1C was collected quarterly during the DCCT in 1,441 individuals. The mean A1C and the SD of A1C variability after stabilization of glycemia (from 6 months onwards) were compared with the risk of retinopathy and nephropathy with adjustments for age, sex, disease duration, treatment group, and baseline A1C. RESULTS—Multivariate Cox regression showed that the variability in A1C added to mean A1C in predicting the risk of development or progression of both retinopathy (hazard ratio 2.26 for every 1% increase in A1C SD [95% CI 1.63–3.14], P < 0.0001) and nephropathy (1.80 [1.37–2.42], P < 0.0001), with the relationship a feature in conventionally treated patients in particular. CONCLUSIONS—This study has shown that variability in A1C adds to the mean value in predicting microvascular complications in type 1 diabetes. Thus, in contrast to analyses of DCCT data investigating the effect of short-term glucose instability on complication risk, longer-term fluctuations in glycemia seem to contribute to the development of retinopathy and nephropathy in type 1 diabetes.

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Association of Serum Potassium with All-Cause Mortality in Patients with and without Heart Failure, Chronic Kidney Disease, and/or Diabetes

Allan J Collins, Bertram Pitt, Nancy Reaven … (2017)

Background: The relationship between serum potassium, mortality, and conditions commonly associated with dyskalemias, such as heart failure (HF), chronic kidney disease (CKD), and/or diabetes mellitus (DM) is largely unknown. Methods: We reviewed electronic medical record data from a geographically diverse population ( n = 911,698) receiving medical care, determined the distribution of serum potassium, and the relationship between an index potassium value and mortality over an 18-month period in those with and without HF, CKD, and/or DM. We examined the association between all-cause mortality and potassium using a cubic spline regression analysis in the total population, a control group, and in HF, CKD, DM, and a combined cohort. Results: 27.6% had a potassium <4.0 mEq/L, and 5.7% had a value ≥5.0 mEq/L. A U-shaped association was noted between serum potassium and mortality in all groups, with lowest all-cause mortality in controls with potassium values between 4.0 and <5.0 mEq/L. All-cause mortality rates per index potassium between 2.5 and 8.0 mEq/L were consistently greater with HF 22%, CKD 16.6%, and DM 6.6% vs. controls 1.2%, and highest in the combined cohort 29.7%. Higher mortality rates were noted in those aged ≥65 vs. 50-64 years. In an adjusted model, all-cause mortality was significantly elevated for every 0.1 mEq/L change in potassium <4.0 mEq/L and ≥5.0 mEq/L. Diuretics and renin-angiotensin-aldosterone system inhibitors were related to hypokalemia and hyperkalemia respectively. Conclusion: Mortality risk progressively increased with dyskalemia and was differentially greater in those with HF, CKD, or DM.

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Yuichi Nakazato: nkzt@hakuyukai.jp

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): 25 June 2020

Publication date PMC-release: 25 June 2020

Publication date Collection: 2020

Volume: 10

Electronic Location Identifier: 10314

Affiliations

[1 ]Division of Nephrology, Yuai Nisshin Clinic, Hakuyukai Medical Corporation, Saitama-City, Saitama Japan

[2 ]ISNI 0000000419368710, GRID grid.47100.32, Department of Pathology, , Yale University, ; New Haven, CT USA

[3 ]ISNI 0000 0000 9064 6198, GRID grid.86715.3d, Groupe de recherche PRIMUS, Department of Family Medicine, , University of Sherbrooke, ; Sherbrooke, Quebec Canada

[4 ]Division of Nephrology, Yuai Clinic, Hakuyukai Medical Corporation, Saitama-City, Saitama Japan

[5 ]Division of Nephrology, Yuai Mihashi Clinic, Hakuyukai Medical Corporation, Saitama-City, Saitama Japan

[6 ]Division of Nephrology, Yuai Nakagawa Clinic, Hakuyukai Medical Corporation, Saitama-City, Saitama Japan

Article

Publisher ID: 66861

DOI: 10.1038/s41598-020-66861-6

PMC ID: 7316742

PubMed ID: 32587279

SO-VID: d66de7bc-d93d-4e07-9366-ff84a40af684

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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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 23 November 2019

Date accepted : 26 May 2020

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ScienceOpen disciplines: Uncategorized

Keywords: ageing,complexity,molecular fluctuations,regulatory networks,renal replacement therapy,diabetes,geriatrics,biomarkers

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ScienceOpen disciplines: Uncategorized

Keywords: ageing, complexity, molecular fluctuations, regulatory networks, renal replacement therapy, diabetes, geriatrics, biomarkers

Estimation of homeostatic dysregulation and frailty using biomarker variability: a principal component analysis of hemodialysis patients

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Aging Pathobiology and Therapeutics

Most cited references 32

Network physiology reveals relations between network topology and physiological function

A1C Variability and the Risk of Microvascular Complications in Type 1 Diabetes

Association of Serum Potassium with All-Cause Mortality in Patients with and without Heart Failure, Chronic Kidney Disease, and/or Diabetes

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