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Augmented renal clearance

T M Tomasa Irriguible
No abstract text is available yet for this article.
March 15, 2018: Medicina Intensiva
Peng Wu, Zhong-Xiuzi Gao, Xin-Peng Duan, Xiao-Tong Su, Ming-Xiao Wang, Dao-Hong Lin, Ruimin Gu, Wen-Hui Wang
AT2R (AngII [angiotensin II] type 2 receptor) is expressed in the distal nephrons. The aim of the present study is to examine whether AT2R regulates NCC (Na-Cl cotransporter) and Kir4.1 of the distal convoluted tubule. AngII inhibited the basolateral 40 pS K channel (a Kir4.1/5.1 heterotetramer) in the distal convoluted tubule treated with losartan but not with PD123319. AT2R agonist also inhibits the K channel, indicating that AT2R was involved in tonic regulation of Kir4.1. The infusion of PD123319 stimulated the expression of tNCC (total NCC) and pNCC (phosphorylated NCC; Thr53 ) by a time-dependent way with the peak at 4 days...
February 26, 2018: Hypertension
Rajbharan Yadav, Kate E Rogers, Phillip J Bergen, Jürgen B Bulitta, Carl M J Kirkpatrick, Steven C Wallis, David L Paterson, Roger L Nation, Jeffrey Lipman, Jason A Roberts, Cornelia B Landersdorfer
Augmented renal clearance (ARC) in critically-ill patients can result in suboptimal drug exposures and treatment failure. Combination dosage regimens accounting for ARC have never been optimized and evaluated against Pseudomonas aeruginosa using the hollow-fiber infection model (HFIM). Using a P. aeruginosa isolate from a critically-ill patient and static concentration time-kill experiments (SCTK), we studied clinically relevant piperacillin and tobramycin concentrations, alone and in combinations, at two inocula (105...
February 20, 2018: Antimicrobial Agents and Chemotherapy
Idoia Bilbao-Meseguer, Alicia Rodríguez-Gascón, Helena Barrasa, Arantxazu Isla, María Ángeles Solinís
BACKGROUND: Traditionally, renal function in critically ill patients has been assessed to identify renal dysfunction, and dose adjustment is generally accepted in such a context. Nevertheless, augmented renal clearance (ARC) is a less well-studied phenomenon that could lead to faster elimination of drugs, resulting in subtherapeutic concentrations and poorer clinical outcomes when standard dosage guidelines are followed. OBJECTIVE: The aim of this systematic review was to gather and summarise all the available evidence on ARC in critically ill patients, including its definition, underlying mechanisms, epidemiology, diagnosis and impact on both drug pharmacokinetics and clinical outcomes...
February 13, 2018: Clinical Pharmacokinetics
Claire Dahyot-Fizelier, Sandrine Marchand, Jeffrey Lipman
No abstract text is available yet for this article.
February 2018: Anaesthesia, Critical Care & Pain Medicine
D Tsai, A A Udy, P C Stewart, S Gourley, N M Morick, J Lipman, J A Roberts
Augmented renal clearance (ARC) refers to the enhanced renal excretion of circulating solute commonly demonstrated in numerous critically ill subgroups. This study aimed to describe the prevalence of ARC in critically ill Indigenous Australian patients and explore the accuracy of commonly employed mathematical estimates of glomerular filtration. We completed a single-centre, prospective, observational study in the intensive care unit (ICU), Alice Springs Hospital, Central Australia. Participants were critically ill adult Indigenous and non-Indigenous Australian patients with a urinary catheter in situ...
January 2018: Anaesthesia and Intensive Care
Shihui Fu, Ping Ping, Fengqi Wang, Leiming Luo
As a family of hormones with pleiotropic effects, natriuretic peptide (NP) system includes atrial NP (ANP), B-type NP (BNP), C-type NP (CNP), dendroaspis NP and urodilatin, with NP receptor-A (guanylate cyclase-A), NP receptor-B (guanylate cyclase-B) and NP receptor-C (clearance receptor). These peptides are genetically distinct, but structurally and functionally related for regulating circulatory homeostasis in vertebrates. In humans, ANP and BNP are encoded by NP precursor A (NPPA) and NPPB genes on chromosome 1, whereas CNP is encoded by NPPC on chromosome 2...
2018: Journal of Biological Engineering
Ming-Xiao Wang, Catherina A Cuevas, Xiao-Tong Su, Peng Wu, Zhong-Xiuzi Gao, Dao-Hong Lin, James A McCormick, Chao-Ling Yang, Wen-Hui Wang, David H Ellison
Kir4.1 in the distal convoluted tubule plays a key role in sensing plasma potassium and in modulating the thiazide-sensitive sodium-chloride cotransporter (NCC). Here we tested whether dietary potassium intake modulates Kir4.1 and whether this is essential for mediating the effect of potassium diet on NCC. High potassium intake inhibited the basolateral 40 pS potassium channel (a Kir4.1/5.1 heterotetramer) in the distal convoluted tubule, decreased basolateral potassium conductance, and depolarized the distal convoluted tubule membrane in Kcnj10flox/flox mice, herein referred to as control mice...
January 6, 2018: Kidney International
Trung N Le, Brian W Blakley
BACKGROUND: Characterization of the blood labyrinth barrier (BLB) is extremely important to determine whether the BLB can be manipulated pharmacologically. However, experiments to investigate the BLB are technically difficult to perform. In this report, we demonstrated a unique method of controlling the BLB, and established the pharmacokinetics of gentamicin in perilymph, cerebrospinal fluid (CSF) and blood with and without mannitol. STUDY DESIGN: Controlled animal research project...
December 11, 2017: Journal of Otolaryngology—Head & Neck Surgery
Kiyotaka Mukai, Yuhichi Kuda, Toshishige Shibamoto, Mamoru Tanida, Yasutaka Kurata, Hitoshi Yokoyama
We determined the renal responses to anaphylaxis and the effects of a nitric oxide synthesis inhibitor, L-NAME, in anesthetized rats and isolated perfused rat kidneys. After the ovalbumin antigen injection, the sensitized rats showed transient and substantial decreases in mean blood pressure and renal blood flow and an increase in renal vascular resistance. Creatinine clearance, a measure of renal function, decreased to 53% baseline at 2 h after antigen. L-NAME pretreatment significantly enhanced the antigen-induced renal vasoconstriction and renal dysfunction...
December 5, 2017: Journal of Physiological Sciences: JPS
Cédric Carrié, Laurent Petit, Nicolas d'Houdain, Noemie Sauvage, Vincent Cottenceau, Melanie Lafitte, Cecile Foumenteze, Quentin Hisz, Deborah Menu, Rachel Legeron, Dominique Breilh, Francois Sztark
This study assessed whether augmented renal clearance (ARC) impacts negatively on antibiotic concentrations and clinical outcomes in patients treated by high-dose β-lactams administered continuously. Over a 9-month period, all critically ill patients without renal impairment treated by one of the monitored β-lactams for a documented infection were eligible. During the first 3 days of antibiotic therapy, every patient underwent 24-h CLCr measurements and therapeutic drug monitoring. The main outcome was the rate of β-lactam underdosing, defined as a free drug concentration <4 × MIC of the known pathogen...
November 24, 2017: International Journal of Antimicrobial Agents
Allison Oswalt, Anny-Claude Joseph, Adam Sima, Lisa Kurczewski
BACKGROUND: Vancomycin is a glycopeptide antibiotic that is primarily cleared by renal elimination. Patients with acute brain injury often exhibit augmented renal clearance which has been associated with subtherapeutic vancomycin concentrations. OBJECTIVE: To determine whether population pharmacokinetics accurately predict vancomycin empiric dose frequency in patients with acute brain injury. METHODS: This was a single-center, retrospective cohort study conducted following institutional review board approval at Virginia Commonwealth University Health System...
January 1, 2017: Journal of Pharmacy Practice
Janelle O Poyant, Robert Albright, Jeremy Clain, Govind Pandompatam, Erin F Barreto
BACKGROUND: Butalbital is a small molecule (approximately 220 Da), with 26% protein binding, a 0.8 L/kg volume of distribution, and is eliminated nearly 80% unchanged in the urine. Although hemodialysis has been used to treat overdoses of other barbiturates, the extracorporeal clearance of butalbital is unknown. The objective of this case is to describe the use of extracorporeal therapy to augment elimination of butalbital after an overdose of aspirin 325 mg-butalbital 50 mg-caffeine 40 mg with codeine 30 mg (Fiorinal with Codeine)...
November 10, 2017: Clinical Toxicology
Katie Elder, David M Hill, William L Hickerson
OBJECTIVE: To characterize the pharmacokinetics of vancomycin dosing in thermal or inhalation injury as they relate to percent total body surface area burn (TBSA) and days since injury (DSI). METHODS: This retrospective 3-year study included patients with thermal or inhalation injury receiving vancomycin. Patient demographics and course data were collected using the institution's electronic medical record. RESULTS: Six hundred and fifty-four patients were included in the study; 124 remained after exclusion...
October 30, 2017: Burns: Journal of the International Society for Burn Injuries
Keith A Rodvold, William W Hope, Sara E Boyd
Bronchoalveolar lavage (BAL) and microdialysis have become the most reliable and relevant methods for measuring lung concentrations of antibiotics, with the majority of BAL studies involving either healthy adult subjects or patients undergoing diagnostic bronchoscopy. Emphasis on the amount of drug that reaches the site of infection is increasingly recognized as necessary to determine whether a dose selection will translate to good clinical outcomes in the treatment of patients with pneumonia. Observed concentrations and/or parameters of exposure (e...
October 2017: Current Opinion in Pharmacology
Senthil Natesan, Manjunath P Pai, Thomas P Lodise
Background: Optimization of the antibiotics for patients with infections due to MDR Pseudomonas aeruginosa (MDR-PA) often requires consideration of alternate dose and infusion times that can be influenced by renal function. Objectives: We sought to identify ceftolozane/tazobactam dosing schemes that optimized the probability of target attainment (PTA) against infections due to MDR-PA with ceftolozane/tazobactam MICs between 4 and 32 mg/L across different categories of renal function...
October 1, 2017: Journal of Antimicrobial Chemotherapy
Jeppe B Rosenbæk, Bodil G Hornstrup, Andreas N Jørgensen, Jesper Mortensen, Erling B Pedersen, Jesper N Bech
OBJECTIVE: Nitric oxide is a key player in regulating vascular tone. Impaired endothelial nitric oxide synthesis plays an important role in hypertension. Replenishing of nitric oxide by sodium nitrite (NaNO2) has not been investigated in patients with essential hypertension (EHT). We aimed to determine the effects of NaNO2 on blood pressure (BP) and renal sodium and water regulation in patients with EHT compared with healthy control study participants (CON). METHODS: In a placebo-controlled, crossover study, we infused 240 μg NaNO2/kg/h or isotonic saline for 2 h in 14 EHT and 14 CON...
October 23, 2017: Journal of Hypertension
Lisa Ehmann, Michael Zoller, Iris K Minichmayr, Christina Scharf, Barbara Maier, Maximilian V Schmitt, Niklas Hartung, Wilhelm Huisinga, Michael Vogeser, Lorenz Frey, Johannes Zander, Charlotte Kloft
BACKGROUND: Severe bacterial infections remain a major challenge in intensive care units because of their high prevalence and mortality. Adequate antibiotic exposure has been associated with clinical success in critically ill patients. The objective of this study was to investigate the target attainment of standard meropenem dosing in a heterogeneous critically ill population, to quantify the impact of the full renal function spectrum on meropenem exposure and target attainment, and ultimately to translate the findings into a tool for practical application...
October 21, 2017: Critical Care: the Official Journal of the Critical Care Forum
Fredrik Sjövall, Abdulaziz S Alobaid, Steven C Wallis, Anders Perner, Jeffrey Lipman, Jason A Roberts
Objectives: To use a population pharmacokinetic approach to define maximally effective meropenem dosing recommendations for treatment of Acinetobacter baumannii and Pseudomonas aeruginosa infections in a large cohort of patients with septic shock. Methods: Adult patients with septic shock and conserved renal function, treated with meropenem, were eligible for inclusion. Seven blood samples were collected during a single dosing interval and meropenem concentrations were measured by a validated HPLC-MS/MS method...
January 1, 2018: Journal of Antimicrobial Chemotherapy
Juan He, Enqiang Mao, Feng Jing, Huiting Jiang, Wenyun Xu, Wanhua Yang, Erzhen Chen
OBJECTIVE: To evaluate the serum trough concentration and the pharmacokinetics/pharmacodynamics (PK/PD) of vancomycin in patients with severe acute pancreatitis (SAP), and analyze the effect of vancomycin continuous infusion for optimizing the characteristics of its PK/PD. METHODS: The inhospital patients with SAP received vancomycin treatment and admitted to emergency intensive care unit (EICU) of Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 2011 to December 2016 were enrolled...
September 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
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