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nephrotoxic drugs

Mikael Persson, Jorrit J Hornberg
High content screening enables parallel acquisition of multiple molecular and cellular readouts. In particular the predictive toxicology field has progressed from the advances in high content screening, as more refined end points that report on cellular health can be studied in combination, at the single cell level, and in relatively high throughput. Here, we discuss how high content screening has become an essential tool for Discovery Safety, the discipline that integrates safety and toxicology in the drug discovery process to identify and mitigate safety concerns with the aim to design drug candidates with a superior safety profile...
October 21, 2016: Chemical Research in Toxicology
Lauren Brasile, Nicholas Henry, Bart Stubenitsky
BACKGROUND: We have previously reported on a novel organ-specific immunomodifying therapy that provides protection from early allograft rejection in the absence of systemic immunosuppressive drugs. This novel therapy is a nano-barrier membrane called ImmunoCloak, consisting of a matrix of laminin, proteoglycans, fibronectin and collagens. The membrane "immunocloaks" the luminal surfaces within the renal vasculature by covering the point of contact between donor vascular endothelial cells and the recipient's immune cells; without adversely affecting renal function...
October 19, 2016: Transplantation
P Fabbrini, K Finkel, M Gallieni, G Capasso, M Cavo, A Santoro, S Pasquali
Acute kidney injury (AKI) is a frequent complication of multiple myeloma and is associated with increased short-term mortality. Additionally, even a single episode of AKI can eventually lead to end-stage renal disease (ESRD), significantly reducing quality of life and long-term survival. In the setting of multiple myeloma, severe AKI (requiring dialysis) is typically secondary to cast nephropathy (CN). Renal injury in CN is due to intratubular obstruction from precipitation of monoclonal serum free light chains (sFLC) as well as direct tubular toxicity of sFLC via stimulation of nuclear factor (NF)κB inflammatory pathways...
October 18, 2016: Journal of Nephrology
Solomon Kadiri
Hypertension prevalence rates in most urbanized areas of Africa range from 20-30%, with a recent systematic review reporting 16.2% for sub-Saharan Africa. These rates are lower than those in the West but the age standardized rates are higher than in other regions of the world. The attendant morbidity and mortality are disproportionately high. For example, failure of nocturnal dipping and microalbuminuria, predictive of vascular disease, occur relatively early in the course of hypertension and predispose to early vascular disease...
September 2016: Journal of Hypertension
Sheikh Farjana Sonia, Mohammad S Hassan, Ferdous Ara, Mohammed Hanif
Aminoglycoside is a widely used antibiotic in neonatal age group at hospital setting in Bangladesh. It has underlying side effect and toxicity which is mostly unseen and ignored. The aim of the study was to evaluate the nephrotoxic effect of aminoglycoside in neonates. This study was conducted in fifty hospital admitted neonates of Dhaka Shishu Hospital from January 2012 to December 2013. Serum creatinine, blood urea nitrogen, and fractional excretion of magnesium (FEMg) were measured before starting and after seven days of aminoglycoside treatment...
September 2016: Saudi Journal of Kidney Diseases and Transplantation
James R Costello, Bobby Kalb, Diego R Martin
Since their clinical introduction in 1988, gadolinium-based contrast agents (GBCAs) have demonstrated an excellent safety profile with a reported acute adverse reaction rate ranging from 0.01% to 2%. By comparison, the acute adverse reaction rate of low osmolar nonionic computed tomography contrast agents (CTCs) ranges from 0.7% to 3.1%. Many of the risk factors associated with CTC reactions (drug allergies, asthma, atopy, prior contrast reaction) also point toward an increased incidence of acute adverse events to GBCAs...
June 29, 2016: Topics in Magnetic Resonance Imaging: TMRI
Christian Schem, Robert J Tower, Philipp Kneissl, Anna-Christina Rambow, Graeme M Campbell, Christine Desel, Timo Damm, Thorsten Heilmann, Sabine Fuchs, Maaz Zuharya, Anna Trauzold, Claus C Glüer, Sarah Schott, Sanjay Tiwari
Bisphosphonates have effects which are anti-resorptive, anti-tumor and anti-apoptotic to osteoblasts and osteocytes, but an effective means of eliciting these multiple activities in the treatment of bone metastases has not been identified. Antimetabolite-bisphosphonate conjugates have potential for improved performance as a class of bone specific anti-neoplastic drugs. The primary objective of the study was to determine whether an antimetabolite-bisphosphonate conjugate will preserve bone formation concomitant with anti-resorptive and anti-tumor activity...
October 7, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Hyun Seon Kim, Sun Woo Lim, Long Jin, Jian Jin, Byung Ha Chung, Chul Woo Yang
BACKGROUND: The use of calcineurin inhibitors is a well-known risk factor for hyperuricemia in kidney transplant recipients. We evaluated the effect of febuxostat (Fx), a new uric acid-lowering drug, on hyperuricemia and renal injury in an experimental model of chronic tacrolimus (Tac)-induced nephropathy. METHODS: Chronic Tac nephropathy was induced by administering Tac (1.5 mg/kg/day) to rats on a low-salt diet (0.05%) with oxonic acid (OA, 2%, 0.2 g/kg/day) for 28 days...
October 5, 2016: Nephron
Jodi M Lestner, Andreas H Groll, Ghaith Aljayyoussi, Nita L Seibel, Aziza Shad, Corina Gonzalez, Lauren V Wood, Paul F Jarosinski, Thomas J Walsh, William W Hope
BACKGROUND: Liposomal amphotericin B (LAmB) is widely used in the treatment of invasive fungal disease (IFD) in adults and children. There are relatively limited PK data to inform optimal dosing in children that achieves systemic drug exposures comparable to those of adults. OBJECTIVES: To describe the pharmacokinetics of LAmB in children aged 1-17 years with suspected or documented IFD. METHODS: Thirty-five children were treated with LAmB at dosages of 2...
October 3, 2016: Antimicrobial Agents and Chemotherapy
Elham Peysepar, Nepton Soltani, Mehdi Nematbakhsh, Fatemeh Eshraghi-Jazi, Ardeshir Talebi
INTRODUCTION: Cisplatin (CP) is a major antineoplastic drug for treatment of solid tumors. CP-induced nephrotoxicity may be gender-related. This is while gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter in the central nervous system that has renoprotective impacts on acute renal injury. OBJECTIVES: This study was designed to investigate the protective role of GABA against CP-induced nephrotoxicity in male and female rats. MATERIALS AND METHODS: Sixty Wistar male and female rats were used in eight experimental groups...
2016: Journal of Renal Injury Prevention
Fatemeh Ahmadi, Mehdi Nematbakhsh, Mehdi Kargarfard, Fatemeh Eshraghi-Jazi, Ardeshir Talebi, Soheila Shirdavani
INTRODUCTION: Vanadium compounds are insulin like drugs which are accompanied with nephrotoxicity and hepatotoxicity as their major side effects. Aerobic exercise is well known as an approach to reduce the side effects of many drugs. OBJECTIVES: This study was designed to determine the role of aerobic exercise against vanadyl sulphate induced nephrotoxicity and hepatotoxicity in male rats. MATERIALS AND METHODS: Twenty-four male Wistar rats were randomly divided into three groups...
2016: Journal of Renal Injury Prevention
Sheetal Gupta, Ghanshyam Singh Sengar, Praveen K Meti, Anil Lahoti, Mukesh Beniwal, Murlidhar Kumawat
OBJECTIVE: To determine incidence, risk factors, and outcome of acute kidney injury (AKI) in Pediatric Intensive Care Unit (PICU). MATERIALS AND METHODS: This is a prospective, observational study conducted in PICU of Department of Paediatrics, S.P. Medical College, Bikaner, from October 2013 to May 2014. In this study, 536 patients of aged 29 days to 16 years were screened for AKI according to the Pediatric Risk, Injury, Failure, Loss, End-stage Renal Disease (pRIFLE) criteria...
September 2016: Indian Journal of Critical Care Medicine
Ying Wang, Xiyu Ke, Zhi Xiang Voo, Serene Si Ling Yap, Chuan Yang, Shujun Gao, Shaoqiong Liu, Shrinivas Venkataraman, Sybil Akua Okyerewa Obuobi, Jasmeet Singh Khara, Yi Yan Yang, Pui Lai Rachel Ee
: Amphotericin B (AmB), a poorly soluble and toxic antifungal drug, was encapsulated into polymeric micelles self-assembled from phenylboronic acid-functionalized polycarbonate/PEG (PEG-PBC) and urea-functionalized polycarbonate/PEG (PEG-PUC) diblock copolymers via hydrogen-bonding, boronate ester bond, and/or ionic interactions between the boronic acid group in the micellar core and amine group in AmB. Three micellar formulations were prepared: AmB/B micelles using PEG-PBC, AmB/U micelles using PEG-PUC and AmB/B+U mixed micelles using 1:1molar ratio of PEG-PBC and PEG-PUC...
September 26, 2016: Acta Biomaterialia
Valeria Cernaro, Alessandra Sfacteria, Claudia Rifici, Francesco Macrì, Giulia Maricchiolo, Antonio Lacquaniti, Carlo Alberto Ricciardi, Antoine Buemi, Giuseppe Costantino, Domenico Santoro, Michele Buemi
BACKGROUND: Gentamicin is an aminoglycoside antibiotic widely used in the treatment of infections caused by Gram-negative bacteria. The main limitation to its therapeutic effectiveness is the potential nephrotoxicity. Erythropoietin has a tissue protective effect widely demonstrated in the kidney. The aim of the present study was to evaluate the renoprotective effects of erythropoietin in a model of zebrafish (Danio rerio) after administration of gentamicin. METHODS: Sixty adult zebrafish were subdivided into three groups: group A was treated with gentamicin; group B received gentamicin and, 24 h later, epoetin alpha; group C received drug diluent only...
September 27, 2016: Journal of Nephrology
Haseeb A Khan, Khalid E Ibrahim, Ayaat Khan, Salman H Alrokayan, Abdullah S Alhomida
Recently, gold nanoparticles (GNPs) have shown promising applications in targeted drug delivery and contrast imaging. Although in vitro cytotoxicity of GNPs has been thoroughly studied, there are limited data on in vivo toxicity of GNPs. In this study, we evaluated the effects of intraperitoneally injected 10 nm and 50 nm GNPs (5 μg/animal) on the expression of proinflammatory cytokines (IL-1β, IL-6 and TNF-α) on day 1 and day 5, post-exposure. The results of immunohistochemistry showed that both 10 nm and 50 nm GNPs induced an acute phase expression of proinflammatory cytokines in renal cortex and medulla...
September 28, 2016: Histology and Histopathology
Shingo Oda, Yuji Shirai, Sho Akai, Akira Nakajima, Koichi Tsuneyama, Tsuyoshi Yokoi
The acyl glucuronide (AG) metabolites of carboxylic acid-containing drugs are potentially chemically reactive and are suggested to be implicated in toxicity, including hepatotoxicity, nephrotoxicity and drug hypersensitivity reactions. However, it remains unknown whether AG formation is related to toxicity in vivo. In this study, we sought to determine whether AG is involved in the pathogenesis of liver injury using a mouse model of diclofenac (DIC)-induced liver injury. Mice that were administered DIC alone exhibited significantly increased plasma alanine aminotransferase levels, whereas mice that were pretreated with the UDP-glucuronosyltransferase inhibitor (-)-borneol (BOR) exhibited suppressed alanine aminotransferase levels at 3 and 6 h after DIC administration although not significant at 12 h...
September 27, 2016: Journal of Applied Toxicology: JAT
Gheorghe Gluhovschi, Florica Gadalean, Cristina Gluhovschi, Silvia Velciov, Ligia Petrica, Flaviu Bob, Gheorghe Bozdog, Adriana Kaycsa
The solitary kidney (SK) undergoes adaptive phenomena of hyperfunction and hyperfiltration. These secondary adaptive phenomena can make it more vulnerable to potentially nephrotoxic therapies. Adverse reactions of the kidneys to ciprofloxacin are rare, but sometimes severe. Therefore, our study sought to assess the reactions to ciprofloxacin of patients with solitary kidney (SK) and urinary tract infection (UTI) by means of urinary biomarkers. We studied 19 patients with SK and urinary tract infection (UTI) who had been administered a 7-day treatment with intravenous ciprofloxacin...
September 23, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Zhe Wei, Jin-Wei He, Wen-Zhen Fu, Zhen-Lin Zhang
CONTEXT: Adefovir dipivoxil (ADV) was an important cause of adult-onset hypophosphatemic osteomalacia. However, its clinical characteristics and mechanisms have not been well defined. OBJECTIVE: The objective of the study was to summarize the clinical characteristics of ADV-induced osteomalacia and to explore the association between ADV-associated tubulopathy and polymorphisms in genes encoding drug transporters. DESIGN, SETTING, PATIENTS, AND MAIN OUTCOME MEASURE: Seventy-six affected patients were clinically studied...
September 21, 2016: Bone
Roberto Filomia, Sergio Maimone, Gaia Caccamo, Carlo Saitta, Luca Visconti, Angela Alibrandi, Simona Caloggero, Antonio Bottari, Maria Stella Franzè, Carmine Gabriele Gambino, Tindaro Lembo, Giovanni Oliva, Irene Cacciola, Giovanni Raimondo, Giovanni Squadrito
Contrast medium administration is one of the leading causes of acute kidney injury (AKI) in different clinical settings. The aim of the study was to investigate occurrence and predisposing factors of AKI in cirrhotic patients undergoing contrast-enhanced computed tomography (CECT).Datasets of 1279 consecutively hospitalized cirrhotic patients were retrospectively analyzed. Two hundred forty-nine of 1279 patients (mean age 64 ± 11 years, 165 male) who had undergone CECT were selected on the basis of the availability of serum creatinine (sCr) values evaluated before and after CECT (CECT group)...
September 2016: Medicine (Baltimore)
Gabriel Fernandes-Silva, Mayara Ivani de Paula, Érika B Rangel
INTRODUCTION: Patient and pancreas allograft survival improved following reductions in surgical complications, tighter donor selection and optimization in immunosuppressive protocols. However, long-term survival of pancreas allografts is adversely affected by rejection and immunosuppressive regimen toxicity. AREAS COVERED: This article reviews the existing literature and knowledge of mammalian target of rapamycin inhibitors (mTORi). Some clinically relevant drug-drug interactions are highlighted...
September 23, 2016: Expert Opinion on Drug Metabolism & Toxicology
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