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Drug induced kidney disease

Alexandre Karras
Cryoglobulins are immunoglobulins that undergo reversible precipitation at low temperatures. They can induce systemic vasculitis, characterized by purpuric cutaneous lesions, arthritis, peripheral neuropathy, hypocomplementemia and glomerular disease. Renal pathology reveals membranoproliferative glomerulonephritis, with particularly intense mesangial cell proliferation and infiltration by macrophages, associated with intracapillary thrombi. This renal disease presents as a nephritic syndrome, with heavy proteinuria, haematuria severe hypertension and rapidly progressive kidney failure that can lead to end-stage renal disease...
March 12, 2018: Néphrologie & Thérapeutique
A M Rodrigues, R S Serralha, C Farias, G R Punaro, M J S Fernandes, Elisa Mieko Suemitsu Higa
Diabetes mellitus is characterized by increased levels of reactive oxygen species (ROS), leading to high levels of adenosine triphosphate (ATP) and the activation of purinergic receptors (P2X7 ), which results in cell death. Klotho was recently described as a modulator of oxidative stress and as having anti-apoptotic properties, among others. However, the roles of P2X7 and klotho in the progression of diabetic nephropathy are still unclear. In this context, the aim of the present study was to characterize P2X7 and klotho in several stages of diabetes in rats...
March 14, 2018: Purinergic Signalling
Georgina P Ossani, Diego J Martino, Jorge E Toblli
Lithium has been approved for the treatment of bipolar disorder since the 1970s and even today it is considered a first-line drug for the treatment of this disease. As bipolar disorder often begins between 15-35 years of age and requires long-term treatment, the assessment of the adverse effects of the drugs used is critical. Recently, there has been renewed interest on the risk of chronic kidney disease and kidney failure induced by lithium, with findings suggesting that both complications could be more frequent than previously considered...
September 2017: Vertex: Revista Argentina de Psiquiatriá
Bharat Kumar, Jennifer Strouse, Melissa Swee, Petar Lenert, Manish Suneja
INTRODUCTION: Hydralazine is an antihypertensive medication that has been associated with drug-induced lupus erythematosus (DIL) as well as ANCA-associated vasculitis (AAV). Although rare, early diagnosis is critical since drug cessation is the mainstay of therapy. This retrospective study aims to characterize the clinical, laboratory, and histopathologic features of this disease. METHODS: Once approval was obtained from the Institutional Review Board at the University of Iowa, all patients carrying a diagnosis of vasculitis (ICD9 code: 447...
January 12, 2018: Seminars in Arthritis and Rheumatism
Yin-Wu Bao, Yuan Yuan, Jiang-Hua Chen, Wei-Qiang Lin
Acute kidney injury (AKI) and chronic kidney disease (CKD) are worldwide public health problems affecting millions of people and have rapidly increased in prevalence in recent years. Due to the multiple causes of renal failure, many animal models have been developed to advance our understanding of human nephropathy. Among these experimental models, rodents have been extensively used to enable mechanistic understanding of kidney disease induction and progression, as well as to identify potential targets for therapy...
March 18, 2018: Zoological Research
Giuliano Ramadori, Patrizia Bosio, Federico Moriconi, Ihtzaz A Malik
BACKGROUND: After orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC), recurrent HCC mostly develops within 2 years. All cases of de novo HCC described so far occurred later than 2 years after OLT. Prevention of post-transplantation HCC has usually been tried to achieve by curing or controlling recurrent liver disease. This has been rationale for treatment with interferon (IFN)/ribavirin of HCV-recurrence in patients after OLT, transplanted for advanced HCV-induced liver disease and/or HCC...
March 6, 2018: BMC Cancer
Shiho Makabe, Toshio Mochizuki, Michihiro Mitobe, Yumi Aoyama, Hiroshi Kataoka, Ken Tsuchiya, Kosaku Nitta
BACKGROUND: In 2014, tolvaptan, a vasopressin receptor antagonist, was approved for the treatment of autosomal dominant polycystic kidney disease (ADPKD) in Japan. Clinical trials of tolvaptan revealed frequent occurrence of the liver function abnormality. According to the package insert in Japan, liver function tests should be performed once a month in patients receiving tolvaptan. Furthermore, immediate discontinuation of tolvaptan is recommended in the appearance of liver function abnormalities...
March 5, 2018: Clinical and Experimental Nephrology
Anne von Mässenhausen, Wulf Tonnus, Nina Himmerkus, Simon Parmentier, Danish Saleh, Diego Rodriquez, Jiraporn Ousingsawat, Rosalind L Ang, Joel M Weinberg, Ana B Sanz, Alberto Ortiz, Adrian Zierleyn, Jan Ulrich Becker, Blandine Baratte, Nathalie Desban, Stéphane Bach, Ina Maria Schiessl, Shoko Nogusa, Siddharth Balachandran, Hans Joachim Anders, Adrian T Ting, Markus Bleich, Alexei Degterev, Karl Kunzelmann, Stefan R Bornstein, Douglas R Green, Christian Hugo, Andreas Linkermann
Receptor-interacting protein kinases 1 and 3 (RIPK1/3) have best been described for their role in mediating a regulated form of necrosis, referred to as necroptosis. During this process, RIPK3 phosphorylates mixed lineage kinase domain-like (MLKL) to cause plasma membrane rupture. RIPK3-deficient mice have recently been demonstrated to be protected in a series of disease models, but direct evidence for activation of necroptosis in vivo is still limited. Here, we sought to further examine the activation of necroptosis in kidney ischemia-reperfusion injury (IRI) and from TNFα-induced severe inflammatory response syndrome (SIRS), two models of RIPK3-dependent injury...
March 2, 2018: Cell Death & Disease
Alex R Chang, Waleed Zafar, Morgan E Grams
As the prevalence of obesity continues to increase worldwide, an increasing number of people are at risk for kidney disease. Thus, there is a critical need to understand how best to assess kidney function in this population, and several challenges exist. The convention of indexing glomerular filtration rate (GFR) to body surface area (BSA) attempts to normalize exposure to metabolic wastes across populations of differing body size. In obese individuals, this convention results in a significantly lower indexed GFR than unindexed GFR, which has practical implications for drug dosing...
January 2018: Advances in Chronic Kidney Disease
Akash Deep, Romit Saxena, Bipin Jose
Acute kidney injury (AKI) is a common accompaniment in patients with liver disease. The causes, risk factors, manifestations and management of AKI in these patients vary according to the liver disease in question (acute liver failure, acute-on-chronic liver failure, post-liver transplantation or metabolic liver disease). There are multiple causes of AKI in patients with liver disease-pre-renal, acute tubular necrosis, post-renal, drug-induced renal failure and hepatorenal syndrome (HRS). Definitions of AKI in liver failure are periodically revised and updated, but pediatric definitions have still to see the light of the day...
March 1, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
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
Niloofar Khalili, Ali Karimi, Mohammad-Taghi Moradi, Hedayatollah Shirzad
CONTEXT: The influenza A virus (IAV) causes severe respiratory disease that remains a leading reason for morbidity and mortality. Previous studies have indicated that influenza complications in addition to viral replication are due to overproduction of pro-inflammatory cytokines. Therefore, a new compound is needed to be used with current antiviral drugs to modulate overproduction of pro-inflammatory cytokines in IAV infection. OBJECTIVE: This study investigated the effect of celastrol on mRNA expression and concentration levels of the pro-inflammatory cytokines tumor necrosis factor alpha (TNFα) and interleukin-6 (IL6) that are induced by influenza A/Puerto Rico/8/34 (H1N1; PR8) in Madin-Darby Canine Kidney (MDCK) cells...
March 1, 2018: Immunopharmacology and Immunotoxicology
Imari Mimura, Yosuke Hirakawa, Yasuharu Kanki, Ryo Nakaki, Yutaka Suzuki, Tetsuhiro Tanaka, Hiroyuki Aburatani, Masaomi Nangaku
Tubulointerstitial fibrosis has been recently reported to be caused by the collapse of the epigenetic regulation of kidney diseases. We examined whether pharmacological inhibition of histone modification is effective against renal fibrosis. DZNep (3-deazaneplanocin A) was originally developed as an anti-cancer drug to inhibit the repressive histone mark, H3K27me3. We used a model of chronic tubulointerstitial fibrosis induced by unilateral ischaemia/reperfusion and administered DZNep intravenously to the mice for 8 weeks...
February 28, 2018: Scientific Reports
Osamu Ichii, Taro Horino
Mature microRNAs (miRNAs) are single-stranded RNAs with approximately 18-25 bases, and their sequences are highly conserved among animals. miRNAs act as posttranscriptional regulators by binding mRNAs, and their main function involves the degradation of their target mRNAs. Recent studies revealed altered expression of miRNAs in the kidneys during the progression of acute kidney injury (AKI) and chronic kidney disease (CKD) in humans and experimental rodent models by using high-throughput screening techniques including microarray and small RNA sequencing...
January 2018: Journal of Toxicologic Pathology
Silvina Fernanda Ruspini, Johanna Romina Zuccoli, Jimena Verónica Lavandera, Marìa Del Carmen Martínez, Leda María Olivieri, Esther Noemí Gerez, Alcira María Del Carmen Batlle, Ana María Buzaleh
BACKGROUND: Acute intermittent porphyria (AIP) is an inherited disease produced by a deficiency of Porphobilinogen deaminase (PBGD). The aim of this work was to evaluate the effects of Isoflurane and Sevoflurane on heme metabolism in a mouse genetic model of AIP to further support our previous proposal for avoiding their use in porphyric patients. A comparative study was performed administering the porphyrinogenic drugs allylisopropylacetamide (AIA), barbital and ethanol, and also between sex and mutation using AIP (PBG-D activity 70% reduced) and T1 (PBG-D activity 50% diminished) mice...
February 21, 2018: Biochimica et Biophysica Acta
Bo Åkerström, Lena Rosenlöf, Anneli Hägerwall, Sigurbjörg Rutardottir, Jonas Ahlstedt, Maria E Johansson, Lena Erlandsson, Maria Allhorn, Magnus G Gram
AIMS: Human A1M (α1-microglobulin) is an endogenous reductase and radical- and heme-binding protein with physiological antioxidant protective functions. Recombinant human A1M (rA1M) has been shown to have therapeutic properties in animal models of preeclampsia, a pregnancy disease associated with oxidative stress. Recombinant A1M, however, lacks glycosylation, and shows lower solubility and stability than A1M purified from human plasma. The aims of this work was to 1) use site-directed mutagenesis to improve the physicochemical properties of rA1M, 2) demonstrate that the physicochemically improved rA1M displays full in vitro cell protective effects as recombinant wild-type A1M (rA1M-wt), and 3) show its therapeutic potential in vivo against acute kidney injury (AKI), another disease associated with oxidative stress...
February 22, 2018: Antioxidants & Redox Signaling
Hina Rasheed, Ruqayya Afridi, Ashraf Ullah Khan, Muhammad Zia Ullah, Sidra Khalid, Ayesha Atiq, Humaira Kashif, Muhammad Naeem Ahmed, Yeong Shik Kim, Salman Khan
Chronic inflammation is pathologically associated with various clinical conditions such as rheumatoid arthritis. Several anti-inflammatory and analgesic drugs currently available in market presents a wide range of problems. Therefore, the current study was aimed to evaluate anti-inflammatory and analgesic activities of newly synthesized compound 2-(5-mercapto-1,3,4-oxadiazol-2-yl)-N-propylbenzenesulphonamide (MOPBS). Carrageenan and CFA-induced models were developed for evaluation of anti-inflammatory and analgesic activity...
February 22, 2018: Inflammopharmacology
Ethan A Everington, Adina G Gibbard, Jerome D Swinny, Mohsen Seifi
Gamma aminobutyric acid (GABA) subtype A receptors (GABAA Rs) are integral membrane ion channels composed of five individual proteins or subunits. Up to 19 different GABAA R subunits (α1-6, β1-3, γ1-3, δ, ε, θ, π, and ρ1-3) have been identified, resulting in anatomically, physiologically, and pharmacologically distinct multiple receptor subtypes, and therefore GABA-mediated inhibition, across the central nervous system (CNS). Additionally, GABAA R-modulating drugs are important tools in clinical medicine, although their use is limited by adverse effects...
2018: Frontiers in Molecular Neuroscience
Swapnil Hiremath, Jeanne Françoise Kayibanda, Benjamin J W Chow, Dean Fergusson, Greg A Knoll, Wael Shabana, Brianna Lahey, Olivia McBride, Alexandra Davis, Ayub Akbari
BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is defined as worsening of renal function after the administration of iodinated contrast material. In patients with cardiovascular disease, kidney disease, and/or diabetes, renin-angiotensin system blockers, non-steroidal anti-inflammatory drugs, diuretics, and metformin can increase the risk of CI-AKI when undergoing contrast imaging. Despite CI-AKI being the leading iatrogenic cause of acute kidney injury, there is a lack of sufficient scientific evidence supporting which drugs should be stopped, when they should be stopped, and when they should be resumed...
February 21, 2018: Systematic Reviews
Philipp F Secker, Sascha Beneke, Nadja Schlichenmaier, Johannes Delp, Simon Gutbier, Marcel Leist, Daniel R Dietrich
Recent FDA Drug Safety Communications report an increased risk for acute kidney injury in patients treated with the gliflozin class of sodium/glucose co-transport inhibitors indicated for treatment of type 2 diabetes mellitus. To identify a potential rationale for the latter, we used an in vitro human renal proximal tubule epithelial cell model system (RPTEC/TERT1), physiologically representing human renal proximal tubule function. A targeted metabolomics approach, contrasting gliflozins to inhibitors of central carbon metabolism and mitochondrial function, revealed a double mode of action for canagliflozin, but not for its analogs dapagliflozin and empagliflozin...
February 14, 2018: Cell Death & Disease
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