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https://www.readbyqxmd.com/read/28550055/potential-drug-interactions-mediated-by-renal-organic-anion-transporter-oatp4c1
#1
Toshihiro Sato, Eikan Mishima, Nariyasu Mano, Takaaki Abe, Hiroaki Yamaguchi
OATP4C1 is an organic anion transporter expressed in the basolateral membrane of the renal proximal tubules. It plays a major role in the urinary excretion of both exogenous drugs and endogenous compounds. Our previous studies have indicated the importance of OATP4C1 in pathological and physiological conditions; however, the majority of its pharmacological characteristics remained unclear. Therefore, to provide essential information for clinical drug therapy decisions and drug development, we, in this study, attempted to clarify drug interactions mediated by OATP4C1...
May 26, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28549670/cilastatin-attenuates-vancomycin-induced-nephrotoxicity-via-p-glycoprotein
#2
Dai Sig Im, Hye Jin Shin, Keum Jin Yang, So Young Jung, Ho Yeon Song, Hyeon Seok Hwang, Hyo-Wook Gil
BACKGROUND: Oxidative stress is one of the main pathogenic mechanisms in vancomycin-induced nephrotoxicity (VIN). Some studies suggest proximal renal tubular cell necrosis by vancomycin accumulation as a mechanism of nephrotoxicity, and other studies demonstrate that cilastatin has protective effects against drug-induced nephrotoxicity. We investigated whether cilastatin regulates P-gp expression and whether cilastation prevents VIN. MATERIALS AND METHODS: We conducted an in vitro study using an immortalized proximal tubule epithelial cell line from a normal adult human kidney (HK-2) and an in vivo study using male C57BL/6J mice...
May 23, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28545475/urinary-neprilysin-in-the-critically-ill-patient
#3
Sahra Pajenda, Karl Mechtler, Ludwig Wagner
BACKGROUND: Critically ill patients in intensive care face hazardous conditions. Among these, acute kidney injury (AKI) is frequently seen as a result of sepsis. Early diagnosis of kidney injury is of the utmost importance in the guidance of interventions or avoidance of treatment-induced kidney injury. On these grounds, we searched for markers that could indicate proximal tubular cell injury. METHODS: Urine samples of 90 patients admitted to the intensive or intermediate care unit were collected over 2 to 5 days...
May 25, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28545410/combined-proximal-tubulopathy-crystal-storing-histiocytosis-and-cast-nephropathy-in-a-patient-with-light-chain-multiple-myeloma
#4
Chung-Kuan Wu, An-Hang Yang, Hung-Chih Lai, Bing-Shi Lin
BACKGROUND: The diagnosis of myeloma, a plasma dyscrasia, often results from the workup of unexplained renal disease. Persistent renal failure in myeloma is commonly caused by tubular nephropathy due to circulating immunoglobulins and free light chains. Myeloma cast nephropathy is characterized by crystalline precipitates of monoclonal light chains within distal tubules. Immunoglobulin crystallization rarely occurs intracellularly, within proximal tubular cells (light chain proximal tubulopathy) and interstitial histiocytes (crystal-storing histiocytosis)...
May 25, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28542560/adiponectin-attenuates-high-glucose-induced-apoptosis-through-the-ampk-p38-mapk-signaling-pathway-in-nrk-52e-cells
#5
Yuanyuan Wang, Juan Zhang, Lian Zhang, Ping Gao, Xiaoyan Wu
Excessive apoptosis of proximal tubule cell is closely related to the development of diabetes. Recent evidence suggests that adiponectin (ADPN) protects cells from high glucose induced apoptosis. However, the precise mechanisms remain poorly understood. We sought to investigate the role of p38 mitogen-activated protein kinase (p38 MAPK) and AMP activated protein kinase (AMPK) in anti-apoptotic of adiponectin under high glucose condition in rat tubular NRK-52E cells. Cells were cultured in constant and oscillating high glucose media with or without recombinant rat adiponectin for 48 h...
2017: PloS One
https://www.readbyqxmd.com/read/28536217/caution-advised-with-dapagliflozin-in-the-setting-of-male-urinary-tract-outlet-obstruction
#6
Victoria Hall, Jason Kwong, Douglas Johnson, Elif Ilhan Ekinci
We describe an adverse outcome in a 70-year-old man with type 2 diabetes mellitus treated with sodium-glucose cotransporter type 2 (SGLT2) inhibitor dapagliflozin. SGLT2 inhibitors act in the proximal tubules to prevent glucose reabsorption and induce urinary glucose excretion, they have been associated with increased risk of urinary tract infection (UTI). Our patient presented to hospital with Escherichia coli septicaemia with positive urine and blood cultures on the background of two previous UTIs occurring post commencement of dapagliflozin in the community...
May 22, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28534445/differential-expression-of-micro-rnas-and-their-predicted-targets-in-renal-cells-exposed-to-amphotericin-b-and-its-complex-with-copper-ii-ions
#7
Joanna Magdalena Gola, Barbara Strzałka-Mrozik, Celina Kruszniewska-Rajs, Jolanta Adamska, Mariusz Gagoś, Urszula Mazurek
MicroRNAs (miRNAs) have been reported to regulate essential biological processes, and their expression was shown to be affected by pathological processes and drug-induced toxicity. Amphotericin B (AmB) can cause liver and kidney injury, but a recently developed complex of AmB with copper (II) ions (AmB-Cu(2+)) exhibits a lower toxicity to human renal cells while retaining a high antifungal activity. The aim of our study was to assess AmB-Cu(2+)- induced changes in the miRNA profile of renal cells and to examine which biological processes are significantly affected by AmB-Cu(2+)...
May 23, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28526628/heparin-based-hydrogels-induce-human-renal-tubulogenesis-in-vitro
#8
Heather M Weber, Mikhail V Tsurkan, Valentina Magno, Uwe Freudenberg, Carsten Werner
Dialysis or kidney transplantation is the only therapeutic option for end stage renal disease. Accordingly, there is a large unmet clinical need for new causative therapeutic treatments. Obtaining robust models that mimic the complex nature of the human kidney is a critical step in the development of new therapeutic strategies. Here we establish a synthetic in vitro human renal tubulogenesis model based on a tunable glycosaminoglycan-hydrogel platform. In this system, renal tubulogenesis can be modulated by the adjustment of hydrogel mechanics and degradability, growth factor signaling, and the presence of insoluble adhesion cues, potentially providing new insights for regenerative therapy...
May 16, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28525621/ros-induced-store-operated-ca2-entry-coupled-to-parp-1-hyperactivation-is-independent-of-parg-activity-in-necrotic-cell-death
#9
Frances M Munoz, Fengjiao Zhang, Argel Islas-Robles, Serrine S Lau, Terrence J Monks
2,3,5-tris(Glutathion-S-yl)hydroquinone (TGHQ), a potent nephrotoxic and nephrocarcinogenic metabolite of benzene and hydroquinone, generates reactive oxygen species (ROS) causing DNA strand breaks and the subsequent activation of DNA repair enzymes, including poly(ADP-ribose) polymerase (PARP)-1. Under robust oxidative DNA damage, PARP-1 is hyperactivated, resulting in the depletion of NAD+ and ATP with accompanying elevations in intracellular calcium concentrations (iCa2+), and ultimately necrotic cell death...
May 19, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28521134/dynamic-palmitoylation-targets-map6-to-the-axon-to-promote-microtubule-stabilization-during-neuronal-polarization
#10
Elena Tortosa, Youri Adolfs, Masaki Fukata, R Jeroen Pasterkamp, Lukas C Kapitein, Casper C Hoogenraad
Microtubule-associated proteins (MAPs) are main candidates to stabilize neuronal microtubules, playing an important role in establishing axon-dendrite polarity. However, how MAPs are selectively targeted to specific neuronal compartments remains poorly understood. Here, we show specific localization of microtubule-associated protein 6 (MAP6)/stable tubule-only polypeptide (STOP) throughout neuronal maturation and its role in axonal development. In unpolarized neurons, MAP6 is present at the Golgi complex and in secretory vesicles...
May 17, 2017: Neuron
https://www.readbyqxmd.com/read/28515173/heme-oxygenase-1-mitigates-ferroptosis-in-renal-proximal-tubule-cells
#11
Oreoluwa Adedoyin, Ravindra Boddu, Amie M Traylor, Jeremie M Lever, Subhashini Bolisetty, James George, Anupam Agarwal
Ferroptosis is an iron-dependent form of regulated, non-apoptotic cell death, which contributes to damage in models of acute kidney injury (AKI). Heme oxygenase-1 (HO-1) is a cytoprotective enzyme induced in response to cellular stress, and is protective against AKI due to its anti-apoptotic and anti-inflammatory properties. However, the role of HO-1 in regulating ferroptosis is unclear. The purpose of this study was to elucidate the role of HO-1 in regulating ferroptotic cell death in renal proximal tubule cells (PTCs)...
May 17, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28515088/loss-of-nherf-1-expression-prevents-dopamine-mediated-na-k-atpase-regulation-in-renal-proximal-tubule-cells-from-rat-models-of-hypertension-aged-f344-and-shrs
#12
Michelle T Barati, Corey J Ketchem, Michael L Merchant, Walter B Kusiak, Pedro A Jose, Edward J Weinman, Amanda J LeBlanc, Eleanor D Lederer, Syed J Khundmiri
Dopamine decreases Na-K ATPase (NKA) activity by PKC-dependent phosphorylation and endocytosis of the NKA alpha1. Dopamine-mediated regulation of NKA is impaired in aging and some forms of hypertension. Using opossum (OK) proximal tubule cells (PTCs), we demonstrated that sodium-hydrogen exchanger regulatory factor-1 (NHERF-1) associates with NKA alpha1 and dopamine-1 receptor (D1R). This association is required for the dopamine-mediated regulation of NKA. In OK cells dopamine decreases NHERF-1 association with NKA alpha1 but increases its association with D1R...
May 17, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28511711/sglt2-inhibitors-a-novel-choice-for-the-combination-therapy-in-diabetic-kidney-disease
#13
REVIEW
Honghong Zou, Baoqin Zhou, Gaosi Xu
Diabetic kidney disease (DKD) is the most common cause of end stage renal disease. The comprehensive management of DKD depends on combined target-therapies for hyperglycemia, hypertension, albuminuria, and hyperlipaemia, etc. Sodium-glucose co-transporter 2 (SGLT2) inhibitors, the most recently developed oral hypoglycemic agents acted on renal proximal tubules, suppress glucose reabsorption and increase urinary glucose excretion. Besides improvements in glycemic control, they presented excellent performances in direct renoprotective effects and the cardiovascular (CV) safety by decreasing albuminuria and the independent CV risk factors such as body weight and blood pressure, etc...
May 16, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28509131/growth-hormone-therapy-for-a-patient-with-idiopathic-fanconi-syndrome-and-growth-hormone-deficiency
#14
Takayuki Okamoto, Yasuyuki Sato, Takeshi Yamazaki, Asako Hayashi, Toshiyuki Takahashi
Idiopathic Fanconi syndrome (FS) is characterized by a generalized dysfunction of the renal proximal tubules. Patients with FS often exhibit growth retardation due to complex factors, such as hypophosphatemia, metabolic acidosis, disturbed vitamin D metabolism and hypokalemia. To date, one FS patient has been reported to exhibit growth failure due to growth hormone deficiency (GHD), but the long-term clinical course of recombinant human GH (rhGH) therapy has not been reported. At 10 months of age, the patient was admitted to our hospital due to growth failure...
May 2017: CEN Case Reports
https://www.readbyqxmd.com/read/28508985/light-chain-fanconi-syndrome-in-a-patient-with-acute-myeloid-leukemia-and-monoclonal-gammopathy-of-undetermined-significance
#15
Daniel W Ross, Rimda Wanchoo, Adriana Guigova, Cristina Ghiuzeli, Steven L Allen, Kenar D Jhaveri
Proximal tubules are a target for paraproteinemic diseases. Cast nephropathy, light chain deposition diseases, and amyloidosis are frequently encountered in patients with multiple myeloma. Rarely, a subset of patients develop light chain Fanconi syndrome (LCFS). LCFS has been reported with multiple myeloma, monoclonal gammopathy of renal significance (MGRS), chronic lymphocytic leukemia, Waldenstrom's macroglobulinemia and diffuse large B-cell lymphoma. No cases have been described with other hematologic malignancies...
November 2016: CEN Case Reports
https://www.readbyqxmd.com/read/28506883/effects-of-cardiotonic-steroids-on-isolated-perfused-kidney-and-nhe3-activity-in-renal-proximal-tubules
#16
Alana N Godinho, Graciana T Costa, Nádia O Oliveira, Bruno A Cardi, Daniel Esdras A Uchoa, Edilberto R Silveira, Luis Eduardo M Quintas, François G Noël, Manassés C Fonteles, Krishnamurti M Carvalho, Cláudia F Santos, Lucília M A Lessa, Nilberto R F do Nascimento
Cardiotonic steroids (CS) are known as modulators of sodium and water homeostasis. These compounds contribute to the excretion of sodium under overload conditions due to its natriuretic property related to the inhibition of renal Na(+)/K(+)-ATPase (NKA) pump α1 isoform. NHE3, the main route for Na(+) reabsorption in the proximal tubule, depends on the Na(+) gradient generated by NKA pump. In the present study we aimed to investigate the effects of marinobufagin (MBG) and telocinobufagin (TBG) on the renal function of isolated perfused rat kidney and on the inhibition of NKA activity...
May 12, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28496550/efficacy-and-safety-of-sglt2-inhibitors-in-reducing-glycated-hemoglobin-and-weight-in-emirati-patients-with-type-2-diabetes
#17
Alaaeldin Bashier, Azza Abdulaziz Khalifa, Fauzia Rashid, Elamin Ibrahim Abdelgadir, Amina Adil Al Qaysi, Razan Ali, Ahmed Eltinay, Jalal Nafach, Fatima Alsayyah, Fatheya Alawadi
BACKGROUND: SGLT2 inhibitors are a new class of drugs that act by inhibiting glucose reabsorption in the proximal renal tubules. Many trials have demonstrated their effectiveness in reducing glycated hemoglobin (HbA1c) and weight, but they have never been examined in Arab or Emirati populations. METHODS: We assessed the efficacy of SGLT2 inhibitors in reducing HbA1c and weight in our population and specifically in an Emirati cohort. We also assessed the effect on fasting blood glucose, blood pressure, lipid profile, serum creatinine, and side effects...
June 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28494417/the-role-of-free-kappa-and-lambda-light-chains-in-the-pathogenesis-and-treatment-of-inflammatory-diseases
#18
REVIEW
Mojgan Esparvarinha, Hamid Nickho, Hamed Mohammadi, Leili Aghebati-Maleki, Jalal Abdolalizadeh, Jafar Majidi
Kappa (κ) or lambda (λ) free light chains (FLCs) are produced from B cells during immunoglobulin synthesis. FLCs have been shown to participate in several key processes of immune responses. They are necessary to adjust PMN functions and assist PMN pre-stimulation. Moreover, they cause mast cell degranulation which releases pro-inflammatory mediators and stimulates local inflammatory responses in some conditions such as inflammatory bowel disease (IBD). Having low molecular weights which may straightly be toxic to proximal tubule cells (PTCs), FLCs can also have an important role in renal diseases...
May 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28493961/aldosterone-signaling-regulates-the-over-expression-of-claudin-4-and-8-at-the-distal-nephron-from-type-1-diabetic-rats
#19
Eduardo Molina-Jijón, Rafael Rodríguez-Muñoz, Ricardo González-Ramírez, Carmen Namorado-Tónix, José Pedraza-Chaverri, Jose L Reyes
Hyperglycemia in diabetes alters tight junction (TJ) proteins in the kidney. We evaluated the participation of aldosterone (ALD), and the effect of spironolactone (SPL), a mineralocorticoid receptor antagonist, on the expressions of claudin-2, -4, -5 and -8, and occludin in glomeruli, proximal and distal tubules isolated from diabetic rats. Type 1 diabetes was induced in female Wistar rats by a single tail vein injection of streptozotocin (STZ), and SPL was administrated daily by gavage, from days 3-21. Twenty-one days after STZ injection the rats were sacrificed...
2017: PloS One
https://www.readbyqxmd.com/read/28493713/cetuximab-prevents-methotrexate-induced-cytotoxicity-in-vitro-through-epidermal-growth-factor-dependent-regulation-of-renal-drug-transporters
#20
Pedro Caetano-Pinto, Amer Jamalpoor, Janneke Ham, Anastasia Goumenou, Monique Mommersteeg, Dirk Pijnenburg, Rob Ruijtenbeek, Natalia Sánchez-Romero, Bertrand van Zelst, Sandra Heil, Jitske Jansen, Martijn J Wilmer, Carla M L van Herpen, Rosalinde Masereeuw
The combination of methotrexate with epidermal growth factor receptor (EGFR) recombinant antibody, cetuximab, is currently being investigated in treatment of head and neck carcinoma. As methotrexate is cleared by renal excretion, we studied the effect of cetuximab on renal methotrexate handling. We used human conditionally immortalized proximal tubule epithelial cells over-expressing either organic anion transporter 1 or 3 (ciPTEC-OAT1/ciPTEC-OAT3) to examine OAT1 and OAT3, and the efflux pumps breast cancer resistance protein (BCRP), multidrug resistance protein 4 (MRP4) and P-glycoprotein (P-gp) in methotrexate handling upon EGF and/or cetuximab treatment...
May 11, 2017: Molecular Pharmaceutics
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