The use of cisplatin in patients with preexisting renal dysfunction and the renal effects of the platinum analogs, carboplatin and oxaliplatin, are discussed. Cisplatin has a number of side effects that can limit its use. Cisplatin is a strong cellular toxin and nephrotoxicity is one of the most important complication of this drug in clinical. For instance, nephrotoxicity from cisplatin can often be prevented by adequately hydrating the patient with iv fluids. Key words cisplatin, nephrotoxic drugs, cisplatin nephrotoxicity. The present study was designed to compare the nephrotoxicity induced by the three platinum compounds cisplatin cddp, carboplatin cbdca and transplatin tddp in vitro and to obtain information to elucidate the mechanism of platinum compoundinduced nephrotoxicity. 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. To reduce the incidence of cisplatininduced nephrotoxicity, we.
The standard approach for prevention of cin is the administration of lower doses of cisplatin in combination with full intravenous hydration prior and after cisplatin administration. Inflammation contributes to cisplatin nephrotoxicity in vivo. Cisplatin is a medicine used alone or with other therapies to treat cancer of the testicles, ovaries, or bladder the drug is also sometimes used offlabel to treat head and neck. Evaluating dose of cisplatin responsible for causing. Amifostine has been studied in an effort to prevent problems. Evidence for nephrotoxicity prevention with cisplatin therapy.
This work was in part supported by arrs slovenian research agency, programs p3054 and. Pdf prevention of cisplatin nephrotoxicity researchgate. Various regimens have been developed to treat cancer based on the type and severity of the tumor. Patients experiencing nephrotoxicity of any grade within 30 days of last cisplatin dose, as defined by nci ctcae 4. Ddp can make renal blood vessels shrink gradually, impacting the glomerular filtration rate and resulting in renal damage. The strong emetic effects of cisplatin can, however, produce dehydration. All statistics were analyzed using spss software version 17. The renal content of peroxynitrite and nitric oxide is increased in cisplatintreated rats. Retrospective analysis of cisplatin nephrotoxicity in patien.
Cisplatin is a potent and valuable chemotherapy agent used to treat a broad spectrum of malignancies. Identifying cisplatininduced kidney damage in paediatric. Cisplatin nephrotoxicity as a model of chronic kidney disease. Cisplatin treatment often produces extensive gastrointestinal side effects, which might lead to more magnesium depletion through anorexia and diarrhea. Risk factors for cisplatininduced nephrotoxicity and potential of. We focus on the docetaxel, cisplatin, and 5fluorouracil regimen, which is called the tpf regimen, where the standard dose of cisplatin is 60 mgm2. Risk factors associated with cisplatininduced nephrotoxicity. Cspm2 hydration protocol for cisplatin chemotherapy. The cisplatin concentration in proximal tubular epithelial cells is about 5 times the serum concentration. The clinical use of cisplatin is often limited due to its nephrotoxicity. Therefore, dca does not influence renal platinum levels during the critical.
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 concurrent radiother. In rodents cisplatin is usually injected intraperitoneally ip and less frequently. Cisplatin is used to treat various types of cancer. Cisplatin information, side effects, warnings and recalls. Nephrotoxicity was reported in the initial clinical trials of cisplatin chemotherapy. Nephrotoxicity doserelated and cumulative renal insufficiency is the major doselimiting toxicity of cisplatin. The univariate and multivariate analyses using a multiple regression analysis were performed to identify the independent factors associated with protection against nephrotoxicity in patients with nonsquamous nsclc who received cisplatin plus pemetrexed using the spss ibm, usa, new york, software program, version 19. Cisplatininduced nephrotoxicity may range from mild and reversible structural alterations in tubular. We first set up a model of cisplatin nephrotoxicity in fischer f344 rats bearing a syngeneic tumour transplanted by injection of 762 mat biii tumour cells.
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. Cisplatin injection can cause doserelated nephrotoxicity, including acute renal failure that becomes more prolonged and severe with repeated courses of the drug. Clinically, cisplatin nephrotoxicity is often seen after 10 days of cisplatin administration and is manifested as lower glomerular. Evaluating dose of cisplatin responsible for causing nephrotoxicity. However, cisplatinbased treatments are limited by the risk of severe and progressive toxicities, such as oto or nephrotoxicity, that can be more serious in very young children expecially when. Cisplatin nephrotoxicity can present in a number of ways table 1. One of the limiting side effects of cisplatin is nephrotoxicity where acute kidney injury aki is highly manifested. Cisplatin fda prescribing information, side effects and uses. Cisplatininduced nephrotoxicity is currently mostly prevented with hyperhydration, magnesium supplementation or mannitolinduced forced diuresis, whereas none of these measures will guarantee. Hydration with magnesium and mannitol without furosemide.
Side effects of cisplatin cisplatin injection, warnings, uses. Cisplatin and magnesium affect the same sodium and water channels in the outer medulla. There are many options to help minimize or prevent the side effects of cisplatin. Cisplatin and other platinum derivatives are the most widely used chemotherapeutic agents to treat solid tumors including ovarian, head and neck, and testicular germ cell tumors. Recommendations issued for preventing druginduced nephrotoxicity. Nephrotoxicity of cancer treatment in children medscape. Cisplatin cisplatin dose, indications, adverse effects. Preventive measures like extra hydration and forced urination can help decrease cisplatin nephrotoxicity side effects. Full text druginduced impairment of renal function ijnrd.
Nephrotoxicity renal toxicity chemotherapy side effect, causes, symptom. The mechanism bywhich cisplatin selectively killsthe proximal tubule cells is still unknown. An irritant is a chemical that can cause inflammation of the vein through which it is. Carboplatin nephrotoxicity is similar to that seen after cisplatin, but it is less frequent, usually milder and often reversible both ifosfamide and cisplatin nephrotoxicity may persist for at. If indicated, inform patients about the use of electrolyte supplements see warnings and precautions. Muraki k, koyama r, honma y, yagishita s, shukuya t, ohashi r, takahashi f, kido k, iwakami s, sasaki s, iwase a, takahashi k. If blood cell counts get very low, this can lead to bleeding problems, infections, or anemia. Concurrent use of cisplatin and other nephrotoxic agents also known to be ototoxic i. Evidence for interventions to prevent nephrotoxicity. Acute kidney injury acute renal failure explained clearly bun creatinine ratio duration. However, knowledge of the links between pathophysiological events is crucial to understanding renal syndromes caused by cisplatin.
Ifosfamide nephrotoxicity in adult patients clinical kidney. Cisplatininduced oxidative stress in the kidney may be prevented by. The nephrotoxic effect of cisplatin is cumulative and dosedependent and often. The disproportionate accumulation of cisplatin in kidney tissue contributes to cisplatininduced nephrotoxicity. Recent study in miceand rats have hypothesized that cisplatin is. Efficient drug screening and nephrotoxicity assessment on co.
Renoprotective effect of scutellarin on cisplatininduced renal injury. For the most part, the effects of these agents on tumor responses to cisplatin have not been examined. The chief limit to its greater efficacy is its nephrotoxicity, which has made it necessary both to lower its dosage and actively hydrate patients to reduce it. Nephrotoxicity of cisplatin, carboplatin and transplatin.
Renal toxicity has been noted in 28% to 36% of patients treated with a single dose of 50 mgm 2. Toxins free fulltext mechanisms of cisplatin nephrotoxicity. Cisplatin is a widely used and highly effective chemotherapeutic agent. Cisplatin dosing, indications, interactions, adverse. Ameliorative effect of daidzein on cisplatininduced. Dichloroacetate prevents cisplatininduced nephrotoxicity without. Oxidative stress and inflammation are part and parcel of cisplatininduced nephrotoxicity. Institutional open access program ioap sciforum preprints scilit sciprofiles mdpi. Renal toxicity induced by cisplatin cispt is a clinical issue in patients with or without chronic kidney disease ckd. No mortality was observed in cisplatin treated rats or the other groups at the end of the experiment. Medcram medical lectures explained clearly 542,855 views.
Pathophysiology of cisplatininduced acute kidney injury. Cisplatin nephrotoxicity refers to kidney damage, which is a major side effect of this cancer drug, especially at high doses. Cisplatin remains the pivotal chemotherapy in squamous cell carcinoma of the head and neck scchn, with nephrotoxicity considered the doselimiting toxicity. The purpose of this work is to study the role of soy isoflavone constituent, daidzein, in cisplatininduced renal damage.
Nephrotoxicity was compared between patients treated using the old protocol and. The primary lesion of cisplatin toxicity is necrosis of the proximal convoluted tubules. Scientists are unsure why cisplatin accumulates in the kidneys at higher levels than in other organs. The aim of this study is to examine the relationship of the dosage of. Nephrotoxicity can be temporary with a temporary elevation of lab values bun andor. This plasma clearance is triphasic with nearly all the drug gone in 4 h, but it has a terminal halflife of over 24 h. Rat or rabbit renal cortical slices were incubated for different periods of time in platinum compoundcontaining media 0. Developing a more clinicallyrelevant mouse model of cisplatin nephrotoxicity cierra n. In this study, we determined the effect of dichloroacetate, a novel anticancer agent, in a mouse model of cisplatininduced aki. Pretreatment with scutellarin prevented cisplatininduced decline of renal function. Certain chemotherapeutic agents and other nephrotoxic drugs can impact significantly on nephrotoxicity. Renal damage has a wide spectrum of sign symptoms e. Statistical analysis was performed with the use of sas software. Cisplatin is a potent chemotherapeutic agent, but its nephrotoxicity, which results in acute kidney injury aki, often limits its clinical application.
Aug 18, 2017 clinical implications of cisplatininduced nephrotoxicity. Ifosfamide nephrotoxicity in adult patients clinical. Each 50 ml or 100 ml amber vial of infusion concentrate contains. The protective effect of curcumin against cisplatin. Retrospective analysis of cisplatin nephrotoxicity in. Quercetin reduces cisplatin nephrotoxicity in rats without. Dichloroacetate prevents cisplatininduced nephrotoxicity.
The copper transporter ctr1 contributes to cisplatin uptake by renal tubular cells during cisplatin nephrotoxicity. Oct 26, 2010 the effects of these agents on cisplatin nephrotoxicity in vivo need to be explored. Efficient drug screening and nephrotoxicity assessment on. Results cisplatininduced nephrotoxicity was observed in 127 patients 32%. The discovery of novel approaches to prevent nephrotoxicity during cp. The severity of the nephrotoxicity can be modified by hydration. Feb 21, 2012 video of cisplatin and nephrotoxicity. Although various approaches have been developed to prevent cisplatin nephrotoxicity, such. Reactive nitrogen species have also been studied in cisplatininduced nephrotoxicity. Original article risk analysis for cisplatininduced. Mar 31, 2015 nephrotoxicity due to a aminoglycosides b cyclophosphamide c cisplatin d radiocontrast e analgesic f amphotericin g crystal forming drug 6. Quercetin reduces cisplatin nephrotoxicity in tumourbearing rats. Tubular damage represents an adverse, and often permanent, sequela of cisplatin exposure, with hypomagnesaemia the most common manifestation in both acute and chronic proximal tubular injury at a prevalence between 30 and 100% depending on the timing of investigation 2, 11, 66,67,68,69.
Electronic records of 1462 consecutive outpatients who received cisplatin at. Use cisplatin with caution in patients with preexisting. We retrospectively analyzed 84 patients treated with cisplatin. Adequate hydration is used in an effort to prevent damage. We retrospectively evaluated potential risk factors for cisplatin induced nephrotoxicity as well as the potential impact of intravenous magnesium supplementation on such toxicity.
Recent evidence has demonstrated that patients with chronic kidney disease ckd have an increased risk of developing acute kidney injury aki. Risk factors for cisplatininduced nephrotoxicity and. Nephrotoxicity of cisplatin combination chemotherapy in thoracic. Cisplatin can cause severe nephrotoxicity including acute renal failure that becomes more prolonged and severe with repeated courses of treatment. Renal toxicity typically begins during the second week after a dose of cisplatin injection. Background nephrotoxicity remains a problem for patients who receive cisplatin chemotherapy. The nephrotoxic effect of cisplatin is cumulative and dosedependent and often necessitates dose reduction or withdrawal. This medicine may lower the ability of the bone marrow to make blood cells that the body needs. Cisplatin can cause tubular toxicity, which often manifests through water and. Proximal tubular injury can result in acute kidney injury aki, which may compromise the course of chemotherapy and the prognosis.
If indicated, inform patients about the use of electrolyte supplements see warnings and precautions 5. Cisplatin dosing, indications, interactions, adverse effects. Because druginduced nephrotoxicity occurs more often in certain patients and in specific clinical situations, successful prevention necessitates knowledge of pathogenic mechanisms of renal injury, patientrelated risk factors, and drugrelated risk factors. Lung cancer is a leading cause of cancer death in japan and other developed countries. The most important rule for preventing such drug interactions is to avoid administering an alkylating drug with any other drug capable of causing similar toxicities. Diagnosis, treatment, and prevention of nephrotoxicity of. Cisplatin induced nephrotoxicity was evident by the histological damage in proximal tubular cells and by the increase in serum neutrophil gelatinaseassociated lipocalin ngal, blood. The protective effect of curcumin against cisplatininduced. Although cisplatin is one of the most widely used anticancer drugs, nephrotoxicity remains a major doselimiting side effect. Evidence for nephrotoxicity prevention with cisplatin.
All statistical analysis was conducted with the prism software package. Nephrotoxicity of cisplatin combination chemotherapy in. 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. A known complication of cisplatin administration is acute kidney injury aki. The purpose of this work is to study the role of soy isoflavone constituent, daidzein, in cisplatin induced renal damage. Nephrotoxicity is one of the most common kidney problems and occurs when your body is exposed to a drug or toxin that causes damage to your kidneys. Inform patients that cisplatin for injection can cause nephrotoxicity and that renal function and electrolyte monitoring during treatment is necessary. Diagnosis, treatment, and prevention of nephrotoxicity of cancer. A number of antiinflammatory substances reduce cisplatin nephrotoxicity in animal models table 3. Although cisplatin induced chronic kidney disease ckd in rodent has been reported, the role of.
Oxidative stress and inflammation are part and parcel of cisplatin induced nephrotoxicity. Cisplatin cpinduced nephrotoxicity is widely accepted as a model for acute kidney injury aki. Cisplatininduced oxidative stress in the kidney may be prevented by natural. This material is provided for educational purposes only. Nephrotoxicity can be induced by single or multiple applications of cisplatin. The dose should be reduced when the persons kidney function is impaired. May use concomitant amifostine to decrease nephrotoxicity. Effects of a dpp4 inhibitor on cisplatininduced acute kidney injury. Cisplatin cddp, an inorganic platinum chemotherapeutic drug, is widely administered either alone or in combination with other agents for the clinical treatment of various solid tumors, including lung, gastric, esophageal, bladder, and head and neck cancers. Cisplatin and others cisplatin nephrotoxicity robert safirstein, md, jonathan winston, md, marvin goldstein, md, donald moel, md, steven dikman, md, and joseph guttenplan, phd cis. The role of oxidantantioxidant systems in chronic nephrotoxicity is uncertain. We found that nephrotoxicity could be caused by a substantially.
Nephrotoxicity renal toxicity managing side effects chemocare. Apr 16, 2020 cisplatininduced nephrotoxicity mechanisms include the following. Sharp april 25, 2016 cisplatin is a nephrotoxic chemotherapeutic that causes acute kidney injury aki in 30% of patients. Cisplatin induced oxidative stress in the kidney may be prevented by. Nephrotoxicity is a wellknown side effect of cisplatin for cancer treatment. Hence, this study aimed to determine whether cisplatininduced renal toxicity could be. Cisplatin induces magnesium depletion, and magnesium deficiency itself may enhance cisplatin nephrotoxicity. Recovery of renal function usually occurs over a period of 24 weeks, though more. Cisplatin side effects, dosage, interactions drugs.
Different strategies have been offered to diminish or prevent nephrotoxicity of cisplatin. Cisplatin injection infusion concentrate is a clear, colorless, sterile aqueous solution available in amber vials. If the dose is found to be effective, another dose of cisplatin is often. Cisplatin platinol, cddp chemotherapy side effects, how its given, how it.