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Translational kidney research

Niloufar Safinia, Nathali Grageda, Cristiano Scottà, Sarah Thirkell, Laura J Fry, Trishan Vaikunthanathan, Robert I Lechler, Giovanna Lombardi
Solid organ transplantation is the treatment of choice for patients with end-stage organ dysfunction. Despite improvements in short-term outcome, long-term outcome is suboptimal due to the increased morbidity and mortality associated with the toxicity of immunosuppressive regimens and chronic rejection (1-5). As such, the attention of the transplant community has focused on the development of novel therapeutic strategies to achieve allograft tolerance, a state whereby the immune system of the recipient can be re-educated to accept the allograft, averting the need for long-term immunosuppression...
2018: Frontiers in Immunology
Wenjing Tian, Hualing Fu, Tuan Xu, Sherry Li Xu, Zhiling Guo, Jijing Tian, Wuqun Tao, Heidi Qunhui Xie, Bin Zhao
The aryl hydrocarbon receptor (AhR) plays an important role in mediating dioxins toxicity. Currently, genes of P450 families are major research interests in studies on AhR-mediated gene alterations caused by dioxins. Genes related to other metabolic pathways or processes may be also responsive to dioxin exposures. Amino acid transporter B0AT1 (encoded by SLC6A19) plays a decisive role in neutral amino acid transport which is present in kidney, intestine and liver. However, effects of dioxins on its expression are still unknown...
March 6, 2018: Environmental Pollution
Ramneek Kaur, Monika Sodhi, Ankita Sharma, Vijay Lakshmi Sharma, Preeti Verma, Shelesh Kumar Swami, Parvesh Kumari, Manishi Mukesh
Selection of reference genes has become an integral step in any real time quantitative PCR (RT-qPCR) based expression studies. The importance of this study stems from the fact that riverine buffaloes are major dairy species of Indian sub-continent and the information generated here will be of great interest to the investigators engaged in functional genomic studies of this important livestock species. In this study, an effort was made to evaluate a panel of 10 candidate reference genes (glyceraldehyde 3-phosphate dehydrogenase (GAPDH), beta- actin (ACTB), ubiquitously expressed transcript (UXT), ribosomal protein S15 (RPS15), ribosomal protein L-4 (RPL4), ribosomal protein S9 (RPS9), ribosomal protein S23 (RPS23), hydroxymethylbilane synthase (HMBS), β2 Microglobulin (β2M) and eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) across 12 tissues (mammary gland, kidney, spleen, liver, heart, intestine, ovary, lung, muscle, brain, subcutaneous fat and testis) of riverine buffaloes...
2018: PloS One
Jens Christian König, Andrea Titieni, Martin Konrad
Hereditary cystic kidney diseases comprise a complex group of genetic disorders representing one of the most common causes of end-stage renal failure in childhood. The main representatives are autosomal recessive polycystic kidney disease, nephronophthisis, Bardet-Biedl syndrome, and hepatocyte nuclear factor-1beta nephropathy. Within the last years, genetic efforts have brought tremendous progress for the molecular understanding of hereditary cystic kidney diseases identifying more than 70 genes. Yet, genetic heterogeneity, phenotypic variability, a lack of reliable genotype-phenotype correlations and the absence of disease-specific biomarkers remain major challenges for physicians treating children with cystic kidney diseases...
2018: Frontiers in Pediatrics
Ke Wang, Bryan Kestenbaum
The secretion of small molecules by the proximal tubules of the kidneys represents a vital homeostatic function for rapidly clearing endogenous solutes and medications from the circulation. After filtration at the glomerulus, renal blood flow is directed through a network of peritubular capillaries, where transporters of the proximal tubules actively secrete putative uremic toxins and hundreds of commonly prescribed drugs into the urine, including protein-bound substances that cannot readily cross the glomerular basement membrane...
February 28, 2018: Clinical Journal of the American Society of Nephrology: CJASN
Antonin Jaros, Hafiz A Sroya, Venita K Wolfe, Vikas Ghai, Maria-Eleni Roumelioti, Kamran Shaffi, Kai Wang, Vernon Shane Pankratz, Mark L Unruh, Christos Argyropoulos
BACKGROUND: Rural areas in the state of New Mexico have been the "ground-zero" for the epidemic of diabetic Chronic Kidney Disease (CKD) in the United States. However, there is limited research about risk factors of diabetic CKD in this area and scarce data regarding the performance of emerging markers of renal filtration and epigenetic biomarkers of renal function and diabetes in this area with its unique ethnic/racial population. We designed the COMPASS study as a community-based program in rural New Mexico aiming to screen for CKD and to discover CKD-related translational biomarkers...
February 27, 2018: BMC Nephrology
Wesley H Self, Matthew W Semler, Jonathan P Wanderer, Li Wang, Daniel W Byrne, Sean P Collins, Corey M Slovis, Christopher J Lindsell, Jesse M Ehrenfeld, Edward D Siew, Andrew D Shaw, Gordon R Bernard, Todd W Rice
BACKGROUND: Comparative clinical effects of balanced crystalloids and saline are uncertain, particularly in noncritically ill patients cared for outside an intensive care unit (ICU). METHODS: We conducted a single-center, pragmatic, multiple-crossover trial comparing balanced crystalloids (lactated Ringer's solution or Plasma-Lyte A) with saline among adults who were treated with intravenous crystalloids in the emergency department and were subsequently hospitalized outside an ICU...
March 1, 2018: New England Journal of Medicine
Matthew W Semler, Wesley H Self, Jonathan P Wanderer, Jesse M Ehrenfeld, Li Wang, Daniel W Byrne, Joanna L Stollings, Avinash B Kumar, Christopher G Hughes, Antonio Hernandez, Oscar D Guillamondegui, Addison K May, Liza Weavind, Jonathan D Casey, Edward D Siew, Andrew D Shaw, Gordon R Bernard, Todd W Rice
BACKGROUND: Both balanced crystalloids and saline are used for intravenous fluid administration in critically ill adults, but it is not known which results in better clinical outcomes. METHODS: In a pragmatic, cluster-randomized, multiple-crossover trial conducted in five intensive care units at an academic center, we assigned 15,802 adults to receive saline (0.9% sodium chloride) or balanced crystalloids (lactated Ringer's solution or Plasma-Lyte A) according to the randomization of the unit to which they were admitted...
March 1, 2018: New England Journal of Medicine
Elizabeth Crellin, Kathryn E Mansfield, Clémence Leyrat, Dorothea Nitsch, Ian J Douglas, Adrian Root, Elizabeth Williamson, Liam Smeeth, Laurie A Tomlinson
OBJECTIVE: To determine if trimethoprim use for urinary tract infection (UTI) is associated with an increased risk of acute kidney injury, hyperkalaemia, or sudden death in the general population. DESIGN: Cohort study. SETTING: UK electronic primary care records from practices contributing to the Clinical Practice Research Datalink linked to the Hospital Episode Statistics database. PARTICIPANTS: Adults aged 65 and over with a prescription for trimethoprim, amoxicillin, cefalexin, ciprofloxacin, or nitrofurantoin prescribed up to three days after a primary care diagnosis of UTI between April 1997 and September 2015...
February 9, 2018: BMJ: British Medical Journal
Avinash Eranki, Navid Farr, Ari Partanen, Karun V Sharma, Christopher T Rossi, Avi Z Rosenberg, AeRang Kim, Matthew Oetgen, Haydar Celik, David Woods, Pavel S Yarmolenko, Peter C W Kim, Bradford J Wood
PURPOSE: High intensity focused ultrasound (HIFU) can non-invasively treat tumors with minimal or no damage to intervening tissues. While continuous-wave HIFU thermally ablates target tissue, the effect of hundreds of microsecond-long pulsed sonications is examined in this work. The objective of this study was to characterize sonication parameter-dependent thermomechanical bioeffects to provide the foundation for future preclinical studies and facilitate clinical translation. METHODS AND MATERIALS: Acoustic power, number of cycles/pulse, sonication time, and pulse repetition frequency (PRF) were varied on a clinical magnetic resonance imaging (MRI) - guided HIFU (MR-HIFU) system...
February 11, 2018: International Journal of Hyperthermia
Kook-Hwan Oh, Seon Ha Baek, Kwon-Wook Joo, Dong Ki Kim, Yon-Su Kim, Sejoong Kim, Yun Kyu Oh, Byoung Geun Han, Jae Hyun Chang, Wookyung Chung, Ki Young Na
INTRODUCTION: In peritoneal dialysis (PD) patients, volume overload is related to cardiac dysfunction and mortality, while intravascular volume depletion is associated with a rapid decline in the residual renal function (RRF). This study sought to determine the clinical usefulness of bioimpedance spectroscopy (BIS)-guided fluid management for preserving RRF and cardiac function in PD patients. SUBJECTS AND METHODS: This is a multicenter, prospective, open-label study that was conducted over a 1-year period (NCT01887262)...
January 31, 2018: Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis
Brittany M Newberry, Dian Dowling Evans
The Research to Practice Column is designed to improve translational research critique skills of advanced practice nurses. In this issue, the article "Risk of Acute Kidney Injury After Intravenous Contrast Media Administration" () is discussed in the context of a patient presenting to the emergency department with acute abdominal pain. The study was designed to assess the risk of acute kidney injury and adverse clinical outcomes in patients receiving intravenous contrast for computed tomography. Advanced practice nurses need to be aware of advances in types of intravenous contrast and current recommendations for administration of intravenous contrast for diagnostic purposes in patients at risk for acute kidney injury to facilitate making timely and accurate diagnoses...
January 2018: Advanced Emergency Nursing Journal
Adeera Levin, Evan Adams, Brendan J Barrett, Heather Beanlands, Kevin D Burns, Helen Hoi-Lun Chiu, Kate Chong, Allison Dart, Jack Ferera, Nicolas Fernandez, Elisabeth Fowler, Amit X Garg, Richard Gilbert, Heather Harris, Rebecca Harvey, Brenda Hemmelgarn, Matthew James, Jeffrey Johnson, Joanne Kappel, Paul Komenda, Michael McCormick, Christopher McIntyre, Farid Mahmud, York Pei, Graham Pollock, Heather Reich, Norman D Rosenblum, James Scholey, Etienne Sochett, Mila Tang, Navdeep Tangri, Marcello Tonelli, Catherine Turner, Michael Walsh, Cathy Woods, Braden Manns
Purpose of review: This article serves to describe the Can-SOLVE CKD network, a program of research projects and infrastructure that has excited patients and given them hope that we can truly transform the care they receive. Issue: Chronic kidney disease (CKD) is a complex disorder that affects more than 4 million Canadians and costs the Canadian health care system more than $40 billion per year. The evidence base for guiding care in CKD is small, and even in areas where evidence exists, uptake of evidence into clinical practice has been slow...
2018: Canadian Journal of Kidney Health and Disease
Jennifer X Ji, Yi Kan Wang, Dawn R Cochrane, David G Huntsman
Clear cell ovarian carcinoma (CCOC) and clear cell renal cell carcinoma (ccRCC) both feature clear cytoplasm due to the accumulation of cytoplasmic glycogen. Genomic studies have demonstrated several mutational similarities between these two diseases including frequent alterations in the chromatin remodeling SWI/SNF and cellular proliferation PI3K/mTOR pathways, as well as a shared hypoxia-like mRNA expression signature. Although many targeted treatment options have been approved for advance stage ccRCC, CCOC patients are still treated with conventional platinum and taxane chemotherapy, to which they are resistant...
January 17, 2018: Journal of Pathology
Laura Bryant, Olga Lozynska, Albert M Maguire, Tomas S Aleman, Jean Bennett
Background: Accurate clinical diagnosis and prognosis of retinal degeneration can be aided by the identification of the disease-causing genetic variant. It can confirm the clinical diagnosis as well as inform the clinician of the risk for potential involvement of other organs such as kidneys. It also aids in genetic counseling for affected individuals who want to have a child. Finally, knowledge of disease-causing variants informs laboratory investigators involved in translational research...
2018: Clinical Ophthalmology
Sree K Venuthurupalli, Wendy E Hoy, Helen G Healy, Anne Cameron, Robert G Fassett
Chronic kidney disease (CKD) was largely a hidden health problem until the publication of an internationally agreed approach to its identification, monitoring, and treatment. The 2002 National Kidney Foundation CKD classification and the subsequent 2006 Kidney Disease Improving Global Outcomes (KDIGO) recommendations are powerful tools for translating thinking about CKD into clinical practice. These guidelines were strongly endorsed by the international community, including Australia, and were incorporated into CKD practice guidelines...
January 2018: KI Reports
Shigenobu Shibata, Akiko Furutani
Circadian clock system has been widely maintained in many spices from prokaryote to mammals. "Circadian" means "approximately day" in Latin, thus circadian rhythm means about 24 hour rhythms. The earth revolves once every 24 hours, and our circadian system has been developed for adjusting to this 24 hour cycles, to get sun light information for getting their foods or for alive in birds or mammals. We have two different circadian systems so-called main oscillator located in the suprachiasmatic nucleus (SCN) of the hypothalamus, and local oscillator located in the various peripheral organ tissues such as liver, kidney and skeletal muscle...
2018: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
Richard Glassock
It is interesting that some of my predictions came true and some did not, but I think the jury is still out on many of them. I start to remind everyone on the glorious past of Nephrology, from the physiology, translational and methodological discoveries that have contributed to the development of our discipline. I predict that the Academic branch of Nephrology will continue to excel in three domains: Creative Research,Teaching (Training) and Innovative Clinical Care. I forsee dramatic changes in Nephrology practice in the short term (10 years) and I discuss which areas will have a most dramatic impact...
October 2017: Jornal Brasileiro de Nefrologia: ʹorgão Oficial de Sociedades Brasileira e Latino-Americana de Nefrologia
Jatin Roper, Tuomas Tammela, Adam Akkad, Mohammad Almeqdadi, Sebastian B Santos, Tyler Jacks, Ömer H Yilmaz
Most genetically engineered mouse models (GEMMs) of colorectal cancer are limited by tumor formation in the small intestine, a high tumor burden that limits metastasis, and the need to generate and cross mutant mice. Cell line or organoid transplantation models generally produce tumors in ectopic locations-such as the subcutaneous space, kidney capsule, or cecal wall-that do not reflect the native stromal environment of the colon mucosa. Here, we describe detailed protocols to rapidly and efficiently induce site-directed tumors in the distal colon of mice that are based on colonoscopy-guided mucosal injection...
February 2018: Nature Protocols
Liping Wang, Grace Jang, Deependra Kumar Ban, Vrinda Sant, Jay Seth, Sami Kazmi, Nirav Patel, Qingqing Yang, Joon Lee, Woraphong Janetanakit, Shanshan Wang, Brian P Head, Gennadi Glinsky, Ratneshwar Lal
Multi-functional nanoshuttles for remotely targeted and on-demand delivery of therapeutic molecules and imaging to defined tissues and organs hold great potentials in personalized medicine, including precise early diagnosis, efficient prevention and therapy without toxicity. Yet, in spite of 25 years of research, there are still no such shuttles available. To this end, we have designed magnetic and gold nanoparticles (NP)-embedded silica nanoshuttles (MGNSs) with nanopores on their surface. Fluorescently labeled Doxorubicin (DOX), a cancer drug, was loaded in the MGNSs as a payload...
2017: Bone Research
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