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. Nephrotoxicity of cancer treatment in children medscape. Pretreatment with scutellarin prevented cisplatininduced decline of renal function. Oct 26, 2010 the effects of these agents on cisplatin nephrotoxicity in vivo need to be explored. Risk factors for cisplatininduced nephrotoxicity and.
Cisplatin nephrotoxicity refers to kidney damage, which is a major side effect of this cancer drug, especially at high doses. Cisplatin nephrotoxicity can present in a number of ways table 1. Renal toxicity induced by cisplatin cispt is a clinical issue in patients with or without chronic kidney disease ckd. 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 dosing, indications, interactions, adverse effects. Evidence for nephrotoxicity prevention with cisplatin therapy. Key words cisplatin, nephrotoxic drugs, cisplatin nephrotoxicity. The disproportionate accumulation of cisplatin in kidney tissue contributes to cisplatininduced nephrotoxicity.
The primary lesion of cisplatin toxicity is necrosis of the proximal convoluted tubules. 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. Therefore, dca does not influence renal platinum levels during the critical. Use cisplatin with caution in patients with preexisting.
Ifosfamide nephrotoxicity in adult patients clinical. Muraki k, koyama r, honma y, yagishita s, shukuya t, ohashi r, takahashi f, kido k, iwakami s, sasaki s, iwase a, takahashi k. Diagnosis, treatment, and prevention of nephrotoxicity of. Cisplatin side effects are often predictable in terms of their onset, duration, and. To reduce the incidence of cisplatininduced nephrotoxicity, we. This work was in part supported by arrs slovenian research agency, programs p3054 and.
Nephrotoxicity is a wellknown side effect of cisplatin for cancer treatment. Efficient drug screening and nephrotoxicity assessment on co. Feb 21, 2012 video of cisplatin and nephrotoxicity. Renal damage has a wide spectrum of sign symptoms e. Cspm2 hydration protocol for cisplatin chemotherapy. 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. Amifostine has been studied in an effort to prevent problems. All statistical analyses were performed using the jmp 9. Apr 16, 2020 cisplatininduced nephrotoxicity mechanisms include the following. Quercetin reduces cisplatin nephrotoxicity in rats without. Clinically, cisplatin nephrotoxicity is often seen after 10 days of cisplatin administration and is manifested as lower glomerular.
May use concomitant amifostine to decrease nephrotoxicity. All statistics were analyzed using spss software version 17. Nephrotoxicity can be temporary with a temporary elevation of lab values bun andor. The role of oxidantantioxidant systems in chronic nephrotoxicity is uncertain. Quercetin reduces cisplatin nephrotoxicity in tumourbearing rats. 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. Ddp can make renal blood vessels shrink gradually, impacting the glomerular filtration rate and resulting in renal damage. Although various approaches have been developed to prevent cisplatin nephrotoxicity, such. Adequate hydration is used in an effort to prevent damage. Risk factors for cisplatininduced nephrotoxicity and potential of. There are many options to help minimize or prevent the side effects of cisplatin. Evaluating dose of cisplatin responsible for causing. If indicated, inform patients about the use of electrolyte supplements see warnings and precautions. Cisplatin can cause tubular toxicity, which often manifests through water and.
Nephrotoxicity can be induced by single or multiple applications of cisplatin. Renoprotective effect of scutellarin on cisplatininduced renal injury. In this study, we determined the effect of dichloroacetate, a novel anticancer agent, in a mouse model of cisplatininduced aki. The renal content of peroxynitrite and nitric oxide is increased in cisplatintreated rats. Nephrotoxicity of cisplatin combination chemotherapy in. Cisplatin is a potent and valuable chemotherapy agent used to treat a broad spectrum of malignancies.
For the most part, the effects of these agents on tumor responses to cisplatin have not been examined. Renal toxicity has been noted in 28% to 36% of patients treated with a single dose of 50 mgm 2. 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. Patients experiencing nephrotoxicity of any grade within 30 days of last cisplatin dose, as defined by nci ctcae 4. Cisplatin treatment often produces extensive gastrointestinal side effects, which might lead to more magnesium depletion through anorexia and diarrhea. 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. Hydration with magnesium and mannitol without furosemide.
Cisplatin induces magnesium depletion, and magnesium deficiency itself may enhance cisplatin nephrotoxicity. Risk factors associated with cisplatininduced nephrotoxicity. Original article risk analysis for cisplatininduced. Cisplatin fda prescribing information, side effects and uses.
For instance, nephrotoxicity from cisplatin can often be prevented by adequately hydrating the patient with iv fluids. Nephrotoxicity doserelated and cumulative renal insufficiency is the major doselimiting toxicity of cisplatin. The nephrotoxic effect of cisplatin is cumulative and dosedependent and often necessitates dose reduction or withdrawal. Cisplatin side effects, dosage, interactions drugs. Evaluating dose of cisplatin responsible for causing nephrotoxicity. 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. The cisplatin concentration in proximal tubular epithelial cells is about 5 times the serum concentration. Lung cancer is a leading cause of cancer death in japan and other developed countries. If the dose is found to be effective, another dose of cisplatin is often. Nephrotoxicity was reported in the initial clinical trials of cisplatin chemotherapy.
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. Various regimens have been developed to treat cancer based on the type and severity of the tumor. Effects of a dpp4 inhibitor on cisplatininduced acute kidney injury. Reactive nitrogen species have also been studied in cisplatininduced nephrotoxicity. Cisplatin is a widely used and highly effective chemotherapeutic agent. Developing a more clinicallyrelevant mouse model of. Evidence for nephrotoxicity prevention with cisplatin. Retrospective analysis of cisplatin nephrotoxicity in patien. We retrospectively analyzed 84 patients treated with cisplatin.
Cisplatin can cause severe nephrotoxicity including acute renal failure that becomes more prolonged and severe with repeated courses of treatment. This medicine may lower the ability of the bone marrow to make blood cells that the body needs. Scientists are unsure why cisplatin accumulates in the kidneys at higher levels than in other organs. Proximal tubular injury can result in acute kidney injury aki, which may compromise the course of chemotherapy and the prognosis. We found that nephrotoxicity could be caused by a substantially. All analyses will be performed using spss statistics software v21. Inflammation contributes to cisplatin nephrotoxicity in vivo. Cisplatin cisplatin dose, indications, adverse effects.
The purpose of this work is to study the role of soy isoflavone constituent, daidzein, in cisplatininduced renal damage. The protective effect of curcumin against cisplatin. Cisplatin remains the pivotal chemotherapy in squamous cell carcinoma of the head and neck scchn, with nephrotoxicity considered the doselimiting toxicity. Retrospective analysis of cisplatin nephrotoxicity in. Cisplatin is a potent chemotherapeutic agent, but its nephrotoxicity, which results in acute kidney injury aki, often limits its clinical application. Cisplatin definition of cisplatin by medical dictionary. Cisplatin has a number of side effects that can limit its use. One of the limiting side effects of cisplatin is nephrotoxicity where acute kidney injury aki is highly manifested. The vulnerability of the kidney to cisplatin is almost certainly related to its primary role in the excretion 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. Cisplatin is a strong cellular toxin and nephrotoxicity is one of the most important complication of this drug in clinical. Efficient drug screening and nephrotoxicity assessment on. Cisplatininduced oxidative stress in the kidney may be prevented by natural.
Different strategies have been offered to diminish or prevent nephrotoxicity of cisplatin. Cisplatin dosing, indications, interactions, adverse. The nephrotoxic effect of cisplatin is cumulative and dosedependent and often. Rat or rabbit renal cortical slices were incubated for different periods of time in platinum compoundcontaining media 0. Diagnosis, treatment, and prevention of nephrotoxicity of cancer. Sharp april 25, 2016 cisplatin is a nephrotoxic chemotherapeutic that causes acute kidney injury aki in 30% of patients. The dose should be reduced when the persons kidney function is impaired. Dichloroacetate prevents cisplatininduced nephrotoxicity without. Each 50 ml or 100 ml amber vial of infusion concentrate contains.
Evidence for interventions to prevent nephrotoxicity. All statistical analysis was conducted with the prism software package. Cisplatininduced oxidative stress in the kidney may be prevented by. 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. Cisplatin injection can cause doserelated nephrotoxicity, including acute renal failure that becomes more prolonged and severe with repeated courses of the drug. Nephrotoxicity renal toxicity managing side effects chemocare. Cisplatininduced nephrotoxicity is currently mostly prevented with hyperhydration, magnesium supplementation or mannitolinduced forced diuresis, whereas none of these measures will guarantee. We focus on the docetaxel, cisplatin, and 5fluorouracil regimen, which is called the tpf regimen, where the standard dose of cisplatin is 60 mgm2. Nephrotoxicity of cisplatin combination chemotherapy in thoracic. Nephrotoxicity of cisplatin, carboplatin and transplatin. Recovery of renal function usually occurs over a period of 24 weeks, though more. Ameliorative effect of daidzein on cisplatininduced.
No mortality was observed in cisplatin treated rats or the other groups at the end of the experiment. If indicated, inform patients about the use of electrolyte supplements see warnings and precautions 5. Toxins free fulltext mechanisms of cisplatin nephrotoxicity. Statistical analysis was performed with the use of sas software. Mar 31, 2015 nephrotoxicity due to a aminoglycosides b cyclophosphamide c cisplatin d radiocontrast e analgesic f amphotericin g crystal forming drug 6. Oxidative stress and inflammation are part and parcel of cisplatin induced nephrotoxicity.
Recent study in miceand rats have hypothesized that cisplatin is. The copper transporter ctr1 contributes to cisplatin uptake by renal tubular cells during cisplatin nephrotoxicity. Cisplatininduced nephrotoxicity may range from mild and reversible structural alterations in tubular. Cisplatin platinol, cddp chemotherapy side effects, how its given, how it. Although cisplatin induced chronic kidney disease ckd in rodent has been reported, the role of. Cisplatin injection infusion concentrate is a clear, colorless, sterile aqueous solution available in amber vials. Oxidative stress and inflammation are part and parcel of cisplatininduced nephrotoxicity. The clinical use of cisplatin is often limited due to its nephrotoxicity. 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. 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.
The discovery of novel approaches to prevent nephrotoxicity during cp. Nephrotoxicity was compared between patients treated using the old protocol and. A number of antiinflammatory substances reduce cisplatin nephrotoxicity in animal models table 3. 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. In rodents cisplatin is usually injected intraperitoneally ip and less frequently. Electronic records of 1462 consecutive outpatients who received cisplatin at. Recommendations issued for preventing druginduced nephrotoxicity. This plasma clearance is triphasic with nearly all the drug gone in 4 h, but it has a terminal halflife of over 24 h. An irritant is a chemical that can cause inflammation of the vein through which it is. Developing a more clinicallyrelevant mouse model of cisplatin nephrotoxicity cierra n. Aminoglycosides can aggravate the nephrotoxicity and electrolyte loss seen with cisplatin if given concurrently or shortly after cisplatin therapy. We retrospectively evaluated potential risk factors for cisplatin induced nephrotoxicity as well as the potential impact of intravenous magnesium supplementation on such toxicity. Cisplatin induced oxidative stress in the kidney may be prevented by.
Dichloroacetate prevents cisplatininduced nephrotoxicity. Pathophysiology of cisplatininduced acute kidney injury. Hence, this study aimed to determine whether cisplatininduced renal toxicity could be. This material is provided for educational purposes only. Inform patients that cisplatin for injection can cause nephrotoxicity and that renal function and electrolyte monitoring during treatment is necessary. Aug 18, 2017 clinical implications of cisplatininduced nephrotoxicity. The severity of the nephrotoxicity can be modified by hydration. If blood cell counts get very low, this can lead to bleeding problems, infections, or anemia. Cisplatin nephrotoxicity as a model of chronic kidney disease.
However, knowledge of the links between pathophysiological events is crucial to understanding renal syndromes caused by cisplatin. Nephrotoxicity renal toxicity chemotherapy side effect, causes, symptom. The mechanism bywhich cisplatin selectively killsthe proximal tubule cells is still unknown. A known complication of cisplatin administration is acute kidney injury aki. Although cisplatin is one of the most widely used anticancer drugs, nephrotoxicity remains a major doselimiting side effect. Ifosfamide nephrotoxicity in adult patients clinical kidney. Background nephrotoxicity remains a problem for patients who receive cisplatin chemotherapy. Recent evidence has demonstrated that patients with chronic kidney disease ckd have an increased risk of developing acute kidney injury aki. The protective effect of curcumin against cisplatininduced.
Medcram medical lectures explained clearly 542,855 views. Side effects of cisplatin cisplatin injection, warnings, uses. Cisplatin information, side effects, warnings and recalls. Cisplatin is used to treat various types of cancer. Identifying cisplatininduced kidney damage in paediatric. The use of cisplatin in patients with preexisting renal dysfunction and the renal effects of the platinum analogs, carboplatin and oxaliplatin, are discussed. Full text druginduced impairment of renal function ijnrd. Acute kidney injury acute renal failure explained clearly bun creatinine ratio duration. Results cisplatininduced nephrotoxicity was observed in 127 patients 32%. Cisplatin cpinduced nephrotoxicity is widely accepted as a model for acute kidney injury aki. 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. 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 aim of this study is to examine the relationship of the dosage of. 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.
The strong emetic effects of cisplatin can, however, produce dehydration. Certain chemotherapeutic agents and other nephrotoxic drugs can impact significantly on nephrotoxicity. Pdf prevention of cisplatin nephrotoxicity researchgate. The purpose of this work is to study the role of soy isoflavone constituent, daidzein, in cisplatin induced renal damage. Renal toxicity typically begins during the second week after a dose of cisplatin injection. 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. 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. 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. Institutional open access program ioap sciforum preprints scilit sciprofiles mdpi. Concurrent use of cisplatin and other nephrotoxic agents also known to be ototoxic i.
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