Chronic kidney disease (CKD), affecting 10-12% of the world's adult population, is associated with a considerably elevated risk of serious comorbidities, in particular, premature vascular disease and death. Although a wide spectrum of causative factors has been identified and/or suggested, there is still a large gap of knowledge regarding the underlying mechanisms and the complexity of the CKD phenotype. Epigenetic factors, which calibrate the genetic code, are emerging as important players in the CKD-associated pathophysiology. In this article, we review some of the current knowledge on epigenetic modifications and aspects on their role in the perturbed uraemic milieu, as well as the prospect of applying epigenotype-based diagnostics and preventive and therapeutic tools of clinical relevance to CKD patients. The practical realization of such a paradigm will require that researchers apply a holistic approach, including the full spectrum of the epigenetic landscape as well as the variability between and within tissues in the uraemic milieu.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1042/CS20160596 | DOI Listing |
Pharmaceuticals (Basel)
December 2024
Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy.
: Chronic kidney disease (CKD) geriatric patients experience a premature aging process, compared with the general population of the same age and sex. The uremic milieu is capable of enhancing oxidative stress (OS) and microinflammation, leading to a pro-aging mechanism and an increased protein catabolism. Moreover, cognitive disorders are observed.
View Article and Find Full Text PDFFront Nephrol
December 2024
Center for Hemolytic Uremic Syndrome (HUS) Prevention, Control, and Management at the Nephrology and Dialysis Unit, Fondazione Scientific Institute for Research, Hospitalization and Healthcare (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
In hemodialysis (HD), complement activation, bioincompatibility, and inflammation are intricately intertwined. In the 1970s, as HD became a routine therapy, the observation of complement pathway activation and transient leukopenia by cellulosic dialysis membranes triggered the bioincompatibility debate and its clinical relevance. Extensive deliberations have covered definitions, assessment markers, scope, and long-term clinical consequences of membrane-dependent bioincompatibility reactions.
View Article and Find Full Text PDFNephrol Dial Transplant
November 2024
Renal Research Institute, New York, NY, USA.
Background And Hypothesis: In patients with advanced chronic kidney disease (CKD), the lifespan of red blood cells (RBC) is often shortened, a condition attributed to the "uremic milieu." We reported recently that the uremic solute 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF) shares structural similarities with Jedi1, a chemical activator of the mechanosensitive cation channel Piezo1, whose activation increases calcium influx into cells. Against this backdrop, we hypothesized that CMPF may induce premature RBC death (eryptosis) through prolonged CMPF-induced activation of Piezo1 located on RBC.
View Article and Find Full Text PDFCurr Opin Nephrol Hypertens
January 2025
American Heart Association Comprehensive Hypertension Center at the University of California Irvine Medical Center, Division of Nephrology, Hypertension and Kidney Transplantation, Department of Medicine, University of California Irvine School of Medicine, Orange, California.
Kidney360
November 2024
Department of Nephrology, St George Hospital, Sydney, New South Wales, Australia.
Our understanding of the pathogenesis of uremic pruritus (also known as CKD-associated pruritus [CKD-aP]) remains elusive. Although multiple discrete changes in the immunochemical milieu of the skin of patients with CKD-aP have been described, a coherent theory of mechanism is absent. This article proposes a theoretical model of mechanism.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!