Review
Medicine, General & Internal
Philip Chiu-Tsun Tang, Alex Siu-Wing Chan, Cai-Bin Zhang, Cristina Alexandra Garcia Cordoba, Ying-Ying Zhang, Ka-Fai To, Kam-Tong Leung, Hui-Yao Lan, Patrick Ming-Kuen Tang
Summary: Chronic kidney disease (CKD) is a major global health issue with complex pathogenic mechanisms and currently lacks effective therapeutic strategies. Immune cell dysfunction leads to inflammation and fibrosis, with TGF-beta 1 playing a critical role in promoting CKD progression.
FRONTIERS IN MEDICINE
(2021)
Article
Pharmacology & Pharmacy
Priyal Patel, Sandip Patel, Piyush Chudasama, Shailesh Soni, Manan Raval
Summary: The present investigation explored the potential treatment option of roflumilast as a PDE4 inhibitor for chronic kidney disease. The results demonstrated that roflumilast significantly reduced serum creatinine, urea, uric acid levels, increased serum calcium, and regulated protein expression of inflammatory markers. Moreover, roflumilast noticeably improved the structure and functioning of glomeruli, tubules, and cells. Therefore, roflumilast has the potential to ameliorate renal injury.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Fatimah K. Khalaf, Chrysan J. Mohammed, Prabhatchandra Dube, Jacob A. Connolly, Apurva Lad, Usman M. Ashraf, Joshua D. Breidenbach, Robin C. Su, Andrew L. Kleinhenz, Deepak Malhotra, Amira F. Gohara, Steven T. Haller, David J. Kennedy
Summary: This study found that decreased PON-1 is associated with the progression of renal inflammation and fibrosis independent of blood pressure. By knockout of the Pon1 gene in a rat model, it was discovered that the absence of PON-1 leads to increased renal fibrosis, sclerosis, and tubular injury, as well as increased recruitment of immune cells in the renal interstitium and the expression of inflammatory genes. Furthermore, the absence of PON-1 also results in a decline in renal function and increased renal oxidative stress.
Article
Biochemistry & Molecular Biology
Omar Emiliano Aparicio-Trejo, Ana Karina Aranda-Rivera, Horacio Osorio-Alonso, Elena Martinez-Klimova, Laura Gabriela Sanchez-Lozada, Jose Pedraza-Chaverri, Edilia Tapia
Summary: Chronic kidney disease (CKD) is a rapidly increasing global health problem, with metabolic reprogramming and changes in redox signaling playing crucial roles in its development. Extracellular vesicles (EVs) play a significant role in the spread of renal injury in CKD and are involved in redox signaling and metabolic reprogramming. Understanding the role of EVs and their cargos in CKD can help prevent its progression.
Review
Medicine, General & Internal
Bin Wang, Zuo-Lin Li, Yi-Lin Zhang, Yi Wen, Yue-Ming Gao, Bi-Cheng Liu
Summary: This review outlines the characteristics, mechanisms, complications, potential therapeutic approaches, and challenges of chronic hypoxia in chronic kidney disease (CKD).
Article
Medical Laboratory Technology
Evan Paul Owens, Helen Grania Healy, David Alan Vesey, Wendy Elizabeth Hoy, Glenda Carolyn Gobe
Summary: This article reviews new and emerging biomarkers for the development and progression of chronic kidney disease (CKD), which can be detected in blood or urine liquid biopsies. These biomarkers play important roles in kidney injury, inflammation, oxidative stress, repair, and fibrosis. However, there are conflicting conclusions regarding the utility of these biomarkers in CKD.
CLINICA CHIMICA ACTA
(2022)
Review
Biochemistry & Molecular Biology
Tadej Petreski, Nejc Piko, Robert Ekart, Radovan Hojs, Sebastjan Bevc
Summary: Chronic kidney disease is a major health problem in modern society, with a continuously rising prevalence. Recent studies have identified novel markers and gained new insights into the pathogenesis of CKD. Further large-scale studies are needed to establish the role of these markers in clinical practice.
Article
Biochemistry & Molecular Biology
Zakaria Boulahtouf, Alessia Virzi, Thomas F. Baumert, Eloi R. Verrier, Joachim Lupberger
Summary: Chronic viral hepatitis is a major cause of liver disease and hepatocellular carcinoma. Despite being caused by different viruses, hepatitis B, C, and D have striking similarities in pathological impact. The advancements in omics and bioinformatics have revealed the important role of signaling networks in viral pathogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Physiology
Roberto Palacios-Ramirez, Ixchel Lima-Posada, Benjamin Bonnard, Marie Genty, Amaya Fernandez-Celis, Judith Hartleib-Geschwindner, Fabienne Foufelle, Natalia Lopez-Andres, Krister Bamberg, Frederic Jaisser
Summary: Obesity and metabolic diseases are linked to chronic kidney disease, and mineralocorticoid receptor antagonists have shown potential in treating non-diabetic chronic kidney disease associated with metabolic diseases. This study used a mouse model to demonstrate the beneficial effects of the mineralocorticoid receptor antagonist canrenoate in improving metabolic function and reducing proteinuria in chronic kidney disease mice, while also preventing the detrimental effects of a high fat diet on renal fibrosis and inflammation.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Agriculture, Dairy & Animal Science
Xiao Wang, Wei Liu, Ying Liu, Yulan Jiao, Chang Rong, Qi Liu, Wanyu Shi
Summary: Early use of florfenicol (FFC) can adversely affect the health of broilers and cause kidney injury. This study used transcriptome and proteome sequencing to explore the regulatory effect of FFC on specific signal pathways in injured kidneys. The results showed that FFC exposure significantly altered the expression levels of hundreds of genes and proteins in chick kidneys, including those involved in the cell adhesion molecules signaling pathway. Further analysis revealed that these changes were associated with inflammation and apoptosis in renal tissues.
Article
Medicine, Research & Experimental
Huiqi Yuan, Chaoyang Zheng, Li Zhu, Ziqing Song, Linfeng Dai, Qingzong Hu, Lei Wang, Yang Chen, Jing Xiong
Summary: TFEB-mediated autophagy plays a crucial role in the pathogenesis of chronic kidney disease, leading to tubulointerstitial injury and renal fibrosis.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Review
Medicine, General & Internal
Amir Shabaka, Clara Cases-Corona, Gema Fernandez-Juarez
Summary: CKD has a significant impact on global morbidity and mortality through its effects on cardiovascular risk and end-stage kidney disease. Optimal management strategies for CKD include blood pressure control, treatment of albuminuria, avoidance of nephrotoxins and obesity, as well as new antihyperglycemic drugs and potassium-lowering therapies. Research efforts are now focusing on unraveling early disease mechanisms and developing novel therapeutic approaches targeting various aspects of CKD progression.
FRONTIERS IN MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Weifeng Wu, Xiao R. Huang, Yongke You, Liang Xue, Xiao-Jing Wang, Xiaoming Meng, Xiang Lin, Jiangang Shen, Xueqing Yu, Hui-Yao Lan, Haiyong Chen
Summary: The study demonstrates that overexpression of latent TGF-beta 1 can protect against the development of DKD in mice, reducing microalbuminuria and inhibiting renal fibrosis and inflammation, without altering blood glucose levels. This protective effect may be associated with the prevention of Arkadia-mediated Smad7 ubiquitin degradation, suggesting a potential mechanism for the inhibition of DKD by latent TGF-beta 1.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Review
Pharmacology & Pharmacy
Jonatan Barrera-Chimal, Frederic Jaisser, Hans-Joachim Anders
Summary: Chronic kidney disease is a major public health concern globally, with MR antagonists emerging as a potential therapeutic approach against various forms of kidney disease. Experimental and clinical studies have shown the protective effects of MRAs in reducing albuminuria and slowing disease progression. Recent evidence also suggests that MRAs can reduce hard kidney outcomes, particularly in CKD associated with type 2 diabetes, highlighting their potential benefit in maximizing organ protection through combination therapy.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Review
Immunology
Sarah Cormican, Matthew D. Griffin
Summary: Innate immune cells play a key role in kidney inflammation and fibrosis, with the CX3CL1-CX3CR1 signaling pathway being closely linked to acute and chronic kidney diseases. Targeting this pathway may offer potential benefits for patients with CKD.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Transplantation
Wen Wen, Ignacio Portales-Castillo, Rituvanthikaa Seethapathy, Scott Krinsky, Daniela Kroshinsky, Sahir Kalim, Jeremy Goverman, Rosalynn M. Nazarian, Vipul Chitalia, Rajeev Malhotra, Rafael Kramann, Cindy K. Malhotra, Sagar U. Nigwekar
Summary: This study evaluated the effects and safety of intravenous sodium thiosulphate (STS) for vascular calcification (VC) in patients with chronic kidney disease (CKD). The results showed that STS treatment could attenuate the progression of VC and arterial stiffness, with no significant adverse effects observed.
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2023)
Article
Oncology
Jennifer Eymael, Martijn van den Broek, Laura Miesen, Valerie Villacorta Monge, Bartholomeus T. van den Berge, Fieke Mooren, Vicky Luna Velez, Jelmer Dijkstra, Meyke Hermsen, Peter Bandi, Michiel Vermeulen, Saskia de Wildt, Brigith Willemsen, Sandrine Florquin, Roy Wetzels, Eric Steenbergen, Rafael Kramann, Marcus Moeller, Michiel F. Schreuder, Jack Fm Wetzels, Johan van der Vlag, Jitske Jansen, Bart Smeets
Summary: Scattered tubular cells (STCs) in the proximal tubule increase in number after acute kidney injury. STCs are preferentially located within the inner bends of the tubule and their number increases with age. STCs represent a transient state of dedifferentiated proximal tubule epithelial cells (PTECs) showing metabolic shift towards glycolysis, facilitating cellular survival after kidney injury.
JOURNAL OF PATHOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Veronica Miguel, Rafael Kramann
Summary: Fibrosis caused by excessive accumulation of ECM is a characteristic of CKD. Myofibroblasts, responsible for ECM production, are activated by communication with injured proximal tubule and immune cells. Recent evidence shows that metabolic alterations play a significant role in renal fibrosis pathogenesis. Using omics technologies and functional data, specific metabolic shifts in different cell types have been found to play specific roles in the fibrogenic response. This review summarizes the main outcomes of metabolic reprogramming in renal fibrosis and provides a future perspective on renal fibrometabolism.
Article
Cardiac & Cardiovascular Systems
Felix Schreibing, Teresa M. Anslinger, Rafael Kramann
Summary: Diseases of the heart and kidney can significantly reduce life expectancy and quality of life. Fibrosis is a common pathway for both organs, making its inhibition a promising therapeutic approach. However, the exact mechanisms driving fibrosis are still unclear. RNA-sequencing, especially single-cell RNA-sequencing, has revolutionized the investigation of pathomechanisms and facilitated the discovery of disease-associated cell types and mechanisms. This review provides an overview of RNA-sequencing techniques, recent insights into heart and kidney fibrosis, and the potential use of transcriptomic data for identifying new drug targets and developing novel therapies.
CIRCULATION RESEARCH
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
Veronica Miguel, Carlos Rey-Serra, Jessica Tituana, Belen Sirera, J. Ignacio Herrero, Irene Ranz, Laura Fernandez, Carolina Castillo, Lucia Sevilla, James Nagai, Katharina C. Reimer, Jitske Jansen, Rafael Kramann, Ivan G. Costa, Ana Castro, Jose Miguel Rodriguez Gonzalez-Moro, Santiago Lamas
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Correction
Multidisciplinary Sciences
Julian Petersen, Lukas Englmaier, Artem V. Artemov, Irina Poverennaya, Ruba Mahmoud, Thibault Bouderlique, Marketa Tesarova, Ruslan Deviatiiarov, Anett Szilvasy-Szabo, Evgeny E. Akkuratov, David Pajuelo Reguera, Hugo Zeberg, Marketa Kaucka, Maria Eleni Kastriti, Jan Krivanek, Tomasz Radaszkiewicz, Kristina Gomoryova, Sarah Knauth, David Potesil, Zbynek Zdrahal, Ranjani Sri Ganji, Anna Grabowski, Miriam E. Buhl, Tomas Zikmund, Michaela Kavkova, Hakan Axelson, David Lindgren, Rafael Kramann, Christoph Kuppe, Ferenc Erdelyi, Zoltan Mate, Gabor Szabo, Till Koehne, Tibor Harkany, Kaj Fried, Jozef Kaiser, Peter Boor, Csaba Fekete, Jan Rozman, Petr Kasparek, Jan Prochazka, Radislav Sedlacek, Vitezslav Bryja, Oleg Gusev, Igor Adameyko
NATURE COMMUNICATIONS
(2023)
Article
Nutrition & Dietetics
Xoana Barros, Xenia Friesen, Vincent Mathias Brandenburg, Elisa Anamaria Liehn, Sonja Steppan, Fabian Kiessling, Rafael Kramann, Juergen Floege, Thilo Krueger, Nadine Kaesler
Summary: Cardiovascular complications are a major cause of death in patients with chronic kidney disease (CKD). Magnesium deficiency is common in CKD. A study on Wistar rats with CKD found that oral magnesium carbonate supplementation restored impaired left ventricular cardiac function and improved aortic wall integrity. This study provides evidence for the beneficial effect of magnesium on cardiovascular function in CKD.
Article
Engineering, Biomedical
Jose L. Gerardo-Nava, Jitske Jansen, Daniel Guenther, Laura Klasen, Anja Lena Thiebes, Bastian Niessing, Cedric Bergerbit, Anna A. Meyer, John Linkhorst, Mareike Barth, Payam Akhyari, Julia Stingl, Saskia Nagel, Thomas Stiehl, Angelika Lampert, Rudolf Leube, Matthias Wessling, Francesca Santoro, Sven Ingebrandt, Stefan Jockenhoevel, Andreas Herrmann, Horst Fischer, Wolfgang Wagner, Robert H. Schmitt, Fabian Kiessling, Rafael Kramann, Laura De Laporte
Summary: Recreating human tissues and organs in the petri dish to establish models as tools in biomedical sciences has gained momentum. Transformative materials play an important role in this evolution, as they can be programmed to direct cell behavior and fate. This paper illustrates state-of-the-art developments in in vitro tissue engineering and the challenges related to the design, production, and translation of transformative materials, emphasizing the need for convergence of different technologies to generate functional human tissue models.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Engineering, Biomedical
Prachi Desai, Anshuman Dasgupta, Alexandros Marios Sofias, Quim Pena, Robert Goestl, Ioana Slabu, Ulrich Schwaneberg, Thomas Stiehl, Wolfgang Wagner, Stefan Jockenhoevel, Julia Stingl, Rafael Kramann, Christian Trautwein, Tim H. Bruemmendorf, Fabian Kiessling, Andreas Herrmann, Twan Lammers
Summary: Drug delivery systems (DDS) control drug availability and activity to achieve a balance between therapeutic efficacy and side effects. They overcome biological barriers encountered by drug molecules and are explored for modulating host-material interfaces. This article provides an overview of barriers and interfaces encountered by DDS in different administration routes and highlights material engineering advances for improved disease treatment.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Cell Biology
Konrad Hoeft, Gideon J. L. Schaefer, Hyojin Kim, David Schumacher, Tore Bleckwehl, Qingqing Long, Barbara Mara Klinkhammer, Fabian Peisker, Lars Koch, James Nagai, Maurice Halder, Susanne Ziegler, Elisa Liehn, Christoph Kuppe, Jennifer Kranz, Sylvia Menzel, Ivan Costa, Adam Wahida, Peter Boor, Rebekka K. Schneider, Sikander Hayat, Rafael Kramann
Summary: Fibrosis is the result of chronic organ injury, causing tissue damage and organ failure. Spp1 macrophages, marked by expression of Spp1, Fn1, and Arg1, expand after organ injury and drive fibrosis. The chemokine CXCL4 plays a crucial role in the differentiation of profibrotic Spp1 macrophages and its loss leads to reduced fibrosis in heart and kidney injury. Platelets contribute to the differentiation of profibrotic Spp1 macrophages through the release of CXCL4. Macrophages orchestrate fibroblast activation through Spp1, Fn1, and Sema3 signaling. Moreover, Spp1 macrophages are found to be expanded in human chronic kidney disease and heart failure.
Review
Medicine, General & Internal
Wen Wen, Ignacio Portales-Castillo, Rituvanthikaa Seethapathy, Olivia Durant, Beza Mengesha, Scott Krinsky, Daniela Kroshinsky, Sahir Kalim, Jeremy Goverman, Rosalynn M. Nazarian, Vipul Chitalia, Rajeev Malhotra, Rafael Kramann, Cindy K. Malhotra, Sagar U. Nigwekar
Summary: This is a meta-analysis on the treatment of calciphylaxis. The study found that intravenous sodium thiosulphate (STS) was not associated with skin lesion improvement or survival benefit compared to non-STS treatment in patients with chronic kidney disease (CKD). Further investigations are needed to examine the efficacy and safety of therapies for patients with calciphylaxis.
Article
Biology
Yang Xu, Rafael Kramann, Rachel Patton McCord, Sikander Hayat
Summary: MASI is a computational pipeline that enables the integration and annotation of large single-cell transcriptomic datasets with limited computational resources. It outperforms other methods in terms of integration, annotation, and speed. MASI can serve as a cheap computational alternative for the single-cell research community.
COMMUNICATIONS BIOLOGY
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Sebastian Billig, Marc Hein, Mare Mechelinck, David Schumacher, Anna B. Roehl, Dieter Fuchs, Rafael Kramann, Moritz Uhlig
Summary: This study investigated the changes in coronary physiology in rats using ultrasound techniques. Both pulsed-wave Doppler (PWD) and myocardial contrast echocardiography (MCE) were used to assess the parameters at rest and under pharmacologically induced stress.
EUROPEAN RADIOLOGY EXPERIMENTAL
(2023)
Article
Biochemical Research Methods
Veronica Miguel, Katharina Charlotte Reimer, Anna Katharina Galyga, Jitske Jansen, Julia Moellmann, Luisa Meyer, Rebekka K. Schneider, Rafael Kramann
Summary: Metabolic derangement plays a crucial role in kidney pathophysiology, and organoids have shown great promise as an in vitro tool for kidney research. In this study, we present a refined protocol for analyzing bioenergetics in single kidney organoids derived from human induced pluripotent stem cells (iPSCs) using Seahorse XF96. Our protocol includes generating self-organized three-dimensional kidney organoids and preparing them for Seahorse XF96 analysis, followed by stress tests to determine mitochondrial and glycolytic rates in the organoids.
Article
Medicine, Research & Experimental
Christina Alter, Anne-Sophie Henseler, Christoph Owenier, Julia Hesse, Zhaoping Ding, Tobias Lautwein, Jasmin Bahr, Sikander Hayat, Rafael Kramann, Eva Kostenis, Juergen Scheller, Juergen Schrader
Summary: Plasma IL-6 is elevated after myocardial infarction (MI) and is mainly produced by cardiac fibroblasts (CFs), which are regulated by adenosine. These findings have important implications for the treatment of post-MI inflammation.
JOURNAL OF CLINICAL INVESTIGATION
(2023)