scholarly journals The urinary excretion of an organic anion transporter as an early biomarker of methotrexate-induced kidney injury

2016 ◽  
Vol 5 (2) ◽  
pp. 530-538 ◽  
Author(s):  
María J. Severin ◽  
Mara S. Trebucobich ◽  
Patricia Buszniez ◽  
Anabel Brandoni ◽  
Adriana M. Torres
Keyword(s):  
Early Detection ◽  
Urinary Excretion ◽  
Organic Anion ◽  
Kidney Injury ◽  
Organic Anion Transporter ◽  
Urinary Biomarker ◽  
Anion Transporter ◽  
Early Biomarker

Oat5 urinary excretion is a novel urinary biomarker for early detection of methotrexate-induced kidney injury.

The Interaction Between Rosuvastatin and Ticagrelor Leading to Rhabdomyolysis: A Case Report and Narrative Review

2020 ◽  
pp. 001857872092826 ◽  
Author(s):  
Rachel A. Sibley ◽  
Alyson Katz ◽  
John Papadopoulos
Keyword(s):  
Organic Anion ◽  
Kidney Injury ◽  
Organic Anion Transporter ◽  
Drug Eluting Stent ◽  
Pharmacokinetic Studies ◽  
Laboratory Findings ◽  
Lower Extremity Weakness ◽  
Anion Transporter ◽  
Baseline Status ◽  
Coronary Syndromes

Objective: Drug interactions are a common cause of morbidity and mortality and may require prompt discontinuation of therapeutic regimens due to harmful side effects. Patients with acute coronary syndromes are likely to be prescribed multiple medications that are metabolized through the cytochrome P450 system, increasing the probability for drug interaction. Atorvastatin and simvastatin are both well known to interact with the oral P2Y12 agent ticagrelor. The purpose of this paper is to describe the interaction of ticagrelor with rosuvastatin leading to rhabdomyolysis, which is less clearly defined in the literature. Method: We report a case of a 74-year-old male who presented with bilateral lower extremity weakness and difficulty ambulating for one month after being prescribed ticagrelor for a drug eluting stent, in the setting of already being on rosuvastatin. His clinical picture and laboratory findings were consistent with a diagnosis of rhabdomyolysis. His medications were adjusted to a regimen of clopidogrel and alirocumab. One month later, he returned to his baseline status. Results: The mechanism of interaction between rosuvastatin and ticagrelor appears to be multifactorial. It may be caused by CYP450-mediated metabolism from a small amount of crossover between isoenzymes. Ticagrelor may also cause acute kidney injury, increasing the concentration of rosuvastatin. Other mechanisms of interaction include genetic differences in the organic anion transporter polypeptides and transportation through p-glycoprotein. Conclusion: Future pharmacokinetic studies are warranted to better understand the interaction.

Renal organic anion transporter 1 is maldistributed and diminishes in proximal tubule cells but increases in vasculature after ischemia and reperfusion

2008 ◽  
Vol 295 (6) ◽  
pp. F1807-F1816 ◽  
Author(s):  
Osun Kwon ◽  
Wei-Wei Wang ◽  
Shane Miller
Keyword(s):  
Proximal Tubule ◽  
Ischemia Reperfusion ◽  
Organic Anion ◽  
Basolateral Membrane ◽  
Kidney Injury ◽  
Organic Anion Transporter ◽  
Membrane Domain ◽  
Proximal Tubule Cells ◽  
Anion Transporter ◽  
Tubule Cells

Renal solute clearances are reduced in ischemic acute kidney injury. However, the mechanisms explaining how solute clearance is impaired have not been clarified. Recently, we reported that cadaveric renal allografts exhibit maldistribution of organic anion transporter 1 (OAT1) in proximal tubule cells after ischemia and reperfusion, resulting in impairment of PAH clearance. In the present study, we characterized renal OAT1 in detail after ischemia-reperfusion using a rat model. We analyzed renal OAT1 using confocal microscopy with a three-dimensional reconstruction of serial optical images, Western blot, and quantitative real-time RT-PCR. OAT1 was distributed to basolateral membranes of proximal tubule cells in controls. With ischemia, OAT1 decreased in basolateral membrane, especially in the lateral membrane domain, and appeared diffusely in cytoplasm. After reperfusion following 60-min ischemia, OAT1 often formed cytoplasmic aggregates. The staining for OAT1 started reappearing in lateral membrane domain 1 h after reperfusion. The basolateral membrane staining was relatively well discernable at 240 h of reperfusion. Of note, a distinct increase in OAT1 expression was noted in vasculature early after ischemia and after reperfusion. The total amount of OAT1 protein expression in the kidney diminished after ischemia-reperfusion in a duration-dependent manner until 72 h, when they began to recover. However, even at 240 h, the amount of OAT1 did not reach control levels. The kidney tissues tended to show a remarkable but transient increase in mRNA expression for OAT1 at 5 min of ischemia. Our findings may provide insights of renal OAT1 in its cellular localization and response during ischemic acute kidney injury and recovery from it.

scholarly journals Deletion of Multispecific Organic Anion Transporter Oat1/Slc22a6 Protects against Mercury-induced Kidney Injury

2011 ◽  
Vol 286 (30) ◽  
pp. 26391-26395 ◽  
Author(s):  
Adriana M. Torres ◽  
Ankur V. Dnyanmote ◽  
Kevin T. Bush ◽  
Wei Wu ◽  
Sanjay K. Nigam
Keyword(s):  
Organic Anion ◽  
Kidney Injury ◽  
Organic Anion Transporter ◽  
Anion Transporter

scholarly journals Organic Anion Transporter 5 Renal Expression and Urinary Excretion in Rats with Vascular Calcification

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
María Herminia Hazelhoff ◽  
Romina Paula Bulacio ◽  
Adriana Mónica Torres
Keyword(s):  
Urinary Excretion ◽  
Vascular Calcification ◽  
Western Blotting ◽  
Renal Injury ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Protein Levels ◽  
Anion Transporter ◽  
Male Wistar Rats ◽  
Renal Expression

It has been described renal damage in rats with vascular calcification. The organic anion transporter 5 (Oat5) is only expressed in kidney, and its urinary excretion was proposed as potential early biomarker of renal injury. The aim of this study was to evaluate the Oat5 renal expression and its urinary excretion in an experimental model of vascular calcification in comparison with traditional markers of renal injury. Vascular calcification was obtained by the administration of an overdose of vitamin D3(300,000 IU/kg, b.w., i.m.) to male Wistar rats. Oat5 urinary abundance was evaluated by Western blotting. Traditional markers of renal injury, such as creatinine and urea plasma levels, urinary protein levels, and urinary alkaline phosphatase (AP) activity, were determined using commercial kits. Histology was assessed by hematoxylin/eosin staining. Oat5 renal expression was evaluated by Western blotting and by immunohistochemistry. An increased expression of Oat5 in renal homogenates, in apical membranes, and in its urinary excretion was observed in rats with vascular calcification. The traditional parameters used to evaluate renal function were not modified, with the exception of histology. It is possible to postulate the urinary excretion of Oat5 as a potential noninvasive biomarker of renal injury associated with vascular calcification.

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