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Augmented renal clearance

Michael Osthoff, Martin Siegemund, Gianmarco Balestra, Mohd Hafiz Abdul-Aziz, Jason A Roberts
Prolonged infusion of β-lactam antibiotics as either extended (over at least 2 hours) or continuous infusion is increasingly applied in intensive care units around the world in an attempt to optimise treatment with this most commonly used class of antibiotics, whose effectiveness is challenged by increasing resistance rates. The pharmacokinetics of β-lactam antibiotics in critically ill patients is profoundly altered secondary to an increased volume of distribution and the presence of altered renal function, including augmented renal clearance...
2016: Swiss Medical Weekly
Yasumasa Kawano, Shinichi Morimoto, Yoshito Izutani, Kentaro Muranishi, Hironari Kaneyama, Kota Hoshino, Takeshi Nishida, Hiroyasu Ishikura
BACKGROUND: Augmented renal clearance (ARC) of circulating solutes and drugs has been recently often reported in intensive care unit (ICU) patients. However, only few studies on ARC have been reported in Japan. The aims of this pilot study were to determine the prevalence and risk factors for ARC in Japanese ICU patients with normal serum creatinine levels and to evaluate the association between ARC and estimated glomerular filtration rate (eGFR) calculated using the Japanese equation...
2016: Journal of Intensive Care
Keita Hirai, Hidetoshi Ishii, Takayuki Shimoshikiryo, Tatsuki Shimomura, Daiki Tsuji, Kazuyuki Inoue, Toshihiko Kadoiri, Kunihiko Itoh
BACKGROUND: Augmented renal clearance (ARC) has frequently been observed in critically ill patients. The risk factors for ARC in patients, including those in the general ward, and their influences on vancomycin (VCM) treatment remain unclear. The aims of this study were to investigate the risk factors for ARC and to evaluate the influence of ARC on the pharmacokinetic parameters of VCM. METHODS: This study included a total of 292 patients with VCM treatment who had normal serum creatinine concentrations...
September 23, 2016: Therapeutic Drug Monitoring
Zhanna Kobalava
The burden of cardiovascular diseases (CVD) in general and heart failure (HF) in particular continues to increase worldwide. CVD are major contributors to death and morbidity and recognized as important drivers of healthcare expenditure. Chronic overactivity of the renin-angiotensin-aldosterone system (RAAS) plays a key role in human hypertension and HF pathophysiology. RAAS is fundamental in the overall regulation of cardiovascular homeostasis through the actions of hormones, which regulate vascular tone, and specifically blood pressure through vasoconstriction and renal sodium and water retention...
September 2016: Journal of Hypertension
Jason M Cota, Alireza FakhriRavari, Matthew P Rowan, Kevin K Chung, Clinton K Murray, Kevin S Akers
PURPOSE: Despite advances in the care of patients with severe burn injury, infection-related morbidity and mortality remain high and can potentially be reduced with antimicrobial dosing optimized for the infecting pathogen. However, anti-infective dose selection is difficult because of the highly abnormal physiologic features of burn patients, which can greatly affect the pharmacokinetic (PK) disposition of these agents. We review published PK data from burn patients and offer evidence-based dosing recommendations for antimicrobial agents in burn-injured patients...
September 2016: Clinical Therapeutics
Stacey Hokke, Victor G Puelles, James A Armitage, Karen Fong, John F Bertram, Luise A Cullen-McEwen
Increasing consumption of a high fat 'Western' diet has led to a growing number of pregnancies complicated by maternal obesity. Maternal overnutrition and obesity have health implications for offspring, yet little is known about their effects on offspring kidney development and renal function. Female C57Bl6 mice were fed a high fat diet (HFD, 21% fat) or matched normal fat diet (NFD, 6% fat) for 6 weeks prior to pregnancy and throughout gestation and lactation. HFD dams were overweight and glucose intolerant prior to mating but not in late gestation...
2016: PloS One
A Jeong Kim, Ju-Yeun Lee, Soo An Choi, Wan Gyoon Shin
Although vancomycin concentrations in neurosurgical patients tend to be lower following standard dosing compared with other patient populations, factors influencing vancomycin pharmacokinetics in neurosurgical patients are poorly understood. In this study, pharmacokinetic (PK) parameters in neurosurgical and non-neurosurgical patients were compared. Furthermore, factors influencing vancomycin PK alterations, including those known to augment renal clearance, were determined. Routine therapeutic drug monitoring data from neurosurgical and non-neurosurgical patients were retrospectively collected...
October 2016: International Journal of Antimicrobial Agents
Jeffrey F Barletta, Alicia J Mangram, Marilyn Byrne, Alexzandra K Hollingworth, Joseph F Sucher, Francis R Ali-Osman, Gina R Shirah, James K Dzandu
BACKGROUND: An accurate assessment of creatinine clearance (CrCl) is essential when dosing medications in critically ill trauma patients. Trauma patients are known to experience augmented renal clearance (i.e., CrCl ≥130 ml/min) and the use of CrCl estimations may be inaccurate leading to under/over dosing of medications. As such, our level I trauma center began using measured CrCl from timed urine collections to better assess CrCl. This study sought to determine the prevalence of augmented renal clearance and the accuracy of calculated CrCl in critically ill trauma patients...
August 16, 2016: Journal of Trauma and Acute Care Surgery
Michael F Papacostas, Margaret Hoge, Michel Baum, Samuel Z Davila
OBJECTIVE: To report a case of salicylate toxicity treated with continuous venovenous hemodiafiltration (CVVHDF) and review the literature regarding the use of continuous renal replacement therapy (CRRT) for salicylate toxicity. CASE: A 16-year-old male presented after ingesting 1901 mg/kg of enteric coated aspirin. Salicylate level was 92 mg/dl 4 h after ingestion. Sequele included seizure, acute kidney injury, pulmonary edema, and prolonged QTc. He received 5...
September 2016: Heart & Lung: the Journal of Critical Care
Andrew Udy, Paul Jarrett, Melissa Lassig-Smith, Janine Stuart, Therese Starr, Rachel Dunlop, Renae Deans, Jason A Roberts, Siva Senthuran, Rob Boots, Kavita Bisht, Andrew C Bulmer, Jeffrey Lipman
Augmented renal clearance (ARC) is being increasingly described in neurocritical care practice. The mechanisms driving this phenomenon are largely unknown. The aim of this project was therefore to explore changes in renal function, cardiac output (CO), and atrial natriuretic peptide (ANP) concentrations in patients with isolated traumatic brain injury (TBI). This prospective observational cohort study was conducted in a tertiary level university affiliated ICU. Patients with normal plasma creatinine concentrations (< 120 μmol/L) at admission and no history of chronic kidney disease, admitted with isolated TBI, were eligible for enrolment...
June 14, 2016: Journal of Neurotrauma
María Julia Severin, María Herminia Hazelhoff, Romina Paula Bulacio, María Eugenia Mamprin, Anabel Brandoni, Adriana Mónica Torres
AIM: Furosemide is a loop diuretic. Different authors demonstrated that continuous administration of furosemide modulates the expression of organic anion transporters. This study was undertaken to simultaneously evaluate the effects of furosemide pretreatment on organic anion transporter 1 (Oat1) and multidrug resistance protein 2 (Mrp2) renal expressions, on p-aminohippurate (PAH) pharmacokinetics and on renal and urinary PAH levels in rats. METHODS: Male Wistar rats were treated with furosemide (6 mg/100 g b...
June 10, 2016: Nephrology
David W Boulton
Saxagliptin is an orally active, highly potent, selective and competitive dipeptidyl peptidase (DPP)-4 inhibitor used in the treatment of type 2 diabetes mellitus at doses of 2.5 or 5 mg once daily. DPP-4 is responsible for degrading the intestinally derived hormones glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide (GIP). Inhibition of DPP-4 increases intact plasma GLP-1 and GIP concentrations, augmenting glucose-dependent insulin secretion. Both saxagliptin and its major active metabolite, 5-hydroxy saxagliptin, demonstrate high degrees of selectivity for DPP-4 compared with other DPP enzymes...
June 9, 2016: Clinical Pharmacokinetics
Antonio Torres, Johan Willem Mouton, Federico Pea
Hospital-acquired pneumonia (HAP) and community-acquired pneumonia (CAP) are among the most common infections treated in the hospital setting, and together they place a significant burden on healthcare systems. Successful management of HAP and CAP depends on rapid initiation of empirical antibiotic therapy with broad-spectrum antibiotics. Ceftobiprole is a new-generation, broad-spectrum cephalosporin antibiotic for the treatment of HAP (excluding ventilator-associated pneumonia) and CAP. It displays potent in vitro activity against a broad range of pathogens important in pneumonia...
June 7, 2016: Clinical Pharmacokinetics
Peter Declercq, Stefaan Nijs, André DʼHoore, Eric Van Wijngaerden, Albert Wolthuis, Anthony de Buck van Overstraeten, Joost Wauters, Isabel Spriet
BACKGROUND: Augmented renal clearance refers to increased renal elimination of circulating solutes as compared with normal baseline and could lead to underexposure of frequently used renally eliminated antimicrobials. The primary objective was to assess the prevalence of augmented renal clearance in an adult non-critically ill surgery population. Besides, predictors for augmented renal clearance were investigated. A prospective observational single-center point prevalence study was conducted...
September 2016: Journal of Trauma and Acute Care Surgery
Yang Chu, Yifan Luo, Lianyue Qu, Chunyang Zhao, Mingyan Jiang
CONTEXT: Augmented renal clearance (ARC) refers to enhanced renal elimination of circulating solute, and has attracted wide attention in recent years. OBJECTIVE: This study evaluates the effects of ARC on serum vancomycin concentration in patients administered vancomycin. MATERIALS AND METHODS: This was a retrospective study in patients receiving vancomycin treatment at a dose of 1000 mg in every 12 h and undergoing serum monitoring admitted over a 2-year period (May 2013 to May 2015), in order to estimate the influence of ARC on serum vancomycin concentration...
June 1, 2016: Pharmaceutical Biology
Toshinori Hirai, Toshimi Kimura, Hirotoshi Echizen
Whether renal dysfunction influences the hypouricemic effect of febuxostat, a xanthine oxidase (XO) inhibitor, in patients with hyperuricemia due to overproduction or underexcretion of uric acid (UA) remains unclear. We aimed to address this question with a modeling and simulation approach. The pharmacokinetics (PK) of febuxostat were analyzed using data from the literature. A kinetic model of UA was retrieved from a previous human study. Renal UA clearance was estimated as a function of creatinine clearance (CLcr) but non-renal UA clearance was assumed constant...
2016: Biological & Pharmaceutical Bulletin
Yuichi Uwai, Tatsuya Kawasaki, Tomohiro Nabekura
Lithium, which is used in the treatment of and prophylaxis for bipolar disease, inhibits glycogen synthase kinase-3β (GSK3β) by producing its phosphorylated form (p-GSK3β). GSK3β plays a role in apoptosis and some kinds of acute kidney injuries, and the formation of p-GSK3β is considered to contribute to protection against acute kidney injury. We previously reported that the sodium-phosphate cotransporter NaPi-IIa (SLC34A1) mediated the reabsorption of lithium in the rat kidney. In the present study, the phosphorylation status of GSK3β in the kidney cortex of rats administered lithium chloride and foscarnet, a typical inhibitor of NaPi-IIa, was examined using Western blotting...
June 2016: Drug Metabolism and Pharmacokinetics
Phillip J Bergen, Jürgen B Bulitta, Carl M J Kirkpatrick, Kate E Rogers, Megan J McGregor, Steven C Wallis, David L Paterson, Jeffrey Lipman, Jason A Roberts, Cornelia B Landersdorfer
BACKGROUND: Pathophysiological changes in critically ill patients can cause severely altered pharmacokinetics and widely varying antibiotic exposures. The impact of altered pharmacokinetics on bacterial killing and resistance has not been characterized in the dynamic hollow-fibre in vitro infection model (HFIM). METHODS: A clinical Pseudomonas aeruginosa isolate (piperacillin MIC 4 mg/L) was studied in the HFIM (inoculum ∼10(7) cfu/mL). Pharmacokinetic profiles of three piperacillin dosing regimens (4 g 8-, 6- and 4-hourly, 30 min intravenous infusion) as observed in critically ill patients with augmented renal clearance (ARC), normal renal function or impaired renal function (creatinine clearances of 250, 110 or 30 mL/min, respectively) were simulated over 7 days...
September 2016: Journal of Antimicrobial Chemotherapy
Keita Hirai, Setsuko Ihara, Ayumi Kinae, Kenichi Ikegaya, Masayuki Suzuki, Keiko Hirano, Kunihiko Itoh
BACKGROUND: Vancomycin (VCM) dosage optimization in the early stages of therapy is required to achieve target trough serum concentrations, particularly in critically ill patients. Augmented renal clearance (ARC), commonly characterized by an enhanced renal clearance, has been associated with subtherapeutic concentrations of antibiotics. The aim of this study was to investigate the risk factors including febrile neutropenia for both ARC and VCM clearance in Japanese pediatric patients...
June 2016: Therapeutic Drug Monitoring
Houshang Najafi, Seyed Mohammad Owji, Eskandar Kamali-Sarvestani, Seyed Mostafa Shid Moosavi
What is the central question of this study? A1 -Adenosine receptor (A1 AR) blockade before renal ischaemia aggravated kidney injury after 24 h reperfusion in several studies, whereas we previously observed a renoprotective effect of A1 AR blockade during a 4 h reperfusion period. What are the underlying mechanisms for this biphasic effect of pretreatment with an A1 AR antagonist at 4 and 24 h reperfusion? What is main finding and its importance? A1 -Adenosine receptor blockade protects the kidney against ischaemia-induced injury during the early hours of reperfusion by attenuating the reduction in renal blood flow and lowering energy expenditure, whereas its inflammatory effects gradually dominate over 24 h reperfusion to intensify kidney injury...
July 1, 2016: Experimental Physiology
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