Sildenafil ameliorates gentamicininduced nephrotoxicity in. Acute tubular necrosis due to ischemia or other insults and the pathogenesis and potential therapy of aminoglycoside nephrotoxicity are discussed separately. Nephrotoxic effects of aminoglycosides on the developing kidney. Farber and moellering found nephrotoxicity in 12 of 34 35% patients receiving concomitant vancomycin and aminoglycosides compared to only 5% of 60 patients receiving vancomycin without aminoglycosides. It implies impairment in renal function an increase in serum creatinine by 25% or 0. The aim of this study was to compare the nephrotoxic potential of amikacin ak and gentamicin gm in patients with normal baseline renal function. Gentamicin and amikacin induced nephrotoxicity was compared based on scr levels figures 1 and 2. Therapy with aminoglycosides should be administered cautiously at reduced dosages in patients with renal impairment, since they may be at increased risk for oto and nephrotoxicity due to drug.
Olive leaf extract ole has been demonstrated to have antioxidant and antiinflammatory. In this forum, i will summarize the renal handling of the aminoglycosides, the pathogenetic mechanisms of nephro toxicity, and the clinical aspects of aminoglycoside induced acute renal failure. In vivo, approximately 90% of a gentamicin dose is recovered in the urine8. Drug induced kidney disease free download as powerpoint presentation. The chronic administration of certain drugs causes nephrotoxicity. Abdelhamid department of pharmacology, and department of pathology faculty of medicine, assiut university abstract gentamicin gent which is a commonly used antibiotic causes nephrotoxicity in man and animals. The current investigation was designed to evaluate the effects of ginseng on gentamicin induced nephrotoxicity. Drug induced kidney injury is a frequent adverse event which contributes to morbidity and increased healthcare utilization.
Nephrotoxicity defined as increase in serum creatinine 44. The incidence of gentamicin associated acute kidney injury aki as defined by the rifle criteria is unknown. Hemodynamic stabilization via intravenous hydration is a priority in hypovolemic states. Electronic surveillance presents a powerful tool to identify susceptible. Finally, determination of a patients or donors genotype of drugmetabolizing genes or of mol ecules involved in csa nephrotoxicity, like tgf. Pdf intermittent exposure to xenon protects against. Corresponding author samira samiee, md, division of pediatric clinical pharmacology, childrens national medical center. The nephrotoxic effect develops more in patients who are already suffering from the renal impairment. Our current knowledge of drug induced kidney disease is limited due to varying definitions of kidney. Nephrotoxicity of combined cephalothin gentamicin regimen fernando cabanillas, md. Gentamicin is a hydrophilic cationic compound that does not readily penetrate cell membranes 7.
Cimetidine appears to have protective effect on gentamicin losartan induced nephrotoxicity in rats. Serum concentrations of aminoglycosides should be monitored when feasible to assure adequate levels and to avoid potentially toxic levels. Protective effect of crocin on gentamicininduced nephrotoxicity in rats. Cyclosporine and tacrolimus are immunosuppressive agents used for prophylaxis against graft rejection in transplantation, and are often used off label due to their inhibition of t cell activation in autoimmune. Pdf how to prevent, recognize, and treat druginduced. Druginduced nephrotoxicity and its biomarkers ncbi. Gentamicin injection is a sterile, nonpyrogenic aqueous solution for. Aminoglycoside antibiotics, such as gentamicin, can produce nephrotoxicity in dogs, due to in part to an imbalance of pro and antioxidants oxidative stress. Oxidative stress due to abnormal production of reactive oxygen species has been implicated in the nephrotoxicity induced by gentamicin. Inhibitory effect of olive leaf extract on gentamicininduced. Gentamicin clinical guidelines for dosing and monitoring.
Patients treated with the calcineurin inhibitors cnis cyclosporine and tacrolimus are at high risk of developing kidney injury. Borade department of pharmacology, rajgad dnyanpeeths college of pharmacy, bhor, m. Pathophysiology and treatment of calcineurin inhibitor. Drug induced nephrotoxicity is an important cause of renal failure in dogs. Table ii shows the baseline clinical and demographic characteristics of the gm and ak groups. Nephrotoxicity associated with ciprofloxacin is uncommon. Inhibition of megalinmediated endocytosis by statins represents a novel approach to the prevention of aminoglycoside induced nephrotoxicity which is currently being evaluated in a clinical trial.
Impact of gender on aminoglycoside induced nephrotoxicity is still controversial and inconclusive. Prevention of nephrotoxicity by aminoglycoside can be focused on reducing or preventing the accumulation of aminoglycosides in the kidney, reduce or prevent aminoglycoside induced phospholipids, protect against necrosis and other cellular alterations, protect against vascular and glomerular effects andor increase the capacity of regeneration. India abstract gentamicin gm induced nephrotoxicity limits its longterm clinical use. We explored whether virgin coconut oil vco could mitigate gentamicin. Full text get a printable copy pdf file of the complete article 698k, or. As the use of aminoglycosides became more widespread, the toxic effects of these agents, most notably ototoxicity and nephrotoxicity, became more apparent. Gender differences in aminoglycoside induced nephrotoxicity. Vancomycin dosing and monitoring 2 years after guidelines. The 3 clinical syndromes that can be recognised in drug induced nephropathy are acute renal failure, chronic interstitial nephritis and the nephrotic syndrome. Effect of cimetidine on gentamicinlosartan induced. In this study we investigated the role of free radicals in gentamicin. Moreover, great at tention should be paid to drug interactions. Oxidative stress and mitrochondrial damage occurred in vancomycin induced nephrotoxicity.
Pdf gentamicin induced nephrotoxicity in albino mice. However, contrast induced nephrotoxicity is still the third leading cause of iatrogenic renal failure. The main concerns with the use of aminoglycoside antibiotics are nephrotoxicity and ototoxicity. To reduce the incidence of cisplatininduced nephrotoxicity, we analyzed possible risk factors. Different classes of drugs, by virtue of immunological mechanisms or direct toxicity initiate certain stereotyped renal responses. The vast majority of these patients do not require hemodialysis. Pdf nephroprotective activity of nelumbo nucifera gaertn. Extract against gentamicininduced nephrotoxicity in rats moustafa m. Study of protective effects of stem bark extracts of ficus racemosa in drug induced nephrogenic diabetes insipidus and nephrotoxicity in animal models department of pharmaceutical sciences jjtu page 8 chapter1 introduction 1. Contrast induced nephrotoxicity cin is a form of acute kidney injury that follows intravascular contrast media exposure.
Gentamicin, cimetidine, losartan, vitamin e, rats, nephrotoxicity. Mehta2 abstract drug induced kidney injury is a frequent adverse event which contributes to morbidity and increased healthcare utilization. The comparison included both the total dose given, frequency, and single vs. Effects of curcumin on anioncation transporters and multidrug. 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. Jul 27, 2015 drug induced nephrotoxicity can lead to acute kidney injury aki or chronic kidney disease in patients and is a major problem for clinicians 2,3. Due to high relative blood flow the kidney is prone to druginduced damage.
We conclude that furosemide use should not be considered a major risk factor for the development of aminoglycosideinduced nephrotoxicity or auditory toxicity. Gentamicin sulphate nephrotoxicity seems to be attributed to the generation of reactive oxygen species. Oct 17, 2012 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. Although the exact mechanism of gentamicininduced nephrotoxicity is not well. 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. Although aminoglycoside induced nephrotoxicity is generally reversible following discontinuation of the drug, death from uremia has occurred rarely. To investigate the antioxidant effect of an orally administered ethanol extract of nettle urtica dioica and its protective role in preventing or ameliorating oxidative stress as a major factor in gentamicininduced nephrotoxicity in male rabbits.
C 7, 10, 32, 48 druginduced renal impairment is generally reversible, provided the nephrotoxicity is recognized early and the offending medication is discontinued. Risk analysis for cisplatininduced nephrotoxicity during first cycle of. Amphotericin b remains the antifungal drug of choice for most systemic infections, but a limiting factor for its use is the development of nephrotoxicity. Herbarium file of individual plant parts was prepared and. Nephrotoxicity due to a aminoglycosides b cyclophosphamide c cisplatin d. Renal and auditory toxicity of highdose, prolonged therapy with gentamicin and tobramycin in pseudomonas endocarditis. Dec 27, 2019 aminoglycosides preferentially affect the proximal tubular cells.
Amphotericin b induced nephrotoxicity is manifested as azotaemia, renal tubular acidosis, impaired renal concentrating ability and electrolyte abnormalities like hypokalaemia and sodium and. While most of these are clinically insignificant, some drugs. Aminoglycosideinduced nephrotoxicity in children pdf. Diallyl sulfide enhances antioxidants and inhibits inflammation through the activation of nrf2 against gentamicin induced nephrotoxicity in.
Recognition of druginduced nephrotoxicity as a signi ficant contributor to kidney. Ciprofloxacininduced nephrotoxicity in patients with cancer. The 6rs of drug induced nephrotoxicity bmc nephrology. Impact of gender on aminoglycosides nephrotoxicity current clinical pharmacology, 2009, vol. Nephrotoxicity can be defined as the adverse effect of substances on renal function perazella, 2009.
New insights into the mechanism of aminoglycoside nephrotoxicity. Cni nephrotoxicity is manifested either as acute kidney injury aki, which is largely reversible after reducing the dose, or as chronic progressive renal disease, which is usually irreversible. Because drug induced 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. Full text druginduced impairment of renal function ijnrd. International institute of cellular and molecular pathology. Pmc free article tablan oc, reyes mp, rintelmann wf, lerner am.
The nephrotoxicity of the aminoglycoside antibiotic gentamicin is well documented. The defensive effects of hesperidin hdn, a bioflavonoid was investigated on gentamicin gen provoked nephrotoxicity in rats. Relationship between aminoglycoside induced nephrotoxicity and auditory toxicity. Serum urea and creatinine levels were evaluated as. Nephrotoxins are the agents displaying nephrotoxicity. Inhibitory effect of olive leaf extract on gentamicin induced nephrotoxicity in rats majid tavafi, 1 hasan ahmadvand, 2 pooran toolabi 3 introduction. In the present study, sildenafil ameliorated gentamicin induced nephrotoxicity as it reduced serum urea and creatinine as well as urinary albumin levels and restored the histological pattern. A number of crude herbal extracts have been reported to ameliorate gentamicin induced nephrotoxicity. Concurrent use of other potentially neurotoxic or nephrotoxic agents, or potent diuretics should be avoided. Gentamicin sulfate, a watersoluble antibiotic of the aminoglycoside group, is derived by the growth of micromonospora purpurea, an actinomycete.
Previously we studied the hydrogen peroxide scavenging activity of eryngium caucasicum. Colistinassociated nephrotoxicity among patients in. Symposium on drug effects on the kidney gentamicininduced nephrotoxicity. The pharmacodynamic properties of gentamicin make once daily administration preferable to the traditional divided doses approach of giving aminoglycosides e. Gentamicin, at doses of 50 or 100 mgkg body wt administered daily to healthy male mf1 mice by i. Nephrotoxic effects of aminoglycosides on the developing.
The 6rs of drug induced nephrotoxicity bmc nephrology full text. Our current knowledge of drug induced kidney disease is limited due to varying definitions of kidney injury, incomplete assessment of concurrent risk factors and lack of long term outcome reporting. Gentamicin induced nephrotoxicity and kidney damage is illustrated by. The 6rs of drug induced nephrotoxicity linda awdishu1,2 and ravindra l. Drug induced nephrotoxicity is a common and potentially serious complication of medication administration that occurs in both inpatient and outpatient settings. Pdf many drugs can injure the kidneys, but they cause renal injury via only a few common mechanisms. Protective role of caffeic acid phenethyl ester cape on gentamicininduced acute renal.
However, all agents also carry adverse drug effect profiles. Protective effect of moringa oleifera leaves against. 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. Pdf effect of silymarin and vitamin e on gentamicin. There are various agents that exert nephrotoxic effects through different pathogenic mechanisms. The plant extract of rhazya stricta has been noted to dosedependently increase the superoxide dismutase activity and the reducedform of glutathione and subsequently decrease lipid peroxides in the renal cortex of gentamicin administered rats. The nephroprotective effect of aqueousethanolic extract of moringa oleifera leaves 150 and 300 mgkg was evaluated against gentamicin induced 80 mgkg renal injury in rabbits. To evaluate the nephroprotective effect of trichosanthes dioica roxb. 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. Due to concerns about nephrotoxicity and ototoxicity, its use should be limited to 3 doses within 48 hours duration wherever possible. Pathophysiology and treatment of calcineurin inhibitor nephrotoxicity jonna kemper, pharmd and kara kniska, pharmd. Introduction gentamicin is an aminoglycoside antibiotic widely used for the treatment of bacterial infections.
Despite significant research in this field, the molecular mechanism associated with gentamicin nephrotoxicity is not completely understood. Pdf histopathological evaluation of nephroprotective. Nephroprotective effect of aqueous extract of pimpinella anisum in. This work was conducted to evaluate the possible renoprotective effect of eryngium caucasicum against gentamicin induced renotoxicity. Intermittent exposure to xenon protects against gentamicininduced nephrotoxicity article pdf available in plos one 85. Drug induced nephrotoxicity can lead to acute kidney injury aki or chronic kidney disease in patients and is a major problem for clinicians 2,3. Manifestations of and risk factors for aminoglycoside. Nephrotoxicity of combined cephalothingentamicin regimen. The nephrotoxicity is due to poisonous effect of some toxic chemicals and certain type of drugs on the kidneys. Drug induced kidney disease dikd clinical pharmacy by. Nephrotoxicity is a kidneyspecific feature in which excretion does not go smoothly owing to toxic chemicals or drugs finn and porter, 2003. Curcumin on oats, octs and mrps in cisplatin nephrotoxicity. These substances can include molds and fungi, cancer therapeutics such as cisplatin, antibiotics such as aminoglycosides, metals such as mercury, arsenic and lead, and drugs of abuse such as cocaine. The term contrastmedium induced nephrotoxicity cmin is widely used to refer to the reduction in renal function induced by contrast media.
Melatonin ameliorates the drug induced nephrotoxicity. Drug induced kidney diseases np singh, a ganguli, a prakash abstract drug induced kidney disease constitutes an important cause of acute renal failure and chronic kidney disease in present day clinical practice. How to prevent, recognize, and treat druginduced nephrotoxicity. Aminoglycosideinduced nephrotoxicity indiana university. Cin may be preventable because its risk factors are well established and the timing of renal insult is commonly known in advance. Pathophysiologic mechanisms of selected types of nephrotoxicity.
Zeynab mohamadi yarijani, houshang najafi, and seyed hamid madani. The kidneys are paired and bean shaped organs, located on either sides of the vertebral. Clinical pharmacology for the nephrologist khaled eldahshan, md lecturer of nephrology, mansoura urology and nephrology center. A large body of in vitro and in vivo evidence indicates that reactive oxygen metabolites or free radicals are important mediators of gentamicin nephrotoxicity. Development of less nephrotoxic drugs is challenging due to the fact that the prediction of nephrotoxicity during drug development remains difficult. Recommendations issued for preventing druginduced nephrotoxicity. The kidney is a major organ of drug excretion and, thus, is exposed to high concentrations of potentially toxic medications. The expression patterns of nuclear factor erythroidderived 2like 2 nrf2, nuclear factor. The offending drugs need to be stopped immediately.
Dailymed gentamicin gentamicin sulfate injection, solution. Keywords aminoglycosides, nephrotoxicity, kidney, infants, fetuses, nephrogenesis. Pharmaceutical agents provide diagnostic and therapeutic utility that are central to patient care. Aminoglycosideinduced nephrotoxicity article pdf available in journal of pharmacy practice 276 september 2014 with 1,227 reads how we measure reads. Aminoglycoside induced ototoxicity is usually irreversible. Drug induced nephrotoxicity and medicinal plants abolfazl khajavi rad,1 reza mohebbati,2 sara hosseinian2 drug induced nephrotoxicity is one of the most common causes of acute kidney injury. N2 aminoglycosides remain critical antibiotics in the armamentarium for serious gramnegative bacterial infections despite their wellknown risk for nephrotoxicity and ototoxicity. Extracts at the doses 200 and 400 mgkgday for 10 consecutive days, by intraperitoneal route i. Mar 31, 2015 molecular mechanism of drug induced nephrotoxicity 1. Nephrotoxicity induced by aminoglycosides manifests clinically as nonoliguric renal failure, with a slow rise in serum creatinine and a hypoosmolar urinary. More importantly, a potential contribution of complement pathway and inflammation in the vancomycin induced renal toxicity has been r ev iew vancomycin nephrotoxicity. Aminoglycosides are concentrationdependent, bactericidal agents that undergo active transport into the cell where they inhibit protein synthesis on the 30s subunit of the bacterial ribosome. C\le\sarbaldiz\lo\n,md gentamicinsulfate garamycin is a broad spectrum antimicrobial agent member of the aminoglycoside group of antibiotics.
Colistinassociated nephrotoxicity among patients in intensive care units icu of hospitals in selangor med j malaysia vol 72 no 2 april 2017 101 monitoring as well as coadministration with other antibiotics and nephrotoxic agents contributed to variability between these study reports. This group, which also includes neomycin sulfate, kanamycin sulfate, and streptomycin sulfate,1 is. The route of administration had a major impact on c max and time to c max t max. Extended interval dosing of aminoglycosides results in a reduction in nephrotoxicity, but its use needs to become more widespread. Prediction of druginduced nephrotoxicity and injury. We performed a retrospective observational study to examine this and the predictive value of rifle stage on patient outcome in this setting.
667 944 1333 198 1469 101 463 496 831 678 1049 1360 1507 1568 1055 60 748 1131 729 1258 453 569 1561 453 219 1310 1478 887 475 903 965 1073 1220 534 873 179 184 596 82 1315