Even though the establishment of cisplatininduced nephrotoxicity can be alleviated. Genipin on cisplatin induced nephrotoxicity, hereby, solemnly declare that this thesis is original research work that has been done and prepared by me under the supervision of dr. Cisplatin cisdiamminedichloroplatinum ii is an antineoplastic agent drug, which is used in the treatment of a broad spectrum of malignancies including head and neck, esophagus, bladder, and metastatic testis, ovarian, breast and nonsmall cell lung cancer 1,2. Cisplatin is a potent and valuable chemotherapy agent used to treat a broad spectrum of malignancies. In the current study, the effects of the administration of aqueousethanolic extract of n. However, all agents also carry adverse drug effect profiles.
Rajesh mohanraj, in the college of medicine and health sciences at uaeu. Many pathways involved in cisplatin nephrotoxicity have been. Cisplatininduced nephrotoxicity is characterized by renal proximal tubular cell dysfunction. Cspm2 hydration protocol for cisplatin chemotherapy. Cisplatininduced nephrotoxicity is mediated by tumor necrosis factoralpha produced by renal parenchymal cells. Retrospective analysis of cisplatin nephrotoxicity in. Druginduced nephrotoxicity tends to be more common among certain patients and in specific clinical situations.
Cisplatininduced apoptosis and atn are reduced in caspase1deficient mice. Numerous studies have demonstrated that several mechanisms, including oxidative stress, dna damage, and inflammatory res ponses, are closely associated with cisplatininduced nephrotoxicity. Cisplatininduced nephrotoxicity and hiv associated. Such druginduced nephrotoxicity, including acute tubular necrosis, inflammation, and altered hemodynamics such as reduction of renal blood flow by the inhibition of prostaglandin, might be associated with an increased risk for cin. Cisplatininduced acute tubular injury and necrosis atiatn. Sharp april 25, 2016 cisplatin is a nephrotoxic chemotherapeutic that causes acute kidney injury aki in 30% of patients. Recommendations issued for preventing druginduced nephrotoxicity.
Nephrotoxicity is the doselimiting toxicity of cisplatin. Cisplatin csp is a potent and widely used chemotherapeutic agent. Soda pdf is the solution for users looking to merge multiple files into a single pdf document. Combine pdfs and other files word documents, excel spreadsheets, powerpoint ppt files, jpgs, pngs, and more into a single organized pdf thats.
Maakt het mogelijk om pdfbestanden samen te voegen met een simpele drag anddrop interface. In the present study, the protective role of tempol, a membranepermeable. Full text druginduced impairment of renal function ijnrd. The protective effect of nigella sativa against cisplatin. Mar 15, 2016 nephrotoxicity is the major side effect that limits the dose of cisplatin that can be safely administered, and it is a clinical problem in cancer patients who received cisplatin combination chemotherapy.
Pdf cisplatininduced nephrotoxicity and targets of. Although recovery can occur after one episode of cisplatin induced aki, studies have indicated multiple episodes may lead to the. Recent progress in the pathophysiology of acute renal failure. Cin may be preventable because its risk factors are well established and the timing of renal insult is commonly known in advance. The cisplatin template of the national comprehensive cancer network nccn. The nephrotoxicity of radiocontrast agents is largely dependent on renal function. Effect of genipin on cisplatin induced nephrotoxicity. Background druginduced nephrotoxicity is a frequent adverse event that can lead to acute or chronic kidney disease and increase the healthcare expenditure. For providing steady state plasma levels of morphine and naltrexone, an opioid antagonist, the daily doses of 5 mg kg and 20 mg kg respectively were employed for 5. Drugs can also interfere with normal transport mechanisms in the kidney, leading to a variety of electrolyte and acidbase disorders. Although recovery can occur after one episode of cisplatininduced aki, studies have indicated multiple episodes may lead to the.
Overall our results authentically confirm agao is a potent nephroprotective drug, which can be a supplementary drug to prevent cisplatininduced nephrotoxicity. Disposition and dose requirements of drugs in renal insufficiency textbook of therapeutics. Cisplatin is a highly effective antitumor agent whose clinical application is limited by the inherent nephrotoxicity. However, clinical efficacy of csp is compromised due to the elicitation of nephrotoxicity and ototoxicity. Follow these steps to quickly combine and arrange documents. Protective effect of magnesium preloading on cisplatininduced nephrotoxicity. However, serum creatinine levels and endogenous creatinine clearance are insensitive indicators of cisplatininduced glomerular toxicity, and underestimate the true frequency of nephrotoxicity. The prediction of proximal tubular toxicity during drug development remains. Data sources include ibm watson micromedex updated 10 apr 2020, cerner multum updated 6. International journal of therapeutic applications issn. Even though the establishment of cisplatin induced nephrotoxicity can be alleviated. Univariate analysis revealed that cardiac disease and use of nonsteroidal antiinflammatory drugs nsaids were associated with cisplatin induced nephrotoxicity odds ratios or 6 and 3. Mar 31, 2015 molecular mechanism of drug induced nephrotoxicity 1.
Ontogenic aspects of cisplatininduced nephrotoxicity in. Background mitochondrial dysfunction is a crucial mechanism by which cisplatin, a potent chemotherapeutic agent, causes nephrotoxicity where mitochondrial electron transport complexes are shifted mostly toward imbalanced reactive oxygen species versus energy production. Learn how to combine files into a single pdf file using adobe acrobat dc. An integrated view of cisplatininduced nephrotoxicity and. In addition to causing aki, chronic drug toxicity can, in some cases, lead to ckd and eventual endstage renal disease. Risk factors associated with cisplatininduced nephrotoxicity. Myelomalike cast nephropathy mlcn has been reported in the literature to occur in various primary renal and nonrenal diseases.
Deze gratis online tool maakt het mogelijk om meerdere pdf bestanden of afbeeldingen te combineren in een pdf document. Polyuria and hypomagnesemia, which are commonly associated with cisplatin nephrotoxicity, may be due to defects in deep nephron or collecting duct fluid and solute transport. Nephrotoxicity of cancer treatment in children medscape. Developing a more clinicallyrelevant mouse model of cisplatin nephrotoxicity cierra n. Nacetylcysteine improves renal hemodynamics in rats with. Recovery of radiolabeled cisplatin and inulin from microinjected tubules rat tubule 195mpt % recovery 3h % recovery a 94. In late 2012, the study institution began measuring serum creatinine on day 7 after administration of cisplatin to identify patients with acute renal failure.
Nephrotoxicity was reported in the initial clinical trials of cisplatin chemotherapy. Many pathways involved in cisplatin nephrotoxicity have been delineated and proposed as. Amelioration of cisplatininduced nephrotoxicity in rats by curcumin and. The biophysicist barnett rosenberg observed that an electrical field generated via platinum electrodes changed the normal short rod morphology of escherichia coli into long filaments. Exposing tubular cells to cisplatin activates signalling pathways that cause. The renal proximal tubule is a main target for druginduced toxicity. Animal models of arf glycerolinduced arf glycerolinduced arf is characterized by myoglobinuria, tubular necrosis 66 and enhanced renal vasoconstriction. Physiologic hallmarks of cisplatin nephrotoxicity cisplatin predictably lowers glomerular. Druginduced nephrotoxicity can lead to acute kidney injury aki or chronic kidney disease in patients and is a major problem for clinicians 2,3.
Importantly, nephrotoxicity was not the main doselimiting toxicity. The pathogenic mechanisms involved in glycerolinduced renal failure include ischemic injury, tubular nephrotoxicity caused by. Mesenchymal stem cells therapy in cisplatininduced nephrotoxicity. How to merge pdfs and combine pdf files adobe acrobat dc. Cisplatin induced apoptosis and atn are reduced in caspase1deficient mice. Klastersky, md renal failure in cancer patients is a common problem in oncology.
Developing a more clinicallyrelevant mouse model of. Recent studies have improved our understanding of the molecular mechanisms of cisplatin induced nephrotoxicity and ototoxicity. No file limit, no ad watermarks a free and beautiful tool to combine your pdf files exactly the way you want it. Sep 17, 2015 cisplatin is one of the most widelyused drugs to treat cancers. Druginduced acute renal hemodynamic dysfunction leads to renal tissue damage and further progression to renal failure 2,3. Nacetylcysteine and renal hemodynamics in cpinduced nephrotoxicity. Hydration with magnesium and mannitol without furosemide. Contrastinduced nephrotoxicity cin is a form of acute kidney injury that follows intravascular contrast media exposure. General preventive measures include using alternative.
The laboratory observation that forced hydration and diuresis may prevent. Effect of treatment with saline, nacetylcysteine nac, 500 mg kg. Genipin on cisplatininduced nephrotoxicity, hereby, solemnly declare that this thesis is original research work that has been done and prepared by me under the supervision of dr. Protective effect of magnesium preloading on cisplatin. In this study, we investigated the morphine effects on nephrotoxicity induced by cisplatin in rats. The cisplatin nephrotoxicity is a major limiting factors in 20% of patients who have received the drug, triggering injuries in renal tubular epithelialcells. Light microscopy of the kidney biopsy specimen reveals dilated tubules with. Some patientrelated risk factors for druginduced nephrotoxicity are age older than 60 years, underlying renal insufficiency e. A histological, ultrastructural and biochemical study in adult albino rats yassa, hanan dawood, gergis, safwat wadie, abdel raheem, hassan on. Therefore, successful prevention requires knowledge of pathogenic mechanisms of renal injury, patientrelated risk factors, drugrelated risk factors, and preemptive measures, coupled with early identification and intervention.
Nephrotoxicity is the most wellknown and clinically important toxicity. Our results emphasize the importance of close monitoring and additional replacement of water and electrolytes as needed. Risk factors for nephrotoxicity associated with cisplatin. Such drug induced nephrotoxicity, including acute tubular necrosis, inflammation, and altered hemodynamics such as reduction of renal blood flow by the inhibition of prostaglandin, might be associated with an increased risk for cin. Jun 14, 2012 neife aparecida guinaim dos santos, maria augusta carvalho rodrigues, nadia maria martins and antonio cardozo dos santos 2012, this issue cisplatin induced nephrotoxicity and targets of nephroprotection. Nephrotoxins are the agents displaying nephrotoxicity. Amelioration of cisplatininduced nephrotoxicity in rats.
Drug induced nephrotoxicity is one of the leading causes of aki worldwide. However, contrastinduced nephrotoxicity is still the third leading cause of iatrogenic renal failure. This is discussed in detail by price et al in this issue of seminars. Nephrotoxicity induced by cancer chemotherapy with special. Development of less nephrotoxic drugs is challenging due to the fact that the prediction of nephrotoxicity during drug development remains difficult. Cisplatin remains the pivotal chemotherapy in squamous cell carcinoma of the head and neck scchn, with nephrotoxicity considered the doselimiting toxicity. Cisplatin induced aki was observed in 18 patients 21.
Retrospective analysis of cisplatin nephrotoxicity in patien. The nephrotoxic effect develops more in patients who are already suffering from the renal impairment. In this study the protective effect of nigella sativa n. Drug induced acute renal hemodynamic dysfunction leads to renal tissue damage and further progression to renal failure 2,3. The laboratory observation that forced hydration and diuresis may prevent nephrotoxicity facilitated the subsequent clinical development of cisplatin. Pharmaceutical agents provide diagnostic and therapeutic utility that are central to patient care. The chronic administration of certain drugs causes nephrotoxicity. Cisplatin interferes with the transport of water and renal tubular cell nutrients. After excluding an electric field effect, analysis of. Renal vulnerability to drug toxicity nephrology selfassessment program vol 9, no 4, july 2010 clin j am soc nephrol 4.
Cisplatininduced kidney dysfunction and perspectives on. In this study, i have investigated the nephroprotective effects of a phytochemical genipin gp isolated from gardenia flower gardenia jasminoides, on a murine model of cisplatininduced nephropathy. Mesenchymal stem cells therapy in cisplatininduced. A read is counted each time someone views a publication summary such as the title, abstract, and list of authors, clicks on a figure, or views or downloads the fulltext. Univariate analysis revealed that cardiac disease and use of nonsteroidal antiinflammatory drugs nsaids were associated with cisplatininduced nephrotoxicity odds ratios or 6 and 3. Finally, determination of a patients or donors genotype of drugmetabolizing genes or of mol ecules involved in csa nephrotoxicity, like tgf. The prediction of proximal tubular toxicity during drug development remains difficult. Patients at highest risk of drug induced nephrotoxicity are those with one or more of the following. Cellular mechanism of drug nephrotoxicity see chapter 104. Numerous studies have demonstrated that several mechanisms, including oxidative stress, dna damage, and inflammatory res ponses, are closely associated with cisplatin induced nephrotoxicity.
Muraki k, koyama r, honma y, yagishita s, shukuya t, ohashi r, takahashi f, kido k, iwakami s, sasaki s, iwase a, takahashi k. The discovery of cisplatins cytotoxic effect was observed serendipitously in 1960s. Druginduced impairment of renal function george sunny pazhayattil, anushree c shirali section of nephrology, yale university school of medicine, new haven, ct, usa abstract. Renal tubular dysfunction and a cumulative impairment in renal function, as manifested by a decline in the glomerular filtration rate gfr, can be dose limiting. International journal of therapeutic applications, volume 27, 2015, 1622 16 abrogation of cisplatininduced nephrotoxicity in rats by lycopene through ameliorating oxidative stress, inflammation and apoptosis elsayed m. However, contrast induced nephrotoxicity is still the third leading cause of iatrogenic renal failure. This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. However, the most serious and one of the more common presentations is acute kidney injury aki which occurs in 2030% of patients.
Nephrotoxicity of cisplatin combination chemotherapy in. The prevalence of cisplatininduced nephrotoxicity varies between 5% and 45%, depending on the study and the definitions used. Moreover, great at tention should be paid to drug interactions. A retrospective study tatsuya yoshida1, seiji niho1, mayuko toda2, koichi goto1, kiyotaka yoh1, shigeki umemura1, shingo matsumoto1, hironobu ohmatsu1 and yuichiro ohe1 1division of thoracic oncology, national cancer center hospital east, kashiwa, chiba and 2division of pharmacy. Contrast induced nephrotoxicity cin is a form of acute kidney injury that follows intravascular contrast media exposure. Morphine aggravates cisplatininduced nephrotoxicity an. Early detection of druginduced renal hemodynamic dysfunction. The purpose of our study was to propose an outpatient highdose cisplatin protocol aimed at preventing nephrotoxicity and to analyze the results of its utilization in patients with scchn treated with. Prediction of druginduced nephrotoxicity and injury. Risk factors for nephrotoxicity associated with cisplatin abstract background. Transport is mediated by sodium pumps in the apical and basolateral face of the cells, such as nakatpase, nak2cl cotransporter, and type iii nah exchanger, and. Neife aparecida guinaim dos santos, maria augusta carvalho rodrigues, nadia maria martins and antonio cardozo dos santos 2012, this issue cisplatininduced nephrotoxicity and targets of nephroprotection.
Hydration with magnesium and mannitol without furosemide prevents the nephrotoxicity induced by cisplatin and pemetrexed in patients with advanced nonsmall cell lung cancer. Cisplatin nephrotoxicity can present in a number of ways including hypomagnesaemia, increased serum creatinine and urea. Cisplatininduced aki was observed in 18 patients 21. Jul 27, 2015 the renal proximal tubule is a main target for drug induced toxicity. A consistent method of measuring and reporting chemotherapy induced nephrotoxicity would be a valuable contribution to the literature. Myeloma cast nephropathy is an obstructing disorder of renal tubules, caused by precipitation of bence jones proteins. However, its nephrotoxic and ototoxic sideeffects remain major clinical limitations. Recent evidence has demonstrated that patients with chronic kidney disease ckd have an increased risk of developing acute kidney injury aki. We present a series of three rare cases of cast nephropathy, two of which are hiv patients, and the third patient is receiving cisplatin.
Cisplatininduced nephrotoxicity and protective supplements it observed increment in mrna levels of inos in the kidney 4 h after cddp injection, and administration of. Low single nephron glomerular filtration rates sngfr during early cisplatinum induced acute renal failure is accompanied by reduced renal. Effect of genipin on cisplatin induced nephrotoxicity by. The current measures of nephroprotection used in patients receiving cisplatin are not satisfactory, and studies have focused on the investigation of new possible protective strategies. How to combine files into a pdf adobe acrobat dczelfstudies. Nephrotoxicity induced by cancer chemotherapy with special emphasis on cisplatin toxicity f. Pdf merge combine pdf files free tool to merge pdf online. A free and open source software to merge, split, rotate and extract pages from pdf files. Diabetes mellitus does not add greatly to the risk of radiocontrast nephrotoxicity. Cisplatin is a strong cellular toxin and nephrotoxicity is one of the most important complication of this drug in clinical. Nephrotoxicity is the major side effect that limits the dose of cisplatin that can be safely administered, and it is a clinical problem in cancer patients who received cisplatin combination chemotherapy. Drug induced nephrotoxicity tends to be more common among certain patients and in specific clinical situations. Cisplatin induced nephrotoxicity occurs in about onethird of patients who receive this chemotherapy drug. Amelioration of cisplatininduced nephrotoxicity in rats by.
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