Special Issue "Comorbidities in Chronic Kidney Disease (CKD)"

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Uremic Toxins".

Deadline for manuscript submissions: 31 March 2020.

Special Issue Editors

Prof. Dr. Joachim Jankowski
E-Mail Website
Guest Editor
University hospital RWTH, Aachen (Germany); Institute for Molecular Cardiovascular Research
Interests: chronic renal failure, hypertension, proteomics, mediator identification, mediator identification, mass-spectrometry, chromatography, pathophysiology of kidney diseases
Dr. Heidi Noels
E-Mail Website
Guest Editor
University hospital RWTH, Aachen (Germany); Institute for Molecular Cardiovascular Research
Interests: pathophysiology of cardiovascular disease

Special Issue Information

Dear Colleagues,

Cardiovascular disease causes 47% of all deaths in Europe, 10% of Europeans suffer from chronic kidney disease, and 5–8% of elderly aged 60 years or older have to live with cognitive impairment. This disease trio is associated with end-organ damage in the kidney, heart, vasculature, and brain and displays as highly frequent comorbidities. Specifically, ~45% of patients with chronic kidney disease stage 4–5 die from cardiovascular disease, and chronic kidney disease and cardiovascular disease raise the risk of cognitive impairment 2–2.5-fold. Of note, risks of cardiovascular disease and cognitive impairment increase with chronic kidney disease severity but are already significantly higher in early chronic kidney disease compared to non-chronic kidney disease.

Chronic kidney disease, cardiovascular disease, and cognitive impairment are most likely triggered by common pathological molecular mechanisms, with chronic kidney disease further amplifying pathological triggers for co-developing cardiovascular disease and cognitive impairment, which is already present at an early stage (chronic kidney disease stage 1–3). This Special Issue will focus on both causative molecular and cellular mechanisms for diagnosis and prognosis of cardiovascular disease and cognitive impairment in chronic kidney disease, as well as biomarkers for diagnosis, prognosis, and monitoring of comorbid patients.

Prof. Dr. Joachim Jankowski
Dr. Heidi Noels
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a double-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxins is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Cardiovascular disease
  • Chronic renal failure
  • Cognitive impairment
  • Molecular mechanisms
  • Molecular mediators
  • Pathway analyses
  • Age and gender aspects
  • In vitro/ex vivo analyses
  • Proteomics
  • Therapy

Published Papers (2 papers)

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Research

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Open AccessArticle
Serum P-Cresyl Sulfate Is a Predictor of Central Arterial Stiffness in Patients on Maintenance Hemodialysis
Toxins 2020, 12(1), 10; https://doi.org/10.3390/toxins12010010 - 21 Dec 2019
Abstract
Arterial stiffness (AS) has an important impact on the outcomes of patients on hemodialysis (HD), and p-cresyl sulfate (PC) can mediate the process of vascular damage. We aimed to investigate the relationship between carotid–femoral pulse wave velocity (cfPWV) and the level of [...] Read more.
Arterial stiffness (AS) has an important impact on the outcomes of patients on hemodialysis (HD), and p-cresyl sulfate (PC) can mediate the process of vascular damage. We aimed to investigate the relationship between carotid–femoral pulse wave velocity (cfPWV) and the level of PCs in HD patients. Serum PCs were quantified using liquid chromatography mass spectrometry. Patients who were on standard HD for more than 3 months were enrolled and categorized according to the cfPWV into the high AS (>10 m/s) and control (≤10 m/s) groups. Forty-nine (41.5%) patients belonged to the high AS group and had a higher incidence of diabetes mellitus (DM) and increased systolic blood pressure, serum C-reactive protein, and PC levels but had lower creatinine, compared with those in the control group. In HD patients, the risk for developing high AS increased in the presence of DM (OR 4.147, 95% confidence interval (CI) 1.497–11.491) and high PCs (OR 1.067, 95% CI 1.002–1.136). Having DM (r = 0.446) and high PC level (r = 0.174) were positively associated with cfPWV. The most optimal cutoff value of PC for predicting AS was 18.99 mg/L (area under the curve 0.661, 95% CI 0.568–0.746). We concluded that DM and PCs were promising predictors of high AS in patients on maintenance HD. Full article
(This article belongs to the Special Issue Comorbidities in Chronic Kidney Disease (CKD))
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Review

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Open AccessReview
Molecular and Cellular Mechanisms that Induce Arterial Calcification by Indoxyl Sulfate and P-Cresyl Sulfate
Toxins 2020, 12(1), 58; https://doi.org/10.3390/toxins12010058 - 19 Jan 2020
Abstract
The protein-bound uremic toxins, indoxyl sulfate (IS) and p-cresyl sulfate (PCS), are considered to be harmful vascular toxins. Arterial media calcification, or the deposition of calcium phosphate crystals in the arteries, contributes significantly to cardiovascular complications, including left ventricular hypertrophy, hypertension, and impaired [...] Read more.
The protein-bound uremic toxins, indoxyl sulfate (IS) and p-cresyl sulfate (PCS), are considered to be harmful vascular toxins. Arterial media calcification, or the deposition of calcium phosphate crystals in the arteries, contributes significantly to cardiovascular complications, including left ventricular hypertrophy, hypertension, and impaired coronary perfusion in the elderly and patients with chronic kidney disease (CKD) and diabetes. Recently, we reported that both IS and PCS trigger moderate to severe calcification in the aorta and peripheral vessels of CKD rats. This review describes the molecular and cellular mechanisms by which these uremic toxins induce arterial media calcification. A complex interplay between inflammation, coagulation, and lipid metabolism pathways, influenced by epigenetic factors, is crucial in IS/PCS-induced arterial media calcification. High levels of glucose are linked to these events, suggesting that a good balance between glucose and lipid levels might be important. On the cellular level, effects on endothelial cells, which act as the primary sensors of circulating pathological triggers, might be as important as those on vascular smooth muscle cells. Endothelial dysfunction, provoked by IS and PCS triggered oxidative stress, may be considered a key event in the onset and development of arterial media calcification. In this review a number of important outstanding questions such as the role of miRNA’s, phenotypic switching of both endothelial and vascular smooth muscle cells and new types of programmed cell death in arterial media calcification related to protein-bound uremic toxins are put forward and discussed. Full article
(This article belongs to the Special Issue Comorbidities in Chronic Kidney Disease (CKD))
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Chronodisruption: A Poorly Recognized Comorbidity in CKD

 Alberto Ortiz et al.

Abstract: Circadian rhythms are required for normal physiology of diverse organs, including the kidneys. Chronodisruption refers to the disruption of circadian rhythms. White there is evidence that circadian rhythms may be altered in kidney disease and that altered circadian rhythms may accelerate CKD progression, there is no comprehensive review of the impact of chronodisruption on CKD and its manifestations. We now discuss evidence for chronodisruption in CKD, the impact of chronodisruption on CKD manifestations, its therapeutic implications and current answered questions.

Should We Consider the Heart While Evaluate CKD-MBD?

 Merita Rroji 1, Andreja Figurek 2, Goce Spasovski 3

1 Department of Nephrology, University Hospital Center” Mother Tereza” Tirana, Albania

2 Institute of Anatomy, University of Zurich, Zurich, Switzerland

3 University Department of Nephrology, Medical Faculty, University of Skopje, Skopje, R. N. Macedonia

Abstract: Cardiovascular (CV) disease is highly prevalent in the population with chronic kidney disease (CKD), where the risk of CV death in early-stages far exceeds the risk of progression to dialysis. The presence of chronic kidney disease-mineral and bone disorder (CKD-MBD) has shown a strong correlation with CV events and mortality. As non-atheromatous processes could point out why standard CV disease–modifying drugs do not provide such an impact on CV mortality in CKD as seen in general population, we summarize here the potential association of those comorbidities with the older (parathyroid hormone, phosphate) and newer (FGF-23, Klotho, sclerostin) CKD-MBD biomarkers. 

 

Molecular and Cellular Mechanisms that Underly Indoxyl Sulfate and p-Cresyl Sulfate Induced Arterial Calcification

Britt Opdebeeck, Patrick C D’Haese and Anja Verhulst

 Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, Belgium

 Abstract: The protein-bound uremic toxins, indoxyl sulfate and p-cresyl sulfate, are considered as harmful vascular toxins. Arterial media calcification, or the deposition of calcium-phosphate crystals in the arteries, contributes significantly to the cardiovascular mortality in elderly and patients with chronic kidney disease (CKD) and diabetes. Recently, we reported that both indoxyl sulfate and p-cresyl sulfate trigger moderate to severe calcification in the aorta and peripheral vessels of CKD rats. This review describes the molecular and cellular mechanisms by which these uremic toxins induce arterial media calcification. A complex interplay between inflammation-, coagulation- and lipid metabolism pathways as well as epigenetic factors is crucial in indoxyl sulfate/p-cresyl sulfate-induced arterial media calcification. High levels of glucose are linked to these events, suggesting that a good balance between glucose and lipid levels might be important. On the cellular level, effects on endothelial cells, which act as the primary sensors of circulating pathological triggers, might be as important as those on vascular smooth muscle cells. Endothelial dysfunction, provoked by indoxyl - and p-cresyl sulfate triggered oxidative stress, may be considered a key event in the onset and development of arterial media calcification. In this review a series of outstanding questions such as the role of miRNA’s, phenotypic switching of both endothelial and smooth muscle cells and new types of (programmed) cell death in arterial media calcification related to protein-bound uremic toxins are put forward and discussed.

Pathogenesis of Impaired Fertility in Patients with CKD

Piotr Kuczera, Marcin Adamczak, Andrzej Wiecek

Department of Nephrology, Transplantation and Infernal Medicine, Medical University of Silesia, Katowice, Poland

Abstract: Impaired fertility is one of the most important comorbidities in women with chronic kidney disease (CKD). It may be caused by several factors – among others: reduced renal clearance of different hormones (e.g. prolactin, leptin), disturbed activity if the pituitary-gonadal axis, impairment of ovarian function and reduced ovarian reserve, accumulation of uremic toxins, sexual function disorders, and depression. Prevalence of impaired fertility is increasing with the degree of kidney function deterioration and is present in more than 90% women with end stage kidney disease (ESKD), therefore pregnancy is ca. 40-times less frequent in women treated with chronic hemodialysis than in age-matched general population. Successful kidney transplantation in women with ESKD reduces accumulation of uremic toxins, restores function of the endocrine system and improves fertility.

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