Editorial

3 pages, 163 KiB

Open AccessEditorial

Editorial for the Special Issue: Pathophysiology of Chronic Kidney Disease and Its Complications

by Yuji Oe

Biomedicines 2024, 12(2), 416; https://doi.org/10.3390/biomedicines12020416 - 10 Feb 2024

Viewed by 816

Chronic kidney disease (CKD) is a risk factor for end-stage kidney disease, requiring renal replacement therapy [...] Full article

(This article belongs to the Special Issue Pathophysiology of Chronic Kidney Disease and Its Complications)

Research

Jump to: Editorial, Review

14 pages, 1514 KiB

Open AccessArticle

Differences in the Profile of Circulating Immune Cell Subsets in Males with Type 2 Cardiorenal Syndrome versus CKD Patients without Established Cardiovascular Disease

by Anila Duni, Athanasios Kitsos, Aris Bechlioulis, Georgios S. Markopoulos, Lampros Lakkas, Gerasimos Baxevanos, Michail Mitsis, George Vartholomatos, Katerina K. Naka and Evangelia Dounousi

Biomedicines 2023, 11(4), 1029; https://doi.org/10.3390/biomedicines11041029 - 27 Mar 2023

Cited by 1 | Viewed by 1106

Abstract

Maladaptive activation of the immune system plays a key role in the pathogenesis of chronic kidney disease (CKD). Our aim was to investigate differences in circulating immune cells between type 2 cardiorenal syndrome (CRS-2) patients and CKD patients without cardiovascular disease (CVD). CRS-2 [...] Read more.

Maladaptive activation of the immune system plays a key role in the pathogenesis of chronic kidney disease (CKD). Our aim was to investigate differences in circulating immune cells between type 2 cardiorenal syndrome (CRS-2) patients and CKD patients without cardiovascular disease (CVD). CRS-2 patients were prospectively followed up, with the primary endpoint being all-cause and cardiovascular mortality. Method: A total of 39 stable males with CRS-2 and 24 male CKD patients matched for eGFR (CKD-EPI) were enrolled. A selected panel of immune cell subsets was measured by flow cytometry. Results: Compared to CKD patients, CRS-2 patients displayed higher levels of proinflammatory CD14++CD16+ monocytes (p = 0.04) and T regulatory cells (Tregs) (p = 0.03), lower lymphocytes (p = 0.04), and lower natural killer cells (p = 0.001). Decreased lymphocytes, T-lymphocytes, CD4+ T-cells, CD8+ T-cells, Tregs, and increased CD14++CD16+ monocytes were associated with mortality at a median follow-up of 30 months (p < 0.05 for all). In a multivariate model including all six immune cell subsets, only CD4+ T-lymphocytes remained independent predictors of mortality (OR 0.66; 95% CI 0.50–0.87; p = 0.004). Conclusion: Patients with CRS-2 exhibit alterations in immune cell profile compared to CKD patients of similar kidney function but without CVD. In the CRS-2 cohort, CD4+ T-lymphocytes independently predicted fatal cardiovascular events. Full article

(This article belongs to the Special Issue Pathophysiology of Chronic Kidney Disease and Its Complications)

► Show Figures

Figure 1

12 pages, 3585 KiB

Open AccessArticle

The Sympathetic Nervous System Regulates Sodium Glucose Co-Transporter 1 Expression in the Kidney

by Jennifer Matthews, Moira Hibbs, Lakshini Herat, Markus Schlaich and Vance Matthews

Biomedicines 2023, 11(3), 819; https://doi.org/10.3390/biomedicines11030819 - 07 Mar 2023

Cited by 2 | Viewed by 1685

Abstract

Hyperactivation of the sympathetic nervous system (SNS) has been demonstrated in various conditions including obesity, hypertension and type 2 diabetes. Elevated levels of the major neurotransmitter of the SNS, norepinephrine (NE), is a cardinal feature of these conditions. Increased levels of the sodium [...] Read more.

Hyperactivation of the sympathetic nervous system (SNS) has been demonstrated in various conditions including obesity, hypertension and type 2 diabetes. Elevated levels of the major neurotransmitter of the SNS, norepinephrine (NE), is a cardinal feature of these conditions. Increased levels of the sodium glucose cotransporter 1 (SGLT1) protein have been shown to occur in the parotid and submandibular glands of hypertensive rodents compared to normotensive controls. However, there was a need to examine SGLT1 expression in other tissues, such as the kidneys. Whether NE may directly affect SGLT1 protein expression has not yet been investigated, although such a link has been shown for sodium glucose cotransporter 2 (SGLT2). Hence, we aimed to determine (i) whether our murine model of neurogenic hypertension displays elevated renal SGLT1 expression and (ii) whether NE may directly promote elevations of SGLT1 in human proximal tubule (HK2) cells. We did indeed demonstrate that in vivo, in our mouse model of neurogenic hypertension, hyperactivation of the SNS promotes SGLT1 expression in the kidneys. In subsequent in vitro experiments in HK2 cells, we found that NE increased SGLT1 protein expression and translocation as assessed by both specific immunohistochemistry and/or a specific SGLT1 ELISA. Additionally, NE promoted a significant elevation in interleukin-6 (IL-6) levels which resulted in the promotion of SGLT1 expression and proliferation in HK2 cells. Our findings suggest that the SNS upregulates SGLT1 protein expression levels with potential adverse consequences for cardiometabolic control. SGLT1 inhibition may therefore provide a useful therapeutic target in conditions characterized by increased SNS activity, such as chronic kidney disease. Full article

(This article belongs to the Special Issue Pathophysiology of Chronic Kidney Disease and Its Complications)

► Show Figures

Figure 1

10 pages, 861 KiB

Open AccessArticle

Comparison of the Prognostic Value of Inflammatory and Nutritional Indices in Nonmetastatic Renal Cell Carcinoma

by Tomoyuki Makino, Kouji Izumi, Hiroaki Iwamoto, Suguru Kadomoto, Yoshifumi Kadono and Atsushi Mizokami

Biomedicines 2023, 11(2), 533; https://doi.org/10.3390/biomedicines11020533 - 12 Feb 2023

Cited by 5 | Viewed by 1440

Abstract

Several markers that reflect inflammation and nutritional status have been associated with oncological outcomes in many tumors. This study aimed to describe the impact of pretreatment inflammatory and nutritional indices on the oncological outcomes in nonmetastatic renal cell carcinoma (RCC). A total of [...] Read more.

Several markers that reflect inflammation and nutritional status have been associated with oncological outcomes in many tumors. This study aimed to describe the impact of pretreatment inflammatory and nutritional indices on the oncological outcomes in nonmetastatic renal cell carcinoma (RCC). A total of 213 Japanese patients with nonmetastatic RCC at Kanazawa University Hospital between October 2007 and December 2018 were included. The inflammatory and nutritional indices, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein-to-albumin ratio (CAR), prognostic nutritional index (PNI), and geriatric nutritional risk index (GNRI), were retrospectively analyzed. The optimal cutoffs for NLR, PLR, CAR, PNI, and GNRI were 2.18, 153.7, 0.025, 48.4, and 98, respectively. According to Kaplan–Meier curves, elevated NLR, PLR, CAR, and GNRI correlated with increased metastasis, while NLR and PNI correlated with worse overall survival (OS). In multivariate analysis, high CAR was an independent poor risk factor for metastasis (hazard ratio (HR), 3.08; 95% confidence interval (CI), 1.24–7.67; p = 0.016). Furthermore, high NLR showed an independent prognostic factor for worse OS (HR, 3.96; 95% CI, 1.01–15.59; p = 0.049). The pretreatment inflammatory and nutritional indices such as NLR and CAR might be promising prognostic factors for nonmetastatic RCC. Full article

(This article belongs to the Special Issue Pathophysiology of Chronic Kidney Disease and Its Complications)

► Show Figures

Figure 1

16 pages, 2472 KiB

Open AccessArticle

Stage II of Chronic Kidney Disease—A Tipping Point in Disease Progression?

by Lovorka Grgurevic, Rudjer Novak, Grgur Salai, Stela Hrkac, Marko Mocibob, Ivana Kovacevic Vojtusek and Mario Laganovic

Biomedicines 2022, 10(7), 1522; https://doi.org/10.3390/biomedicines10071522 - 27 Jun 2022

Cited by 2 | Viewed by 2598

Abstract

Chronic kidney disease (CKD) is the progressive loss of renal function. Although advances have been made in understanding the progression of CKD, key molecular events in complex pathophysiological mechanisms that mark each stage of renal failure remain largely unknown. Changes in plasma protein [...] Read more.

Chronic kidney disease (CKD) is the progressive loss of renal function. Although advances have been made in understanding the progression of CKD, key molecular events in complex pathophysiological mechanisms that mark each stage of renal failure remain largely unknown. Changes in plasma protein profiles in different disease stages are important for identification of early diagnostic markers and potential therapeutic targets. The goal of this study was to determine the molecular profile of each CKD stage (from 1 to 5), aiming to specifically point out markedly expressed or downregulated proteins. We performed a cross-sectional shotgun-proteomic study of pooled plasma across CKD stages and compared them to healthy controls. After sample pooling and heparin-column purification we analysed proteomes from healthy to CKD stage 1 through 5 participants’ plasma by liquid-chromatography/mass-spectrometry. We identified 453 proteins across all study groups. Our results indicate that key events, which may later affect the course of disease progression and the overall pathophysiological background, are most pronounced in CKD stage 2, with an emphasis on inflammation, lipoprotein metabolism, angiogenesis and tissue regeneration. We hypothesize that CKD stage 2 is the tipping point in disease progression and a suitable point in disease course for the development of therapeutic solutions. Full article

(This article belongs to the Special Issue Pathophysiology of Chronic Kidney Disease and Its Complications)

► Show Figures

Figure 1

10 pages, 529 KiB

Open AccessArticle

Association between Advanced Glycation End-Products and Sarcopenia in Patients with Chronic Kidney Disease

by Paolo Molinari, Lara Caldiroli, Elena Dozio, Roberta Rigolini, Paola Giubbilini, Massimiliano M. Corsi Romanelli, Giuseppe Castellano and Simone Vettoretti

Biomedicines 2022, 10(7), 1489; https://doi.org/10.3390/biomedicines10071489 - 23 Jun 2022

Cited by 2 | Viewed by 1542

Abstract

Background: In patients with chronic kidney disease (CKD), there is an overproduction and accumulation of advanced glycation end-products (AGEs). Since AGEs may have detrimental effects on muscular trophism and performance, we evaluated whether they may contribute to the onset of sarcopenia in CKD [...] Read more.

Background: In patients with chronic kidney disease (CKD), there is an overproduction and accumulation of advanced glycation end-products (AGEs). Since AGEs may have detrimental effects on muscular trophism and performance, we evaluated whether they may contribute to the onset of sarcopenia in CKD patients. Methods: We enrolled 117 patients. The AGEs were quantified by fluorescence intensity using a fluorescence spectrophotometer and soluble receptor for AGE (sRAGE) isoforms by ELISA. As for the sarcopenia definition, we used the European Working Group on Sarcopenia in Older People (EWGSOP2) criteria. Results: The average age was 80 ± 11 years, 70% were males, and the mean eGFR was 25 + 11 mL/min/1.73 m². Sarcopenia was diagnosed in 26 patients (with a prevalence of 22%). The sarcopenic patients had higher levels of circulating AGEs (3405 ± 951 vs. 2912 ± 722 A.U., p = 0.005). AGEs were higher in subjects with a lower midarm muscle circumference (MAMC) (3322 ± 919 vs. 2883 ± 700 A.U., respectively; p = 0.005) and were directly correlated with the gait test time (r = 0.180, p = 0.049). The total sRAGE and its different isoforms (esRAGE and cRAGE) did not differ in patients with or without sarcopenia. Conclusions: In older CKD patients, AGEs, but not sRAGE, are associated with the presence of sarcopenia. Therefore, AGEs may contribute to the complex pathophysiology leading to the development of sarcopenia in CKD patients. Full article

(This article belongs to the Special Issue Pathophysiology of Chronic Kidney Disease and Its Complications)

► Show Figures

Figure 1

Review

Jump to: Editorial, Research

15 pages, 958 KiB

Open AccessReview

Obesity-Related Kidney Disease: Current Understanding and Future Perspectives

by Frederik F. Kreiner, Philip Andreas Schytz, Hiddo J. L. Heerspink, Bernt Johan von Scholten and Thomas Idorn

Biomedicines 2023, 11(9), 2498; https://doi.org/10.3390/biomedicines11092498 - 09 Sep 2023

Cited by 5 | Viewed by 2812

Abstract

Obesity is a serious chronic disease and an independent risk factor for the new onset and progression of chronic kidney disease (CKD). CKD prevalence is expected to increase, at least partly due to the continuous rise in the prevalence of obesity. The concept [...] Read more.

Obesity is a serious chronic disease and an independent risk factor for the new onset and progression of chronic kidney disease (CKD). CKD prevalence is expected to increase, at least partly due to the continuous rise in the prevalence of obesity. The concept of obesity-related kidney disease (OKD) has been introduced to describe the still incompletely understood interplay between obesity, CKD, and other cardiometabolic conditions, including risk factors for OKD and cardiovascular disease, such as diabetes and hypertension. Current therapeutics target obesity and CKD individually. Non-pharmacological interventions play a major part, but the efficacy and clinical applicability of lifestyle changes and metabolic surgery remain debatable, because the strategies do not benefit everyone, and it remains questionable whether lifestyle changes can be sustained in the long term. Pharmacological interventions, such as sodium-glucose co-transporter 2 inhibitors and the non-steroidal mineralocorticoid receptor antagonist finerenone, provide kidney protection but have limited or no impact on body weight. Medicines based on glucagon-like peptide-1 (GLP-1) induce clinically relevant weight loss and may also offer kidney benefits. An urgent medical need remains for investigations to better understand the intertwined pathophysiologies in OKD, paving the way for the best possible therapeutic strategies in this increasingly prevalent disease complex. Full article

(This article belongs to the Special Issue Pathophysiology of Chronic Kidney Disease and Its Complications)

► Show Figures

Figure 1

13 pages, 349 KiB

Open AccessReview

Epidemiology and Risk Factors for Stroke in Chronic Kidney Disease: A Narrative Review

by Christodoula Kourtidou and Konstantinos Tziomalos

Biomedicines 2023, 11(9), 2398; https://doi.org/10.3390/biomedicines11092398 - 27 Aug 2023

Cited by 1 | Viewed by 1397

Abstract

Patients with chronic kidney disease (CKD) have a higher risk ofboth ischemic and hemorrhagic stroke. This association appears to be partly independent from the higher prevalence of established risk factors for stroke in patients with CKD, including hypertension and atrial fibrillation. In the [...] Read more.

Patients with chronic kidney disease (CKD) have a higher risk ofboth ischemic and hemorrhagic stroke. This association appears to be partly independent from the higher prevalence of established risk factors for stroke in patients with CKD, including hypertension and atrial fibrillation. In the present review we aim to discuss the impact of CKD on the risk of stroke and stroke-related consequences, and explore the pathophysiology underpinning the increased risk of stroke in patients with CKD. We cover the clinical association between renal dysfunction and cerebrovascular disease including stroke, silent brain infarct, cerebral small vessel disease, microbleeds, and white matter hyperintensity, and discuss the underlying mechanisms. Full article

(This article belongs to the Special Issue Pathophysiology of Chronic Kidney Disease and Its Complications)

14 pages, 819 KiB

Open AccessReview

New Insights into Molecular Mechanisms of Chronic Kidney Disease

by Weronika Frąk, Joanna Kućmierz, Magdalena Szlagor, Ewelina Młynarska, Jacek Rysz and Beata Franczyk

Biomedicines 2022, 10(11), 2846; https://doi.org/10.3390/biomedicines10112846 - 08 Nov 2022

Cited by 5 | Viewed by 3092

Abstract

Chronic kidney disease (CKD) is a major public health problem with a developing incidence and prevalence. As a consequence of the growing number of patients diagnosed with renal dysfunction leading to the development of CKD, it is particularly important to explain the mechanisms [...] Read more.

Chronic kidney disease (CKD) is a major public health problem with a developing incidence and prevalence. As a consequence of the growing number of patients diagnosed with renal dysfunction leading to the development of CKD, it is particularly important to explain the mechanisms of its underlying causes. In our paper, we discuss the molecular mechanisms of the development and progression of CKD, focusing on oxidative stress, the role of the immune system, neutrophil gelatinase-associated lipocalin, and matrix metalloproteinases. Moreover, growing evidence shows the importance of the role of the gut–kidney axis in the maintenance of normal homeostasis and of the dysregulation of this axis in CKD. Further, we discuss the therapeutic potential and highlight the future research directions for the therapeutic targeting of CKD. However, additional investigation is crucial to improve our knowledge of CKD progression and, more importantly, accelerate basic research to improve our understanding of the mechanism of pathophysiology. Full article

(This article belongs to the Special Issue Pathophysiology of Chronic Kidney Disease and Its Complications)

► Show Figures

Figure 1

13 pages, 1003 KiB

Open AccessReview

Tissue Factor, Thrombosis, and Chronic Kidney Disease

by Yuji Oe and Nobuyuki Takahashi

Biomedicines 2022, 10(11), 2737; https://doi.org/10.3390/biomedicines10112737 - 28 Oct 2022

Cited by 5 | Viewed by 2139

Abstract

Coagulation abnormalities are common in chronic kidney disease (CKD). Tissue factor (TF, factor III) is a master regulator of the extrinsic coagulation system, activating downstream coagulation proteases, such as factor Xa and thrombin, and promoting fibrin formation. TF and coagulation proteases also activate [...] Read more.

Coagulation abnormalities are common in chronic kidney disease (CKD). Tissue factor (TF, factor III) is a master regulator of the extrinsic coagulation system, activating downstream coagulation proteases, such as factor Xa and thrombin, and promoting fibrin formation. TF and coagulation proteases also activate protease-activated receptors (PARs) and are implicated in various organ injuries. Recent studies have shown the mechanisms by which thrombotic tendency is increased under CKD-specific conditions. Uremic toxins, such as indoxyl sulfate and kynurenine, are accumulated in CKD and activate TF and coagulation; in addition, the TF–coagulation protease–PAR pathway enhances inflammation and fibrosis, thereby exacerbating renal injury. Herein, we review the recent research studies to understand the role of TF in increasing the thrombotic risk and CKD progression. Full article

(This article belongs to the Special Issue Pathophysiology of Chronic Kidney Disease and Its Complications)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Pathophysiology of Chronic Kidney Disease and Its Complications

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Related Special Issue

Published Papers (10 papers)

Editorial

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI