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https://www.readbyqxmd.com/read/29150543/toxicokinetics-and-physiologically-based-pharmacokinetic-modeling-of-the-shellfish-toxin-domoic-acid-in-nonhuman-primates
#1
Jing Jing, Rebekah Petroff, Sara Shum, Brenda Crouthamel, Ariel R Topletz, Kimberly S Grant, Thomas M Burbacher, Nina Isoherranen
Domoic acid (DA), a neurotoxin, is produced by marine algae and has caused toxications worldwide in animals and humans. However, the toxicokinetics of DA has not been fully evaluated, and information is missing on the disposition of DA following oral exposures at doses that are considered safe for human consumption. In this study, toxicokinetics of DA were investigated in cynomolgus monkeys, following single doses of 5 µg/kg DA iv, 0.075 mg/kg DA po and 0.15 mg/kg DA po. Following iv dosing, DA had a systemic clearance of 124 ± 71 ml/hr/kg, volume of distribution at steady state of 131±71 ml/kg and elimination half-life of 1...
November 17, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29150412/clinical-benefits-of-using-inulin-clearance-and-cystatin-c-for-determining-glomerular-filtration-rate-in-hiv-1-infected-individuals-treated-with-dolutegravir
#2
Satomi Yukawa, Dai Watanabe, Tomoko Uehira, Takuma Shirasaka
INTRODUCTION: Dolutegravir may inhibit creatinine transporters in renal tubules and elevate serum creatinine levels. We investigated the usefulness of glomerular filtration rate (GFR) measured using inulin clearance (Cin), creatinine clearance (Ccr), and estimated GFR based on both serum creatinine (eGFRcre) and serum cystatin C (eGFRcys). PATIENTS & METHODS: HIV-1-infected Japanese patients with suppressed viremia and whose antiretroviral drug was switched to dolutegravir from other drugs were included (n = 108, Study 1)...
November 14, 2017: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/29149950/structural-and-functional-adaptation-of-the-remnant-kidney-after-living-kidney-donation-long-term-follow-up
#3
M Meier, J Winterhoff, L Fricke, H Lehnert, M Nitschke
OBJECTIVE: Several adjustments occur after nephrectomy (NT) in the donor's remnant kidney. We investigated kidney donors 10 years after NT and compared several parameters before and after transplantation. METHODS: A total of 42 kidney donors of the University of Luebeck's Transplant Center were scheduled for a 10-year follow-up and were offered several investigations: laboratory tests, urinalysis and kidney ultrasound examination including determination of kidney volume (KV), resistive index (RI) and pulsatility index (PI)...
November 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/29146282/-measurement-and-estimation-of-glomerular-filtration-rate
#4
Emmanuelle Vidal-Petiot, Martin Flamant
Glomerular filtration rate is the best quantitative marker of renal function. It allows diagnosis and classification of severe chronic kidney disease into five stages. Theoretically, the measurement of glomerular filtration rate is based on the calculation of urinary clearance of exogenous substances such as chromium 51-labeled inulin or ethylenediaminetetraacetic acid ([(51)Cr]-EDTA). In practice, glomerular filtration rate is most often estimated from equations derived from plasma creatinine. This article reviews the range of methods used to measure or approximate glomerular filtration rate and attempts to describe recent developments in this area, including those related to plasma creatinine assay methods, creatinine and cystatin C concentration-derived estimations...
November 13, 2017: Néphrologie & Thérapeutique
https://www.readbyqxmd.com/read/29145399/point-mutation-in-d8c-domain-of-tamm-horsfall-protein-uromodulin-in-transgenic-mice-causes-progressive-renal-damage-and-hyperuricemia
#5
Lijie Ma, Yan Liu, Nichole K Landry, Tarek M El-Achkar, John C Lieske, Xue-Ru Wu
Hereditary mutations in Tamm-Horsfall protein (THP/uromodulin) gene cause autosomal dominant kidney diseases characterized by juvenile-onset hyperuricemia, gout and progressive kidney failure, although the disease pathogenesis remains unclear. Here we show that targeted expression in transgenic mice of a mutation within the domain of 8 cysteines of THP in kidneys' thick ascending limb (TAL) caused unfolded protein response in younger (1-month old) mice and apoptosis in older (12-month old) mice. While the young mice had urine concentration defects and polyuria, such defects progressively reversed in the older mice to marked oliguria, highly concentrated urine, fibrotic kidneys and reduced creatinine clearance...
2017: PloS One
https://www.readbyqxmd.com/read/29142968/the-effect-of-renal-function-and-hemodialysis-treatment-on-plasma-vasopressin-and-copeptin-levels
#6
Esmée M Ettema, Judith Heida, Niek F Casteleijn, Lianne Boesten, Ralf Westerhuis, Carlo A J M Gaillard, Ron T Gansevoort, Casper F M Franssen, Debbie Zittema
Introduction: Copeptin is increasingly used in epidemiological studies as a substitute for vasopressin. The effect of renal function per se on copeptin and vasopressin concentrations as well as their ratio have, however, not been well described. Methods: Copeptin and vasopressin levels were measured in 127 patients with various stages of chronic kidney disease, including 42 hemodialysis patients and 16 healthy participants in this observational study. Linear (segmental) regression analyses were performed to assess the association between renal function and copeptin, vasopressin and the C/V ratio...
May 2017: KI Reports
https://www.readbyqxmd.com/read/29139376/the-longitudinal-effects-of-peritonitis-on-peritoneal-membrane-function%C3%A2
#7
Christopher S B Sia, Eldho Paul, Peter Tregaskis, Rowan G Walker, Scott G Wilson
BACKGROUND: The longitudinal effects of peritoneal dialysis (PD) peritonitis on small solute clearance and ultrafiltration are controversial. MATERIALS AND METHODS: We identified 27 patients with PD peritonitis over a 4-year period at a tertiary hospital. Adequacy tests at an "early" (1 - 3 months), "intermediate" (6 ± 2 months), and a "late" (12 ± 2 months) time period after the episode were compared with a pre-peritonitis baseline. The effect of time on serum albumin, weekly creatinine clearance, Kt/V, and net fluid volume removal was assessed...
December 2017: Clinical Nephrology
https://www.readbyqxmd.com/read/29135137/-renal-function-after-laparoscopic-partial-nephrectomy-with-superselective-balloon-embolization-of-renal-artery
#8
A V Maksimov, A G Martov, L P Pavlov
AIM: To evaluate the functional state of the renal parenchyma after partial nephrectomy, depending on surgical technique. MATERIALS AND METHODS: The study comprised 21 patients with kidney neoplasms of stage T1-2N0M0. The patients underwent either laparoscopic partial nephrectomy with superselective balloon embolization of the renal artery (study group, n=11), or partial nephrectomy with vascular clamping (control group, n=10). The mean age of the patients in the study group (3 men and 8 women) was 56...
October 2017: Urologii︠a︡
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
#9
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/29134428/the-influence-of-hepatic-and-renal-impairment-on-the-pharmacokinetics-of-a-treatment-for-herpes-zoster-amenamevir-asp2151-phase-1-open-label-single-dose-parallel-group-studies
#10
Tomohiro Kusawake, Donna Kowalski, Akitsugu Takada, Kota Kato, Masataka Katashima, James J Keirns, Michaelene Lewand, Kenneth C Lasseter, Thomas C Marbury, Richard A Preston
INTRODUCTION: Amenamevir (ASP2151) is a nonnucleoside human herpesvirus helicase-primase inhibitor that was approved in Japan for the treatment of herpes zoster (shingles) in 2017. This article reports the results of two clinical trials that investigated the effects of renal and hepatic impairment on the pharmacokinetics of amenamevir. METHODS: These studies were phase 1, open-label, single-dose (oral 400 mg), parallel-group studies evaluating the pharmacokinetics, safety, and tolerability of amenamevir in healthy participants and participants with moderate hepatic impairment and mild, moderate, and severe renal impairment...
November 13, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/29134426/pharmacokinetics-and-safety-of-amenamevir-in-healthy-subjects-analysis-of-four-randomized-phase-1-studies
#11
Tomohiro Kusawake, James J Keirns, Donna Kowalski, Martin den Adel, Dorien Groenendaal-van de Meent, Akitsugu Takada, Yoshiaki Ohtsu, Masataka Katashima
INTRODUCTION: Amenamevir (ASP2151) is a nonnucleoside antiherpesvirus compound available for the treatment of varicella-zoster virus infections. In this article we summarize the findings of four phase 1 studies in healthy participants. METHODS: Four randomized phase 1 studies investigated the safety and pharmacokinetics of single and multiple doses of amenamevir, including the assessment of age group effect (nonelderly vs elderly), food effect, and the relative bioavailability of two formulations...
November 13, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/29134277/should-mini-percutaneous-nephrolithotomy-minipnl-miniperc-be-the-ideal-tract-for-medium-sized-renal-calculi-15-30%C3%A2-mm
#12
Rajesh A Kukreja
INTRODUCTION: Reducing the percutaneous nephrolithotomy (PCNL) tract size reduces the morbidity associated with the procedure. Prolonged procedure time is a concern. Modification in technique required is to fragment the stone into smaller particles and remove them using the vacuum cleaner effect. This prospective study compares the efficacy and morbidity of reducing the tract size from the standard 24-16.5 Fr for stones sized from 16 to 30 mm. METHODS: 123 patients were enrolled in this prospective study and distributed into 2 groups based on the tract size used (group A 16...
November 13, 2017: World Journal of Urology
https://www.readbyqxmd.com/read/29133918/fast-simultaneous-assessment-of-renal-and-liver-function-using-polymethine-dyes-in-animal-models-of-chronic-and-acute-organ-injury
#13
A T Press, M J Butans, T P Haider, C Weber, S Neugebauer, M Kiehntopf, U S Schubert, M G Clemens, M Bauer, A Kortgen
Simultaneous assessment of excretory liver and kidney function is still an unmet need in experimental stress models as well as in critical care. The aim of the study was to characterize two polymethine-dyes potentially suitable for this purpose in vivo. Plasma disappearance rate and elimination measurements of simultaneously injected fluorescent dyes DY-780 (hepato-biliary elimination) and DY-654(renal elimination) were conducted using catheter techniques and intravital microscopy in animals subjected to different organ injuries, i...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29132650/non-vitamin-k-antagonist-oral-anticoagulants-in-patients-with-atrial-fibrillation-and-end-stage-renal-disease
#14
REVIEW
Marin Nishimura, Jonathan C Hsu
Over the past decade, there have been tremendous advancements in anticoagulation therapies for stroke prevention in patients with atrial fibrillation (AF). Although the non-vitamin K antagonist oral anticoagulants (NOACs) demonstrated favorable clinical outcomes compared with warfarin overall, the decision to anticoagulate and the choice of appropriate agent in patients with AF and concomitant chronic kidney disease (CKD) or end-stage renal disease (ESRD) are a particularly complex issue. CKD and ESRD increase both the risk of stroke and bleeding, and since all of the NOACs undergo various levels of renal clearance, renal dysfunction inevitably affects the pharmacokinetics of the drug in each patient...
October 12, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/29130954/effects-of-tolvaptan-addition-to-furosemide-in-normo-and-hyponatremia-patients-with-heart-failure-and-chronic-kidney-disease-stages-g3b-5-a-subanalysis-of-the-k-star-study
#15
Naoto Tominaga, Keisuke Kida, Takayuki Inomata, Naoki Sato, Tohru Izumi, Yoshihiro J Akashi, Yugo Shibagaki
BACKGROUND: Tolvaptan increases free water clearance (aquaresis) and thereby improves hyponatremia. Although hyponatremia on admission is common in patients with congestive heart failure (CHF), little is known regarding the response to tolvaptan in those who also have chronic kidney disease (CKD) with or without hyponatremia. The aim of this subanalysis was to investigate the differences in treatment response between normo- and hyponatremia patients with CHF and CKD stages G3b-5. METHODS: The Kanagawa Aquaresis Investigators Trial of Tolvaptan on HF Patients with Renal Impairment (K-STAR) was a multicenter, open-label, randomized, controlled prospective clinical trial that included 81 Japanese patients with CHF and residual signs of congestion despite oral furosemide treatment (≥40 mg/day)...
November 7, 2017: American Journal of Nephrology
https://www.readbyqxmd.com/read/29129959/cancer-targeting-ultrasmall-silica-nanoparticles-for-clinical-translation-physicochemical-structure-and-biological-property-correlations
#16
Feng Chen, Kai Ma, Miriam Benezra, Li Zhang, Sarah M Cheal, Evan Phillips, Barney Yoo, Mohan Pauliah, Michael Overholtzer, Pat Zanzonico, Sonia Sequeira, Mithat Gonen, Thomas Quinn, Ulrich Wiesner, Michelle S Bradbury
Although a large body of literature exists on the potential use of nanoparticles for medical applications, the number of probes translated into human clinical trials is remarkably small. A major challenge of particle probe development and their translation is the elucidation of safety profiles associated with their structural complexity, not only in terms of size distribution and heterogeneities in particle composition but also their effects on biological activities and the relationship between particle structure and pharmacokinetics...
October 24, 2017: Chemistry of Materials: a Publication of the American Chemical Society
https://www.readbyqxmd.com/read/29129251/the-relationship-of-renal-function-to-outcome-a-post-hoc-analysis-from-the-edoxaban-versus-warfarin-in-subjects-undergoing-cardioversion-of-atrial-fibrillation-ensure-af-study
#17
Gregory Y H Lip, Naab Al-Saady, Michael D Ezekowitz, Maciej Banach, Andreas Goette
The ENSURE-AF study (NCT 02072434) of anticoagulation for electrical cardioversion in nonvalvular atrial fibrillation (NVAF) showed comparable low rates of bleeding and thromboembolism between the edoxaban and the enoxaparin-warfarin treatment arms. This post hoc analysis investigated the relationship between renal function and clinical outcomes. METHODS: ENSURE-AF was a multicenter, PROBE evaluation trial of edoxaban 60 mg, or dose reduced to 30 mg/d for weight≤60 kg, creatinine clearance (CrCl; Cockcroft-Gault) ≤50 mL/min, or concomitant P-glycoprotein inhibitors compared with therapeutically monitored enoxaparin-warfarin in 2,199 NVAF patients undergoing electrical cardioversion...
November 2017: American Heart Journal
https://www.readbyqxmd.com/read/29128808/attenuation-of-renal-damage-in-type-i-diabetic-rats-by-umbelliferone-a-coumarin-derivative
#18
Mayuresh S Garud, Yogesh A Kulkarni
BACKGROUND: It is well known that diabetes is one of the non-communicable disease affecting a large population worldwide. When diabetes remains untreated or uncontrolled, it leads to further serious complications, affecting vital organs like eyes, kidney, heart, etc. The present study was designed to evaluate effects of umbelliferone, a phytochemical, in treatment of diabetic nephropathy. METHODS: Experimental model used was streptozotocin (55mg/kg, ip) induced diabetic nephropathy in male Sprague Dawley rats...
June 27, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29127010/cyclosporine-a-exhibits-gender-specific-nephrotoxicity-in-rats-effect-on-renal-tissue-inflammation
#19
Hany M El-Bassossy, Basma G Eid
Cyclosporine A (CSA) is a widely used immunosuppressant drug known to commonly cause cardio and nephrotoxicity. A study looking at the sex specificity of the cardiotoxicity of CSA revealed that sexual dimorphism existed when looking at the electrocardiographs and left ventricles of CSA-treated rats. We hypothesized that cyclosporine A exhibited gender-specific nephrotoxicity by testing various parameters of kidney function in male and female rats treated for 21 days with 15 mg/kg CSA versus control male and female rats that received a vehicle consisting of 18% kolliphore and 2% ethanol in sterile saline...
November 7, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29125269/direct-oral-anticoagulants-use-in-elderly-patients-with-non-valvular-atrial-fibrillation-state-of-evidence
#20
Giulia Benedetti, Matteo Neccia, Luciano Agati
Non-valvular atrial fibrillation (NVAF) increases the risk of stroke by three- to five-fold, especially in elderly patients, creating a huge burden on medical system as well as a negative impact on patients lives. Balancing efficacy and bleeding risk is a challenge when considering anticoagulation therapy in elderly patients, because of their frequent high risk of both stroke and bleeding. Real world data reveal the underuse of anticoagulation in the elderly, especially due to physicians' fear of bleeding, often neglecting the thromboembolic risk...
November 10, 2017: Minerva Cardioangiologica
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