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https://www.readbyqxmd.com/read/29761868/evaluating-the-use-of-kim-1-in-drug-development-and-research-following-fda-qualification
#1
Ru Chen, Sarmistha Sanyal, Aliza Thompson, Joachim H Ix, Kylie Haskins, Laurie Muldowney, Shashi Amur
The Biomarker Qualification Program was established at the Center for Drug Evaluation and Research (CDER), Food and Drug Administration (FDA) to expedite the integration of promising biomarkers across multiple drug development programs. The first set of biomarkers qualified in 2008 consisted of seven nonclinical safety biomarkers for the detection of acute drug-induced nephrotoxicity in rats, and included urinary kidney injury molecule-1 (KIM-1). This article discusses the use of KIM-1 in drug development and research before and after CDER's qualification of KIM-1...
May 15, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29758129/twenty-four-hour-normothermic-perfusion-of-discarded-human-kidneys-with-urine-recirculation
#2
Annemarie Weissenbacher, Letizia Lo Faro, Olga Boubriak, Maria F Soares, Ian S Roberts, James P Hunter, Daniel Voyce, Nikolay Mikov, Andrew Cook, Rutger J Ploeg, Constantin C Coussios, Peter J Friend
Transportable normothermic kidney perfusion for 24 hours or longer could enable viability assessment of marginal grafts, increased organ utilization and improved transplantation logistics. Eleven clinically-declined kidneys were perfused normothermically, six from donors after brain stem death (DBD, median cold ischemia time 33±36.9 hours) and five from donors after circulatory death (DCD, 36.2±38.3 hours): n=3 kidneys were perfused using Ringer's lactate to replace excreted urine volume, and n=8 using urine recirculation to maintain perfusate volume without fluid replenishment...
May 14, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29738843/transporter-dependent-cytotoxicity-of-antiviral-drugs-in-primary-cultures-of-human-proximal-tubular-cells
#3
Lawrence H Lash, Caroline A Lee, Clynn Wilker, Vishal Shah
The role of plasma membrane transporters in the nephrotoxicity of two antiretroviral drugs, cidofovir and tenofovir, was studied in primary cultures of human proximal tubular (hPT) cells. Cells were grown on Transwell filter inserts to maintain epithelial polarity and access to either the apical or basolateral plasma membrane. The function of relevant membrane transporters, organic anion transporter 1 and 3 (OAT1/3), P-glycoprotein (multidrug resistance protein-1; P-gp or MDR1), and organic cation transporter 2 (OCT2), was validated by measurements of apical-to-basolateral and basolateral-to-apical fluxes of furosemide, digoxin, and metformin, respectively...
May 5, 2018: Toxicology
https://www.readbyqxmd.com/read/29733821/mir-182-enhances-acute-kidney-injury-by-promoting-apoptosis-involving-the-targeting-and-regulation-of-tcf7l2-wnt-%C3%AE-catenins-pathway
#4
Huicong Li, Yali Ma, Baoping Chen, Jun Shi
Acute kidney injury (AKI)is a sudden decay in renal function leading to increasing morbidity and mortality. miR-182 has been reported to be actively involved in kidney diseases. However, the function and molecular mechanism of miR-182 in AKI still need to be elucidated. The levels of serum creatinine (SCr), blood urea nitrogen (BUN), and urine Kim-1 in I/R-induced rat AKI model were detected by a Beckman Autoanalyzer. miR-182 and transcription factor 7-like-2 (TCF7L2) mRNA expression were measured by qRT-PCR...
May 4, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29728821/moringa-oleifera-leaves-extract-protects-titanium-dioxide-nanoparticles-induced-nephrotoxicity-via-nrf2-ho-1-signaling-and-amelioration-of-oxidative-stress
#5
K H Abdou, Walaa A Moselhy, Hanaa M Mohamed, El-Shaymaa El-Nahass, Ahlam G Khalifa
The efficacy of Moringa oleifera leaf extract (MO) in alleviating nephrotoxicity induced by titanium dioxide nanoparticles (TiO2 NPs) was studied. Rats were divided into four groups. Group I received distilled water. Group II received TiO2 NPs. Group III received both TiO2 NPs suspension beside MO. Group IV received MO only. Kidney KIM-1, NF-кB TNF-α, and HSP-70 expression were significantly upregulated while both Nrf2 and HO-1were significantly downregulated in TiO2 NPs-treated rats. MO decreases expression of KIM-1, NF-кB, TNF-α, and HSP-70...
May 4, 2018: Biological Trace Element Research
https://www.readbyqxmd.com/read/29725632/urinary-biomarkers-to-identify-autosomal-dominant-polycystic-kidney-disease-patients-with-a-high-likelihood-of-disease-progression
#6
A Lianne Messchendorp, Esther Meijer, Wendy E Boertien, Gerwin E Engels, Niek F Casteleijn, Edwin M Spithoven, Monique Losekoot, Johannes G M Burgerhof, Dorien J M Peters, Ron T Gansevoort
Introduction: The variable disease course of autosomal dominant polycystic kidney disease (ADPKD) makes it important to develop biomarkers that can predict disease progression, from a patient perspective and to select patients for renoprotective treatment. We therefore investigated whether easy-to-measure urinary biomarkers are associated with disease progression and have additional value over that of conventional risk markers. Methods: At baseline, inflammatory, glomerular, and tubular damage markers were measured in 24-hour urine collections (albumin, IgG, kidney injury molecule-1 (KIM-1), N -acetyl-β-d-glucosaminidase (NAG), β2 microglobulin (β2MG), heart-type fatty acid binding protein (HFABP), macrophage migration inhibitory factor (MIF), neutrophil gelatinase-associated lipocalin (NGAL), and monocyte chemotactic protein-1 (MCP-1)...
March 2018: KI Reports
https://www.readbyqxmd.com/read/29706810/novel-renal-biomarker-evaluation-for-early-detection-of-acute-kidney-injury-after-transcatheter-aortic-valve-implantation
#7
Mani Arsalan, Ethan Ungchusri, Robert Farkas, Melissa Johnson, Rebeca J Kim, Giovanni Filardo, Benjamin D Pollock, Molly Szerlip, Michael J Mack, Elizabeth M Holper
Acute kidney injury (AKI) following transcatheter aortic valve implantation (TAVI) is associated with increased morbidity and mortality. The biomarkers neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18) are predictive of AKI after cardiac surgery, but there is little data regarding these biomarkers after TAVI. We evaluated the associations between NGAL, KIM-1, and IL-18 levels and the incidence and severity of AKI and changes in serum creatinine after TAVI...
April 2018: Proceedings of the Baylor University Medical Center
https://www.readbyqxmd.com/read/29694984/camel-milk-ameliorates-5-fluorouracil-induced-renal-injury-in-rats-targeting-mapks-nf-%C3%AE%C2%BAb-and-pi3k-akt-enos-pathways
#8
Hany H Arab, Samir A Salama, Ibrahim A Maghrabi
BACKGROUND/AIMS: The clinical utility of 5-fluorouracil (5-FU) is limited by its nephrotoxicity. Camel milk (CM) has previously displayed beneficial effects in toxicant-induced nephropathies. The current study aimed to investigate the potential of CM to attenuate 5-FU-induced nephrotoxicity in rats. METHODS: Renal tissues were studied in terms of oxidative stress, inflammation and apoptosis. The levels of renal injury markers, inflammatory cytokines along with NOX-1, Nrf-2 and HO-1 were assessed by ELISA...
April 20, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29693725/tctex-1-a-novel-interaction-partner-of-kidney-injury-molecule-1-is-required-for-efferocytosis
#9
Ola Z Ismail, Saranga Sriranganathan, Xizhong Zhang, Joseph V Bonventre, Antonis S Zervos, Lakshman Gunaratnam
Kidney injury molecule-1 (KIM-1) is a phosphatidylserine receptor that is specifically upregulated on proximal tubular epithelial cells (PTECs) during acute kidney injury and mitigates tissue damage by mediating efferocytosis (the phagocytic clearance of apoptotic cells). The signaling molecules that regulate efferocytosis in TECs are not well understood. Using a yeast two-hybrid screen, we identified the dynein light chain protein, Tctex-1, as a novel KIM-1-interacting protein. Immunoprecipitation and confocal imaging studies suggested that Tctex-1 associates with KIM-1 in cells at baseline, but, dissociates from KIM-1 within 90 min of initiation of efferocytosis...
April 25, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29693449/a-translational-model-of-chronic-kidney-disease-in-swine
#10
Alejandro R Chade, Maxx L Williams, Jason E Engel, Erika Guise, Taylor W Harvey
Animal models of chronic kidney disease (CKD) are critical for understanding its pathophysiology and for therapeutic development. The cardiovascular and renal anatomy and physiology of the pig are virtually identical to humans. This study aimed to develop a novel translational model of CKD that mimics the pathological features of CKD in humans. CKD was induced in 7 domestic pigs by bilateral renal artery stenosis and diet-induced dyslipidemia. Animals were observed for a total of 14 weeks. Renal hemodynamics and function were quantified in vivo using multi-detector CT after 6, 10, and 14 weeks of CKD...
April 25, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29693324/circulating-cytokine-profiles-and-anca-specificity-in-patients-with-anca-associated-vasculitis
#11
Alvise Berti, Roscoe Warner, Kent Johnson, Divi Cornec, Darrell Schroeder, Brian Kabat, Carol A Langford, Gary S Hoffman, Fernanado C Fervenza, Cees G M Kallenberg, Philip Seo, Robert Spiera, E William St Clair, Paul Brunetta, John H Stone, Peter A Merkel, Ulrich Specks, Paul A Monach
OBJECTIVES: To evaluate circulating cytokine profiles in patients with ANCA-associated vasculitis (AAV), classified by ANCA specificity (proteinase 3 (PR3)-ANCA versus myeloperoxidase (MPO)-ANCA) or by clinical diagnosis (granulomatosis with polyangiitis (GPA) versus microscopic polyangiitis (MPA)). METHODS: A panel of 29 cytokines was tested in 186 patients with active AAV at inclusion into the Rituximab in AAV (RAVE) trial. Cytokine concentrations were compared between groups within each classification system...
April 25, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29684554/short-term-oral-gavage-administration-of-adenine-induces-a-model-of-fibrotic-kidney-disease-in-rats
#12
Chang Z Zhu, Kelly J Doyle, Arthur L Nikkel, Lauren Olsen, Marian T Namovic, Katherine Salte, Deborah Widomski, Zhi Su, Diana L Donnelly-Roberts, Murali M Gopalakrishnan, Steve McGaraughty
INTRODUCTION: The adenine model of kidney disease typically involves dietary delivery of adenine over several weeks. This model can be variable in its disease progression and can result in significant mortality. In the current study, the amount of adenine delivered to rats was controlled by utilizing oral gavage administration over a short period in an attempt to induce robust renal pathology while addressing variability and viability of the animals. METHODS: Adenine (150 or 200 mg/kg) was administered via oral gavage for 10 consecutive days, and assessed over a total of 20 days...
April 20, 2018: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/29677080/corm-401-reduces-ischemia-reperfusion-injury-in-an-ex-vivo-renal-porcine-model-of-the-donation-after-cardiac-death
#13
Rabindra N Bhattacharjee, Mahms Richard-Mohamed, Qizhi Sun, Aaron Haig, Ghaleb Aboalsamh, Peter Barrett, Richard Mayer, Ibrahim Alhasan, Karen Pineda-Solis, Larry Jiang, Hajed Alharbi, Manujendra Saha, Eric Patterson, Alp Sener, Gediminas Cepinskas, Anthony M Jevnikar, Patrick P W Luke
BACKGROUND: Carbon monoxide (CO) inhalation protects organ by reducing inflammation and cell death during transplantation processes in animal model. However, using CO in clinical transplantation is difficult due to its delivery in a controlled manner. A manganese-containing CORM-401 has recently been synthesized which can efficiently deliver 3 molar equivalents of CO. We report the ability of this anti-inflammatory CORM-401 to reduce ischemia reperfusion injury associated with prolonged cold storage of renal allografts obtained from donation after cardiac death in a porcine model of transplantation...
April 19, 2018: Transplantation
https://www.readbyqxmd.com/read/29667662/camel-milk-attenuates-methotrexate-induced-kidney-injury-via-activation-of-pi3k-akt-enos-signaling-and-intervention-with-oxidative-aberrations
#14
Hany H Arab, Samir A Salama, Ibrahim A Maghrabi
Methotrexate (MTX) is a classical chemotherapeutic agent with nephrotoxicity as the most disturbing adverse effect. So far, its underlying molecular mechanisms, particularly PI3K/Akt/eNOS transduction, are inadequately explored. Several antioxidant modalities have been characterized to ameliorate MTX-induced renal injury. In this regard, Camel milk (CM) is a natural product with recognized antioxidant and anti-inflammatory features. Thus, the current study aimed to investigate the potential ameliorating effects of CM in MTX-induced kidney injury in rats...
April 18, 2018: Food & Function
https://www.readbyqxmd.com/read/29667173/efficacy-of-corticosteroids-in-prevention-of-acute-kidney-injury-in-neonates-undergoing-cardiac-surgery-a-randomized-controlled-trial
#15
T Jahnukainen, J Keski-Nisula, J Tainio, H Valkonen, T Pätilä, H Jalanko, P Suominen
BACKGROUND: Heart surgery requiring cardiopulmonary bypass (CPB) causes an inflammatory response which may further induce acute kidney injury (AKI). In the present randomized controlled study we evaluated whether corticosteroids can prevent CPB related AKI in neonates undergoing heart surgery. METHODS: Forty neonates were randomized to receive 2 mg/kg methylprednisolone followed by hydrocortisone infusion 0.2 mg/kg/h perioperatively with tapering doses for 5 days, or placebo administered in a similar fashion...
April 17, 2018: Acta Anaesthesiologica Scandinavica
https://www.readbyqxmd.com/read/29665669/-effects-of-intermittent-hypoxia-exposure-on-renal-tubular-epithelial-cell-injury-and-autophagy-in-rats
#16
C Wang, J Tan, B Y Chen, Q Zhang
Objective: To investigate the effects of intermittent hypoxia (IH) exposure on renal tubular epithelial cell injury and autophagy in rats. Methods: A total of 12 Sprague Dawley (SD) rats were randomly divided into two groups: normal control (NC) group and IH group, with 6 rats in each group. An IH animal model was established to observe the effects of IH on renal tubular epithelial cell damage and autophagy in rats. Microalbumin (mAlb) was detected by immunoturbidimetry. Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1(KIM-1)in urine were assessed by enzyme-linked immunosorbent assay (ELISA) test...
March 27, 2018: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/29661344/clinical-significance-of-urinary-biomarkers-in-patients-with-primary-focal-segmental-glomerulosclerosis
#17
Qingyan Zhang, Chunming Jiang, Tianfeng Tang, Hengjin Wang, Yangyang Xia, Qiuyuan Shao, Miao Zhang
BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is often accompanied with tubulointerstitial lesion. This study aimed to assess the role of urinary biomarkers in predicting tubulointerstitial lesion and treatment response in FSGS patients. METHODS: Urinary neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), N-acetyl-β-d-glucosaminidase (NAG) and retinol-binding protein (RBP) were measured in 32 FSGS patients and 22 patients with minimal change nephrotic syndrome...
April 2018: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/29608440/serum-and-urine-toxicometabolomics-following-gentamicin-induced-nephrotoxicity-in-male-sprague-dawley-rats
#18
Sung Ha Ryu, Ji Won Kim, Dahye Yoon, Suhkmann Kim, Kyu-Bong Kim
Gentamicin (GM) is an aminoglycoside antibiotic used in treatment of various types of bacterial infections, but the major adverse effect is drug-induced nephrotoxicity. This study aimed to determine biomarkers that might predict nephrotoxicity initiated by GM using serum or urinary proton nuclear magnetic resonance (1 H NMR) spectral data in male Sprague-Dawley rats. GM (0, 30, or 300 mg/kg/d) was intraperitoneally administered for 3 consecutive days. Animals were sacrificed 2 d (D2) or 8 d (D8) after last administration of GM in order to perform analysis of serum biochemistries and histopathologic examination...
April 2, 2018: Journal of Toxicology and Environmental Health. Part A
https://www.readbyqxmd.com/read/29607326/ischemic-preconditioning-promotes-autophagy-and-alleviates-renal-ischemia-reperfusion-injury
#19
Ying Xie, Jing Xiao, Chensheng Fu, Zhenxing Zhang, Zhibin Ye, Xiaoli Zhang
Autophagy is important for cellular survival during renal ischemia/reperfusion (I/R) injury. Ischemic preconditioning (IPC) has a strong renoprotective effect during renal I/R. Our study here aimed to explore the effect of IPC on autophagy during renal I/R injury. Rats were subjected to unilateral renal ischemia with or without prior IPC. Hypoxia/reoxygenation (H/R) injury was induced in HK-2 cells with or without prior hypoxic preconditioning (HPC). Autophagy and apoptosis were detected after reperfusion or reoxygenation for different time...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29603641/donor-kidney-injury-molecule-1-promotes-graft-recovery-by-regulating-systemic-necroinflammation
#20
Ji Yun Lee, Ola Z Ismail, Xizhong Zhang, Aaron Haig, Dameng Lian, Lakshman Gunaratnam
Ischemia-reperfusion injury during kidney transplantation predisposes to delayed graft function, rejection, and premature graft failure. Exacerbation of tissue damage and alloimmune responses may be explained by necroinflammation: an autoamplification loop of cell death and inflammation, which is mediated by the release of damage-associated molecular patterns (e.g. HMGB1) from necrotic cells that activate both innate and adaptive immune pathways. Kidney Injury Molecule-1 (KIM-1) is a phosphatidylserine receptor that is upregulated on injured proximal tubular epithelial cells and enables them to clear apoptotic and necrotic cells...
March 30, 2018: American Journal of Transplantation
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