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Exploring the Molecular Mechanisms of Chronic Kidney Disease

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Guest Editor
Vascular and Renal Translational Research Group, Biomedical Research Institute of Lleida (IRBLleida), Arnau de Vilanova University Hospital, 25198 Lleida, Spain
Interests: bone disease; mineral metabolism; renal disease; vascular calcification; calcium-sensing receptor; fibroblast growth factor 23; sclerostin; vitamin D; parathyroid hormone
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Special Issue Information

Dear Colleagues,

Chronic kidney disease (CKD) is a global challenge, currently affecting approximately 1 in 10 individuals, accounting for over 800 million people with CKD worldwide. Unfortunately, the prevalence of CKD is increasing, estimated to become the fifth leading cause of death by 2040, which underscores the significant social and economic impact of this devastating disease. Research efforts focus on the prevention of CKD progression and associated complications that usually lead to increased hospitalization and higher mortality risk. Understanding the distinct molecular mechanisms underlying CKD development is key for identifying new therapeutic approaches and achieving the optimization of patient care.

This Special Issue aims to compile cutting-edge research on the molecular features of renal diseases and CKD-associated disorders, including metabolic bone disease, anemia, cardiovascular disease, diabetes and hypertension. In addition, novel molecular actions of current treatments and emerging drugs, as well as future strategies for preventing complications associated with dialysis or renal transplantation are also included.

Dr. Juan Miguel Diaz-Tocados
Guest Editor

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Keywords

  • chronic kidney disease
  • hereditary renal disease
  • renal hypertension
  • diabetic nephropathy
  • secondary hyperparathyroidism
  • cardiovascular disease
  • renal osteodystrophy
  • peritoneal dialysis
  • hemodialysis
  • anemia
  • metabolic acidosis

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Published Papers (2 papers)

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Research

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12 pages, 2365 KiB  
Article
Citrate Dialysate with and without Magnesium Supplementation in Hemodiafiltration: A Comparative Study Versus Acetate
by Diana Rodríguez-Espinosa, Elena Cuadrado-Payán, Naira Rico, Mercè Torra, Rosa María Fernández, Gregori Casals, María Rodríguez-García, Francisco Maduell and José Jesús Broseta
Int. J. Mol. Sci. 2024, 25(15), 8491; https://doi.org/10.3390/ijms25158491 - 3 Aug 2024
Viewed by 823
Abstract
The choice of dialysate buffer in hemodialysis is crucial, with acetate being widely used despite complications. Citrate has emerged as an alternative because of its favorable effects, yet concerns persist about its impact on calcium and magnesium levels. This study investigates the influence [...] Read more.
The choice of dialysate buffer in hemodialysis is crucial, with acetate being widely used despite complications. Citrate has emerged as an alternative because of its favorable effects, yet concerns persist about its impact on calcium and magnesium levels. This study investigates the influence of citrate dialysates (CDs) with and without additional magnesium supplementation on CKD-MBD biomarkers and assesses their ability to chelate divalent metals compared to acetate dialysates (ADs). A prospective crossover study was conducted in a single center, involving patients on thrice-weekly online hemodiafiltration (HDF). The following four dialysates were compared: two acetate-based and two citrate-based. Calcium, magnesium, iPTH, iron, selenium, cadmium, copper, zinc, BUN, albumin, creatinine, bicarbonate, and pH were monitored before and after each dialysis session. Seventy-two HDF sessions were performed on eighteen patients. The CDs showed stability in iPTH levels and reduced post-dialysis total calcium, with no significant increase in adverse events. Magnesium supplementation with CDs prevented hypomagnesemia. However, no significant differences among dialysates were observed in the chelation of other divalent metals. CDs, particularly with higher magnesium concentrations, offer promising benefits, including prevention of hypomagnesemia and stabilization of CKD-MBD parameters, suggesting citrate as a viable alternative to acetate. Further studies are warranted to elucidate long-term outcomes and optimize dialysate formulations. Until then, given our results, we recommend that when a CD is used, it should be used with a 0.75 mmol/L Mg concentration rather than a 0.5 mmol/L one. Full article
(This article belongs to the Special Issue Exploring the Molecular Mechanisms of Chronic Kidney Disease)
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Review

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21 pages, 4656 KiB  
Review
Clinical Properties and Non-Clinical Testing of Mineralocorticoid Receptor Antagonists in In Vitro Cell Models
by Luka Varda, Robert Ekart, Mitja Lainscak, Uroš Maver and Sebastjan Bevc
Int. J. Mol. Sci. 2024, 25(16), 9088; https://doi.org/10.3390/ijms25169088 - 22 Aug 2024
Viewed by 901
Abstract
Mineralocorticoid receptor antagonists (MRAs) are one of the renin–angiotensin–aldosterone system inhibitors widely used in clinical practice. While spironolactone and eplerenone have a long-standing profile in clinical medicine, finerenone is a novel agent within the MRA class. It has a higher specificity for mineralocorticoid [...] Read more.
Mineralocorticoid receptor antagonists (MRAs) are one of the renin–angiotensin–aldosterone system inhibitors widely used in clinical practice. While spironolactone and eplerenone have a long-standing profile in clinical medicine, finerenone is a novel agent within the MRA class. It has a higher specificity for mineralocorticoid receptors, eliciting less pronounced adverse effects. Although approved for clinical use in patients with chronic kidney disease and heart failure, intensive non-clinical research aims to further elucidate its mechanism of action, including dose-related selectivity. Within the field, animal models remain the gold standard for non-clinical testing of drug pharmacological and toxicological properties. Their role, however, has been challenged by recent advances in in vitro models, mainly through sophisticated analytical tools and developments in data analysis. Currently, in vitro models are gaining momentum as possible platforms for advanced pharmacological and pathophysiological studies. This article focuses on past, current, and possibly future in vitro cell models research with clinically relevant MRAs. Full article
(This article belongs to the Special Issue Exploring the Molecular Mechanisms of Chronic Kidney Disease)
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