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Renal function reserve

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https://www.readbyqxmd.com/read/29148041/fscn1-predicts-survival-and-is-regulated-by-a-pi3k-dependent-mechanism-in-renal-cell-carcinoma
#1
Mengping Zhang, Zhijian Zhao, Xiaolu Duan, Ping Chen, Zhenwei Peng, Huijuan Qiu
While overexpression of FSCN1 is reported in several cancers, the prognostic significance of FSCN1 in renal cell carcinoma (RCC) and the molecular mechanisms involved remain largely unclear. We retrospectively enrolled 194 patients with non-metastatic clear-cell RCC undergoing nephrectomy in our center between 2008 and 2011. FSCN1 expression was assessed by immunohistochemical staining and its association with clinicopathologic features and survival were evaluated. Functional effects of a modulated FSCN1 expression were analyzed with regard to invasion in RCC cell lines and metastasis in vivo...
November 17, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29143318/calcineurin-inhibitor-induced-complement-system-activation-via-erk1-2-signalling-is-inhibited-by-socs-3-in-human-renal-tubule-cells
#2
Beatrix Loeschenberger, Lea Niess, Reinhard Würzner, Hubert Schwelberger, Iris E Eder, Martin Puhr, Julia Guenther, Jakob Troppmair, Michael Rudnicki, Hannes Neuwirt
One factor that significantly contributes to renal allograft loss is chronic calcineurin inhibitor (CNI) nephrotoxicity (CIN). Among other factors, the complement (C-) system has been proposed to be involved CIN development. Hence, we investigated the impact of CNIs on intracellular signalling and the effects on the C-system in human renal tubule cells. In a qPCR array, CNI treatment upregulated C-factors and downregulated SOCS-3 and the complement inhibitors CD46 and CD55. Additionally, ERK1/-2 was required for these regulations...
November 15, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29134648/pharmacokinetics-pharmacodynamics-and-proposed-dosing-of-the-oral-jak1-and-jak2-inhibitor-baricitinib-in-pediatric-and-young-adult-candle-and-savi-patients
#3
Hanna Kim, Kristina M Brooks, Cheng Cai Tang, Paul Wakim, Mary Blake, Stephen R Brooks, Gina A Montealegre Sanchez, Adriana A de Jesus, Yan Huang, Wanxia Li Tsai, Massimo Gadina, Apurva Prakash, Jonathan Marcus Janes, Xin Zhang, William L Macias, Parag Kumar, Raphaela Goldbach-Mansky
Population pharmacokinetic (popPK) modeling was used to characterize the PK profile of the oral janus kinase (JAK)1/JAK2 inhibitor, baricitinib, in 18 patients with Mendelian interferonopathies who are enrolled in a compassionate use program. Patients received doses between 0.1 to 17 mg per day. Covariates of weight and renal function significantly influenced volume-of-distribution and clearance respectively. The half-life of baricitinib in patients less than 40kg was substantially shorter than in adult populations, requiring the need for dosing up to 4 times daily...
November 14, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29131259/microrna-21-functions-as-an-oncogene-and-promotes-cell-proliferation-and-invasion-via-timp3-in-renal-cancer
#4
J Chen, Y Gu, W Shen
OBJECTIVE: Renal cell carcinoma (RCC) displays an increasing incidence and mortality rate worldwide in recent years. More and more evidence identified microRNAs function as positive or negative regulatory factors in many cancers, but the role of miR-21 in RCC remains unclear. PATIENTS AND METHODS: Relative expression levels of miR-21 in human RCC tissue samples and RCC-derived cell lines were measured using quantitative real-time Polymerase Chain Reaction (PCR)...
October 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29127736/liver-x-receptor-activation-inhibits-sglt2-mediated-glucose-transport-in-human-renal-proximal-tubular-cells
#5
Pattira Chonlaket, Teerasak Wongwan, Sunhapas Soodvilai
Liver X receptors (LXRs) are members of a nuclear receptor family consisting of two isoforms, LXR-α and LXR-β. They play a major role in energy metabolism including lipid and glucose metabolism. Recent studies reported LXRs regulate plasma glucose although the mechanism is still uncertain. The present study investigated whether LXR activation regulates sodium glucose cotransporter2 (SGLT2) in human renal proximal tubular cells. LXR agonists, T0901317 and GW3965, inhibited SGLT2-mediated glucose uptake in concentration-dependent manners...
November 11, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/29116680/emergency-department-utilization-among-kidney-transplant-recipients-in-the-united-states
#6
Brendan P Lovasik, Rebecca Zhang, Jason M Hockenberry, Justin D Schrager, Stephen O Pastan, Andrew B Adams, Sumit Mohan, Christian P Larsen, Rachel E Patzer
Patients with End Stage Renal Disease (ESRD) use the emergency department (ED) at a 6-fold higher rate than U.S. adults. No national studies have described ED utilization rates among kidney transplant (KTx) recipients, and the factors associated with higher ED utilization. We examined a cohort of 132,725 adult KTx recipients in the United States Renal Data System (2005-2013). ED visits, hospitalization, and outpatient nephrology visits were obtained from Medicare claims databases. Nearly half (46.1%) of KTx recipients had at least one ED visit (1...
November 8, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/29115052/dose-selection-based-on-modeling-and-simulation-for-rivipansel-in-pediatric-patients-aged-6-to-11-years-with-sickle-cell-disease
#7
Brinda K Tammara, Lutz O Harnisch
This modeling and simulation exercise aimed to provide dosing recommendations for rivipansel phase 3 studies in children aged 6 to 11 years with sickle cell disease (SCD). Pharmacokinetic data from 109 patients aged 12 to 51 years who received rivipansel (2-40 mg/kg) in previous studies (3 phase 1, one phase 2) were integrated to build a 3-compartmental simulation model. Renal clearance simulations across the age range accounted for renal function development and postulated hyperfiltration in SCD. Simulated demographic distributions for the pediatric SCD population were used to predict concentration-time profiles from 3 dosing regimens, which were then compared against efficacious average steady-state concentrations observed in phase 2...
November 8, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/29111576/oxidative-stress-induces-renal-failure-a-review-of-possible-molecular-pathways
#8
Habib Yaribeygi, Farin Rashid Farrokhi, Ramin Rezaee, Amirhossein Sahebkar
BACKGROUND: It has been reported that oxidative stress has a pivotal role in many disorders such as chronic kidney diseases. Free radicals can directly attack cellular elements, trigger intracellular signaling pathways or induce systemic responses leading to renal damages. In the current review, we evaluated the literature focusing on the main recognized effects of oxidative stress on the pathophysiology of chronic renal disorders. METHODS: We searched the PubMed-Medline and Scopus databases by using the following key words: oxidative stress, kidney, chronic kidney diseases, and free radicals and found about 200 related articles...
November 7, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29108104/renal-function-after-intravitreal-administration-of-vascular-endothelial-growth-factor-inhibitors-in-patients-with-diabetes-and-chronic-kidney-disease
#9
Yusuke Kameda, Tetsuya Babazono, Yasuko Uchigata, Shigehiko Kitano
This study aimed to determine whether intravitreal administration of vascular endothelial growth factor inhibitors is associated with deterioration of renal function, as seen with systemic administration, in patients with diabetes and chronic kidney disease. Estimated glomerular filtration rates before and after 160 intravitreal injections of vascular endothelial growth factor inhibitors (aflibercept, bevacizumab, or ranibizumab) were compared in 69 patients with diabetes and with a baseline estimated glomerular filtration rate <60 mL/min/1...
November 6, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/29105751/real-life-use-of-neurohormonal-antagonists-and-loop-diuretics-in-chronic-heart-failure-analysis-of-serial-biomarker-measurements-and-clinical-outcome
#10
Milos Brankovic, K Martijn Akkerhuis, Nick van Boven, Olivier Manintveld, Tjeerd Germans, Jasper Brugts, Kadir Caliskan, Victor Umans, Alina Constantinescu, Isabella Kardys
We determined the temporal effects of neurohormonal antagonists and loop diuretics on serially assessed (3-monthly) cardio-renal biomarkers, functional status, and clinical outcomes in 250 patients with chronic heart failure (CHF) with reduced ejection fraction. In blood, we measured NT-proBNP, troponin T, C-reactive protein, creatinine, cystatin C; in urine, N-acetyl-beta-d-glucosaminidase and kidney-injury-molecule-1. ACE-inhibitors/ARB were inversely associated with cardiac impairment, inflammation and renal tubular damage, but not with glomerular dysfunction...
November 6, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29095517/jekyll-and-hyde-of-chemotherapy-treatment-method-for-patient-specific-dosing-of-chemotherapy-medications
#11
Dean Tatlow
Currently chemotherapy dosing is determined by a patient's weight, height and renal function. Dosing chemotherapy based on these parameters is generally effective, assuming all other physiological conditions are normal. In hypoalbuminemia patients a decrease in albumin often results in more severe side-effects, since this may lead to higher chemotherapy free drug levels. A new method to dose chemotherapy based on a patients albumin will maintain the same effective free drug levels as in patients with normal albumin...
November 2, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29094471/antifibrillatory-effects-of-renal-denervation-on-ventricular-fibrillation-in-a-canine-model-of-pacing-induced-heart-failure
#12
Qingzhi Luo, Qi Jin, Ning Zhang, Shangwei Huang, Yanxin Han, Changjian Lin, Tianyou Ling, Kang Chen, Wenqi Pan, Liqun Wu
This study investigated the effects of renal denervation (RDN) on vulnerability to ventricular fibrillation (VF) and ventricular electrical properties in a canine model of pacing-induced heart failure (HF). Eighteen beagles were divided into the following three groups: control (n = 6), HF (n = 6) and HF+RDN (n = 6). HF was induced by rapid right ventricular pacing. RDN was performed simultaneously with the pacemaker implantation in the HF+RDN group. A 64-unipolar basket catheter was used to perform global endocardial mapping of the left ventricle...
November 2, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/29080224/safety-tolerability-and-pharmacokinetics-of-l-ornithine-phenylacetate-in-patients-with-acute-liver-injury-failure-and-hyperammonemia
#13
R Todd Stravitz, Michelle Gottfried, Valerie Durkalski, Robert J Fontana, A James Hanje, David Koch, Bilal Hameed, Daniel Ganger, Ram M Subramanian, Stan Bukofzer, William R Ravis, Kristen Clasen, Averell Sherker, Lanna Little, William M Lee
Cerebral edema remains a significant cause of morbidity and mortality in patients with acute liver failure (ALF) and has been linked to elevated blood ammonia levels. L-ornithine phenylacetate (OPA) may decrease ammonia by promoting its renal excretion as phenylacetylglutamine (PAGN), decreasing the risk of cerebral edema. We evaluated the safety, tolerability, and pharmacokinetics of OPA in patients with ALF and acute liver injury (ALI), including those with renal failure. Forty-seven patients with ALI/ALF and ammonia ≥60µM were enrolled...
October 28, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29072806/strategies-for-success-a-multi-institutional-study-on-robotic-partial-nephrectomy-for-complex-renal-lesions
#14
D B Hennessey, G Wei, D Moon, N Kinnear, D M Bolton, N Lawrentschuk, Y K Chan
OBJECTIVE: Due to their size, location and proximity to the hilum, some complex renal tumours may preclude a minimally invasive approach to nephron sparing surgery. We describe our technique, illustrated with images and videos, of robotic partial nephrectomy for challenging renal tumours. PATIENTS AND METHODS: A study of 249 patients who underwent robotic partial nephrectomy (RPN) in multiple institutions was performed. Patients were identified using prospective RPN databases...
October 26, 2017: BJU International
https://www.readbyqxmd.com/read/29068795/the-role-of-renal-response-to-amino-acid-infusion-and-oral-protein-load-in-normal-kidneys-and-kidney-with-acute-and-chronic-disease
#15
Francis B Gabbai
PURPOSE OF REVIEW: High protein intake and hyperfiltration have been a focus of major interest as potential mechanism(s) of progression of renal disease. This review will examine: the renal response to a protein meal or amino acid infusion and its use to test the renal functional reserve (RFR); new methods to evaluate RFR; the use of RFR in various pathophysiologic conditions. RECENT FINDINGS: The renal response to protein/amino acid infusion involves several mechanisms, including nitric oxide, insulin, glucagon, arginine vasopressin, urea, the renal N-Methyl-D-Aspartate Glutamate receptor and modulation of the activity of the tubuloglomerular feedback system...
October 23, 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/29064576/molecular-characterization-of-hepatitis-c-virus-in-end-stage-renal-disease-patients-under-hemodialysis
#16
Rafael Alves da Silva, Jardelina de Souza Todão, Fernando Luiz Kamitani, Antonio Eduardo Benedito Silva, Roberto José de Carvalho-Filho, Maria Lucia Cardoso Gomes Ferraz, Isabel Maria Vicente Guedes de Carvalho
New direct-acting antiviral (DAA) agents are in development or already approved for the treatment of chronic hepatitis C virus (HCV) infection. The effectiveness of these drugs is related to the previous existence of resistant variants. Certain clinical conditions can allow changes in immunological characteristics of the host and even modify genetic features of viral populations. The aim of this study was to perform HCV molecular characterization from samples of end-stage renal disease patients on hemodialysis (ESRD-HD)...
October 24, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/29064133/-double-carbapenem-and-oral-fosfomycin-for-the-treatment-of-complicated-urinary-tract-infections-caused-by-blandm-harboring-enterobacteriaceae-in-kidney-transplantation
#17
Rossana Rosa, Susan D Rudin, Laura J Rojas, Andrea M Hujer, Armando Perez-Cardona, Federico Perez, Robert A Bonomo, Octavio Martinez, Lilian M Abbo, Jose F Camargo
Infections with carbapenemase-producing carbapenem-resistant Enterobacteriaceae represent an emergent problem worldwide. Treatment of infections caused by New Delhi metallo-beta-lactamase (NDM)-harboring Enterobacteriaceae is particularly challenging as it frequently involves the use of nephrotoxic agents, which is problematic in kidney transplant recipients and non-renal transplants with marginal kidney function. We present two cases of urinary tract infections caused by NDM-harboring Enterobacteriaceae successfully treated with a combination of "double carbapenem" and oral fosfomycin...
October 24, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/29052906/evaluation-of-adherence-and-tolerability-of-prolonged-release-tacrolimus-advagraf-%C3%A2-in-kidney-transplant-patients-in-germany-a-multicenter-non-interventional-study
#18
Lukas J Lehner, Petra Reinke, Jan Hörstrup, Thomas Rath, Barbara Suwelack, Bernhard K Krämer, Klemens Budde, Bernhard Banas
This study assessed adherence to prolonged-release tacrolimus (PR-T)-based immunosuppression during routine maintenance of renal transplant recipients in Germany. Patients had received PR-T for ≥1 month at inclusion. Data were collected during four visits (V): baseline (V1), 6 (V2), 12 (V3) and 18 (V4) months. Composite primary endpoint: non-adherence at V4, defined as self-reported non-adherence on the Basel Assessment of Adherence with Immunosuppressive Medication Scale (BAASIS©), investigator-rated non-adherence, and/or V4 tacrolimus trough level outside a pre-defined range...
October 20, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/29044509/comprehensive-transcriptome-analysis-of-fluid-shear-stress-altered-gene-expression-in-renal-epithelial-cells
#19
Steven J Kunnen, Tareq B Malas, Cornelis M Semeins, Astrid D Bakker, Dorien J M Peters
Renal epithelial cells are exposed to mechanical forces due to flow-induced shear stress within the nephrons. Shear stress is altered in renal diseases caused by tubular dilation, obstruction and hyperfiltration, which occur to compensate for lost nephrons. Fundamental in regulation of shear stress are primary cilia and other mechano-sensors, and defects in cilia formation and function have profound effects on development and physiology of kidneys and other organs. We applied RNA sequencing to get a comprehensive overview of fluid-shear regulated genes and pathways in renal epithelial cells...
October 16, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29031353/regulation-of-acid-base-balance-in-chronic-kidney-disease
#20
REVIEW
Glenn T Nagami, L Lee Hamm
The kidneys play a major role in the regulation of acid-base balance by reabsorbing bicarbonate filtered by the glomeruli and excreting titratable acids and ammonia into the urine. In CKD, with declining kidney function, acid retention and metabolic acidosis occur, but the extent of acid retention depends not only on the degree of kidney impairment but also on the dietary acid load. Acid retention can occur even when the serum bicarbonate level is apparently normal. With reduced kidney function, acid transport processes in the surviving nephrons are augmented but as disease progresses ammonia excretion and, in some individuals, the ability to reabsorb bicarbonate falls, whereas titratable acid excretion is preserved until kidney function is severely impaired...
September 2017: Advances in Chronic Kidney Disease
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