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Translational kidney research

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https://www.readbyqxmd.com/read/29740155/an-update-on-the-genetics-of-hyperuricaemia-and-gout
#1
REVIEW
Tanya J Major, Nicola Dalbeth, Eli A Stahl, Tony R Merriman
A central aspect of the pathogenesis of gout is elevated urate concentrations, which lead to the formation of monosodium urate crystals. The clinical features of gout result from an individual's immune response to these deposited crystals. Genome-wide association studies (GWAS) have confirmed the importance of urate excretion in the control of serum urate levels and the risk of gout and have identified the kidneys, the gut and the liver as sites of urate regulation. The genetic contribution to the progression from hyperuricaemia to gout remains relatively poorly understood, although genes encoding proteins that are involved in the NLRP3 (NOD-, LRR- and pyrin domain-containing 3) inflammasome pathway play a part...
May 8, 2018: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/29727369/blue-light-enhances-bacterial-clearance-and-reduces-organ-injury-during-sepsis
#2
Anthony J Lewis, Xianghong Zhang, John E Griepentrog, Du Yuan, Richard D Collage, Paul K Waltz, Derek C Angus, Brian S Zuckerbraun, Matthew R Rosengart
OBJECTIVES: The physiology of nearly all mammalian organisms are entrained by light and exhibit circadian rhythm. The data derived from animal studies show that light influences immunity, and these neurophysiologic pathways are maximally entrained by the blue spectrum. Here, we hypothesize that bright blue light reduces acute kidney injury by comparison with either bright red or standard, white fluorescent light in mice subjected to sepsis. To further translational relevance, we performed a pilot clinical trial of blue light therapy in human subjects with appendicitis...
May 4, 2018: Critical Care Medicine
https://www.readbyqxmd.com/read/29700419/the-correlation-between-the-immune-and-epithelial-mesenchymal-transition-signatures-suggests-potential-therapeutic-targets-and-prognosis-prediction-approaches-in-kidney-cancer
#3
Jiayu Liang, Zhihong Liu, Zijun Zou, Yongquan Tang, Chuan Zhou, Jian Yang, Xin Wei, Yiping Lu
Both epithelial-mesenchymal transition (EMT) and immune regulation are important biological process in malignant tumours. The current research aims to comprehensively explore the potential association between the epithelial-mesenchymal transition (EMT) signature and immune checkpoint signature and its role in predicting the prognosis of clear-cell renal cell carcinoma (ccRCC) patients. EMT-related genes were collected from an experiment-based study and then were investigated using data from the Cancer Genome Atlas...
April 26, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29697462/ex-vivo-machine-perfusion-for-kidney-preservation
#4
Matyas Hamar, Markus Selzner
PURPOSE OF REVIEW: Machine perfusion is a novel strategy to decrease preservation injury, improve graft assessment, and increase organ acceptance for transplantation. This review summarizes the current advances in ex-vivo machine-based kidney preservation technologies over the last year. RECENT FINDINGS: Ex-vivo perfusion technologies, such as hypothermic and normothermic machine perfusion and controlled oxygenated rewarming, have gained high interest in the field of organ preservation...
April 24, 2018: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/29695925/primary-iga-nephropathy-current-challenges-and-future-prospects
#5
REVIEW
Rose S Penfold, Maria Prendecki, Stephen McAdoo, Frederick Wk Tam
IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide, exhibiting a variable clinical and pathological course and significantly contributing to the global burden of chronic kidney disease and end-stage renal disease. Current standards of care focus on optimization of antihypertensive and antiproteinuric therapies (typically renin- angiotensin system blockade) to reduce disease progression. Much recent attention has focused on whether additional immunosuppression confers better outcomes than supportive management alone, and indeed, several trials have demonstrated renoprotective effects following the use of oral corticosteroids...
2018: International Journal of Nephrology and Renovascular Disease
https://www.readbyqxmd.com/read/29669934/divergent-responses-to-kisspeptin-in-children-with-delayed-puberty
#6
Yee-Ming Chan, Margaret F Lippincott, Temitope O Kusa, Stephanie B Seminara
BACKGROUND: The neuropeptide kisspeptin stimulates luteinizing hormone (LH) secretion in healthy adults but not in adults with idiopathic hypogonadotropic hypogonadism. We hypothesized that, in children presenting with delayed or stalled puberty, kisspeptin would elicit LH secretion in those children found on detailed nighttime neuroendocrine profiling to have evidence of emerging reproductive endocrine function. METHODS: Eleven boys and four girls were admitted overnight to assess LH secretion at baseline, after a single intravenous bolus of kisspeptin, and after a single intravenous bolus of gonadotropin-releasing hormone (GnRH)...
April 19, 2018: JCI Insight
https://www.readbyqxmd.com/read/29669318/neurod-expression-in-podocytes-and-interrelationships-with-nephrin-at-both-nuclear-and-cytoplasmic-sites
#7
Silvia Armelloni, Masami Ikehata, Deborah Mattinzoli, Min Li, Carlo Maria Alfieri, Mariapia Rastaldi, Piergiorgio Messa
Background/Aims The research of genes implicated in kidney glomerular function, eliciting cell fate program, is always at the forefront in nephrological studies. Several neurological molecules have been recently the object of study not only for their involvement in the central nervous system differentiation but also for their importance in the functionality of other organs and for mature phenotype, as in kidney. NeuroD, in CNS, is related to two functional roles, the early survival and the differentiation. The aim of our study was to ascertain the presence of NeuroD transcription factor in glomeruli and to understand which targets and mechanisms NeuroD controls...
April 13, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29574063/connective-tissue-growth-factor-ctgf-from-basics-to-clinics
#8
REVIEW
Yasaman Ramazani, Noël Knops, Mohamed A Elmonem, Tri Q Nguyen, Fanny Oliveira Arcolino, Lambert van den Heuvel, Elena Levtchenko, Dirk Kuypers, Roel Goldschmeding
Connective tissue growth factor, also known as CCN2, is a cysteine-rich matricellular protein involved in the control of biological processes, such as cell proliferation, differentiation, adhesion and angiogenesis, as well as multiple pathologies, such as tumor development and tissue fibrosis. Here, we describe the molecular and biological characteristics of CTGF, its regulation and various functions in the spectrum of development and regeneration to fibrosis. We further outline the preclinical and clinical studies concerning compounds targeting CTGF in various pathologies with the focus on heart, lung, liver, kidney and solid organ transplantation...
March 21, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29566839/cost-effectiveness-of-first-line-sevelamer-and-lanthanum-versus-calcium-based-binders-for-hyperphosphatemia-of-chronic-kidney-disease
#9
COMPARATIVE STUDY
Steven Habbous, Sebastian Przech, Janet Martin, Amit X Garg, Sisira Sarma
BACKGROUND: Phosphate binders are used to treat hyperphosphatemia among patients with chronic kidney disease (CKD). OBJECTIVES: To conduct an economic evaluation comparing calcium-free binders sevelamer and lanthanum with calcium-based binders for patients with CKD. METHODS: Effectiveness data were obtained from a recent meta-analysis of randomized trials. Effectiveness was measured as life-years gained and translated to quality-adjusted life-years (QALYs) using utility weights from the literature...
March 2018: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/29535728/cell-therapy-in-organ-transplantation-our-experience-on-the-clinical-translation-of-regulatory-t-cells
#10
REVIEW
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
https://www.readbyqxmd.com/read/29522993/slc6a19-is-a-novel-putative-gene-induced-by-dioxins-via-ahr-in-human-hepatoma-hepg2-cells
#11
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...
June 2018: Environmental Pollution
https://www.readbyqxmd.com/read/29509770/selection-of-suitable-reference-genes-for-normalization-of-quantitative-rt-pcr-rt-qpcr-expression-data-across-twelve-tissues-of-riverine-buffaloes-bubalus-bubalis
#12
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
https://www.readbyqxmd.com/read/29497606/network-for-early-onset-cystic-kidney-diseases-a-comprehensive-multidisciplinary-approach-to-hereditary-cystic-kidney-diseases-in-childhood
#13
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
https://www.readbyqxmd.com/read/29490976/proximal-tubular-secretory-clearance-a-neglected-partner-of-kidney-function
#14
REVIEW
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
https://www.readbyqxmd.com/read/29486722/study-protocol-rationale-and-design-of-the-community-based-prospective-cohort-study-of-kidney-function-and-diabetes-in-rural-new-mexico-the-compass-study
#15
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
https://www.readbyqxmd.com/read/29485926/balanced-crystalloids-versus-saline-in-noncritically-ill-adults
#16
RANDOMIZED CONTROLLED TRIAL
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
https://www.readbyqxmd.com/read/29485925/balanced-crystalloids-versus-saline-in-critically-ill-adults
#17
RANDOMIZED CONTROLLED TRIAL
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
https://www.readbyqxmd.com/read/29438980/trimethoprim-use-for-urinary-tract-infection-and-risk-of-adverse-outcomes-in-older-patients-cohort-study
#18
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
https://www.readbyqxmd.com/read/29429375/mechanical-fractionation-of-tissues-using-microsecond-long-hifu-pulses-on-a-clinical-mr-hifu-system
#19
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 focussed ultrasound (HIFU) can non-invasively treat tumours 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 characterise 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 22, 2018: International Journal of Hyperthermia
https://www.readbyqxmd.com/read/29386302/does-routine-bioimpedance-guided-fluid-management-provide-additional-benefit-to-non-anuric-peritoneal-dialysis-patients-results-from-compass-clinical-trial
#20
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)...
March 2018: Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis
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