An integrated view of cisplatininduced nephrotoxicity and. The 3 clinical syndromes that can be recognised in drug induced nephropathy are acute renal failure, chronic interstitial nephritis and the nephrotic syndrome. 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. Various regimens have been developed to treat cancer based on the type and severity of the tumor. Protective role of hydroalcoholic extract of ficus carica. The aim of the present study is to investigate the effect of microwaveassisted processing on the protective effect of ginseng and. Consistently, there was a significant correlation between plasma cadmium level and alteration of renal function in cervical cancer patients who underwent chemotherapy with cisplatin. Gentamicin gm induced nephrotoxicity limits its longterm clinical use. Of independent risk factors amikacin or cyclosporine treatment, mean daily. Although aminoglycoside induced nephrotoxicity has been the subject of multiple studies, the short and longterm effect of aminoglycosides administration on the developing kidney of the fetus or premature newborn has not yet been determined. The cisplatin nephrotoxicity is a major limiting factors in 20% of patients who have received the. Klastersky, md renal failure in cancer patients is a common problem in oncology.
Full text druginduced impairment of renal function ijnrd. The chronic administration of certain drugs causes nephrotoxicity. Pharmaceutical agents provide diagnostic and therapeutic utility that are central to patient care. Effect of crocus sativus on gentamicin induced nephrotoxicity scielo. Cisplatin induced nephrotoxicity is characterized by renal proximal tubular cell dysfunction. Previous studies have suggested that the incidence of amphotericin b induced nephrotoxicity may be as high as 80%.
Nephrotoxicity induced by cancer chemotherapy with special emphasis on cisplatin toxicity f. Numerous studies have demonstrated that several mechanisms, including oxidative stress, dna damage, and inflammatory res ponses, are closely associated with cisplatin induced nephrotoxicity. Prevention of cisplatin induced nephrotoxicity despite the recent advances in understanding the mechanism of cisplatin induced nephrotoxicity, prevention still relies on drug dosage decrease, specific measures of hydration, and active screening for renal abnormalities as part. C 7, 10, 32, 48 druginduced renal impairment is generally reversible, provided the nephrotoxicity is recognized early and the offending medication is discontinued. Pdf role of curcumin in prevention of cisplatininduced. Druginduced nephrotoxicity analysis in hiv therapy. Original article serum metabonomic analysis of rats with cisplatin induced nephrotoxicity and panax notoginseng saponins treatment yue qiu, yufang yang, zhenguang huang, xiaoqin zou, jinling zhou, xinwen liu department of pharmacy, the first affiliated hospital of guangxi medical university, nanning, guangxi, peoples republic of china. There is a growing number of hospitalised patients who develop a drug induced renal problem because increasing numbers of potent drugs have been added to the therapeutic arsenal in recent years. Version 2020 of the acr manual on contrast media was published in january 2020 as a webbased product. Nephrotoxins are the agents displaying nephrotoxicity. This lack of specificity and sensitivity can lead to false positive and false.
Frontiers sirt1 mediates effects of fgf21 to ameliorate. A combination of csainduced hemodynamic changes and direct toxic effects of csa on tubular epithelial cells is thought to play a role 19. Development of less nephrotoxic drugs is challenging due to the fact that the prediction of nephrotoxicity during. It is a poisonous effect of some substances, both toxic chemicals and medications, on kidney function. Cspm2 hydration protocol for cisplatin chemotherapy. Protective effects of processed ginseng and its active. The severe nephrotoxicity was reversible and was rarely associated with dialysis. The authors of the report found that the nephrotoxicity might have been prevented if the vancomycin levels had been measured sooner. While most of these are clinically insignificant, some drugs. Moreover, cadmium exposure markedly exacerbated nephrotoxicity induced by cisplatin, an oct2 substrate, by increasing its accumulation in the mouse kidney. Previous investigations showed that panax ginseng contains components that exhibit protective activity against cisplatin induced nephropathy.
Data was collected from clinical files and students t testp were used as statistical tests. Hewei granules hwkl combat cisplatin induced nephrotoxicity and myelosuppression in rats by inhibiting oxidative stress, inflammatory cytokines and apoptosis zehai song, a hang chang, a na han, a zhihui liu, a ye liu, b hui wang, b jingxuan shao, a zhonglin wang, a hao gao a and jun yin a. Kidney function is closely related to patients quality of life and tumor prognosis. Cisplatin induced aki was observed in 18 patients 21. Recognition of druginduced nephrotoxicity as a signi ficant contributor to kidney. Preincubation with hucmscexosomes prevents cisplatininduced.
The nephrotoxic effect develops more in patients who are already suffering from the renal impairment. The degree of vancomycin induced renal dysfunction is usually modest, with a typical decrease of 3545% in creatinine clearance from baseline. Many pathways involved in cisplatin nephrotoxicity have been delineated and proposed as. Prediction of druginduced nephrotoxicity and injury. Drugs that may increase the risk of csaassociated nephrotoxicity 115. Cisplatininduced nephrotoxicity primarily occurs in kidney proximal tubule epithelial cells, neurotoxicity in the upper and lower extremities, and ototoxicity within the mechanosensory outer hair cells of the cochlea. Several agentsstrategies were attempted to prevent gm nephrotoxicity but were not found suitable for clinical practice. Druginduced nephrotoxicity can lead to acute kidney injury aki or chronic kidney disease in patients and is a major problem for clinicians 2,3.
Molecular hydrogen alleviates nephrotoxicity induced by an anticancer drug cisplatin without compromising antitumor activity in mice. Risk analysis for cisplatin induced nephrotoxicity during first cycle of chemotherapy ryo kobayashi 1, akio suzuki, katsuhiko matsuura1,2, naomi yamada3, masahiro nakano4, takashi deguchi4, kimio yasuda3, yoshinori itoh1 1department of pharmacy, gifu university hospital, 11 yanagido, gifu 5011194, japan. Drug induced nephrotoxicity is responsible for 20% to 60% of cases of acute kidney injury in hospitalized patients and is associated with increased morbidity and mortality in both children and adults. The nephrotoxicity is due to poisonous effect of some toxic chemicals and certain type of drugs on the kidneys. Nephrotoxicity induced by cancer chemotherapy with special. Nephrotoxicity is the most wellknown and clinically important toxicity. Development of less nephrotoxic drugs is challenging due to the fact that the prediction of nephrotoxicity during drug development remains difficult. Nephroprotective activity of combretum micranthum g. Within the mgps subgroups, mean os was different table 2, being practically twofold in patients with mgps0p 0,01. Acute acyclovir nephrotoxicity in a patient with hiv and. The one patient requiring haemodialysis had numerous other risk factors for renal dysfunction. Original article serum metabonomic analysis of rats with. Drug induced impairment of renal function george sunny pazhayattil, anushree c shirali section of nephrology, yale university school of medicine, new haven, ct, usa abstract.
Acyclovir is commonly used to treat herpes simplex virus hsv and varicellazoster virus vzv. Mechanisms of antimicrobialinduced nephrotoxicity in. However, all agents also carry adverse drug effect profiles. The george washington university medical center, washington, dc. The full text of this article is available in pdf format. The cisplatin nephrotoxicity is a major limiting factors in 20% of patients who have received the drug, triggering injuries in renal tubular epithelialcells. This study aimed to acquire the concentration of vancomycin in the renal tubules and kidneys in humans using physiologically based pharmacokinetic pbpk modeling and simulation. Patients with cancer are frequently exposed to risk of renal injuries associated with diseaserelated or iatrogenic causes. These agents are freely filtered by the glomeruli and quickly taken up by the proximal tubular epithelial cells, where they are incorporated into lysosomes after first interacting with phospholipids on the brush border membranes. Risk factors for nephrotoxicity associated with cisplatin abstract background. Both in vitro and in vivo studies have shown that directly blocking cell death pathways can ameliorate cisplatininduced renal cell death and nephrotoxicity. Risk factors for amphotericin b induced nephrotoxicity.
Figure s1a and induced differentiation additional file 1. Cisplatin is a highly effective antitumor agent whose clinical application is limited by the inherent nephrotoxicity. Many patients who develop renal injury after drug exposure have identifiable risk factors that could be modified or that should preclude the use of these drugs in the first place. Despite intensive research, the mechanism of cisplatininduced nephrotoxicity remains unclear, and renoprotective approaches during cisplatinbased chemotherapy are lacking. The onset of vancomycin nephrotoxicity typically ranges from three to eight days from the start of therapy. Original article risk analysis for cisplatininduced. Antimicrobials are one of the most common classes of medications prescribed globally and also among the most common causes of nephrotoxicity. Cisplatininduced kidney dysfunction and perspectives on. We focus on the docetaxel, cisplatin, and 5fluorouracil regimen, which is called the tpf regimen, where the standard dose of cisplatin is 60 mgm2. The aim of this study is to examine the relationship of the dosage of.
Risk factors for nephrotoxicity associated with cisplatin. Melatonin ameliorates the drug induced nephrotoxicity. Drug induced nephrotoxicity analysis in hiv therapy. Recent work has further suggested that cdk2 inhibitors can protect renal tubular cells and kidneys against cisplatin injury. Serious doselimiting side effects like ototoxicity, nephrotoxicity and neurotoxicity occur with the use of this agent. Risk factors of drug induced nephrotoxicity include drug overdose, drugdrug interactions and drugrelated adverse effects. Cisplatin is a chemotherapeutic agent that is widely used to treat a variety of malignant tumors. Results we present our sample characterization in table 1. Nephrotoxicity of cisplatin combination chemotherapy in. It has been reported that fgf21 has a renalprotective function, but the mechanisms by which it does so remain unclear.
Nephrotoxicity is a wellknown side effect of cisplatin for cancer treatment. 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. Nephroprotective effect of aqueous extract of pimpinella anisum in. Nephrotoxicity is a potential adverse effect of anticancer agents and may result in a variety of functional abnormalities, including glomerular or tubular dysfunction, hypertension and disturbance of the renal endocrine function. In another study, the inhibition of enzymes apn, rdp, and cs lyase did not protect rats given 10 mgkg of cisplatin andor rats treated with 6 mgkg from cisplatin induced nephrotoxicity. The administration of cisplatin is limited due to its nephrotoxic side effects. In conclusion, these findings of the present study strongly suggest the role of oxidative stress in the pathophysiology of cisplatin induced nephrotoxicity and that carvedilol can be used for the. The laboratory observation that forced hydration and diuresis may prevent nephrotoxicity facilitated the subsequent clinical development of cisplatin.
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. Acute kidney injury aki is a common complication in cancer patients. Although cisplatin can dramatically improve the survival rate in cancer patients, its use is limited by its nephrotoxicity. Phytotherapy for anticancer druginduced nephrotoxicity. Content changes may take place as a result of changes in technology, clinical treatment, or other evidence ba sed. Even though the establishment of cisplatin induced nephrotoxicity can be alleviated. Nephrotoxic effects of aminoglycosides on the developing. In late 2012, the study institution began measuring serum creatinine on day 7 after administration of cisplatin to identify patients with acute renal failure.
Evaluating dose of cisplatin responsible for causing. However, the use of cisplatin is limited by its nephrotoxicity. Cisplatin is a widely used cancer therapy drug that unfortunately has major side effects in normal tissues, notably nephrotoxicity in kidneys. Hydroalcohalic extract of ficus carica hefc retard the progression of certain types of cancers, cardiovascular and renal disorders. Cadmium exposure enhances organic cation transporter 2. These sideeffects include nephrotoxicity, neurotoxicity, and ototoxicity. Review of the scientific literature pertaining to exploratory studies in. Acute acyclovir nephrotoxicity in a patient with hiv and herpes zoster. Since the usage of some nephrotoxic drugs is still unavoidable in the clinical setting, understanding the pathogenic mechanisms of their nephrotoxicities is critical to decrease the incidence of kidney injury. Functional impairment, which may begin soon after commencing. Drug induced nephrotoxicity tends to be more common among certain patients and in specific clinical situations.
1265 494 815 1010 31 780 1428 129 856 586 937 288 879 983 108 1341 919 1115 744 1403 727 1502 618 611 1406 136 881 662 1230 1305 1273 1109 534 1414 820 352 36 191 661 1167 835