Our current knowledge of drug induced kidney disease is limited due to varying definitions of kidney. Jan 19, 2016 dikddin drug induced nephrotoxicity din common complication of several diagnostic and therapeutic agents manifested as acidbase abnormalities, electrolyte imbalances urine sediment abnormalities proteinuria, pyuria, and hematuria decline in the glomerular filtration rate gfr rise in the serum creatinine. Within the extensive group of medications associated with aki, antibiotics and other antimicrobials are well recognized triggers of structural and functional renal impairment. However, certain drugs have direct toxic effects on podocytes. Pdf antiviral druginduced nephrotoxicity vincent launay.
Therefore, successful prevention requires knowledge of pathogenic mechanisms of renal injury, patientrelated risk factors, drugrelated risk factors, and preemptive measures, coupled with vigilance and early intervention. Druginduced liver injury is responsible for 5% of all hospital admissions and 50% of all acute liver failures. Numerous toxicogenomics studies, including transcriptomics, proteomics, and metabolomics, have been performed by both industry and academia. Crystalinduced acute kidney injury aki is caused by the intratubular precipitation of.
The kidney is a major target for drug induced toxicity. Heavy metal nephropathy genitourinary disorders msd. Drug induced nephrotoxicity is caused by nephrotoxic drugs or toxins which damage kidneys and can lead to nephritis or renal toxicity. Discussion of drug induced nephrotoxicity must consider some important points that are presented below.
Drug induced nephrotoxicity is one of the leading causes of aki worldwide. The 6rs of drug induced nephrotoxicity linda awdishu1,2 and ravindra l. Crystalforming drug nephrotoxicity crystalinduced aki most commonly occurs as a result of acute uric acid nephropathy and following the administration of drugs or toxins that are poorly soluble or have metabolites that are poorly soluble in urine. Druginduced nephrotoxicity american family physician. Therefore, successful prevention requires knowledge of pathogenic mechanisms of renal injury, patientrelated risk factors, drug related risk factors, and preemptive measures, coupled with vigilance and early intervention. Bennett, md division of nephrology, hypertension, and clinical pharmacology oregon health sciences university portland, oregon, usa the kidney is the major site of damage from many drugs and chemicals that are used in. The causative drug must be identified and its use must be. Druginduced renal disorders journal of renal injury prevention.
The presentation varies from an acute or chronic reduced glomerular filtration rate gfr to nephrotic syndrome and hydroelectrolytic disorders hed related, respectively, to. In addition to causing aki, chronic drug toxicity can, in some cases, lead to ckd and eventual endstage renal disease. The incidence of druginduced nephrotoxicity has been increasing with the ever increasing number of drugs and with easy availability of overthecounter. Creatinine is concluded as a good safety marker in 25 studies, with a total sample size of 4789 patients with a clear association with drug induced nephrotoxicity in hiv patients of all the antiretroviral drugs used to treat hiv, tenofovir either as a monotherapy or in combination with other drugs induced nephrotoxicity as evaluated by the. Druginduced nephrotoxicity is more common in hospitalized patients. Smx, the drug should be used with caution in patients with uncontrolled diabetes 12. The exact frequency of nephrotoxicity induced by antiviral drugs is dif.
Druginduced nephrotoxicity tends to be more common among certain patients and in specific clinical situations. Druginduced nephrotoxicity are more common among infants and young children and in. Antiviral druginduced nephrotoxicity american journal of. The 6rs of drug induced nephrotoxicity bmc nephrology. Many nephrotoxins are taken up by the renal target cell, where they are effectively capable of exerting. The presentation varies from an acute or chronic reduced glomerular filtration rate gfr to nephrotic syndrome and hydroelectrolytic disorders hed related, respectively, to glomerular and tubular damage. Drug induced nephrotoxicity remains a major problem in the clinical setting, where the use of nephrotoxic drugs is often unavoidable. Drug use and nephrotoxicity in the intensive care unit. The condition can be costly and may require multiple interventions, including hospitalization 5.
The reason for such high rates of drug induced kidney injury is the function of drug and metabolite excretion performed by the kidneys, with the consequent exposure of its structures with high energy need glomeruli and tubules to the high concentration of exogenous substances2. Nephrotoxicity is a significant concern in pediatrics with 16% of hospitalized aki events being attributable primarily to a drug 4. Druginduced nephrotoxicity is a common problem in clinical medicine and the incidence of drugrelated acute kidney injury aki may be as high as 60 percent 14. The nephrotoxic potential of many other widely used drugs, including newer agents, eg, the nonsteroidal. Druginduced nephrotoxicity in adults is approximately 14%26% in prospective cohort studies of aki, whereas 16% of hospitalized aki is due to drugs in the pediatric population 14.
Renal vulnerability to drug toxicity nephrology selfassessment program vol 9, no 4, july 2010 clin j am soc nephrol 4. Druginduced kidney injury is a major side effect in clinical practice, frequently leading to acute renal failure arf. Podocytes, which maintain the filtration barrier in glomeruli, are also targets of druginduced nephrotoxicity 17. Similar to acute interstitial nephritis, drug induced podocyte injury is often mediated by immune mechanisms. Prediction of druginduced nephrotoxicity and injury mechanisms with human induced pluripotent stem cell. 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. Prediction of druginduced nephrotoxicity with a hydroxyl. Druginduced nephrotoxicity is defined by the presence of any kidney injury caused directly or indirectly by medication. Discussion of druginduced nephrotoxicity must consider some important points that are presented below. The development of welldesigned nanoprobes for specific imaging of multiple biomarkers in renal cells will afford beneficial information related to the transmutation process of drug induced kidney injury diki. Our current knowledge of drug induced kidney disease is. The exact frequency of nephrotoxicity induced by antiviral drugs is difficult to determine. It accounts for more than 2% to 15% of cases of arf in patients admitted to the hospital or in the intensive care unit, respectively.
Table 3 outlines dose adjustments for kidney disease patients. Bennett, md division of nephrology, hypertension, and clinical pharmacology oregon health sciences university portland, oregon, usa the kidney is the major site of damage from many drugs and chemicals that are used in clinical medicine and are present in our environment. Nephrotoxicity can be defined as the adverse effect of substances on renal function perazella, 2009. Prediction of drug induced nephrotoxicity and injury mechanisms with human induced pluripotent stem cellderived cells and machine learning methods. Most commonly druginduced nephrotoxicity is manifested by tubular necrosis, interstitial nephritis, crystal nephropathy, angiopathy, alterations in. Mar 31, 2015 crystalforming drug nephrotoxicity crystal induced aki most commonly occurs as a result of acute uric acid nephropathy and following the administration of drugs or toxins that are poorly soluble or have metabolites that are poorly soluble in urine. Aminoglycosides amg amg are prototype drugs having nephrotoxicity as major side. One strategy to avoid such problems would be the development of drugs with decreased nephrotoxic potential. Prediction of druginduced nephrotoxicity and injury. Sep 01, 2015 drug induced nephrotoxicity is a common problem in clinical medicine and the incidence of drug related acute kidney injury aki may be as high as 60 percent 14. Druginduced nephrotoxicity is caused by nephrotoxic drugs or toxins which damage kidneys and can lead to nephritis or renal toxicity. Nephrotoxicity of antimicrobials and antibiotics advances.
Advances in predictive in vitro models of druginduced. Drug induced nephrotoxicity tends to be more common among certain patients and in specific clinical situations. Aminoglycosides amg amg are prototype drugs having nephrotoxicity as major side effect. Pharmacology behind common drug nephrotoxicities american. The reason for such high rates of druginduced kidney injury is the function of drug and metabolite excretion performed by the kidneys, with the consequent exposure of its structures with high energy need glomeruli and tubules to the high concentration of exogenous substances2.
Medicationinduced nephrotoxicity remains one of the most common causes of acute kidney injury aki among hospitalized patients. Nephrotoxicity is a major reason for drug withdrawal postmarket, indicating that the current clinical biomarkers and preclinical tests used to detect kidney injury are not sensitive enough and inadequate. Risk factors of druginduced nephrotoxicity include drug overdose, drugdrug interactions and drugrelated adverse effects. Drug induced nephrotoxicity is defined by the pres. Antimicrobials are one of the most common classes of medications prescribed globally and also among the most common causes of nephrotoxicity. 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 14 figure6 various sites of the drug induced nephrotoxicity the nephrotoxic substances causes nephrotoxicity. Mechanisms for druginduced nephrotoxicity include changes in glomerular hemodynamics, tubular cell toxicity, inflammation, crystal nephropathy, rhabdomyolysis, and thrombotic microangiopathy. Druginduced renal dysfunction is not an uncommon event, which can cause significant morbidity and can be easily overlooked. Patients at highest risk of druginduced nephrotoxicity are those with one or more of the following. Full text druginduced impairment of renal function ijnrd.
Patients at highest risk of drug induced nephrotoxicity are those with one or more of the following. Pathophysiologic mechanisms of selected types of nephrotoxicity. However, the most reported nanoprobes for diki detection were dependent on singlesignal output and lack of kidney targeting. Drugs can also interfere with normal transport mechanisms in the kidney, leading to a variety of electrolyte and acidbase disorders. 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. Mechanisms of antimicrobialinduced nephrotoxicity in. The summary of management of drug induced kidney diseases is mentioned in table 2. Drug induced nephrotoxicity boca raton regional hospital.
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. Druginduced nephrotoxicity analysis in hiv therapy. Examples of drug induced nephrotoxicity with mrsa type a 75 year old patient treated with iv vancomycin trough levels 1520 mgdl after 2 weeks of therapy baseline creatinine. Perazella1 1department of medicine, section of nephrology, yale university school of medicine, new haven, connecticut, usa patients cared for in the intensive care unit icu undergo multiple interventions to treat serious medical conditions. Many medications can lead to renal dysfunction through various mechanisms. Druginduced 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. Mechanisms for druginduced nephrotoxicity include changes in glomerular. The 3 clinical syndromes that can be recognised in drug induced nephropathy are acute renal failure, chronic interstitial nephritis and the nephrotic syndrome. The 6rs of drug induced nephrotoxicity bmc nephrology full text. Clinical manifestations range from mild forms of tubular injury to significant.
Risk factors of drug induced nephrotoxicity include drug overdose, drug drug interactions and drug related adverse effects. Drug induced nephrotoxicity is defined by the presence of any kidney injury caused directly or indirectly by medication. Podocytes, which maintain the filtration barrier in glomeruli, are also targets of drug induced nephrotoxicity 17. Drug induced renal dysfunction is not an uncommon event, which can cause significant morbidity and can be easily overlooked. Prospective cohort studies of aki have documented the frequency of druginduced nephrotoxicity to be approximately 1426% in adult populations. The most common medications or classes of medications along with their clinical presentations are discussed in this article. Drugs can also interfere with normal transport mechanisms in the. Learn vocabulary, terms, and more with flashcards, games, and other study tools. The summary of management of druginduced kidney diseases is mentioned in table 2. A drug may give rise to renal damage in different parts of the nephron and different drugs can have the same intracellular target 5. Treatment for druginduced nephrotoxicity is the same as other forms of acute kidney injuries.
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. The kidney is a major target for druginduced toxicity. This leads frequently to acute kidney injury, and current problems are discussed. In cases where additional evaluation of drug effect on the kidney is deemed useful, the sponsor and.
Druginduced nephrotoxicity is one of the leading causes of aki worldwide. In this work, we reported a renal cell targeting and dual. Drug use and nephrotoxicity in the intensive care unit mark a. Chemicals often cause subclinical injury to liver which manifests only as abnormal liver enzyme tests. Druginduced nephrotoxicity remains a major problem in the clinical setting, where the use of nephrotoxic drugs is often unavoidable. The development of welldesigned nanoprobes for specific imaging of multiple biomarkers in renal cells will afford beneficial information related to the transmutation process of druginduced kidney injury diki. How to prevent, recognize, and treat druginduced nephrotoxicity. Treatment early recognition of a kidney injury is critical. Druginduced nephrotoxicity is more common in hospitalized patients, in particular intensive care unit patients 2,5. 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.
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. Mehta2 abstract drug induced kidney injury is a frequent adverse event which contributes to morbidity and increased healthcare utilization. Druginduced nephrotoxicity and its biomarkers ncbi. The kidneys are remarkably susceptible to damage by drugs. Biomarkers have been identifi ed for the assessment of nephrotoxicity. Review of qualification data for biomarkers of nephrotoxicity. Druginduced nephrotoxicity jama dermatology jama network. The 3 clinical syndromes that can be recognised in druginduced nephropathy are acute renal failure, chronic interstitial nephritis and the nephrotic syndrome. Druginduced nephrotoxicity is more common in hospitalized patients, in. Creatinine is concluded as a good safety marker in 25 studies, with a total sample size of 4789 patients with a clear association with druginduced nephrotoxicity in hiv patients of all the antiretroviral drugs used to treat hiv, tenofovir either as a monotherapy or in combination with other drugs induced nephrotoxicity as evaluated by the. Similar to acute interstitial nephritis, druginduced podocyte injury is often mediated by immune mechanisms.
689 1048 446 510 593 1092 758 48 1114 1031 1197 1404 598 1351 847 375 1048 177 432 689 1343 440 1428 953 10 1266 963 1177 1466 269