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New Insights into CKD and Age-Related Bone and Mineral Disorders

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (29 February 2024) | Viewed by 3870

Special Issue Editors


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Guest Editor
1. Metabolismo Óseo, Vascular y Enfermedades Inflamatorias Crónicas, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain
2. Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS2040, Kidney Disease), 28040 Madrid, Spain
Interests: calcification; chronic kidney disease-mineral and bone disorder; blood vessel calcification; chronic renal failure; fibrosis in CKD
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Unidad de Gestión Clínica de Metabolismo Óseo, Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Retic REDinREN-ISCIII, Universidad de Oviedo, 33003 Oviedo, España
Interests: bone metabolism; vascular metabolism; chronic inflammatory diseases
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Bone and Mineral Research Unit, Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Retic REDinREN-ISCIII, Avda. Roma, sn., 33011 Oviedo, Spain
Interests: bone metabolism; vascular metabolism; chronic inflammatory diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Chronic kidney disease (CKD) is a highly prevalent disorder that leads to premature ageing, with important impacts on the cardiovascular and bone systems, among other organs, decreasing quality of life and increasing morbidity as well as mortality. In the general population, the ageing process itself also follows a similar pattern, sharing the same risk factors as those of CKD. Among the potentially modifiable risk factors that contribute to the impairment of these two conditions, hypertension, obesity, and diabetes play important roles.

The scenarios of CKD and ageing, both associated with important changes in the regulation of and interactions between multiple organs, imply the need to have a holistic and interdisciplinary approach to improve the management of these patients.

Led by Guest Editors and assisted by our Topical Advisory Panel Member Dr. Beatriz Martín-Carro, this Special Issue aims to update some of the latest relevant molecular and clinical findings in the whole field of CKD, but particularly in aspects related to the bone, mineral, and cardiovascular disorders of CKD (CKD-MBD).

Dr. Natalia Carrillo-López
Dr. Sara Panizo
Dr. Cristina Alonso-Montes
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 submissions that pass pre-check are 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 single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • chronic kidney disease
  • CKD
  • CKD-MBD
  • mineral and bone disorder

Published Papers (4 papers)

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Research

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12 pages, 2975 KiB  
Article
Cognitive Impairment Related to Chronic Kidney Disease Is Associated with a Decreased Abundance of Membrane-Bound Klotho in the Cerebral Cortex
by María E. Rodríguez-Ortiz, Daniel Jurado-Montoya, Karen Valdés-Díaz, Raquel M. García-Sáez, Ana I. Torralbo, Teresa Obrero, Victoria Vidal-Jiménez, María J. Jiménez, Andrés Carmona, Fátima Guerrero, María V. Pendón-Ruiz de Mier, Cristian Rodelo-Haad, Antonio Canalejo, Mariano Rodríguez, Sagrario Soriano-Cabrera and Juan R. Muñoz-Castañeda
Int. J. Mol. Sci. 2024, 25(8), 4194; https://doi.org/10.3390/ijms25084194 - 10 Apr 2024
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Abstract
Cognitive impairment (CI) is a complication of chronic kidney disease (CKD) that is frequently observed among patients. The aim of this study was to evaluate the potential crosstalk between changes in cognitive function and the levels of Klotho in the brain cortex in [...] Read more.
Cognitive impairment (CI) is a complication of chronic kidney disease (CKD) that is frequently observed among patients. The aim of this study was to evaluate the potential crosstalk between changes in cognitive function and the levels of Klotho in the brain cortex in an experimental model of CKD. To induce renal damage, Wistar rats received a diet containing 0.25% adenine for six weeks, while the control group was fed a standard diet. The animals underwent different tests for the assessment of cognitive function. At sacrifice, changes in the parameters of mineral metabolism and the expression of Klotho in the kidney and frontal cortex were evaluated. The animals with CKD exhibited impaired behavior in the cognitive tests in comparison with the rats with normal renal function. At sacrifice, CKD-associated mineral disorder was confirmed by the presence of the expected disturbances in the plasma phosphorus, PTH, and both intact and c-terminal FGF23, along with a reduced abundance of renal Klotho. Interestingly, a marked and significant decrease in Klotho was observed in the cerebral cortex of the animals with renal dysfunction. In sum, the loss in cerebral Klotho observed in experimental CKD may contribute to the cognitive dysfunction frequently observed among patients. Although further studies are required, Klotho might have a relevant role in the development of CKD-associated CI and represent a potential target in the management of this complication. Full article
(This article belongs to the Special Issue New Insights into CKD and Age-Related Bone and Mineral Disorders)
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10 pages, 287 KiB  
Article
Hyperparathyroidism, Serum Phosphorus and Dietary Intake in Hemodialysis Patients: Is There a Novel Relationship?
by Cristina Garagarza, Ana Valente, Cátia Queirós, Inês Pastor Neto, Joana Sebastião, Melanie Gomes and Aníbal Ferreira
Int. J. Mol. Sci. 2024, 25(4), 2006; https://doi.org/10.3390/ijms25042006 - 7 Feb 2024
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Abstract
The management of hyperparathyroidism (intact parathyroid hormone (iPTH) serum levels > 585 pg/mL), frequently focuses on the appropriate control of mineral and bone markers, with the decrease in serum and dietary phosphorus as two of the targets. We aimed to investigate the association [...] Read more.
The management of hyperparathyroidism (intact parathyroid hormone (iPTH) serum levels > 585 pg/mL), frequently focuses on the appropriate control of mineral and bone markers, with the decrease in serum and dietary phosphorus as two of the targets. We aimed to investigate the association between iPTH, serum phosphorus levels and dietary intake. This was a cross-sectional, multicenter, observational study with 561 patients on hemodialysis treatment. Clinical parameters, body composition and dietary intake were assessed. For the analysis, patients were divided into three groups: (a) iPTH < 130, (b) iPTH between 130 and 585 and (c) iPTH > 585 pg/mL. The association between PTH, serum phosphorus and dietary intake was analyzed using linear regression models. In the whole sample, 23.2% of patients presented an iPTH > 585 pg/mL. Patients with higher iPTH levels were those with longer HD vintage and lower ages, higher serum phosphorus, serum calcium, Ca/P product, albumin and caffeine intake, and a lower dietary intake of phosphorus, fiber, riboflavin and folate. Higher serum phosphorus predicted higher iPTH levels, even in the adjusted model. However, lower dietary phosphorus and fiber intake were predictors of higher iPTH levels, including in the adjusted model. Our results bring new data to the relationship between dietary intake and iPTH values. Despite higher serum phosphorus being observed in patients with HPTH, an opposite association was noted regarding dietary phosphate and fiber. Full article
(This article belongs to the Special Issue New Insights into CKD and Age-Related Bone and Mineral Disorders)

Review

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18 pages, 574 KiB  
Review
Post-Transplant Bone Disease in Kidney Transplant Recipients: Diagnosis and Management
by Jia Wei Teh, Conall Mac Gearailt and David W. P. Lappin
Int. J. Mol. Sci. 2024, 25(3), 1859; https://doi.org/10.3390/ijms25031859 - 3 Feb 2024
Cited by 1 | Viewed by 1107
Abstract
Kidney transplantation is the preferred gold standard modality of treatment for kidney failure. Bone disease after kidney transplantation is highly prevalent in patients living with a kidney transplant and is associated with high rates of hip fractures. Fractures are associated with increased healthcare [...] Read more.
Kidney transplantation is the preferred gold standard modality of treatment for kidney failure. Bone disease after kidney transplantation is highly prevalent in patients living with a kidney transplant and is associated with high rates of hip fractures. Fractures are associated with increased healthcare costs, morbidity and mortality. Post-transplant bone disease (PTBD) includes renal osteodystrophy, osteoporosis, osteonecrosis and bone fractures. PTBD is complex as it encompasses pre-existing chronic kidney disease–mineral bone disease and compounding factors after transplantation, including the use of immunosuppression and the development of de novo bone disease. After transplantation, the persistence of secondary and tertiary hyperparathyroidism, renal osteodystrophy, relative vitamin D deficiency and high levels of fibroblast growth factor-23 contribute to post-transplant bone disease. Risk assessment includes identifying both general risk factors and kidney-specific risk factors. Diagnosis is complex as the gold standard bone biopsy with double-tetracycline labelling to diagnose the PTBD subtype is not always readily available. Therefore, alternative diagnostic tools may be used to aid its diagnosis. Both non-pharmacological and pharmacological therapy can be employed to treat PTBD. In this review, we will discuss pathophysiology, risk assessment, diagnosis and management strategies to manage PTBD after kidney transplantation. Full article
(This article belongs to the Special Issue New Insights into CKD and Age-Related Bone and Mineral Disorders)
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14 pages, 1130 KiB  
Review
Soluble Klotho, a Potential Biomarker of Chronic Kidney Disease–Mineral Bone Disorders Involved in Healthy Ageing: Lights and Shadows
by Julia Martín-Vírgala, Beatriz Martín-Carro, Sara Fernández-Villabrille, María Piedad Ruiz-Torres, Carlos Gómez-Alonso, Minerva Rodríguez-García, José Luis Fernández-Martín, Cristina Alonso-Montes, Sara Panizo, Jorge B. Cannata-Andía, Manuel Naves-Díaz and Natalia Carrillo-López
Int. J. Mol. Sci. 2024, 25(3), 1843; https://doi.org/10.3390/ijms25031843 - 3 Feb 2024
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Abstract
Shortly after the discovery of Klotho, interest grew in its potential role in chronic kidney disease (CKD). There are three isoforms of the Klotho protein: αKlotho, βKlotho and γKlotho. This review will focus on αKlotho due to its relevance as a biomarker in [...] Read more.
Shortly after the discovery of Klotho, interest grew in its potential role in chronic kidney disease (CKD). There are three isoforms of the Klotho protein: αKlotho, βKlotho and γKlotho. This review will focus on αKlotho due to its relevance as a biomarker in CKD. αKlotho is synthesized mainly in the kidneys, but it can be released into the bloodstream and urine as soluble Klotho (sKlotho), which undertakes systemic actions, independently or in combination with FGF23. It is usually accepted that sKlotho levels are reduced early in CKD and that lower levels of sKlotho might be associated with the main chronic kidney disease–mineral bone disorders (CKD-MBDs): cardiovascular and bone disease. However, as results are inconsistent, the applicability of sKlotho as a CKD-MBD biomarker is still a matter of controversy. Much of the inconsistency can be explained due to low sample numbers, the low quality of clinical studies, the lack of standardized assays to assess sKlotho and a lack of consensus on sample processing, especially in urine. In recent decades, because of our longer life expectancies, the prevalence of accelerated-ageing diseases, such as CKD, has increased. Exercise, social interaction and caloric restriction are considered key factors for healthy ageing. While exercise and social interaction seem to be related to higher serum sKlotho levels, it is not clear whether serum sKlotho might be influenced by caloric restriction. This review focuses on the possible role of sKlotho as a biomarker in CKD-MBD, highlighting the difference between solid knowledge and areas requiring further research, including the role of sKlotho in healthy ageing. Full article
(This article belongs to the Special Issue New Insights into CKD and Age-Related Bone and Mineral Disorders)
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