The condition can be costly and may require multiple interventions, including hospitalization. However, all agents also carry adverse drug effect profiles. We recently examined five patients with glomerular disease and druginduced interstitial nephritis. The most common etiology of ain is drug induced disease, which results from a reaction to certain medications. Sep 01, 2015 drug induced renal disorders are more common in certain patients and in specific clinical situations. While most of these are clinically insignificant, some drugs. Drugs can cause acute renal injury, intrarenal obstruction, interstitial nephritis, nephrotic syndrome, and acidbase. The pathogenesis of druginduced renal cystic disease. Druginduced acute renal dysfunction karen shalansky, pharm. The prediction of proximal tubular toxicity during drug development remains difficult.
Druginduced kidney disease pharmacotherapy quick guide. Rarely, renal failure itself may be associated with hearing loss due to the underlying disease eg, alport syndrome, wegeners granulomatosis and by a variety of mechanisms such as axonal uraemic neuropathy80 and the increased susceptibility to ototoxins. Acute interstitial nephritis ain is a common cause of acute kidney injury. Progressive renal insufficiency associated with amiodarone. Patients are exposed to numerous prescribed and overthecounter medications. Renal dysfunction and renal disease due to drugs are common and can lead to renal failure, both acute and chronic. Pepper professor of public health and preventive medicine professor of biostatistics and epidemiology, medicine, and pharmacology vice dean for institutional affairs university of pennsylvania. Jul 27, 2015 the renal proximal tubule is a main target for drug induced toxicity.
Drug induced kidney disorder disease dkid is an origin of kidney disease followed by acute renal failure. Drug induced kidney disease occurs primarily in patients with underlying risk factors. Druginduced nephrotoxicity tends to occur more frequently in patients. A high index of suspicion is warranted if a renal biopsy is suggestive of fabry disease, because these patients and their family members may benefit from. Din accounts for 7% of all drug toxicities and 20% to 30% of acute renal failures among inpatients. Drug induced nephrotoxicity are more common among infants and young children and in certain clinical situations such as underlying renal dysfunction and cardiovascular disease. Mar 21, 2007 patients with underlying disease, such as the elderly and those with hypotension and dehydration, are at particular risk for dirf. 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. Markowitz and others were the first to report the association between pamidronate and collapsing glomerulopathy. A number of factors enhance the vulnerability of the kidney to the nephrotoxic effects of drugs and toxins. Drugs can cause acute renal injury, intrarenal obstruction, interstitial nephritis, nephrotic.
Over the years, multiple other agents have been linked to immunemediated glomerular disease, often with associated autoantibody formation. Dec 10, 20 since it is virtually impossible to distinguish an iatrogenic druginduced pl from fabrys disease on ultrastructural analysis of kidney tissue, the clinician has to use the patients family history, extrarenal symptoms, and biochemical features, such as a reduced. Certain clinical and laboratory features may distinguish these. Certain drugs can cause alteration in intraglomerular hemodynamics. Drug induced pseudo renal failure bun due to protein catabolism steroids, tetracyclines scr due to competitive inhibition of creatinine secretion trimethoprim, cimetidine, triamterene with trimethoprim 1535% rise scr fully expressed after 3 days more sig in pts with preexisting renal dysfunction can. The inclusion of the levels of evidence classification scheme for identifying drug induced diseases. A new section on drug induced dermatologic diseases.
Introduction the japan renal biopsy registry jrbr was started in 2007 by the committee for the standardization of renal pathological diagnosis and the committee for the kidney disease registry of the japanese society of nephrology. Chloroquineinduced lipidosis mimicking fabry disease. Pdf druginduced acute interstitial nephritis pathology. Unfortunately, drugs remain a relatively common cause of acute and chronic kidney injury.
Drug induced acute interstitial nephritis pathology, pathogenesis, and treatment article pdf available in iranian journal of kidney diseases 91. They are broadly categorized as patientspecific, kidney related, and drug related factors. Drug induced kidney disease alwin hl loh and arthur h cohen cellular, tip and collapsing. Although nephrotoxicity is most commonly associated with injury in the tubulointerstitial compartment as either acute tubular necrosis or acute interstitial nephritis, a growing body of literature has also highlighted the potential for drug induced glomerular lesions. Now in its third edition, this essential and comprehensive resource provides a detailed analysis of how to identify, prevent, and manage drug induced diseases. Less commonly, therapeutic agents may induce injury to blood vessels or produce a variety of patterns of glomerular disease. Chair and professor, department of biostatistics and epidemiology director, center for clinical epidemiology and biostatistics george s. Druginduced renal disorders journal of renal injury. Drug induced kidney disease is a frequent cause of renal dysfunction. Pharmacologic agents responsible for inducing this entity include antibiotics, diuretics, and nonsteroidal antiinflammatory drugs. Drug induced kidney injury is a frequent adverse event which contributes to morbidity and increased healthcare utilization. Druginduced renal disease, like other iatrogenic disorders, bedevils the patient and humbles the physician. Oral administration of 2amino4,5diphenyl thiazole hci to rats over a period of 11 weeks produced marked, diffuse, progressive renal cystic disease without significant tubular obstruction or interstitial fibrosis.
A combination of factors including the innate nephrotoxicity of drugs, underlying patient characteristics that increase their risk for kidney injury, and the metabolism and pathway of excretion by the kidneys of the various. The kidney is particularly vulnerable to drugs and other agents that cause renal damage. The 6rs of drug induced nephrotoxicity bmc nephrology full text. 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. Drug induced kidney disease dikd accounts for approximately 1926% of cases of acute kidney injury aki in hospitalized patients. Druginduced nephrotoxicity is increasingly recognized as a significant contributor to kidney disease including acute kidney injury aki and. Nonsteroidal antiinflammatory drug induced acute kidney. Demonstrate knowledge of protein, caloric, electrolyte, and trace element requirements in aki with and without renal replacement therapy rrt. There are no standards to identify drug induced nephrotoxicity and as a result dikd is often unrecognized.
This article provides a summary of the most common mechanisms of drug induced nephrotoxicity and prevention strategies. Different classes of drugs, by virtue of immunological mechanisms or direct toxicity initiate certain. Drug induced renal toxicity is more common in infants and young children in certain. Drug induced autoimmune disease was initially described decades ago, with reports of vasculitis and a lupuslike syndrome in patients taking hydralazine, procainamide, and sulfadiazine. Druginduced nephrotoxicity american family physician. A, b, and c are good, moderate, and poor evidence to support recommendation, respectively. Prediction of druginduced nephrotoxicity and injury. Drugs can cause acute renal injury, intrarenal obstruction, interstitial nephritis, nephrotic syndrome, and acidbase and fluid electrolytes disorders. Pharmacology behind common drug nephrotoxicities american. Renal vulnerability to drug toxicity american society of.
Renal phospholipidosis possibly induced by ranolazine. 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. Mechanisms of drug induced tubulointerstitial disease generally fall. Druginduced kidney disease kidney kidney disease free. Drug induced kidney disease 1 drug induced kidney disease 2 introduction. Druginduced interstitial nephritis is being recognized with increasing frequency. An overview of drug induced acute kidney injury neesh pannu, md, sm, frcp. Miller, with contributions from experts distinguished in their respective specialties, drug induced diseases is organized logically and is easy. Drug induced nephrotoxicity tends to occur more frequently in patients with intravascular volume depletion. Different classes of drugs, by virtue of immunological mechanisms or direct toxicity initiate certain stereotyped renal responses. Since then, toxicity of an everincreasing number of drugs has been linked to selective toxicity in the mitochondrion chapter 4.
Dhrs account for fewer than 15% of reported adverse drug. Druginduced kidney disease 1 druginduced kidney disease 2 introduction. One, two, or all three of the factor categories can act to promote various forms of renal injury. Phenotype standardization for drug induced kidney disease. The potential of medications to cause kidney injury is well known. In summary, phospholipidosis can be induced by a number of cationic amphiphilic drugs, including amiodarone, which cause renal and corneal morphological findings mimicking fabry disease. Apply knowledge of organ crosstalk to predict changes in drug pharmacokinetics. Gentamycin, chloroquine, and hydroxychloroquine are cationic amphiphilic drugs that have been reported as causes of druginduced phospholipidosis with renal biopsy findings similar to those in fabry disease, 1 x 1. The majority of drug induced renal injury involves the tubules and interstitium. The challenge is how to accurately estimate a patients kidney function in both acute and chronic kidney disease and determine the influence of renal replacement therapies on drug disposition. The perspectives of patients with lithiuminduced endstage. The clinical manifestations of drug induced renal disease may include all the manifestations attributed to natural or spontaneous renal diseases such as acute renal failure, chronic renal failure, acute nephritic syndrome, nephrotic syndrome, renal colic, haematuria, selective tubular defects, obstructive nephropathy, etc. Druginduced kidney disease pathology and current concepts. Druginduced kidney disease constitutes an important cause of acute renal failure and chronic kidney disease in present day clinical practice.
Distinguish among the different types of acute kidney injury aki and identify drug induced causes. Nadim, md a cute kidney injury aki is a relatively common condition in the intensive care unit and occurs in 20% to 30% of critically ill patients, with approximately 6% eventually requiring renal replacement therapy 1. Druginduced nephrotoxicity are more common among infants and young children and in certain clinical situations such as underlying renal dysfunction and cardiovascular disease. 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. Doserelated nephrotoxicity subsequent to administration of certain chloroethylnitrosourea compounds carmustine, semustine and streptozocin is commonly heralded by increased serum creatinine levels, uraemia and proteinuria. The 6rs of drug induced nephrotoxicity bmc nephrology. Acute kidney injury aki may occur 3 to 16 months after cpi exposure, which makes extended renal function monitoring critical for detection and treatment. Anticancer druginduced kidney disorders springerlink. Patients at highest risk of drug induced nephrotoxicity are those with one or more of the following. Pdf druginduced kidney disease pathology and current. Druginduced renal disorders journal of renal injury prevention. Druginduced renal disease is common and responsible for a variety of pathological effects on the kidney, many of which are potentially recoverable.
Drug induced pseudorenal failure bun due to protein catabolism steroids, tetracyclines scr due to competitive inhibition of creatinine secretion trimethoprim, cimetidine, triamterene with trimethoprim 1535% rise scr fully expressed after 3 days more sig in pts with preexisting renal dysfunction can. Download fulltext pdf download fulltext pdf druginduced hematologic syndromes article pdf available in advances in hematology 20096. Renal disease induced by drugs was studied by percutaneous biopsy in 40 patients. Druginduced kidney diseasealwin hl loh and arthur h cohen cellular, tip and collapsing. Drug induced kidney diseases free download as powerpoint presentation. Drug induced nephrotoxicity din is relatively common. Druginduced kidney disease free download as powerpoint presentation. Drug induced kidney disease pathology and current concepts. Drug dosage adjustment for patients with acute or chronic kidney disease is an accepted standard of practice.
The concept of the mitochondrion as a major target of drug induced toxicity was raised only as recently as the early 1980s. Neutrophil gelatinaseassociated lipocalin is a 25kda pro tein from the lipocalin family. Nephrolithiasis formation of renal calculi or kidney stones occurs as the result of abnormal crystal precipitation in the renal collecting system intratubular precipitation of crystallinematerial prevalence of drug induced nephrolithiasis is 1% signs and symptoms pain, haematuria, infection, or, occasionally, urinary. Drug induced kidney diseases nonsteroidal anti inflammatory. Pharmaceutical agents provide diagnostic and therapeutic utility that are central to patient care. The purpose of this report is to clarify drug induced kidney disease dikd of renal biopsied cases in japan.
Chronic kidney disease affects renal drug elimination and other phar macokinetic processes involved in drug disposition e. The initial diagnosis of drug induced kidney disease dikd typically involves detection of elevated serum creatinine s cr and blood urea nitrogen, for which there is a temporal relationship between the toxicity and use of a potentially nephrotoxic drug drug induced kidney disease is best prevented by avoiding the use of potentially nephrotoxic agents for patients at. Ppt druginduced kidney disease powerpoint presentation. Fanconis syndrome fs was first described by lignac in 1924. Hall 1 from the 1 swiss national centre of competence in research nccr kidney control of homeostasis, institute of anatomy, university of zurich, zurich, switzerland, 2 ucl centre for nephrology, royal free hospital, london, uk and 3 department of cellular pathology, royal free hospital, london, uk.
Cardinal symptoms of the syndrome are hyperaminoaciduria. Nonsteroidal antiinflammatory drugs nsaids are a common cause of adverse drug events ades, but renal risks of nsaids are less well quantified than gastrointestinal and cardiac risks. Aki, tubulointerstitial disease and renal scarring. Drug induced acute interstitial nephritis diain is a drug hypersensitivity reaction dhr that manifests 7 to 10 days after exposure to the culprit drug. It is upregulated after ischemic or nephrotoxic aki, is detected in the urine 3 hours postinjury, and peaks 6 hours postinjury. Full text druginduced impairment of renal function ijnrd. New drugs implicated as the cause of specific disease s. Electronic surveillance presents a powerful tool to identify susceptible. Associated with numerous varieties of inherited and acquired conditions, fs is characterized by a generalized transport defect in the proximal tubules, leading to renal losses of glucose, phosphate, calcium, uric acid, amino acids, bicarbonates, and other organic compounds.
Compared with 30 years ago, the average patient today is older, has more comorbidities. Infants and young children with extracellular volume depletion, sepsis, renal impairment, cardiovascular disease, diabetes, or prior exposure to radio contrast agents are at risk of developing drug nephrotoxicity. Intensive monitoring of kidney functioning helps to reveal early decline in renal failure. This study investigates the views and experiences of bd patients who have developed endstage renal disease and were receiving renal replacement. We convened a panel of international, adult and pediatric, nephrologists and pharmacists. Patients with underlying disease, such as the elderly and those with hypotension and dehydration, are at particular risk for dirf. Drug induced renal disease, like other iatrogenic disorders, bedevils the patient and humbles the physician when he finds that he has done harm at the time he thought he was doing good. Jan 19, 2016 nephrolithiasis formation of renal calculi or kidney stones occurs as the result of abnormal crystal precipitation in the renal collecting system intratubular precipitation of crystallinematerial prevalence of drug induced nephrolithiasis is 1% signs and symptoms pain, haematuria, infection, or, occasionally, urinary. Pharmacotherapeutic specialist, vgh clinical professor, ubc apr 8, 2010 outline pseudo renal failure acute renal failure prerenal nsaids, cyatacrolimus, aceiarb, diuretics intrinsic atn vs ain atn aminoglycosides, amphotericin b, radiocontrast media. Drug induced renal disease is common and responsible for a variety of pathological effects on the kidney, many of which are potentially recoverable.
Drug dosing adjustments in patients with chronic kidney. The main types of renal injury predominantly involve the tubules and interstitium, leading to acute tubular injury and necrosis, or interstitial nephritis with inflammatory tubular injury. Druginduced renal disease, like other iatrogenic disorders, bedevils the patient and humbles the physician when he finds that he has done harm at the time he thought he was doing good. Lithium is the treatment of choice for patients suffering from bipolar disorder bd but prolonged use induces renal dysfunction in at least 20% of patient. It is therefore vital in any patient with renal disease whatever the. Scribd is the worlds largest social reading and publishing site. The kidney maintains the vital functions of clearing excess body fluid and removing metabolic and exogenous toxins from the blood. As more investigators have taken advantage of relatively new methods to isolate pure nonparenchymal cells, there have been rapid gains in information on the contribution of kupffer cells, sinusoidal endothelial cells, and stellate cells to a variety of liver diseases, including drug and toxin induced liver injury chapter 10. Jul 07, 2009 acute interstitial nephritis ain is a form of inflammatory renal disease affecting predominantly the tubules and the interstitium.
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