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nephrotoxic drugs

Lucy Chen, G V Ramesh Prasad
Tacrolimus is a commonly used immunosuppressant after kidney transplantation. It has a narrow therapeutic range and demonstrates wide interindividual variability in pharmacokinetics, leading to potential underimmunosuppression or toxicity. Genetic polymorphism in CYP3A5 enzyme expression contributes to differences in tacrolimus bioavailability between individuals. Individuals carrying one or more copies of the wild-type allele *1 express CYP3A5, which increases tacrolimus clearance. CYP3A5 expressers require 1...
2018: Pharmacogenomics and Personalized Medicine
Francielle Tatiana Mathias, Douglas Henrique Fockink, Geonildo Rodrigo Disner, Viviane Prodocimo, João Luiz Coelho Ribas, Luiz Pereira Ramos, Marta Margarete Cestari, Helena Cristina Silva de Assis
Ibuprofen is a pharmaceutical drug widely used by the global population and it has been found in aquatic ecosystems in several countries. This study evaluated the effects of ibuprofen in environmental concentrations (0, 0.1, 1 and 10 μg/L) on the freshwaterspecies Rhamdia quelen exposed for 14 days. In the posterior kidney, ibuprofen increased glutathione-S-transferase activity in all groups exposed. Furthermore, increased glutathione peroxidase activity and the levels of reduced glutathione in the group exposed to 10 μg/L...
March 11, 2018: Environmental Toxicology and Pharmacology
Karl Waked, Marc Schepens
During open thoracoabdominal aortic aneurysm repair (OTAAAR), there is an inevitable organ ischemic period that occurs when the abdominal arteries are being reattached to the aortic graft. Despite various protective techniques, the incidence of renal and visceral complications remains substantial. This state-of-the-art review gives an overview of the current and most evidence-based organ protection methods during OTAAAR, based on the most recent publications and personal experience. An electronic search was performed in four medical databases, using the following MeSH terms: thoracoabdominal aneurysm, TAAAR, visceral protection, renal protection, kidney, perfusion, and intestines...
2018: Journal of Visualized Surgery
Hassan Izzedine
Drug-induced nephrotoxicity (DIN) remains a current problem with economic and medical consequences. It affects all nephron segments. Recovery of renal function is based on the identification of risk factors, early diagnosis of renal disease, rapid (if possible) cessation of the causative agent and, in some cases, adjunctive therapy. Prevention is based on identification of early markers of DIN, correction of risk factors, initial assessment of renal function for adequate dosage adjustment and exclusion of other nephrotoxic factors...
March 11, 2018: Néphrologie & Thérapeutique
Haesol Lee, Dahae Lee, Ki Sung Kang, Ji Hoon Song, You-Kyoung Choi
Cisplatin is a well-known anticancer drug frequently used for treating solid tumors, including ovarian, testicular, bladder, and cervical tumors. However, usage of cisplatin has been limited because of its adverse effects, particularly nephrotoxicity. Therefore, the present study sought to investigate the protective effect of formononetin against cisplatin-induced cytotoxicity in LLC-PK1 pig kidney epithelial cells as well as the anticancer effect of cisplatin in three different human cervical cancer cell lines, including HeLa, SiHa, and CaSKi cells...
March 12, 2018: International Journal of Molecular Sciences
Miguel Fontecha-Barriuso, Diego Martin-Sanchez, Olga Ruiz-Andres, Jonay Poveda, Maria Dolores Sanchez-Niño, Lara Valiño-Rivas, Marta Ruiz-Ortega, Alberto Ortiz, Ana Belén Sanz
Epigenetics refers to heritable changes in gene expression patterns not caused by an altered nucleotide sequence, and includes non-coding RNAs and covalent modifications of DNA and histones. This review focuses on functional evidence for the involvement of DNA and histone epigenetic modifications in the pathogenesis of kidney disease and the potential therapeutic implications. There is evidence of activation of epigenetic regulatory mechanisms in acute kidney injury (AKI), chronic kidney disease (CKD) and the AKI-to-CKD transition of diverse aetiologies, including ischaemia-reperfusion injury, nephrotoxicity, ureteral obstruction, diabetes, glomerulonephritis and polycystic kidney disease...
March 9, 2018: Nephrology, Dialysis, Transplantation
Simin Dashti-Khavidaki, Hossein Khalili, Mohsen Nasiri-Toosi
There was no report of nephrotoxicity during clinical trials assessed sofosbuvir for treatment of hepatitis C (HCV) infection. This may be due to excluding patients with severe kidney dysfunction, as a main population at risk for drug-induced nephrotoxicity from these studies. There are some reports of acute kidney injury (AKI) possibly related to sofosbuvir-containing treatments from real-life experiences. Areas covered: Available data on epidemiology, type, and possible risk factors for nephrotoxicity of sofosbuvir-containing treatment are reviewed...
March 14, 2018: Expert Review of Clinical Pharmacology
Sanyog Jain, Pooja Yadav, Rajan Swami, Nitin Kumar Swarnakar, Varun Kushwah, Sameer S Katiyar
Implication of different dietary specific lipids such as phytantriol (PT) and glyceryl monooleate (GMO) on enhancing the oral bioavailability of amphotericin B (AmB) was examined. Liquid crystalline nanoparticles (LCNPs) were prepared using hydrotrope method, followed by in vitro characterization, Caco-2 cell monolayer uptake, and in vivo pharmacokinetic and toxicity evaluation. Optimized AmB-LCNPs displayed small particle size (< 210 nm) with a narrow distribution (~ 0.2), sustained drug release and high gastrointestinal stability, and reduced hemolytic toxicity...
March 12, 2018: AAPS PharmSciTech
Marguerite L Monogue, Jessica K Ortwine, Wenjing Wei, Khalid Eljaaly, Kavita P Bhavan
BACKGROUND: Anti-staphylococcal penicillins have long been the first-line treatment option for methicillin-susceptible Staphylococcus aureus (MSSA) infections. Recent retrospective data comparing nafcillin and cefazolin report similar clinical efficacy despite concerns about high inoculum MSSA infections. METHODS: This was a retrospective, non-inferiority, cohort study comparing treatment failure rates between nafcillin and cefazolin in patients with MSSA bacteremia from any source, other than meningitis...
March 8, 2018: Journal of Infection and Public Health
Jeonghwan Lee, Sejoong Kim
The kidneys play a pivotal role in most drug-removal processes and are important when evaluating drug safety. Kidney dysfunction resulting from various drugs is an important issue in clinical practice and during the drug development process. Traditional in vivo animal experiments are limited with respect to evaluating drug efficacy and nephrotoxicity due to discrepancies in drug pharmacokinetics and pharmacodynamics between humans and animals, and static cell culture experiments cannot fully reflect the actual microphysiological environment in humans...
March 8, 2018: Current Drug Metabolism
Garrett T Dow, James B Thoden, Hazel M Holden
The aminoglycoside antibiotics, discovered as natural products in the 1940s, demonstrate a broad anti-microbial spectrum. Due to their nephrotoxic and ototoxic side effects, however, their widespread clinical usage has typically been limited to the treatment of serious infections. Neomycin B, first isolated from strains of Streptomyces in 1948, is one such drug that was approved for human use by the U. S. Food and Drug Administration in 1964. Only within the last 11 years has the biochemical pathway for its production been elaborated, however...
March 8, 2018: Protein Science: a Publication of the Protein Society
Tom Tg Nieskens, Janny Gp Peters, Dina Dabaghie, Daphne Korte, Katja Jansen, Alexander H Van Asbeck, Neslihan N Tavraz, Thomas Friedrich, Frans Russel, Rosalinde Masereeuw, Martijn J Wilmer
Cisplatin is a cytostatic drug used for treatment of solid organ tumors. The main adverse effect is organic cation transporter 2 (OCT2)-mediated nephrotoxicity, observed in 30% of patients. The contribution of other renal drug transporters is elusive. Here, cisplatin-induced toxicity was evaluated in human-derived proximal tubule epithelial cells (ciPTEC) expressing renal drug transporters, including OCT2 and organic anion transporter 1 (OAT1) or 3 (OAT3). Parent ciPTEC demonstrated OCT2-dependent cisplatin toxicity (TC50 34±1 μM after 24 h exposure), as determined by cell viability...
March 7, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Wui K Chong, Virginie Papadopoulou, Paul A Dayton
Microbubble ultrasound contrast agents (UCAs) were recently approved by the Food and Drug administration for non-cardiac imaging. The physical principles of UCAs, methods of administration, dosage, adverse effects, and imaging techniques both current and future are described. UCAs consist of microbubbles in suspension which strongly interact with the ultrasound beam and are readily detectable by ultrasound imaging systems. They are confined to the blood pool when administered intravenously, unlike iodinated and gadolinium contrast agents...
March 5, 2018: Abdominal Radiology
Karolina Tecza, Jolanta Pamula-Pilat, Joanna Lanuszewska, Dorota Butkiewicz, Ewa Grzybowska
The differences in patients' response to the same medication, toxicity included, are one of the major problems in breast cancer treatment. Chemotherapy toxicity makes a significant clinical problem due to decreased quality of life, prolongation of treatment and reinforcement of negative emotions associated with therapy. In this study we evaluated the genetic and clinical risk factors of FAC chemotherapy-related toxicities in the group of 324 breast cancer patients. Selected genes and their polymorphisms were involved in FAC drugs transport ( ABCB1, ABCC2, ABCG2,SLC22A16 ), metabolism ( ALDH3A1, CBR1, CYP1B1, CYP2C19, DPYD, GSTM1, GSTP1, GSTT1, MTHFR,TYMS ), DNA damage recognition, repair and cell cycle control ( ATM, ERCC1, ERCC2, TP53, XRCC1 )...
February 6, 2018: Oncotarget
Hisato Shima, Manabu Tashiro, Satoshi Yamada, Motokazu Matsuura, Kazuyoshi Okada, Toshio Doi, Jun Minakuchi, Shu Kawashima
BACKGROUND: Cilostazol is an antiplatelet drug that is widely prescribed for the prevention of secondary stroke. Adverse reactions to cilostazol include headaches, palpitations, and diarrhea. Little is known about the nephrotoxicity of cilostazol, such as acute kidney injury. We report a biopsy-proven case of diffuse tubulointerstitial nephritis induced by cilostazol. CASE PRESENTATION: A 69-year-old woman prescribed cilostazol was hospitalized for acute kidney injury...
March 5, 2018: BMC Nephrology
Karen Steindorf, Martina E Schmidt, Philipp Zimmer
A growing number of literature reports positive effects of physical activity and exercise. These effects concern prevention, mortality and progress of cancer. Furthermore they show a reduction of disease- and treatment-specific side effects, which implies a better patients' quality of life. Evidence shows a decreased mortality risk in patients with physically active cancer of colon, breast, ovaries and prostate. Activity recommendations for patients with cancer do not differ from those for healthy persons...
March 2018: Deutsche Medizinische Wochenschrift
Eduardo C Gomes, Diego R Falci, Pedro Bergo, Alexandre P Zavascki, Maria Helena Rigatto
OBJECTIVES: To evaluate the impact of polymyxin B (PMB)- associated Acute Kidney Injury (AKI) in 1-year mortality and renal function recovery. METHODS: Patients >18 years old who survived the first 30-days after PMB therapy were followed for 1-year. The impact of AKI and Renal Failure (using RIFLE score) in 1-year mortality was analyzed, along with other confounding variables. Variables with a P value ≤0.2 were included in a forward stepwise Cox regression model...
March 1, 2018: International Journal of Antimicrobial Agents
Daniel Brustolin Ludwig, Luciana Erzinger Alves de Camargo, Najeh Maissar Khalil, Marcos Ereno Auler, Rubiana Mara Mainardes
Amphotericin B (AmB) is one of the most used drugs for the treatment of systemic fungal infections; however, the treatment causes several toxic manifestations, including nephrotoxicity and hemolytic anemia. Chitosan-coated poly(lactide-co-glycolide) (PLGA) nanoparticles containing AmB were developed with the aim to decrease AmB toxicity and propose the oral route for AmB delivery. In this work, the antifungal efficacy of chitosan-coated PLGA nanoparticles containing AmB was evaluated in 20 strains of fungus isolates from patients with vulvovaginal candidiasis (01 Candida glabrata and 03 Candida albicans), bloodstream infections (04 C...
March 1, 2018: Mycopathologia
Simon Lagies, Roman Pichler, Michael M Kaminski, Manuel Schlimpert, Gerd Walz, Soeren S Lienkamp, Bernd Kammerer
Fibroblasts can be directly reprogrammed to induced renal tubular epithelial cells (iRECs) using four transcription factors. These engineered cells may be used for disease modeling, cell replacement therapy or drug and toxicity testing. Direct reprogramming induces drastic changes in the transcriptional landscape, protein expression, morphological and functional properties of cells. However, how the metabolome is changed by reprogramming and to what degree it resembles the target cell type remains unknown. Using untargeted gas chromatography-mass spectrometry (GC-MS) and targeted liquid chromatography-MS, we characterized the metabolome of mouse embryonic fibroblasts (MEFs), iRECs, mIMCD-3 cells, and whole kidneys...
March 1, 2018: Scientific Reports
Martti Vaara
Polymyxin B and colistin (polymyxin E) are bactericidal pentacationic lipopeptides that act specifically on Gram-negative bacteria, first by disrupting their outermost permeability barrier, the outer membrane (OM), and then damaging the cytoplasmic membrane. The discovery of both polymyxin B and colistin was published independently by three laboratories as early as in 1947. They were subsequently used in intravenous therapy. Unfortunately, they also exhibit significant and dose-limiting nephrotoxicity. Therefore, polymyxins were reserved as agents of last-line defense...
February 27, 2018: Medicinal Research Reviews
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