Review
Pharmacology & Pharmacy
Min Young Kim, Daniel C. Brennan
Summary: Significant progress has been made in the pathophysiology, diagnosis, and treatment of antibody-mediated rejection (ABMR) in recent decades, but effective treatment for chronic ABMR remains a challenge. Chronic ABMR has a distinct phenotype from active ABMR and is mainly caused by de novo donor specific antibodies (DSA), leading to progressive graft injury.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Medicine, Research & Experimental
Fatemeh Sabet Sarvestani, Negar Azarpira, Ismail H. Al-Abdullah, Ali-Mohammad Tamaddon
Summary: Ischemia reperfusion injury can lead to tissue damage, especially during organ transplantation. By manipulating miRNAs level, they can be used as a biomarker for early diagnosis of IRI or suggestive to be therapeutic agents in clinical situation in future.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Medicine, General & Internal
Nora Jahn, Ulrich Sack, Sebastian Stehr, Maria Theresa Voeelker, Sven Laudi, Daniel Seehofer, Selim Atay, Panagiota Zgoura, Richard Viebahn, Andreas Boldt, Hans-Michael Hau
Summary: Peripheral blood innate immune cells and clinical factors can be used to predict early renal graft injury (eRGI) after kidney transplantation. Monocyte and NK cell levels on postoperative day 7 are highly predictive for eRGI. Patient age, body mass index, cardiovascular disease, donor age, donor source, and cold ischemia time are also associated with eRGI.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Urology & Nephrology
Eric Langewisch, Roslyn B. Mannon
Summary: With the improved long-term kidney transplant survival, attention has shifted to understanding the causes of transplanted allograft failure. Chronic allograft injury involves both immune-mediated and nonimmune-mediated injuries, presenting an opportunity to identify those at greater risk and implement new strategies. The research highlights the need to identify markers of injury and mechanisms of injury in order to better understand late graft failure.
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2021)
Review
Pharmacology & Pharmacy
Yuanbo Qi, Mingyao Hu, Zhigang Wang, Wenjun Shang
Summary: The injury caused by ischemia and reperfusion during kidney transplantation remains unsatisfactory. Iron plays a pathological role in tissue damage induced by I/R, but the effects of iron-related therapy are controversial. Mitochondria regulate iron homeostasis and contribute to I/R injury development. The understanding of mitochondrial iron regulation may provide insights for potential therapeutic targets to improve kidney graft outcomes and other I/R injuries.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Johanna Stoermer, Wilfried Gwinner, Katja Derlin, Stephan Immenschuh, Song Rong, Mi-Sun Jang, Nelli Shushakova, Hermann Haller, Faikah Gueler, Robert Greite
Summary: This study investigated the effects of diclofenac on the progression of AKI and long-term renal consequences in the setting of pre-existing subclinical AKI. The results showed that diclofenac aggravated renal injury in a dose and time-dependent manner and even a single dose can cause progression to chronic kidney disease.
Review
Gastroenterology & Hepatology
Jiang Liu, Kwan Man
Summary: Ischemia/reperfusion injury is an inevitable process during liver transplantation, leading to high rates of dysfunction and failure. The mechanism involves microcirculation dysfunction, hypoxia, oxidative stress, and cell death. The immune response also plays a crucial role. Studies on living donor liver transplantation have identified specific mitochondrial and metabolic dysfunction in certain types of graft injury. These findings have paved the way for new biomarkers and potential therapeutics, but further validation and clinical trials are needed. This review emphasizes the importance of the spatiotemporal microenvironment resulting from various factors in liver ischemia/reperfusion injury.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Simona Granata, Valentina Votrico, Federica Spadaccino, Valeria Catalano, Giuseppe Stefano Netti, Elena Ranieri, Giovanni Stallone, Gianluigi Zaza
Summary: Although there have been advances in kidney transplant medicine, patients may still experience complications after transplantation. Ischemia/reperfusion injury plays a major role in these complications, leading to delayed graft function and potential kidney damage. Understanding the pathways involved, such as ferroptosis and mitophagy, could aid in the development of noninvasive diagnostic biomarkers and pharmacological strategies for these complications.
Article
Biochemistry & Molecular Biology
Ramio Cabello, Miguel Fontecha-Barriuso, Diego Martin-Sanchez, Ana M. Lopez-Diaz, Susana Carrasco, Ignacio Mahillo, Carmen Gonzalez-Enguita, Maria D. Sanchez-Nino, Alberto Ortiz, Ana B. Sanz
Summary: CypA is a potential biomarker of kidney injury, released by kidney tubular cells during different forms of cell death, and increased during IRI-induced clinical kidney injury independently from kidney function parameters.
Article
Gastroenterology & Hepatology
Vatche G. Agopian, Daniela Markovic, Goran B. Klintmalm, Giovanna Saracino, William C. Chapman, Neeta Vachharajani, Sander S. Florman, Parissa Tabrizian, Brandy Haydel, David Nasralla, Peter J. Friend, Yuri L. Boteon, Rutger Ploeg, Michael P. Harlander-Locke, Victor Xia, Joseph DiNorcia, Fady M. Kaldas, Hasan Yersiz, Douglas G. Farmer, Ronald W. Busuttil
Summary: This study validated the accuracy and superiority of the L-GrAFT7 risk score in multicenter cohorts, which can accurately predict early liver graft function and post-transplant complications.
JOURNAL OF HEPATOLOGY
(2021)
Article
Multidisciplinary Sciences
Wenjun Li, Yuriko Terada, Yulia Y. Tyurina, Vladimir A. Tyurin, Amit Bery, Jason M. Gauthier, Ryuji Higashikubo, Alice Y. Tong, Dequan Zhou, Felix Nunez-Santana, Emilia Lecuona, Adil Hassan, Kohei Hashimoto, Davide Scozzi, Varun Puri, Ruben G. Nava, Alexander S. Krupnick, Kory J. Lavine, Andrew E. Gelman, Mark J. Miller, Valerian E. Kagan, Ankit Bharat, Daniel Kreisel
Summary: Ischemia reperfusion injury is a common pathological condition triggered by the release of endogenous ligands. In this study, the researchers discovered that necroptosis, a nonapoptotic form of cell death, triggers the recruitment of neutrophils in injured lungs. Initially, neutrophils traffic predominantly to subpleural vessels, guided by chemoattractants produced by nonclassical monocytes. The disruption of pulmonary capillaries by neutrophils leads to vascular leakage and impaired graft function. The study also found that TLR4 signaling and NADPH oxidase 4 expression mediate the arrest of neutrophils, preventing their extravasation. The formation of neutrophil extracellular traps in injured lungs can be disrupted with DNase to prevent vascular leakage and improve graft dysfunction. These findings could have important implications for the development of therapeutics to protect lungs from ischemia reperfusion injury.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Physiology
Xue Hong, Yanni Zhou, Dedong Wang, Fuping Lyu, Tianjun Guan, Youhua Liu, Liangxiang Xiao
Summary: The study found that in vivo expression of exogenous Wnt1 before ischemia/reperfusion injury (IRI) protected mice against acute kidney injury (AKI) and impeded its progression to chronic kidney disease (CKD. In contrast, pretreatment with ICG-001 had no effect on renal Wnt/beta-catenin signaling or the progression of AKI to CKD. Exogenous Wnt1 suppressed proapoptotic proteins and reduced inflammatory responses in AKI and CKD mice.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Nadezda V. Andrianova, Ljubava D. Zorova, Irina B. Pevzner, Nataliya G. Kolosova, Egor Y. Plotnikov, Dmitry B. Zorov
Summary: Kidney diseases are common among elderly people due to age-related changes in renal tissue. The lack of targeted pharmacotherapies for acute kidney injury (AKI) results in high mortality rates. This study investigated the protective effects of calorie restriction (CR) on ischemic AKI in OXYS rats and found that CR provided significant nephroprotection. Improvements in mitochondrial functioning may be one of the mechanisms for the beneficial effects of CR.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Nora A. Spraakman, Annemieke M. Coester, Arno R. Bourgonje, Vincent B. Nieuwenhuijs, Jan-Stephan F. Sanders, Henri G. D. Leuvenink, Harry van Goor, Gertrude J. Nieuwenhuijs-Moeke
Summary: In this study, the researchers investigated the changes in R-SH levels during kidney transplantation and found that renal ischemia-reperfusion injury can result in trans-renal oxidative stress. The levels of R-SH in systemic and renal samples of transplant recipients were found to reflect the graft function changes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Augustinas Bausys, Juste Maneikyte, Bettina Leber, Jennifer Weber, Nicole Feldbacher, Kestutis Strupas, Thomas Bernd Dschietzig, Peter Schemmer, Philipp Stiegler
Summary: The study demonstrated that RLX significantly reduced IRI through antioxidant and anti-apoptotic mechanisms. Adding synthetic human RLX to preservation solutions may be a novel approach to protect against IRI.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Immunology
Marina Noris, Miriam Galbusera
Summary: The complement and hemostatic systems have functional interactions and play important roles in regulating immune response and preventing bleeding. Both systems involve proteins that activate each other and regulate the function of endothelial cells, platelets, and immune cells. Dysregulation of either system can lead to severe thromboinflammatory events.
IMMUNOLOGICAL REVIEWS
(2023)
Review
Immunology
Erica Daina, Monica Cortinovis, Giuseppe Remuzzi
Summary: Dysregulation and accelerated activation of the alternative pathway of complement play important roles in kidney diseases, and complement-directed therapies have shown potential for treatment. Although there have been successful cases, incorporating these therapies into clinical practice still faces challenges.
IMMUNOLOGICAL REVIEWS
(2023)
Article
Biochemistry & Molecular Biology
Lin Kang, Ai-Lun Yang, Chao-Han Lai, Tsan-Ju Chen, Sung-Yen Lin, Yan-Hsiung Wang, Chau-Zen Wang, Edward M. Conway, Hua-Lin Wu, Mei-Ling Ho, Je-Ken Chang, Chung-Hwan Chen, Tsung-Lin Cheng
Summary: The study found that thrombomodulin (TM) plays a crucial protective role in osteoarthritis (OA) by enhancing chondrocyte growth and migration, blocking inflammatory signaling, and protecting knee function and bone integrity. Increasing TM expression can effectively protect cartilage from damage. These findings contribute to the development of novel therapeutic approaches against OA.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Endocrinology & Metabolism
Aneliya Parvanova, Manuela Abbate, Aina Maria Yanez, Miquel Bennasar-Veny, Angel Arturo Lopez-Gonzalez, Jose Ignacio Ramirez-Manent, Ilian Petrov Iliev, Sergio Fresneda, Maria Arias-Fernandez, Giuseppe Remuzzi, Piero Ruggenenti
Summary: This study investigated the prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) in prediabetes, visceral obesity, and preserved kidney function, and explored the association between MAFLD and hyperfiltration. It was found that MAFLD was more frequent in hyperfiltering subjects and was independently associated with hyperfiltration, as well as potentiated the age-related decline in estimated glomerular filtration rate (eGFR).
DIABETES RESEARCH AND CLINICAL PRACTICE
(2023)
Article
Biochemistry & Molecular Biology
Piera Trionfini, Elena Romano, Marco Varinelli, Lorena Longaretti, Paola Rizzo, Roberta Giampietro, Annalina Caroli, Sistiana Aiello, Marta Todeschini, Federica Casiraghi, Giuseppe Remuzzi, Ariela Benigni, Susanna Tomasoni
Summary: Induced pluripotent stem cells (iPSC) have the potential for cell therapy due to their self-renewal and differentiation capabilities. However, the high production costs and limited use for acute conditions hinder their applications. An allogeneic iPSC-based strategy may overcome these issues, but immune rejection is a concern. In this study, CRISPR/Cas9 was used to create hypoimmunogenic iPSCs that can differentiate into liver cells, providing a cost-effective and off-the-shelf opportunity for liver disease cell therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Urology & Nephrology
Norberto Perico, Giuseppe Remuzzi, Matthew D. Griffin, Paul Cockwell, Alexander P. Maxwell, Federica Casiraghi, Nadia Rubis, Tobia Peracchi, Alessandro Villa, Marta Todeschini, Fabiola Carrara, Bernadette A. Magee, Piero L. Ruggenenti, Stefano Rota, Laura Cappelletti, Veronica Mcinerney, Tomas P. Griffin, Md Nahidul Islam, Martino Introna, Olga Pedrini, Josee Golay, Andrew A. Finnerty, Jon Smythe, Willem E. Fibbe, Stephen J. Elliman, Timothy O'Brien, NEPHSTROM Trial Consortium
Summary: The NEPHSTROM study evaluates the safety, tolerability, and preliminary efficacy of ORBCEL-M cell therapy in adults with type 2 diabetes and progressive diabetic kidney disease. The results show that ORBCEL-M cell therapy is safe and well-tolerated in the lowest dose cohort, and significantly reduces the decline rate of eGFR over 18 months.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2023)
Article
Multidisciplinary Sciences
Anna Pezzotta, Luca Perico, Daniela Corna, Marina Morigi, Giuseppe Remuzzi, Ariela Benigni, Barbara Imberti
Summary: SIRT3 plays a crucial regulatory role in the kidney, and its dysregulation may lead to vascular dysfunction and progression of kidney disease. In the presence of nephrotoxic stimulus, Sirt3-deficient mice exhibit aggravated endothelial rarefaction and oxidative stress, resulting in more severe kidney injury.
Article
Medicine, General & Internal
Damiano Baldassarre, Licia Iacoviello, Roberta Baetta, Maria Carla Roncaglioni, Gianluigi Condorelli, Giuseppe Remuzzi, Gianfranco Gensini, Luigi Frati, Walter Ricciardi, Pier Giulio Conaldi, Antonio Uccelli, Fabio Blandini, Silvano Bosari, Giovanni Scambia, Massimo Fini, Antonio Di Malta, Mauro Amato, Fabrizio Veglia, Alice Bonomi, Catherine Klersy, Francesca Colazzo, Martino Pengo, Francesca Gorini, Luciana Auteri, Giuseppe Ferrante, Marta Baviera, Giuseppe Ambrosio, Alberico Catapano, Alessandro Gialluisi, Alexis Elias Malavazos, Serenella Castelvecchio, Massimiliano Marco Corsi-Romanelli, Rosanna Cardani, Maria Teresa La Rovere, Valentina Agnese, Bianca Pane, Daniele Prati, Laura Spinardi, Giovanna Liuzzo, Eloisa Arbustini, Maurizio Volterrani, Marco Visconti, Jose Pablo Werba, Stefano Genovese, Grzegorz Bilo, Cecilia Invitti, Anna Di Blasio, Carolina Lombardi, Andrea Faini, Debora Rosa, Luisa Ojeda-Fernandez, Andreana Foresta, Amalia De Curtis, Augusto Di Castelnuovo, Simonetta Scalvini, Antonia Pierobon, Alessandra Gorini, Luca Valenti, Livio Luzi, Annarosa Racca, Manuela Bandi, Elena Tremoli, Lorenzo Menicanti, Gianfranco Parati, Giulio Pompilio
Summary: The CV-PREVITAL study is a multicentre, prospective, randomised, controlled, open-label interventional trial aiming to compare the effectiveness of an educational and motivational mobile health intervention with usual care in reducing cardiovascular risk. The trial plans to enrol approximately 80,000 subjects without overt cardiovascular diseases and evaluate the short-term endpoints, as well as conduct a long-term follow-up to assess the incidence of major adverse cardiovascular events.
Editorial Material
Surgery
Giuseppe Remuzzi
UPDATES IN SURGERY
(2023)
Article
Multidisciplinary Sciences
Matteo Breno, Marina Noris, Nadia Rubis, Aneliya Ilieva Parvanova, Davide Martinetti, Sara Gamba, Lucia Liguori, Caterina Mele, Rossella Piras, Silvia Orisio, Elisabetta Valoti, Marta Alberti, Olimpia Diadei, Elena Bresin, Miriam Rigoldi, Silvia Prandini, Tiziano Gamba, Nadia Stucchi, Fabiola Carrara, Erica Daina, Ariela Benigni, ORIGIN Study Grp
Summary: This study conducted a genetic association study on the outcome of COVID-19 in a homogeneous population from Bergamo province, which was heavily impacted by the SARS-CoV-2 pandemic in Europe. The results showed an association between the 3p21.31 locus and disease severity, with a stronger effect in severely ill patients. Additionally, transcriptome-wide association study identified eQTLs for LZTFL1 and CCR9, and 17 previously unreported loci were suggestive for an association with COVID-19 severity or susceptibility.
Article
Multidisciplinary Sciences
Angelo M. Lavecchia, Polyxeni Mantzouratou, Domenico Cerullo, Monica Locatelli, Sara Conti, Matteo Tironi, Fabio Sangalli, Daniela Corna, Carlamaria Zoja, Giuseppe Remuzzi, Christodoulos Xinaris
Summary: Research shows that activation of thyroid hormone (TH) signaling can counteract cellular remodeling and pathological alterations caused by diabetes, providing a potential approach for the treatment of diabetes and its complications.
Article
Radiology, Nuclear Medicine & Medical Imaging
Anna Caroli, Giulia Villa, Paolo Brambilla, Matias Trillini, Kanishka Sharma, Sandro Sironi, Giuseppe Remuzzi, Norberto Perico, Andrea Remuzzi
Summary: This study presents and validates a diffusion MRI (DWI)-based method for quantifying total kidney and cyst volume (TCV) and characterizing non-cystic tissue microstructure in autosomal dominant polycystic kidney disease (ADPKD). DWI shows potential in ADPKD to assess and predict disease progression, evaluate the impact of novel therapies, and identify microcysts and peritubular interstitial fibrosis in non-cystic kidney tissue.
EUROPEAN RADIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Federica Casiraghi, Marta Todeschini, Manuel Alfredo Podesta, Marilena Mister, Barbara Ruggiero, Matias Trillini, Camillo Carrara, Olimpia Diadei, Alessandro Villa, Ariela Benigni, Giuseppe Remuzzi
Summary: Immune dysregulation plays a key role in the pathogenesis of steroid-dependent/frequently relapsing nephrotic syndrome (SDNS/FRNS). However, no major B- or T-cell alterations have been described for adults, unlike in pediatric cases. This study found that patients with SDNS/FRNS have expansion of memory B cells and reduced memory Tregs. The levels of CD45RO(+) Tregs at baseline may help predict which patients will achieve sustained remission following rituximab infusion.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Monica Locatelli, Daniela Rottoli, Rayan Mahmoud, Mauro Abbate, Daniela Corna, Domenico Cerullo, Susanna Tomasoni, Giuseppe Remuzzi, Carlamaria Zoja, Ariela Benigni, Daniela Macconi
Summary: In BTBR ob/ob mice with type 2 diabetic nephropathy, peritubular capillaries show endothelial cell abnormalities and basement membrane thickening. Remodeling and focal loss of the endothelial glycocalyx were observed in diabetic kidneys, and ACEi treatment preserved the glycocalyx and attenuated the ultrastructural abnormalities of peritubular capillaries.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)