Identification of metabolomic biomarkers for druginduced. Acute kidney injury serum creatinine increase of 0. Electronic surveillance presents a powerful tool to identify susceptible. 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. Acrylamide induced acute nephrotoxicity in rats keivan jmahidi department of pathology, faculty of veterinary science, islamic azad university, garmsar branch, garmsar, iran abstract acrylamide acr has been shown to cause neurotoxic effects in humans and neurotoxic, genotoxic, reproductive, and carcinogenic effects in laboratory animals. Nephrotoxicity is an important and preventable cause of nephrotoxin induced acute kidney injury aki as well as chronic kidney disease ckd. The aim of the present study is to clarify the possible corrective role of curcumin on the nephrotoxicity induced by lead acetate. Warning lasix furosemide is a potent diuretic which, if. The considerable side effects that are associated with cnis therapy include arterial hypertension and nephrotoxicity. Key words cadmium fanconi syndrome glomerular filtration rate gout kidney lead nephrotoxicity proteinuria obtained as a byproduct of zinc refining, is used. Nephrotoxicity was induced in the rats of group ii by administering gentamicin 80mgkg, i. There is a growing number of hospitalised patients who develop a druginduced renal problem because increasing numbers of potent drugs have been added to the therapeutic arsenal in recent years. Cisplatin interferes with the transport of water and renal tubular cell nutrients. As the list of drugs, natural products, industrial chemicals and environmental pollutants that.
Nephrotoxins are the agents displaying nephrotoxicity. Injection route solution therapy has been associated with potential neurotoxicity, ototoxicity, and nephrotoxicity. The nephrotoxicity is due to poisonous effect of some toxic chemicals and certain type of drugs on the kidneys. 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. Druginduced nephrotoxicity accounts for approximately 20% of all acute kidney injuries 1. Cisplatininduced acute tubular injury and necrosis atiatn. Lasix furosemide is a potent diuretic which, if given in excessive amounts, can lead to a profound diuresis with water and electrolyte depletion. Nephrotoxicity is one of the most common kidney problems and occurs when body is exposed to a drug or toxin. 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.
Druginduced nephrotoxicity refers to kidney damage induced by medication administered for the purpose of diagnosing or treating another medical disorder. The 6rs of drug induced nephrotoxicity bmc nephrology. How to prevent, recognize, and treat druginduced nephrotoxicity. The use of iodinated contrast medium can result in nephropathy. Pdf how to prevent, recognize, and treat druginduced. Monitor renal and auditory function during therapy and discontinue therapy or adjust dose if there is evidence. However, risk is lower with newer contrast agents, which are nonionic and have a lower osmolality than older agents, whose osmolality is about 1400 to 1800 mosmkg or mmolkg.
Nephrotoxicity and agents responsible nephrotoxic injury is damage to one or both kidenys that result from exposure to a toxic substance. C 7, 10, 32, 48 druginduced renal impairment is generally reversible, provided the nephrotoxicity is recognized early and the offending medication is discontinued. While most of these are clinically insignificant, some drugs. Amelioration of cisplatininduced nephrotoxicity in rats. The chronic administration of certain drugs causes nephrotoxicity. Cisplatininduced nephrotoxicity is characterized by renal proximal tubular cell dysfunction.
Felix braun, matthias behrend, in side effects of drugs annual, 2008. Nacetylcysteine prevents ifosfamideinduced nephrotoxicity in rats. Pathophysiological mechanisms of calcineurin inhibitor. With acute lead nephrotoxicity, these leadprotein complexes are observed as typical intracellular inclusions.
Druginduced nephrotoxicity tends to be more common among certain patients and in specific clinical situations. Lasix can increase the risk of cephalosporin induced nephrotoxicity even in the setting of. Light microscopy of the kidney biopsy specimen reveals dilated tubules with. The onset of vancomycin nephrotoxicity typically ranges from three to eight days from the start of therapy. Full text druginduced impairment of renal function ijnrd. Renal vulnerability to drug toxicity nephrology selfassessment program vol 9, no 4, july 2010 clin j am soc nephrol 4.
Introduction the use of plants in medicine is an agelong practice in various parts of the globe for both timated that about 80% of the world population relies on. It is a poisonous effect of some substances, both toxic chemicals and medications, on kidney function. Pathophysiology and treatment of calcineurin inhibitor. Transport is mediated by sodium pumps in the apical and basolateral face of the cells, such as nakatpase, nak2cl cotransporter, and type iii nah exchanger, and. The tt genotype at the abcb1 3435ct polymorphism is associated with reduced expression of p. Kidney function was assessed by measuring urine urea and creatinine and serum urea and creatinine. Different classes of drugs, by virtue of immunological mechanisms or direct toxicity initiate certain stereotyped renal responses. The renal proximal tubule is a main target for druginduced toxicity. Oxidative stress plays a key role in leadinduced nephrotoxicity. Effect of dimethyl sulfoxide on gentamicininduced nephrotoxicity in rats. Drugs and toxins may cause renal injury based on several pathophysiological mechanisms. Prediction of druginduced nephrotoxicity and injury. Leadinduced chronic renal failuredefinitionlead pb nephrotoxicity relates to experimental, epidemiologic, and clinical evidence of renal damage and hypertension associated to environmental or occupational pb exposure. Histopathological and nephroprotective study of aqueous.
Lithiuminduced nephrotoxicity is a complication known since lithium was introduced in the treatment of mood disorders 68. There are various agents that exert nephrotoxic effects. Contrastinduced nephropathy is most commonly defined as acute renal failure occurring within 48 hr of exposure to intravascular radiographic contrast material that is not attributable to other causes. Renal complications include impairment of tubular function particularly the development of nephrogenic diabetes insipidus and renal tubular acidosis and progressive chronic kidney disease secondary to lithiuminduced. There are various forms, and some drugs may affect kidney function in more than one way. Cadmium accumulates in renal tubular lining cells bound to metallothionein, a small protein containing 30% cystine. The spectrum of injury may vary from subtle to severe. A retrospective study tatsuya yoshida1, seiji niho1, mayuko toda2, koichi goto1, kiyotaka yoh1, shigeki umemura1, shingo matsumoto1, hironobu ohmatsu1 and yuichiro ohe1 1division of thoracic oncology, national cancer center hospital east, kashiwa, chiba and 2division of pharmacy. Druginduced impairment of renal function george sunny pazhayattil, anushree c shirali section of nephrology, yale university school of medicine, new haven, ct, usa abstract. P glycoprotein contributes substantially to ciclosporin nephrotoxicity. There is a growing number of hospitalised patients who develop a druginduced renal problem because increasing numbers of potent drugs have. Lead is absorbed by the proximal tubular cells of the renal tubules, where it binds to specific leadbinding proteins. Nephrotoxicity is the doselimiting toxicity of cisplatin.
The immunosuppressive effects of cnis result from the inhibition of interleukin2 synthesis and reduced proliferation of t cells due to calcineurin blockade. Moreover, great at tention should be paid to drug interactions. Finally, determination of a patients or donors genotype of drugmetabolizing genes or of mol. Our current knowledge of drug induced kidney disease is. Influence of iron, deferoxamine and ascorbic acid on gentamicininduced nephrotoxicity in rats. Ideally, the impairment of renal function should be measured by serial creatinine clearance, but because this step may be neither practical nor costeffective in many centers, most of the. More side effects increased nephrotoxicity change in the drug metabolism 4. However, serum creatinine levels and endogenous creatinine clearance are insensitive indicators of cisplatininduced glomerular toxicity, and underestimate the. The nephrotoxic effect develops more in patients who are already suffering from the renal impairment. Data are emerging that like other chemotherapeutic agents, it also appears to manifest nephrotoxic potential. Mechanism of renal injury previously, it was believed that paracetamolinduced. The 3 clinical syndromes that can be recognised in druginduced nephropathy are acute renal failure, chronic interstitial nephritis and the nephrotic syndrome. Whether isoosmolar contrast medium is less nephrotoxic than lowosmolar contrast medium in highrisk patients is uncertain. Nephrotoxicity of cancer treatment in children medscape.
Analgesicinduced nephropathy is associated with 1% to 3% of the cases of endstage renal disease in the united states. Efficacy of curcumin on lead induced nephrotoxicity in. Thirty mature female albino rats 190 225 g were randomly divided into five equal groups, first and second. Pharmaceutical agents provide diagnostic and therapeutic utility that are central to patient care. Because of the strong association between gout and chronic lead nephropathy, emmerson and coworkers studied the renal handling of uric acid in patients with saturnine gout. Ciclosporin nephrotoxicity leads to impaired renal function and chronic allograft nephropathy, which is a major predictor of graft loss. Chronic lead nephrotoxicity consists of interstitial fibrosis and progressive nephron loss, azotaemia and renal failure. Pathophysiology of nephrotoxic acute renal failure h umans are exposed intentionally and unintentionally to a variety of diverse chemicals that harm the kidney. Contrast nephropathy merck manuals professional edition. Deltamethrin, nephrotoxicity, basil, oxidative stress.
Nephrotoxins are chemicals displaying nephrotoxicity. The 6rs of drug induced nephrotoxicity linda awdishu1,2 and ravindra l. Patients with impaired renal function, advanced age, dehydration, and those who receive high dosage or prolonged therapy are at an increased risk of toxicity. These drugs require special consideration prior to prescribing them. Contrast nephropathy is acute tubular necrosis caused by an iodinated radiocontrast agent, all of which are nephrotoxic. A number of therapeutic agents can adversely affect the kidney resulting in acute renal failure, chronic interstitial nephritis and nephritic syndrome because increasing number of potent therapeutic drugs like aminoglycoside antibiotics, chemotherapeutic agents and nsaids. However, all agents also carry adverse drug effect profiles. Nephrotoxicity associated with acute paracetamol overdose. Effect of superoxide dismutase treatment on gentamicin nephrotoxicity in rats. And although druginduced nephrotoxicity may occur in dogs of any age, older dogs are more susceptible. Pathophysiology and treatment of calcineurin inhibitor nephrotoxicity jonna kemper, pharmd and kara kniska, pharmd. The prediction of proximal tubular toxicity during drug development remains difficult.
Protective effect of magnesium preloading on cisplatin. Potential complications of lead nephropathy include gout and hypertension. Pdf nephrotoxic effects in highrisk patients undergoing. Druginduced nephrotoxicity and medicinal plants abolfazl khajavi rad,1 reza mohebbati,2 sara hosseinian2 druginduced nephrotoxicity is one of the most common causes of acute kidney injury. Drug induced kidney injury is a frequent adverse event which contributes to morbidity and increased healthcare utilization. Mehta2 abstract drug induced kidney injury is a frequent adverse event which contributes to morbidity and increased healthcare utilization. Protective effect of magnesium preloading on cisplatininduced nephrotoxicity. Druginduced kidney diseases np singh, a ganguli, a prakash abstract druginduced kidney disease constitutes an important cause of acute renal failure and chronic kidney disease in present day clinical practice. The degree of vancomycininduced renal dysfunction is usually modest, with a typical decrease of 3545% in creatinine clearance from baseline. Nephrotoxins are substances displaying nephrotoxicity nephrotoxicity should not be confused with the fact that some medications are predominantly excreted by. Pemetrexed is an antifolate utilized for certain cancers such as advanced nonsmall cell lung cancer and pleural mesothelioma.