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Chronic Kidney Disease: The Global Challenge

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Guest Editor
1. Department of Nephrology, Hospital Clinico Universitario de Valenciadisabled, Valencia, Spain
2. Institute of Health Research-INCLIVA, Valencia, Spain
3. Facultad de Ciencias de la Salud, Health Sciences School, Universidad Cardenal Herrera CEU, Spain
Interests: chronic kidney disease; cardiovascular and diabetic kidney disease; bone mineral metabolism; cardioremal disease
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Chief Guest Editor
1. Department of Nephrology, Hospital Clinico Universitario de Valenciadisabled, Valencia, Spain
2. Department of Medicine, University of Valencia, Valencia, Spain
Interests: chronic kidney disease; diabitic kidney disease; anemia; cardiorenal disease

Special Issue Information

Dear Colleagues,

Chronic kidney disease is positioned as one of the greatest public health challenges in the following decades due, among other problems, to its high complexity index and the elevated consumption of economic and human resources that it supposes. On the one hand, the rapid growth in the number of diabetic patients encountered in developed countries, derived from sedentary lifestyle and diets rich in carbohydrates, causes a high incidence of diabetic kidney disease, this being the main cause of end stage kidney disease with the need for renal replacement therapies. Moreover, the coexistence of other risk factors of chronic kidney disease such as hypertension and adiposity contributes to the higher cardiovascular morbidity and mortality rates observed in these patients. Beyond the classical cardiovascular risk factors, other factors inherent to kidney disease itself such as alterations in bone mineral metabolism, anemia or electrolyte disorders have been the target of intensive research in recent years. Of note, the inherent link between heart and kidney disease is a matter of intense and fertile debate.

Currently, we are witness to remarkable advances that make us look to the future with optimism. The introduction of drugs such as iSGLT2 or GLP-1, with the ability to slow the progression of kidney damage, together with all the advantages that they provide in the field of cardiovascular disease or the recent advances in the knowledge of the pathophysiology of anemia, and the development of new molecules, such as proline hydroxylase inhibitors, position nephrology at the forefront of the advancement of medicine. Of interest, new evidence supports the safe use of mineralocorticoid receptor antagonists and potassium resins to control proteinuria and hyperpotassemia associated with kidney disease, without of course forgetting the key role of kidney transplantation, which is a primary objective in renal replacement treatment and key to the sustainable maintenance of the system both from a medical and economic point of view.

Dr. María Jesús Puchades
Dr. Luis D' Marco
Guest Editors

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Keywords

  • Chronic kidney disease
  • Diabetes mellitus
  • Diabetic kidney disease
  • Hypertension
  • Adiposity
  • Cardiorenal syndrome
  • iSGLT2
  • Anemia in chronic kidney disease
  • HIF
  • Kidney transplantation

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Published Papers (8 papers)

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Editorial

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6 pages, 634 KiB  
Editorial
SARS-CoV-2 vs. Hepatitis Virus Infection Risk in the Hemodialysis Population: What Should We Expect?
by Luis D’Marco, María Jesús Puchades, Miguel Ángel Serra, Lorena Gandía, Sergio Romero-Alcaide, Elena Giménez-Civera, Pablo Molina, Nayara Panizo, Javier Reque and José Luis Gorriz
Int. J. Environ. Res. Public Health 2021, 18(11), 5748; https://doi.org/10.3390/ijerph18115748 - 27 May 2021
Cited by 2 | Viewed by 2381
Abstract
Since the dramatic rise of the coronavirus infection disease 2019 (COVID-19) pandemic, patients receiving dialysis have emerged as especially susceptible to this infection because of their impaired immunologic state, chronic inflammation and the high incidence of comorbidities. Although several strategies have thus been [...] Read more.
Since the dramatic rise of the coronavirus infection disease 2019 (COVID-19) pandemic, patients receiving dialysis have emerged as especially susceptible to this infection because of their impaired immunologic state, chronic inflammation and the high incidence of comorbidities. Although several strategies have thus been implemented to minimize the risk of transmission and acquisition in this population worldwide, the reported severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence varies across studies but is higher than in the general population. On the contrary, the screening for hepatitis viruses (HBV and HCV) has seen significant improvements in recent years, with vaccination in the case of HBV and effective viral infection treatment for HCV. In this sense, a universal SARS-CoV-2 screening and contact precaution appear to be effective in preventing further transmission. Finally, regarding the progress, an international consensus with updated protocols that prioritize between old and new indicators would seem a reasonable tool to address these unexpended changes for the nephrology community. Full article
(This article belongs to the Special Issue Chronic Kidney Disease: The Global Challenge)
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Research

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14 pages, 1188 KiB  
Article
Cost of Type 2 Diabetes Patients with Chronic Kidney Disease Based on Real-World Data: An Observational Population-Based Study in Spain
by Ruth Usó-Talamantes, Silvia González-de-Julián, Javier Díaz-Carnicero, Inmaculada Saurí-Ferrer, José Luis Trillo-Mata, Marc Carrasco-Pérez, Jorge Navarro-Pérez, José Luis Górriz, David Vivas-Consuelo and Josep Redón
Int. J. Environ. Res. Public Health 2021, 18(18), 9853; https://doi.org/10.3390/ijerph18189853 - 18 Sep 2021
Cited by 3 | Viewed by 3387
Abstract
This study analyzed the prevalence, costs and economic impact of chronic kidney disease CKD in patients with T2D in a Spanish Health District using real-world data. Observational cross-sectional study in adult patients with T2D was through data extracted from the information systems of [...] Read more.
This study analyzed the prevalence, costs and economic impact of chronic kidney disease CKD in patients with T2D in a Spanish Health District using real-world data. Observational cross-sectional study in adult patients with T2D was through data extracted from the information systems of the Valencia Clínico–La Malvarrosa Health District in the year 2015. Patients were stratified with the KDIGO classification for CKD. Additionally, patients were assigned to Clinical Risk Groups (CRGs) according to multimorbidity. Direct costs of primary and specialized care, and medication were estimated. The prevalence of T2D in the database population (n = 28,345) was 10.8% (mean age (SD) = 67.8 years (13.9); 51.5% male). Up to 14.935 patients (52.6%) had data on kidney function. According to the KDIGO classification, 66.2% of the patients were at low risk of CKD, 20.6% at moderately increased risk, 7.9% at high risk, and 5.2% at very high risk. The average healthcare costs associated with these four risk groups were EUR 3437, EUR 4936, EUR 5899 and EUR 7389, respectively. The large number of T2D patients with CKD in the early stages of the disease generated a significant increase in direct healthcare costs. The economic impact could be mitigated by early and comprehensive therapeutic approaches. Full article
(This article belongs to the Special Issue Chronic Kidney Disease: The Global Challenge)
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15 pages, 1713 KiB  
Article
Oxidative Stress in Non-Dialysis-Dependent Chronic Kidney Disease Patients
by Patricia Tomás-Simó, Luis D’Marco, María Romero-Parra, Mari Carmen Tormos-Muñoz, Guillermo Sáez, Isidro Torregrosa, Nuria Estañ-Capell, Alfonso Miguel, José Luis Gorriz and María Jesús Puchades
Int. J. Environ. Res. Public Health 2021, 18(15), 7806; https://doi.org/10.3390/ijerph18157806 - 23 Jul 2021
Cited by 12 | Viewed by 3702
Abstract
Background: Cardiovascular complications are the leading cause of morbidity and mortality at any stage of chronic kidney disease (CKD). Moreover, the high rate of cardiovascular mortality observed in these patients is associated with an accelerated atherosclerosis process that likely starts at the early [...] Read more.
Background: Cardiovascular complications are the leading cause of morbidity and mortality at any stage of chronic kidney disease (CKD). Moreover, the high rate of cardiovascular mortality observed in these patients is associated with an accelerated atherosclerosis process that likely starts at the early stages of CKD. Thus, traditional and non-traditional or uremic-related factors represent a link between CKD and cardiovascular risk. Among non-conventional risk factors, particular focus has been placed on anaemia, mineral and bone disorders, inflammation, malnutrition and oxidative stress and, in this regard, connections have been reported between oxidative stress and cardiovascular disease in dialysis patients. Methods: We evaluated the oxidation process in different molecular lines (proteins, lipids and genetic material) in 155 non-dialysis patients at different stages of CKD and 45 healthy controls. To assess oxidative stress status, we analyzed oxidized glutathione (GSSG), reduced glutathione (GSH) and the oxidized/reduced glutathione ratio (GSSG/GSH) and other oxidation indicators, including malondialdehyde (MDA) and 8-oxo-2’-deoxyguanosine (8-oxo-dG). Results: An active grade of oxidative stress was found from the early stages of CKD onwards, which affected all of the molecular lines studied. We observed a heightened oxidative state (indicated by a higher level of oxidized molecules together with decreased levels of antioxidant molecules) as kidney function declined. Furthermore, oxidative stress-related alterations were significantly greater in CKD patients than in the control group. Conclusions: CKD patients exhibit significantly higher oxidative stress than healthy individuals, and these alterations intensify as eGFR declines, showing significant differences between CKD stages. Thus, future research is warranted to provide clearer results in this area. Full article
(This article belongs to the Special Issue Chronic Kidney Disease: The Global Challenge)
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13 pages, 1497 KiB  
Article
The Effect of Bilateral Nephrectomy on Renalase and Catecholamines in Hemodialysis Patients
by Magda Wiśniewska, Natalia Serwin, Violetta Dziedziejko, Małgorzata Marchelek-Myśliwiec, Barbara Dołęgowska, Leszek Domański, Kazimierz Ciechanowski, Krzysztof Safranow, Tomasz Gołębiowski and Andrzej Pawlik
Int. J. Environ. Res. Public Health 2021, 18(12), 6282; https://doi.org/10.3390/ijerph18126282 - 10 Jun 2021
Cited by 1 | Viewed by 2755
Abstract
Background/Aims: Renalase is an enzyme with monoamine oxidase activity that metabolizes catecholamines; therefore, it has a significant influence on arterial blood pressure regulation and the development of cardiovascular diseases. Renalase is mainly produced in the kidneys. Nephrectomy and hemodialysis (HD) may alter the [...] Read more.
Background/Aims: Renalase is an enzyme with monoamine oxidase activity that metabolizes catecholamines; therefore, it has a significant influence on arterial blood pressure regulation and the development of cardiovascular diseases. Renalase is mainly produced in the kidneys. Nephrectomy and hemodialysis (HD) may alter the production and metabolism of renalase. The aim of this study was to examine the effect of bilateral nephrectomy on renalase levels in the serum and erythrocytes of hemodialysis patients. Methods: This study included 27 hemodialysis patients post-bilateral nephrectomy, 46 hemodialysis patients without nephrectomy but with chronic kidney disease and anuria and 30 healthy subjects with normal kidney function. Renalase levels in the serum and erythrocytes were measured using an ELISA kit. Results: Serum concentrations of renalase were significantly higher in post-bilateral nephrectomy patients when compared with those of control subjects (101.1 ± 65.5 vs. 19.6 ± 5.0; p < 0.01). Additionally, renalase concentrations, calculated per gram of hemoglobin, were significantly higher in patients after bilateral nephrectomy in comparison with those of healthy subjects (994.9 ± 345.5 vs. 697.6 ± 273.4, p = 0.015). There were no statistically significant differences in plasma concentrations of noradrenaline or adrenaline. In contrast, the concentration of dopamine was significantly lower in post-nephrectomy patients when compared with those of healthy subjects (116.8 ± 147.7 vs. 440.9 ± 343.2, p < 0.01). Conclusions: Increased serum levels of renalase in post-bilateral nephrectomy hemodialysis patients are likely related to production in extra-renal organs as a result of changes in the cardiovascular system and hypertension. Full article
(This article belongs to the Special Issue Chronic Kidney Disease: The Global Challenge)
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Review

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24 pages, 4405 KiB  
Review
Advanced Glycation End Products: New Clinical and Molecular Perspectives
by Juan Salazar, Carla Navarro, Ángel Ortega, Manuel Nava, Daniela Morillo, Wheeler Torres, Marlon Hernández, Mayela Cabrera, Lissé Angarita, Rina Ortiz, Maricarmen Chacín, Luis D’Marco and Valmore Bermúdez
Int. J. Environ. Res. Public Health 2021, 18(14), 7236; https://doi.org/10.3390/ijerph18147236 - 6 Jul 2021
Cited by 28 | Viewed by 6926
Abstract
Diabetes mellitus (DM) is considered one of the most massive epidemics of the twenty-first century due to its high mortality rates caused mainly due to its complications; therefore, the early identification of such complications becomes a race against time to establish a prompt [...] Read more.
Diabetes mellitus (DM) is considered one of the most massive epidemics of the twenty-first century due to its high mortality rates caused mainly due to its complications; therefore, the early identification of such complications becomes a race against time to establish a prompt diagnosis. The research of complications of DM over the years has allowed the development of numerous alternatives for diagnosis. Among these emerge the quantification of advanced glycation end products (AGEs) given their increased levels due to chronic hyperglycemia, while also being related to the induction of different stress-associated cellular responses and proinflammatory mechanisms involved in the progression of chronic complications of DM. Additionally, the investigation for more valuable and safe techniques has led to developing a newer, noninvasive, and effective tool, termed skin fluorescence (SAF). Hence, this study aimed to establish an update about the molecular mechanisms induced by AGEs during the evolution of chronic complications of DM and describe the newer measurement techniques available, highlighting SAF as a possible tool to measure the risk of developing DM chronic complications. Full article
(This article belongs to the Special Issue Chronic Kidney Disease: The Global Challenge)
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14 pages, 1990 KiB  
Review
Population Kidney Health. A New Paradigm for Chronic Kidney Disease Management
by Rafael Burgos-Calderón, Santos Ángel Depine and Gustavo Aroca-Martínez
Int. J. Environ. Res. Public Health 2021, 18(13), 6786; https://doi.org/10.3390/ijerph18136786 - 24 Jun 2021
Cited by 22 | Viewed by 5427
Abstract
Statistical data extracted from national databases demonstrate a continuous growth in the incidence and prevalence of chronic kidney disease (CKD) and the ineffectiveness of current policies and strategies based on individual risk factors to reduce them, as well as their mortality and costs. [...] Read more.
Statistical data extracted from national databases demonstrate a continuous growth in the incidence and prevalence of chronic kidney disease (CKD) and the ineffectiveness of current policies and strategies based on individual risk factors to reduce them, as well as their mortality and costs. Some innovative programs, telemedicine and government interest in the prevention of CKD did not facilitate timely access to care, continuing the increased demand for dialysis and transplants, high morbidity and long-term disability. In contrast, new forms of kidney disease of unknown etiology affected populations in developing countries and underrepresented minorities, who face socioeconomic and cultural disadvantages. With this background, our objective was to analyze in the existing literature the effects of social determinants in CKD, concluding that it is necessary to strengthen current kidney health strategies, designing in a transdisciplinary way, a model that considers demographic characteristics integrated into individual risk factors and risk factors population, incorporating the population health perspective in public health policies to improve results in kidney health care, since CKD continues to be an important and growing contributor to chronic diseases. Full article
(This article belongs to the Special Issue Chronic Kidney Disease: The Global Challenge)
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Other

6 pages, 649 KiB  
Opinion
Congestive Nephropathy
by Luis D’ Marco
Int. J. Environ. Res. Public Health 2022, 19(5), 2499; https://doi.org/10.3390/ijerph19052499 - 22 Feb 2022
Cited by 6 | Viewed by 3803
Abstract
The complex interaction between cardiac and renal functions is known. However, when these functions are disrupted, many intricate and sensitive interactions between these organs are failed by several pathophysiological ways. As a result, this malfunction is clinically evident by sign and symptoms associated [...] Read more.
The complex interaction between cardiac and renal functions is known. However, when these functions are disrupted, many intricate and sensitive interactions between these organs are failed by several pathophysiological ways. As a result, this malfunction is clinically evident by sign and symptoms associated to intravascular and interstitial congestion. In this sense, the adverse impact of venous congestion on renal function has long been recognized. Currently, the presence of a specific subtype of nephropathy associated to congestion has been suggested. Even though no diagnosis criteria has been clearly stablished, and no renal specific histological pattern were reported; studies regarding this issue may help to improve the handling and therapeutic principles in affected patients. Full article
(This article belongs to the Special Issue Chronic Kidney Disease: The Global Challenge)
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7 pages, 894 KiB  
Opinion
Insulin Withdrawal in Diabetic Kidney Disease: What Are We Waiting for?
by Carlos Morillas, Luis D’Marco, María Jesús Puchades, Eva Solá-Izquierdo, Carmen Gorriz-Zambrano, Valmore Bermúdez and José Luis Gorriz
Int. J. Environ. Res. Public Health 2021, 18(10), 5388; https://doi.org/10.3390/ijerph18105388 - 18 May 2021
Cited by 9 | Viewed by 4721
Abstract
The prevalence of type 2 diabetes mellitus worldwide stands at nearly 9.3% and it is estimated that 20–40% of these patients will develop diabetic kidney disease (DKD). DKD is the leading cause of chronic kidney disease (CKD), and these patients often present high [...] Read more.
The prevalence of type 2 diabetes mellitus worldwide stands at nearly 9.3% and it is estimated that 20–40% of these patients will develop diabetic kidney disease (DKD). DKD is the leading cause of chronic kidney disease (CKD), and these patients often present high morbidity and mortality rates, particularly in those patients with poorly controlled risk factors. Furthermore, many are overweight or obese, due primarily to insulin compensation resulting from insulin resistance. In the last decade, treatment with sodium–glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1-RA) have been shown to be beneficial in renal and cardiovascular targets; however, in patients with CKD, the previous guidelines recommended the use of drugs such as repaglinide or dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors), plus insulin therapy. However, new guidelines have paved the way for new treatments, such as SGLT2i or GLP1-RA in patients with CKD. Currently, the new evidence supports the use of GLP1-RA in patients with an estimated glomerular filtration rate (eGFR) of up to 15 mL/min/1.73 m2 and an SGLT2i should be started with an eGFR > 60 mL/min/1.73 m2. Regarding those patients in advanced stages of CKD, the usual approach is to switch to insulin. Thus, the add-on of GLP1-RA and/or SGLT2i to insulin therapy can reduce the dose of insulin, or even allow for its withdrawal, as well as achieve a good glycaemic control with no weight gain and reduced risk of hypoglycaemia, with the added advantage of cardiorenal benefits. Full article
(This article belongs to the Special Issue Chronic Kidney Disease: The Global Challenge)
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