Cisplatin is one of the most widelyused drugs to treat cancers. Contrastinduced nephrotoxicity in renal allograft recipients. Cisplatin, a platinumbased antineoplastic agent, is the cornerstone for the treatment of many malignancies. Nissim i, horyn o, daikhin y, nissim i, luhovyy b, phillips pc, et al.
Nephrotoxicity was reported in the initial clinical trials of cisplatin chemotherapy. As a result, bax and bak become free to form oligomer pores on the outer. The kidney is a major target for druginduced toxicity. Cisplatin induced injury to renal epithelial cells causes release of damps, which activate. Cisplatin mediates its tumorcidal effects via a number of different cytotoxic mechanisms. Review article plantderived agents for counteracting cisplatininduced nephrotoxicity shreeshojha, 1 balajivenkataraman, 1 amanikurdi, 2 eglalmahgoub, 1 bassemsadek, 1 andmohanrajrajesh 1 department of pharmacology ander apeutics, college of medicine and health sciences, united arab emirates university. Cisplatin caused a significant decrease in gentamicin clearance. Cisplatin cpinduced nephrotoxicity is widely accepted as a model for acute kidney injury aki. Evidence for interventions to prevent nephrotoxicity. Download fulltext pdf download fulltext pdf download. A wellknown side effect of cisplatin is nephrotoxicity, which is the primary doselimiting toxicity. Paracetamol, also known as acetaminophen is commonly prescribed antipyretic and analgesic drug producing dosedependent toxicity of liver and renal. Druginduced nephrotoxicity is a renal dysfunction that occurs as a result of exposure to nephrotoxic.
This leads frequently to acute kidney injury, and current problems are discussed. Recent research has shed significant new lights on the mechanism of cisplatin nephrotoxicity, especially on the signaling pathways leading to tubular cell death. It remains an important and effective therapy in many forms of cancer today. Review article plantderived agents for counteracting. The nephrotoxicity induced by cisplatin is characterized by morphological destruction of intracellular organelles, cellular necrosis, loss of microvilli, alterations in the number and size of the lysosomes and mitochondrial vacuolization, followed by functional alterations including inhibition of protein synthesis, gsh depletion, lipid. Rat or rabbit renal cortical slices were incubated for different periods of time in platinum compoundcontaining. Cisplatininduced nephrotoxicity and targets of nephroprotectionan. The role of nacetylcysteine therapy in the setting of acetaminopheninduced renal failure is unclear. Approximately 20% of nephrotoxocity is induced by drugs, but medication of the elderly increases the incidence of nephrotoxicity up to 66% as the average life span increases. The present study was conducted to investigate the efficacy of dpinitol, against cisplatininduced nephrotoxicity in swiss albino mice.
Pdf we investigated the effects of methanolic leaves extract of azadirachta indica. A casecontrol study analyzing mannitol dosing for prevention of. The toxicity of the drug has been attributed to the induction of oxidative free radicals. The effects of cisplatininduced nephrotoxicity on the pharmacokinetics of a renally excreted antibiotic, gentamicin, were studied in f344 rats. Effect of combination sildenafil and gemfibrozil on cisplatininduced. Risk factors for cisplatininduced nephrotoxicity and. Nephrotoxicity is a significant concern in pediatrics with 16% of hospitalized aki events being attributable primarily to a drug 4. See chemotherapy nephrotoxicity and dose modification in patients with renal insufficiency. Our current knowledge of drug induced kidney disease is. Acetaminopheninduced renal failure becomes evident after hepatotoxicity in most cases, but can be differentiated from the hepatorenal syndrome, which may complicate fulminant hepatic failure. The search was performed by using combinations of the following key words and or their equivalents. The laboratory observation that forced hydration and diuresis may prevent.
Druginduced nephrotoxicity can lead to acute kidney injury aki or chronic kidney disease in patients and is a major problem for clinicians 2,3. The use of cisplatin in patients with preexisting renal dysfunction and the renal effects of the platinum analogs, carboplatin and oxaliplatin, are discussed elsewhere. Neither the rates of overall nephrotoxicity, glomerular toxicity and tubular toxicity, nor the mean overall, glomerular and tubular toxicity scores differed significantly among the cpl and ct groups p. Sixty male and female wistar rats were randomly divided into five groups. Pdf protection against cisplatininduced nephrotoxicity. Effects of cisplatininduced nephrotoxicity on gentamicin. Background nephrotoxicity remains a problem for patients who receive 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. Druginduced nephrotoxicity remains a major problem in the clinical setting, where the use of nephrotoxic drugs is often unavoidable. View the article pdf and any associated supplements and figures for a period of 48 hours. Life science research center, nagano childrens hospital, azumino, japan. Nephrotoxicity is a kidneyspecific feature in which excretion does not go smoothly owing to toxic chemicals or drugs finn and porter, 2003.
Pdf cisplatin is a highly effective antitumor agent whose clinical application is limited by the inherent nephrotoxicity. Results 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. The approved therapeutic indication for immune checkpoint inhibitors cpis are rapidly expanding including treatment in the adjuvant setting, the immune related toxicities associated with cpi can limit the efficacy of these agents. Hydration in conjunction with appropriate diuresis can decrease the incidence of nephrotoxicity. Oxidative stress is caused by various freeoxygen radicals including superoxide anion, hydrogen peroxide and hydroxyl radical. In this forum, i will summarize the renal handling of the aminoglycosides, the pathogenetic mechanisms of nephrotoxicity, and the clinical aspects of aminoglycosideinduced acute renal failure. Dpinitol attenuates cisplatininduced nephrotoxicity in. Cisplatin is one of the most widely used and most potent chemotherapy drugs.
Mannitol administration has been used as a means to negate this toxicity. 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. The effect of nacetylcysteine on ifosfamideinduced nephrotoxicity. Evidence for nephrotoxicity prevention with cisplatin. Prevention of cisplatininduced nephrotoxicity by glucosides of ascorbic acid and. Recent studies have improved our understanding of the molecular mechanisms of cisplatin induced nephrotoxicity and ototoxicity. A single dose of gentamicin 30 mgkg, iv was given to different groups of rats alone, at the same time as, or on day 4, 7, 15, or 29 following cisplatin administration 6 mgkg, iv.
The potentially nephrotoxic antibiotics in current clinical use are neomycin, kanamycin, paromomycin, bacitracin, the polymyxins polymyxin b, and colistin, and amphotericin b. Cisplatin is a platinum containing drug first approved as an antineoplastic agent in 1978. Protection against cisplatininduced nephrotoxicity by spirulina in rats article pdf available in cancer chemotherapy and pharmacology 586. Nephrotoxic drug, nephrotoxin, druginduced nephrotoxicity, medication causes of acute kidney injury, medication causes of acute tubular necrosis, medication causes of interstitial nephritis, medication causes of glomerulonephritis, medication causes of prerenal failure, medication causes of postrenal failure, toxic nephropathy, drug. Cisplatin is a potent and valuable chemotherapy agent used to treat a broad spectrum of malignancies.
That means that cil not only inhibits dhpimediated metabolism toward imp, but also abolishes impinduced nephrotoxicity. Cisplatin and related platinumbased therapeutics are now being used for the. N cisplatininduced nephrotoxicity and targets of nephroprotection. Prediction of druginduced nephrotoxicity and injury. There are various forms, and some drugs may affect kidney function in more than one way. Cisplatin nephrotoxicity nephrotoxicity was reported in the initial clinical trials of cisplatin chemotherapy. Pemetrexedinduced acute kidney failure following irreversible renal damage. All the animals in groups 25 received single dose of cp 10 mgkg. This article aims to identify best practices in supportive therapy for patients. The mainstay doselimiting toxicity of cisplatin is nephrotoxicity. As patients with renal transplantation may be at a higher risk of contrastinduced nephrotoxicity cin due to concomitant use of cyclosporine and higher prevalence of diabetes and renal insufficiency, we retrospectively studied development of cin in these patients. Nephrotoxicity is the primary doselimiting toxicity, and various hydration regimens and supplementation strategies are used to prevent cisplatininduced kidney injury. Cyclosporineinduced sympathetic activation and hypertension after heart transplantation. One of the main therapeutic limitations of cisplatin cp is nephrotoxicity which is timedependent.
Prospective cohort studies of aki have documented the frequency of druginduced nephrotoxicity to be approximately 1426% in adult populations. Nephrotoxicity of immune checkpoint inhibitors beyond. Patients at highest risk of druginduced nephrotoxicity are those with one or more of the following. The literature on the nephrotoxicity of cpi is limited. Understanding the mechanism of cisplatin nephrotoxicity could lead to novel renoprotective interventions. However, nephrotoxicity is the major limiting factor for its clinical use. Druginduced nephrotoxicity and its biomarkers ncbi. Mehta2 abstract drug induced kidney injury is a frequent adverse event which contributes to morbidity and increased healthcare utilization. The 6rs of drug induced nephrotoxicity linda awdishu1,2 and ravindra l. Nephrotoxicity and clinical outcomes in patients treated. Impact of obesity on acyclovirinduced nephrotoxicity. To evaluate cisplatininduced nephrotoxicity in outpatients receiving chemotherapy with cisplatin alone or in combination with other agents using a short hydration method. It is a poisonous effect of some substances, both toxic chemicals and medications, on kidney function.
Fortynine patients enrolled in the study were monitored during 3 cycles of chemotherapy. Pdf the predictive role of the biomarker kidney molecule1 kim. Cisplatin nephrotoxicity as a model of chronic kidney. Department of laboratory medicine, nagano childrens hospital, azumino, japan. Effect of simvastatin on cisplatininduced nephrotoxicity in male rats. Melatonin ameliorates the drug induced nephrotoxicity. Nephrotoxicity of cisplatin, carboplatin and transplatin. Cisplatininduced nephrotoxicity and targets of nephroprotection. However, side effects in normal tissues and organs, notably nephrotoxicity in the kidneys, limit the use of cisplatin and related platinumbased therapeutics. Aminoglycoside nephrotoxicity kidney international. The purpose of this study was to determine the optimal timing for initiation of cp toxicity.
Azadirachta indica attenuates cisplatininduced nephrotoxicity and oxidative stress. N cisplatin induced nephrotoxicity and targets of nephroprotection. This page includes the following topics and synonyms. An integrated view of cisplatininduced nephrotoxicity and. Nephrotoxicity evaluation in outpatients treated with. Here, we present cases of biopsy proven acute tubulointerstitial nephritis atin and glomerulonephritis. Although cisplatininduced chronic kidney disease ckd in rodent has been reported, the role of. Data regarding the efficacy of mannitol use in this context are conflicting and limited.
Time course of cisplatininduced nephrotoxicity and. Pdf azadirachta indica attenuates cisplatininduced. Pdf cisplatininduced nephrotoxicity and targets of. Chemotherapyinduced tubular toxicity might be due to decreasing of mitochondrial function, interfering with tubular transport, increasing oxidative stress, and formation of free radicals. Cisplatin has been used as a chemotherapeutic agent to treat many different cancers. Pemetrexed induced acute kidney injury in patients with nonsmall cell lung cancer. Cisplatin is an anticancer agent used largely in treatment of solid tumors. We retrospectively evaluated potential risk factors for cisplatininduced nephrotoxicity as well as the potential impact of intravenous magnesium supplementation on such toxicity. Unlimited viewing of the articlechapter pdf and any associated supplements and. Although it is best known for dna damage, cisplatin also causes cytoplasmic organelle dysfunction particularly with the endoplasmic. However, its nephrotoxic and ototoxic sideeffects remain major clinical limitations. Cisplatininduced nephrotoxicity is a dose limiting adverse effect that occurs in nearly onethird of patients. Fortunately, the nephrotoxicity of each of these drugs appears.
The 6rs of drug induced nephrotoxicity bmc nephrology. Nephrotoxicity induced by imp in monkeys and rabbits, unexpectedly, was prevented completely by coadministration of cil9. Cilastatin protects against imipeneminduced nephrotoxicity via inhibition of renal organic anion transporters oats author links open overlay panel xiaokui huo a b c qiang meng a b c changyuan wang a b c yanna zhu a zhihao liu a xiaodong ma a xiaochi ma a b c. For full access to this pdf, sign in to an existing account, or purchase an annual subscription. One strategy to avoid such problems would be the development of drugs with decreased nephrotoxic potential. Molecular mechanisms of cisplatininduced nephrotoxicity.
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