scholarly journals Chronodisruption: A Poorly Recognized Feature of CKD

Toxins ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 151 ◽  
Author(s):  
Sol Carriazo ◽  
Adrián M Ramos ◽  
Ana B Sanz ◽  
Maria Dolores Sanchez-Niño ◽  
Mehmet Kanbay ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Kidney Disease ◽  
Biological Rhythms ◽  
Molecular Clocks ◽  
Ckd Progression ◽  
Therapeutic Implications ◽  
Physiological Variables ◽  
Peripheral Clocks ◽  
Central Clock ◽  
The Impact

Multiple physiological variables change over time in a predictable and repetitive manner, guided by molecular clocks that respond to external and internal clues and are coordinated by a central clock. The kidney is the site of one of the most active peripheral clocks. Biological rhythms, of which the best known are circadian rhythms, are required for normal physiology of the kidneys and other organs. Chronodisruption refers to the chronic disruption of circadian rhythms leading to disease. While there is evidence that circadian rhythms may be altered in kidney disease and that altered circadian rhythms may accelerate chronic kidney disease (CKD) progression, there is no comprehensive review on chronodisruption and chronodisruptors in CKD and its manifestations. Indeed, the term chronodisruption has been rarely applied to CKD despite chronodisruptors being potential therapeutic targets in CKD patients. We now discuss evidence for chronodisruption in CKD and the impact of chronodisruption on CKD manifestations, identify potential chronodisruptors, some of them uremic toxins, and their therapeutic implications, and discuss current unanswered questions on this topic.

scholarly journals Circadian Clock, Sleep, and Diet

2021 ◽  
Author(s):  
Junichiro Irie
Keyword(s):  
Circadian Rhythm ◽  
Circadian Rhythms ◽  
Metabolic Regulation ◽  
Biological Clocks ◽  
Metabolic Alterations ◽  
Sleep Homeostasis ◽  
Peripheral Clocks ◽  
Central Clock ◽  
The Impact

Circadian rhythm is a fundamental process of sustaining metabolic homeostasis by predicting changes in the environment. This is driven by biological clocks, which operate within a 24-h period to orchestrate daily variation of metabolism and sleep. The central clock in the hypothalamus is the master keeper of the circadian rhythm and is primarily reset by light, while the feeding-fasting rhythm, that is, nutritional stimulus, entrains peripheral clocks in peripheral organs such as the intestine and liver. Nutritional stimuli are important modulators of peripheral circadian rhythms and may affect the central clock and sleep homeostasis through metabolic alterations. In this chapter, I will summarize the significance of circadian rhythm and sleep in metabolic regulation as well as discuss the impact that diet has on circadian rhythm and sleep.

scholarly journals Impact of nutrients on circadian rhythmicity

2015 ◽  
Vol 308 (5) ◽  
pp. R337-R350 ◽  
Author(s):  
Johanneke E. Oosterman ◽  
Andries Kalsbeek ◽  
Susanne E. la Fleur ◽  
Denise D. Belsham
Keyword(s):  
Circadian Rhythms ◽  
Circadian Clock ◽  
The Body ◽  
Circadian Rhythmicity ◽  
Energy Status ◽  
Peripheral Oscillators ◽  
Peripheral Clocks ◽  
Central Pacemaker ◽  
Almost All ◽  
The Impact

The suprachiasmatic nucleus (SCN) in the mammalian hypothalamus functions as an endogenous pacemaker that generates and maintains circadian rhythms throughout the body. Next to this central clock, peripheral oscillators exist in almost all mammalian tissues. Whereas the SCN is mainly entrained to the environment by light, peripheral clocks are entrained by various factors, of which feeding/fasting is the most important. Desynchronization between the central and peripheral clocks by, for instance, altered timing of food intake can lead to uncoupling of peripheral clocks from the central pacemaker and is, in humans, related to the development of metabolic disorders, including obesity and Type 2 diabetes. Diets high in fat or sugar have been shown to alter circadian clock function. This review discusses the recent findings concerning the influence of nutrients, in particular fatty acids and glucose, on behavioral and molecular circadian rhythms and will summarize critical studies describing putative mechanisms by which these nutrients are able to alter normal circadian rhythmicity, in the SCN, in non-SCN brain areas, as well as in peripheral organs. As the effects of fat and sugar on the clock could be through alterations in energy status, the role of specific nutrient sensors will be outlined, as well as the molecular studies linking these components to metabolism. Understanding the impact of specific macronutrients on the circadian clock will allow for guidance toward the composition and timing of meals optimal for physiological health, as well as putative therapeutic targets to regulate the molecular clock.

scholarly journals Klotho, the elusive kidney-derived anti-ageing factor

2019 ◽  
Vol 13 (2) ◽  
pp. 125-127 ◽  
Author(s):  
Maria Dolores Sanchez-Niño ◽  
Beatriz Fernandez-Fernandez ◽  
Alberto Ortiz
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Early Diagnosis ◽  
Cardiovascular Mortality ◽  
Causes Of Death ◽  
Negative Impact ◽  
Kidney Injury ◽  
Ckd Progression ◽  
The Impact

Abstract Chronic kidney disease (CKD) is one of the fastest growing causes of death worldwide. Only early diagnosis will allow prevention of both CKD progression and the negative impact of CKD on all-cause and cardiovascular mortality. Klotho is a protein produced by the kidneys that has anti-ageing and phosphaturic properties, preventing excess positive phosphate balance. There is evidence that Klotho downregulation is one of the earliest consequences of kidney injury. Thus the development of reliable assays to monitor Klotho levels may allow an early diagnosis of CKD and monitoring the impact of therapies aimed at preserving Klotho expression or at preventing CKD progression. However, the performance of Klotho assays has been suboptimal so far. In this issue of Clinical Kidney Journal, Neyra et al. explore methods to improve the reliability of Klotho assays.

scholarly journals A robust and self-sustained peripheral circadian oscillator reveals differences in temperature compensation properties with central brain clocks

2020 ◽  
Author(s):  
Marijke Versteven ◽  
Karla-Marlen Ernst ◽  
Ralf Stanewsky
Keyword(s):  
Temperature Compensation ◽  
Biological Rhythms ◽  
The Body ◽  
Circadian Clocks ◽  
Luciferase Reporter ◽  
Pigment Dispersing Factor ◽  
Peripheral Oscillators ◽  
Peripheral Clocks ◽  
Central Clock ◽  
Fitness And Health

AbstractCircadian clocks temporally organize physiology and behavior of organisms exposed to the daily changes of light and temperature on our planet, thereby contributing to fitness and health. Circadian clocks and the biological rhythms they control are characterized by three properties. (1) The rhythms are self-sustained in constant conditions with a period of ~ 24 hr, (2), they can be synchronized to the environmental cycles of light and temperature, and (3), they are temperature compensated, meaning they run with the same speed at different temperatures within the physiological range of the organism. Apart from the central clocks located in or near the brain, which regulate the daily activity rhythms of animals, the so-called peripheral clocks are dispersed throughout the body of insects and vertebrates. Based on the three defining properties, it has been difficult to determine if these peripheral clocks are true circadian clocks. We used a set of clock gene – luciferase reporter genes to address this question in Drosophila circadian clocks. We show that self-sustained fly peripheral oscillators over compensate temperature changes, i.e., they slow down with increasing temperature. This over-compensation is not observed in central clock neurons in the fly brain, both in intact flies and in cultured brains, suggesting that neural network properties contribute to temperature compensation. However, an important neuropeptide for synchronizing the circadian neuronal network, the Pigment Dispersing Factor (PDF), is not required for self-sustained and temperature-compensated oscillations in subsets of the central clock neurons. Our findings reveal a fundamental difference between central and peripheral clocks, which likely also applies for vertebrate clocks.

scholarly journals Circadian Rhythm Variations and Nutrition in Children

2018 ◽  
Vol 08 (01) ◽  
pp. e60-e66 ◽  
Author(s):  
Marie Gombert ◽  
Joaquín Carrasco-Luna ◽  
Gonzalo Pin-Arboledas ◽  
Pilar Codoñer-Franch
Keyword(s):  
Circadian Rhythms ◽  
Metabolic Diseases ◽  
Clock Genes ◽  
Light Exposure ◽  
Daily Basis ◽  
Biological Processes ◽  
Life Habits ◽  
Peripheral Clocks ◽  
Opposite Situation ◽  
Central Clock

AbstractCircadian rhythms are the changes in biological processes that occur on a daily basis. Among these processes are reactions involved in metabolic homeostasis. Circadian rhythms are structured by the central clock in the suprachiasmatic nucleus of the hypothalamus via the control of melatonin expression. Circadian rhythms are also controlled by the peripheral clocks, which are intracellular mechanisms composed of the clock genes, whose expression follows a circadian pattern. Circadian rhythms are impacted by signals from the environment called zeitgebers, or time givers, which include light exposure, feeding schedule and composition, sleeping schedule and pattern, temperature, and physical exercise. When the signals from the environment are synchronized with the internal clocks, metabolism is optimized. The term chronodisruption is used to describe the opposite situation. The latest research has demonstrated that life habits coherent with the internal clocks should be adopted, especially during childhood, to prevent metabolic diseases. Nevertheless, a few studies have investigated this link in children, and key information remains unknown.

scholarly journals Global costs attributed to chronic kidney disease: a systematic review

2018 ◽  
Vol 64 (12) ◽  
pp. 1108-1116 ◽  
Author(s):  
Geraldo Bezerra da Silva Junior ◽  
Juliana Gomes Ramalho de Oliveira ◽  
Marcel Rodrigo Barros de Oliveira ◽  
Luiza Jane Eyre de Souza Vieira ◽  
Eduardo Rocha Dias
Keyword(s):  
Systematic Review ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Health Systems ◽  
Treatment Modalities ◽  
Regional Studies ◽  
Ckd Progression ◽  
Public And Private ◽  
Study Protocols ◽  
The Impact

SUMMARY The aim of this study is to discuss the global costs attributed to chronic kidney disease (CKD) and its impact on healthcare systems of developing countries, such as Brazil. This is a systematic review based on data from PubMed/Medline, using the key words “costs” and “chronic kidney disease”, in January 2017. The search was also done in other databases, such as Scielo and Google Scholar, aiming to identify regional studies related to this subject, published in journal not indexed in PubMed. Only papers published from 2012 on were included. Studies on CKD costs and treatment modalities were prioritized. The search resulted in 392 articles, from which 291 were excluded because they were related to other aspects of CKD. From the 101 remaining articles, we have excluded the reviews, comments and study protocols. A total of 37 articles were included, all focusing on global costs related to CKD. Despite methods and analysis were diverse, the results of these studies were unanimous in alerting for the impact (financial and social) of CKD on health systems (public and private) and also on family and society. To massively invest in prevention and measures to slow CKD progression into its end-stages and, then, avoid the requirement for dialysis and transplant, can represent a huge, and not yet calculated, economy for patients and health systems all over the world.

MO462TIME-TRAJECTORIES OF RENAL FUNCTION AND OUTCOMES IN ELDERLY INDIVIDUALS WITH CKD OF VARIOUS ETIOLOGY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Mariateresa Zicarelli ◽  
Alessandro Comi ◽  
Gemma Patella ◽  
Paola Cianfrone ◽  
Giuseppe Coppolino ◽  
...  
Keyword(s):  
Renal Function ◽  
Kidney Disease ◽  
Left Ventricular ◽  
Renal Outcome ◽  
Hypertensive Retinopathy ◽  
Ckd Progression ◽  
Elderly Individuals ◽  
Older Populations ◽  
The Impact

Abstract Background and Aims Despite hypertension ranks among the leading causes of chronic kidney disease (CKD), the impact of chronic hypertensive nephropathy, the so-called “nephrosclerosis” (NS), on CKD progression towards end-stage kidney disease (ESKD) is often unpredictable, particularly in older populations. We run a prospective, observational study to define renal function patterns and outcomes in elderly individuals with or without NS-related CKD. Method 304 elderly patients with already established CKD (mean age 69±4 y; mean eGFR 44.2±19.6 mL/min/1.73 m2; male= 64.1%), followed in our outpatients’ clinic were categorized according to the etiology of CKD. NS was defined as the presence of CKD associated with long-term essential hypertension, hypertensive retinopathy, left ventricular hypertrophy and minimal proteinuria. Time-trajectories in eGFR (CKD-Epi) were computed over a 4-year follow-up. In addition, we analysed the occurrence of a composite outcome of doubling of serum creatinine, eGFR reduction≥ 25% and/or ESKD needing dialysis or kidney transplantation. Results CKD was secondary to nephrosclerosis (CKD-NS) in 220 (72.3%) patients. Among the remaining 84 (27.7%), glomerular/diabetic diseases were the most frequent cause of CKD (47.6%). In the whole cohort, the average estimated annual GFR slope was of 1.8 mL/min/1.73 m2. eGFR decline was slower in CKD-NS as compared with the one of others (1.4 vs. 3.4 mL/min/1.73 m2; p<0.001. Figure 1). The composite renal outcome during follow-up (median 36 mo.; range 6-48) occurred less frequently among elderly with CKD-NS (16/204 vs 14/70; p=0.01 Crude HR 0.43, 95%CI 0.22-0.85) and was associated at logistic analyses with etiology of CKD, serum total cholesterol, serum LDL cholesterol levels and glycemia (p ranging from 0.01 to 0.04). Conclusion Despite being highly prevalent in the elderly, NS is associated with a more favorable renal disease course as compared with other conditions. Therapeutic efforts to delay CKD progression in older populations should go beyond just optimizing blood pressure control and focus more on concomitant diseases.

scholarly journals Pre-dialysis chronic kidney disease progression over 4 years in the context of the Public Health System in Brazil: is ethnicity a factor?

HU Revista ◽  
2021 ◽  
Vol 47 ◽  
Author(s):  
Luciana dos Santos Tirapani Dalamura ◽  
Lucas Fernandes Suassuna ◽  
João Eduardo Cascelli Schelb Scalla Pereira ◽  
Rosália Maria Nunes Henriques Huaira ◽  
Neimar da Silva Fernandes ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Health System ◽  
Disease Progression ◽  
Laboratory Data ◽  
High Density Lipoproteins ◽  
Ckd Progression ◽  
Converting Enzyme Inhibitors ◽  
Black Patients ◽  
The Impact

Introduction: The prevalence of chronic kidney disease (CKD) significantly increased, and populations with high social vulnerability tend to have worse CKD progression. Objective: To evaluate the impact of ethnicity on the control of pre-dialytic CKD in a Brazilian Unified Health System interdisciplinary outpatient clinic. Material and Methods: Data of 1,992 CKD patients were retrospectively collected from August/2010 to December/2014. Patients referred by primary health care, >18 years, ≥ two consultations were included. Sociodemographic data were collected upon admission; clinical and laboratory data were obtained at each consultation. Patients were divided into groups according to skin colour (self-identified). A descriptive analysis was performed; variables were compared using ANOVA, chi-square or Mann-Whitney U tests. Variables associated with the delta of the estimated glomerular filtration rate (eGFR) were evaluated using linear regression, adjusting for confounding variables. Results: 25.1% were black, 34.4% brown, and 40.5% white. Approximately 51.2% had income ≤ two minimum wages, 84.8% had low level education, 14.0% were illiterate. Black patients were younger and had lower education level; they had higher systolic blood pressure, total cholesterol, high-density lipoproteins, intact parathyroid hormone; their haemoglobin and vitamin D were lower. The median annual eGFR loss was 0 (P25 −6.70, P75 +8.76), 36.5% had rapid eGFR loss (>5 ml/min/year). Only use of angiotensin-converting enzyme inhibitors and low proteinuria were determined as significant for the outcome (RR: 0.92, CI: 0.010–0.684, p=0.02; RR: 0.8, CI: 0.998-0.999, p=0.001). Conclusion: Ethnicity did not impact CKD progression, even though black patients presented clinical and sociodemographic characteristics associated with worse disease progression.

The Impact of Translational Research in Breast Cancer Care: Can we Improve the Therapeutic Scenario?

2018 ◽  
Vol 18 (6) ◽  
pp. 832-836
Author(s):  
Giuseppe Buono ◽  
Francesco Schettini ◽  
Francesco Perri ◽  
Grazia Arpino ◽  
Roberto Bianco ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Translational Research ◽  
Cell Biology ◽  
Cancer Biology ◽  
Hormone Receptors ◽  
Treatment Strategies ◽  
Growth Factor Receptor ◽  
Molecular Heterogeneity ◽  
Therapeutic Implications ◽  
The Impact

Traditionally, breast cancer (BC) is divided into different subtypes defined by immunohistochemistry (IHC) according to the expression of hormone receptors and overexpression/amplification of human epidermal growth factor receptor 2 (HER2), with crucial therapeutic implications. In the last few years, the definition of different BC molecular subgroups within the IHC-defined subtypes and the identification of the important role that molecular heterogeneity can play in tumor progression and treatment resistance have inspired the search for personalized therapeutic approaches. In this scenario, translational research represents a key strategy to apply knowledge from cancer biology to the clinical setting, through the study of all the tumors “omics”, including genomics, transcriptomics, proteomics, epigenomics, and metabolomics. Importantly, the introduction of new high-throughput technologies, such as next generation sequencing (NGS) for the study of cancer genome and transcriptome, greatly amplifies the potential and the applications of translational research in the oncology field. Moreover, the introduction of new experimental approaches, such as liquid biopsy, as well as new-concept clinical trials, such as biomarker-driven adaptive studies, may represent a turning point for BC translational research. </P><P> It is likely that translational research will have in the near future a significant impact on BC care, especially by giving us the possibility to dissect the complexity of tumor cell biology and develop new personalized treatment strategies.

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