Further, from the observed baseline characteristics of 125,000 patients with CKD who have hyperkalaemia (HK), AZ found that this cohort face a higher comorbidity burden, which increases as HK severity increases and CKD advances compared to CKD patients without HK. Little Bookham AstraZeneca presented new findings from the DISCOVER Chronic Kidney Disease (CKD) study at the American Society of Nephrologists (ASN) Kidney Week 2020 Congress last week.. The ultimate aim will be to try to induce disease conditions and then treat them. When we put two cell types together, we suddenly see that they behave differently – one cell influences the results from the other. Why this happens is still a mystery; we hope this technology might help bring some answers. Click ‘cancel’ to return to AstraZeneca’s site or ‘continue’ to proceed. “Rigorous clinical trials are the gold standard for collecting evidence on a treatment’s safety and efficacy, but helping patients live longer and healthier lives doesn’t just involve researching new treatments. According to the pharma company, Farxiga (dapagliflozin) is the first therapy shown to significantly prolong patient survival in CKD … Understanding that APOL-1 is a genetic driver of disease leads us a step closer to addressing a high unmet need in a defined population. An application for the use on the AstraZeneca DISCOVER-CKD study, involving patients with chronic kidney disease. Mansard House London, 27 January 2021: In 2019, BenevolentAI and AstraZeneca entered a strategic collaboration aiming to discover new drugs for CKD and idiopathic pulmonary fibrosis (IPF). Exome sequencing is emerging as an important analytical and potential diagnostic technique in many fields, and we are now applying it to CKD. Organs-on-Chip technology could help solve this challenge. Principal Scientist, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, Senior Vice President, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, Head of the Centre for Genomics Research, Discovery Sciences, R&D, Senior Director, Bioscience CKD, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, Director, Bioscience CKD, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, Chief Operating Officer, Ionis Pharmaceuticals, Senior Project Leader, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, https://www.kidneycareuk.org/news-and-campaigns/news/estimated-1-10-people-worldwide-have-chronic-kidney-disease/, https://www.sciencedirect.com/science/article/pii/S0914508710001802, https://www.kidney-international.org/article/S0085-2538(17)30095-9/pdf, https://www.kidney.org/kidneydisease/howkidneyswrk, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4198006/, ttps://www.asn-online.org/education/kidneyweek/2018/program-abstract.aspx?controlId=3011451, Bioinformatics and ‘omics analysis to classify patients and uncover new genetic disease drivers, The development of advanced models for target validation and understanding disease development, New modalities for previously undruggable targets. Collapse. E: subscriptions@pharmatimes.com It is also involved in metabolism and vitamin D production, and produces hormones that regulate red blood cell production and blood pressure.4 This all happens as a result of complex interplay with other organs, so CKD has knock-on effects throughout the entire body.5. 3D bioprinting also offers us unique flexibility – we print a matrix, to which we can effectively add any cell type we want in an almost modular fashion. Although we are not at this stage yet, it is not outside the realm of future possibility. Our antisense-based drug discovery platform is a rapid and efficient route to use genomic information to make novel drug candidates. Inspiration can sometimes come from unexpected places. Julie Williams believes that one reason for the limited number of treatment options for kidney patients is strongly linked to the lack of translatable systems as there is a high attrition rate with kidney candidate drugs in clinical trials. At AstraZeneca, our CaReMe approach is to see and embrace the full cardio-renal and metabolic picture and use this knowledge to redefine the way these diseases are understood and treated. We are in a stronger position than ever before to look for targets and treatments now we have a deeper molecular understanding of CKD. This platform allows us to explore drug candidates that specifically address disease targets, many of which cannot be treated by traditional drug types. People of West-African ancestry are at increased risk of developing end stage renal disease, and common APOL-1 polymorphisms may account for this risk.6. Published in the New England Journal of Medicine, the study is based on the results of exome sequencing more than 3,300 patients. With organ on a chip technology we can go even further than this and add conditions such as flow and shear stress, mimicking the conditions in the kidney even further. Many of the underlying mechanisms of CKD have been a mystery until recently. New data will be presented from DISCOVER-CKD, a trial that assesses current real-world practice patterns and clinical management of patients with CKD. For the first time, distinct disease categories based on molecular data which are different from previous clinical classifications for CKD could be seen. There is an unmet need in CKD. Any reference in these archives to AstraZeneca products or their uses may not reflect current medical knowledge and should not be used as a source of information on the present product label, efficacy data or safety data. For these reasons, we take a holistic view of the patient – the CaReMe approach – and are guided by the commonalities between these diseases in our research. Imagine how much more information we will get from this system. Anaemia in NDD patients with CKD is frequent and largely undertreated, and rescue therapies including blood transfusions are more often used as first-line treatments than preventative therapies such as intravenous iron or erythropoiesis-stimulating agents. These are then populated with cells to create biological structures. ASOs can be designed to bind to almost any defined genetic sequences, meaning they have potential for use in diseases with genetic origin. ANN ARBOR, Mich -- Patients with Chronic Kidney Disease (CKD) may benefit from a new collaboration between the University of Michigan (U-M) and AstraZeneca who have partnered to … Many individuals with these diseases have either symptoms or underlying pathologies associated with more than one of these diseases, so treating them collaboratively is essential. The DISCOVER-CKD retrospective cohort of patients was extracted … We also need an equivalent standard for understanding the experiences of patients in the real world,” said Joris Silon, senior vice president for cardiovascular, renal and metabolism at AZ. Go to the App Store or Google Play and search for 'PharmaTimes' to download our free app. Read more. These are short chains of nucleotides that bind to mRNA, thereby modulating protein expression. We now have the possibility of using 3D bioprinting to delve deeper into cellular crosstalk. This work emphasizes the critical role of careful genomic analyses, both in the management of patients living with chronic kidney disease and in the appropriate design of trials dedicated to the evaluation of new and more effective treatments. We are looking to a future where we can identify drugs that target the root cause of disease and recruit patients with specific genotypes to the right trials. Modelling this interplay, which would take place in a real, living kidney is crucial for the creation of a realistic, relevant model system. With these groundbreaking techniques, we can test compound behaviour and hope to shed new light on previously elusive disease mechanisms. Reviews Review policy and info. In collaboration with Columbia University, led by Professor David Goldstein and Professor Ali Gharavi, we have conducted the largest-ever exome sequencing study of CKD patients. AstraZeneca and BenevolentAI today began a long-term collaboration to use artificial intelligence (AI) and machine learning for the discovery and development of new treatments for chronic kidney disease (CKD… Observing a complete system enables a better understanding of kidney function – and dysfunction. Organs-on-Chip technology provides an environment that emulates key aspects of the physiology of a real kidney; including fluidic channels that are lined with living cells in the correct architecture. DISCOVER CKD is an international observational cohort study on patients with CKD. This research could represent a significant breakthrough for those patients with a genetic diagnosis, as these data could potentially provide novel clinical insights to help inform treatment and care options. The flow represents the flow of blood carrying nutrients, takes away waste products, and also creates mechanical forces, all critical factors for the functioning of the kidney. In addition, patients with CKD were found to have a high pharmacotherapy burden, with a range of time to initiation of key therapies and increased medication use as CKD stages advance over time. The complexity of the kidney means it has been virtually impossible to emulate in classical in vitro systems, while in vivo models are resource intensive to produce, and not always translatable to human systems. The DISCOVER CKD retrospective cohort of patients was extracted using the integrated Limited Claims and EHR data. The study included patients aged >18 years (>20 JMDV) with a diagnostic CKD … We encourage you to read the privacy policy of every website you visit. We have already bioprinted a 3D model with both kidney tubules and blood vessels, which replicates the behaviour of the two structures and importantly the interactions between the different tissue types. In collaboration with scientists from Columbia University, we have shown for the first time that adult onset CKD can be stratified into distinct underlying causes through the use of genetics, with direct relevance both to clinical care and clinical trial design. Animal models go some way towards addressing this; although even mammalian systems can lack translatability to human systems, especially with compounds that show species differences in metabolism and toxicity. Anna Reznichenko, Principal Scientist, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, has devised a novel method based on market segmentation analysis for handling massive datasets drawn from the financial industry. DISCOVER CKD is an international observational cohort study in patients with CKD, comprising both prospective and retrospective patient cohorts. The study’s mission is to collect real-world data to assess gaps in the patient journey – looking at early treatment experience, treatment patterns, treatment effectiveness and safety, as well as the quality of life of CKD … The DISCOVER CKD study is characterising contemporary real-world management of CKD, to provides insights into the current gaps in treatment and management of CKD… Using data from the Renal Pre-competitive Consortium (RPC2) – a unique partnership of industrial and academic collaborators – gives Anna access to the largest-ever patient sample bank for renal transcriptomics (analysis of gene expression in kidney biopsies), containing over 250 genome-wide expression profiled samples, with data from patients at all stages of disease. At AstraZeneca, we are dedicated to changing the future for CKD patients. DISCOVER CKD is an observational study in patients with CKD, data was extracted using the integrated Limited Claims and Electronic Health Record data. Our ambitions are high: we want to stop disease progression, manage morbidity and mortality, and ultimately modify and even reverse the disease itself. This website is intended for people seeking information on AstraZeneca's worldwide business. Creating realistic, living components of a healthy kidney will be a vital tool for understanding kidney function. One emerging treatment strategy is to target protein expression using antisense oligonucleotides (ASOs). Sometimes I look around the room when we have big meetings and consider that every tenth person in the room will have kidney disease. The research results have given us valuable clinical insights into the genetic causes and therapeutic opportunities for this condition. Chronic kidney disease (CKD) is a common and debilitating condition that affects around 1 in 10 people worldwide,1 and the prevalence is increasing. We describe treatment pathways of key medications prescribed to CKD patients in DISCOVER CKD. Our country sites can be located in the AZ Network. Patients were aged ≥18 years, with ≥1 UACR measure and two measures of eGFR 0 … We have, for years, been investigating cells in isolation in a dish. The international hybrid observational cohort study, undertaken in collaboration with a scientific committee, includes both prospective and retrospective cohorts of patient with CKD. In Japan, male or female patients over the age of 20 years are included. While there are currently available treatments that benefit patients with CKD, there are no treatments that specifically target the cause of CKD. In the age of ‘omics and data processing, we believe we have reached a turning point. T: +44 (0)20 7240 6999 The 20 abstracts being presented, including four oral presentations, will include data on Lokelma (sodium zirconium cyclosilicate), roxadustat and Farxiga (dapagliflozin) across different stages of chronic kidney disease (CKD) and AstraZeneca… Important notice for users Methods. LONDON, Jan. 27, 2021 /PRNewswire/ -- BenevolentAI today announced that the biopharmaceutical company AstraZeneca has selected a novel chronic kidney disease (CKD) target … As such, CKD is not a disease to be studied in isolation. The study does not attempt to test any … AstraZeneca is not responsible for the privacy policy of any third party websites. It identified potentially causative genetic variants for a significant number (~9%) of patients. New data will be presented from DISCOVER-CKD, … We are investing in the development of new, sophisticated models that mimic the human kidney more accurately than has ever previously been possible. In the initial key findings, AZ found that over 600,000 patients with non-dialysis-dependent-CKD (NDD-CKD) have been identified in the study cohort which aims to describe baseline characteristics of an NDD-CKD population with and without anaemia. If we can target the high-risk APOL-1 variants, this could lead to potential treatments for people who have limited options. ABOUT IONIS PHARMACEUTICALS, INC. Ionis is the leading company in RNA … Too often the condition is diagnosed late and progresses to become severe enough to require dialysis or transplants. You have selected a link that will take you to a site maintained by a third party who is solely responsible for its contents. However, we have moved a step closer towards modelling the human system by using 3D bioprinting in our collaboration with world-leading experts at Harvard University. The study is also using mobile technology to allow patients to provide their own experiences with CKD and improve patient dialogue as well as assess AZ’s specific outcomes via prospective data collection. This cohort’s size provides information into a highly comorbid population with conditions including hypertension, heart failure, stroke and type 2 diabetes. We are excited to partner with AstraZeneca to increase the complexity and utility of our 3D kidney tissue models – bioprinting enables us to rapidly design and fabricate a wide range of vascularised human tissues. This approach has revealed distinct new patient categories, and could be used as the base for precision medicine in the future. We are now looking to identify urinary biomarkers which could be used to reveal patients’ molecular disease classes non-invasively, allowing us greater precision when allocating the right patients to the right trials and in the future, potentially provide tailored treatments based on scientifically-determined individual disease categories. Gaps exist in real-world data to understand treatment pathways of CKD patients. The next step on from our breakthrough genetic research and increased understanding of disease mechanisms is using precision medicine approaches with the aim of targeting the underlying causes of CKD. We aim to close this gap: enrolling the right people for the right trial is critical for research success and patient health. We hope then to be able to classify patients more accurately, and identify new biomarkers and disease targets. Roxadustat is under regulatory review for the treatment of anemia of chronic kidney disease (CKD). This approach means we are uncovering different underlying molecular disease profiles. Leatherhead We are investigating the drivers of disease and progression of CKD using a rigorous, science-led approach and adopting techniques that aim to break new ground in research. DISCOVER-CKD encompasses large retrospective electronic medical records (EMRs) and claims data between 2008 and 2020. AstraZeneca will also present new insights into patients’ experiences living with CKD as well as actionable gaps in treatment and management. By focusing on early disease detection underpinned by precision medicine, we hope that in the future patients will be matched with treatments most likely to work for them. We are not only using ‘omics in our attempts to classify disease, but to build an understanding of its cause. 1. https://www.kidneycareuk.org/news-and-campaigns/news/estimated-1-10-people-worldwide-have-chronic-kidney-disease/, 2. https://www.sciencedirect.com/science/article/pii/S0914508710001802, 3. https://www.kidney-international.org/article/S0085-2538(17)30095-9/pdf, 4. https://www.kidney.org/kidneydisease/howkidneyswrk, 5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4198006/, 6. ttps://www.asn-online.org/education/kidneyweek/2018/program-abstract.aspx?controlId=3011451. The DISCOVER CKD study population for all countries except Japan includes male and female patients with CKD aged 18 years or over. To use this new knowledge to our best advantage, we need the right research tools to simulate the disease and test our hypotheses. 3D bioprinting involves printing-like techniques, where fugitive ‘ink’ is printed onto a gelatin/fibrogen matrix to pattern open vascular and tubular channels. Ultimately, the logical conclusion of this work would be to print all the components needed to create an entire synthetic kidney. The data advance AstraZeneca’s ambition to create a coordinated pathway for renal patients to advance earlier diagnosis and help prevent or slow the progression of chronic kidney disease (CKD… We are using them to model the glomerulus – the kidney’s filtration barrier – which breaks down in CKD. Watch our video to discover what open innovation can do for you, for medical science, and for patients. AstraZeneca will present a series of sub-analyses from the Lokelma Phase IIIb DIALIZE trial reinforcing the effectiveness of this medicine to manage hyperkalaemia in patients with CKD on … The current symptom-based approach ignores the different underlying molecular causes of disease and leaves potential for misdiagnosis. This is an exciting time – recent advances in three important areas lay the foundations for a new era in CKD research: CKD encompasses various primary disorders and stages of progression, and the patient population is highly heterogenous – CKD is really an umbrella term for many diseases. We’re excited to work with AstraZeneca on this and other targets with the hope to provide benefits to patients with unmet medical needs. However, access to the data itself is only part of the picture: the next step is analysing the patterns within the data points. We describe patient characteristics and the prevalence of CKD according to the 2012 KDIGO categories in patients with CKD. Garcia Sanchez JJ et al. Around 40% of patients with heart failure also have CKD,2 and patients with both diabetes and early kidney disease may have a reduced life expectancy compared to a healthy person.3, The kidney has critical roles in the human physiology, removing waste products and balancing the body’s fluids. People living with CKD progressively lose kidney function, but may not know they even have the disease until the later stages. The research also revealed that six genes collectively account for almost two thirds of genetic diagnoses, and genetic diagnoses could be assigned to ~17% of previously uncharacterised CKD cases. Scientific advances have increased our understanding of the links between cardiovascular, renal and metabolic diseases. “Following the ground-breaking DAPA-CKD … F: +44 (0)20 7240 4479, Get the latest pharma news delivered to your inbox. Kidneys are made up of over 20 different cell types, arranged within an intricate architecture. Church Road LONDON, Jan. 27, 2021 /PRNewswire/ -- BenevolentAI today announced that the biopharmaceutical company AstraZeneca has selected a novel chronic kidney disease (CKD) … The DISCOVER CKD study is characterising contemporary real-world management of CKD, to provides insights into the current gaps in treatment and management of CKD, as well as care pathways and novel endpoints. AstraZeneca presented new findings from the DISCOVER Chronic Kidney Disease (CKD) study at the American Society of Nephrologists (ASN) Kidney Week 2020 Congress last week. AZ also observed that the recording of urine-album-creatinine ratio (UACR) in real-world electronic health record (EHR) data is limited, emphasising the need for clinicians to routinely capture and record UACR data as part of routine treatment. As our aim is also to understand kidney dysfunction, we also are embarking on an ambitious project to create kidney components with diseased cells, using human induced pluripotent stem (iPS) cells from real patients. It is concerning that we have this on an epidemic scale. In partnership with Ionis Pharmaceuticals, we are researching APOL-1 – a gene with variants that is related to an increased risk of early onset kidney disease and rapid progression.