DOCSLIB.ORG

Drug-Induced Nephrotoxicity Cynthia A

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Drug-Induced Nephrotoxicity Cynthia A Drug-Induced Nephrotoxicity CYNTHIA a. nAUGHTON, PharmD, BCPS, North Dakota State University College of Pharmacy, Nursing, and Allied Sciences, Fargo, North Dakota Drugs are a common source of acute kidney injury. Compared with 30 years ago, the average patient today is older, has more comorbidities, and is exposed to more diagnostic and therapeutic procedures with the potential to harm kidney function. Drugs shown to cause nephrotoxicity exert their toxic effects by one or more common pathogenic mechanisms. Drug-induced nephrotoxicity tends to be more common among certain patients and in specific clinical situations. Therefore, successful prevention requires knowledge of pathogenic mechanisms of renal injury, patient- related risk factors, drug-related risk factors, and preemptive measures, coupled with vigilance and early intervention. Some patient-related risk factors for drug-induced nephrotoxicity are age older than 60 years, underlying renal insuf- ficiency (e.g., glomerular filtration rate of less than 60 mL per minute per 1.73 m2), volume depletion, diabetes, heart failure, and sepsis. General preventive measures include using alternative non-nephrotoxic drugs whenever possible; correcting risk factors, if possible; assessing baseline renal function before initiation of therapy, followed by adjusting the dosage; monitoring renal function and vital signs during therapy; and avoiding nephrotoxic drug combinations. (Am Fam Physician. 2008;78(6):743-750. Copyright © 2008 American Academy of Family Physicians.) rugs cause approximately 20 per- ALTERED INTRAGLOMERULAR HEMODYNamiCS cent of community- and hospital- In an otherwise healthy young adult, approxi- acquired episodes of acute renal mately 120 mL of plasma is filtered under failure.1-3 Among older adults, pressure through the glomerulus per minute, D the incidence of drug-induced nephrotoxicity which corresponds to the glomerular filtration may be as high as 66 percent.4 Compared with rate (GFR). The kidney maintains or autoreg- 30 years ago, patients today are older, have a ulates intraglomerular pressure by modulat- higher incidence of diabetes and cardiovascu- ing the afferent and efferent arterial tone to lar disease, take multiple medications, and are preserve GFR and urine output. For instance, exposed to more diagnostic and therapeutic in patients with volume depletion, renal per- procedures with the potential to harm kid- fusion depends on circulating prostaglandins ney function.5 Although renal impairment is to vasodilate the afferent arterioles, allowing often reversible if the offending drug is dis- more blood flow through the glomerulus. continued, the condition can be costly and At the same time, intraglomerular pres- may require multiple interventions, including sure is sustained by the action of angiotensin- hospitalization.6 This article provides a sum- II–mediated vasoconstriction of the efferent mary of the most common mechanisms of arteriole. Drugs with antiprostaglandin activ- drug-induced nephrotoxicity and prevention ity (e.g., nonsteroidal anti-inflammatory drugs strategies. [NSAIDs]) or those with antiangiotensin-II activity (e.g., angiotensin-converting enzyme Pathogenic Mechanisms [ACE] inhibitors, angiotensin receptor block- Most drugs found to cause nephrotoxicity ers [ARBs]) can interfere with the kidneys’ exert toxic effects by one or more common ability to autoregulate glomerular pressure and pathogenic mechanisms. These include altered decrease GFR.10,32 Other drugs, such as calci- intraglomerular hemodynamics, tubular cell neurin inhibitors (e.g., cyclosporine [Neoral], toxicity, inflammation, crystal nephropathy, tacrolimus [Prograf]), cause dose-dependent rhabdomyolysis, and thrombotic microan- vasoconstriction of the afferent arterioles, lead- giopathy.7-9 Knowledge of offending drugs ing to renal impairment in at-risk patients.11 and their particular pathogenic mechanisms of renal injury is critical to recognizing and TUBULAR cELL tOXICITY preventing drug-induced renal impairment Renal tubular cells, in particular proximal (Table 110-31). tubule cells, are vulnerable to the toxic effects Downloaded from the American Family Physician Web site at www.aafp.org/afp. Copyright © 2008 American Academy of Family Physicians. For the private, noncommercial use of one individual user of the Web site. All other rights reserved. Contact [email protected] for copyright questions and/or permission requests. SORT: KEY RECOMMENDATIONS FOR PRACTICE Evidence Clinical recommendation rating References Patients at highest risk of drug-induced nephrotoxicity are those with one or more of the following: C 1-3, 7, 34, 35 age older than 60 years, baseline renal insufficiency (e.g., GFR < 60 mL per minute per 1.73 m2), volume depletion, multiple exposures to nephrotoxins, diabetes, heart failure, and sepsis. Assess baseline renal function using the MDRD or Cockcroft-Gault GFR estimation equation and C 7, 33, 41-43 consider a patient’s renal function when prescribing a new drug. Monitor renal function and vital signs after starting or increasing the dose of drugs associated C 7, 10, 32, 48 with nephrotoxicity, especially when used chronically. Drug-induced renal impairment is generally reversible, provided the nephrotoxicity is recognized C 52 early and the offending medication is discontinued. GFR = glomerular filtration rate; MDRD = Modification of Diet in Renal Disease. A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease- oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp. org/afpsort.xml. of drugs because their role in concentrating and reabsorbing glomerular filtrate exposes Table 1. Drugs Associated with Nephrotoxicity them to high levels of circulating toxins.12 Drugs that cause tubular cell toxicity do so by Pathophysiologic mechanism impairing mitochondrial function, interfer- Drug class/drug(s) of renal injury ing with tubular transport, increasing oxida- Analgesics 8,13 tive stress, or forming free radicals. Drugs Acetaminophen, aspirin Chronic interstitial nephritis associated with this pathogenic mechanism Nonsteroidal anti-inflammatory drugs Acute interstitial nephritis, altered of injury include aminoglycosides, ampho- intraglomerular hemodynamics, tericin B (Fungizone; brand not available in chronic interstitial nephritis, glomerulonephritis the United States), antiretrovirals (adefo- Antidepressants/mood stabilizers vir [Hepsera], cidofovir [Vistide], tenofo- Amitriptyline (Elavil*), doxepin Rhabdomyolysis vir [Viread]), cisplatin (Platinol), contrast (Zonalon), fluoxetine (Prozac) dye, foscarnet (Foscavir), and zoledronate Lithium Chronic interstitial nephritis, (Zometa).12-14 glomerulonephritis, rhabdomyolysis Antihistamines INFLammaTION Diphenhydramine (Benadryl), Rhabdomyolysis Drugs can cause inflammatory changes in doxylamine (Unisom) the glomerulus, renal tubular cells, and the Antimicrobials surrounding interstitium, leading to fibro- Acyclovir (Zovirax) Acute interstitial nephritis, crystal nephropathy sis and renal scarring. Glomerulonephritis Aminoglycosides Tubular cell toxicity is an inflammatory condition caused pri- Amphotericin B (Fungizone*; Tubular cell toxicity marily by immune mechanisms and is often deoxycholic acid formulation more associated with proteinuria in the nephrotic so than the lipid formulation) range.12 Medications such as gold therapy, Beta lactams (penicillins, Acute interstitial nephritis, glome- hydralazine (Apresoline; brand not avail- cephalosporins) rulonephritis (ampicillin, penicillin) able in the United States), interferon-alfa Foscarnet (Foscavir) Crystal nephropathy, tubular cell toxicity (Intron A), lithium, NSAIDs, propylthioura- Ganciclovir (Cytovene) Crystal nephropathy cil, and pamidronate (Aredia; in high doses Pentamidine (Pentam) Tubular cell toxicity or prolonged courses) have been reported as Quinolones Acute interstitial nephritis, crystal causative agents.12,13,15 nephropathy (ciprofloxacin [Cipro]) Acute interstitial nephritis, which can Rifampin (Rifadin) Acute interstitial nephritis result from an allergic response to a sus- Sulfonamides Acute interstitial nephritis, crystal pected drug, develops in an idiosyncratic, nephropathy non–dose-dependent fashion.16 Medications Vancomycin (Vancocin) Acute interstitial nephritis that cause acute interstitial nephritis are (continued) thought to bind to antigens in the kidney or 744 American Family Physician www.aafp.org/afp Volume 78, Number 6 ◆ September 15, 2008 Table 1. (continued) Pathophysiologic mechanism Drug class/drug(s) of renal injury act as antigens that are then deposited into Antiretrovirals the interstitium, inducing an immune reac- Adefovir (Hepsera), cidofovir Tubular cell toxicity 16 (Vistide), tenofovir (Viread) tion. However, classic symptoms of a hyper- Indinavir (Crixivan) Acute interstitial nephritis, crystal sensitivity reaction (i.e., fever, rash, and nephropathy eosinophilia) are not always observed.13,16 Benzodiazepines Rhabdomyolysis Numerous drugs have been implicated, Calcineurin inhibitors including allopurinol (Zyloprim); antibi- Cyclosporine (Neoral) Altered intraglomerular otics (especially beta lactams, quinolones, hemodynamics, chronic rifampin [Rifadin], sulfonamides, and van- interstitial nephritis, thrombotic microangiopathy comycin [Vancocin]); antivirals (especially Tacrolimus (Prograf) Altered intraglomerular
Load more

Recommended publications
  • Effect of Renin-Angiotensin System Inhibitors on the Comparative Nephrotoxicity of Nsaids and Opioids During Hospitalization
    Kidney360 Publish Ahead of Print, published on April 27, 2020 as doi:10.34067/KID.0001432020 Effect of renin-angiotensin system inhibitors on the comparative nephrotoxicity of NSAIDs and opioids during hospitalization Todd A. Miano1,2,3; Michael G. S. Shashaty2,4; Wei Yang1,2,3; Jeremiah R. Brown5,6,7; Athena Zuppa8; Sean Hennessy1,2,3 Affiliations: 1. Center for Pharmacoepidemiology Research and Training, Perelman School of Medicine at the University of Pennsylvania 2. Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania 3. Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine at the University of Pennsylvania 4. Pulmonary, Allergy, and Critical Care Division, Perelman School of Medicine at the University of Pennsylvania 5. The Dartmouth Institute for Health Policy and Clinical Practice, Lebanon, New Hampshire 6. Department of Epidemiology, Geisel School of Medicine, Hanover, New Hampshire 7. Department of Biomedical Data Science, Geisel School of Medicine, Hanover, New Hampshire 8. Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA Corresponding author: Todd A. Miano, PharmD, PhD; Address: 423 Guardian Drive, 725 Blockley Hall, Philadelphia, PA 19104; E-mail: [email protected] ; twitter: @Miano81 Copyright 2020 by American Society of Nephrology. Abstract Background: Nonsteroidal anti-inflammatory drugs (NSAIDS) are increasingly important alternatives to opioids for analgesia during hospitalization, as health systems implement opioid minimization initiatives. Increasing NSAID use may increase acute kidney injury (AKI) rates, particularly in patients with predisposing risk factors. Inconclusive data in outpatient populations suggests that NSAID nephrotoxicity is magnified by renin-angiotensin system inhibitors (RAS-I).
    [Show full text]
  • Non-Steroidal Anti-Inflammatory Nephrotoxicity* RICHARD MANIGLIA, B.A.T ALLAN B
    ANNALS OF CLINICAL AND LABORATORY SCIENCE, Vol. 18, No. 3 Copyright © 1988, Institute for Clinical Science, Inc. Non-Steroidal Anti-Inflammatory Nephrotoxicity* RICHARD MANIGLIA, B.A.t ALLAN B. SCHWARTZ, M.D.,$ and SHEILA MORIBER-KATZ, M.D.f§ f Department of Pathology and Laboratory Medicine, tDepartment of Medicine, §Division of Renal Pathology and Electron Microscopy, Hahnemann University School of Medicine, Philadelphia, PA 19102 ABSTRACT Non-steroidal anti-inflammatory drugs have a wide range of use in clini­ cal practice because of their analgesic and anti-inflammatory properties. However, their potential nephrotoxicity has been noted. The case histo­ ries were studied, retrospectively, in 13 patients who were taking non-ste- roidal anti-inflammatory drugs as follows: four on fenoprofen (Nalfon®), three on naproxen (Naprosyn®), two on ibuprofen (Motrin®), two on sulin- dac (Clinoril®), one on tolmetin (Tolectin®), and one on indomethacin (Indocin®) and who exhibited abnormal urinalysis or a deterioration in renal function. Nine of the patients underwent renal biopsies, and eight of these biopsies were positive for interstitial nephritis. In addition to the presentation of additional cases of non-steroidal anti-inflammatory drug nephrotoxicity, a brief review of the current theories of the nephrotoxic mechanism is presented. Introduction this paper will be the non-aspirin, non­ steroidal anti-inflammatory drugs Numerous reports exist that document (NSAID). Since these drugs have a wide the nephrotoxicity of drugs such as the spectrum of use in clinical practice, their synthetic penicillin (methacillin, carben- deleterious actions are of more than just icillin, ampicillin), other antibiotics academic interest. It is hoped that by (aminoglycosides, amphotericin B), understanding the nephrotoxic patho­ thiazide and loop diuretics, and anti­ physiologic mechanisms of non-steroidal neoplastic agents.
    [Show full text]
  • Pathophysiologic Mechanisms of Selected Types of Nephrotoxicity 3/12/14, 10:45 AM
    Pathophysiologic Mechanisms of Selected Types of Nephrotoxicity 3/12/14, 10:45 AM Today News Reference Education Log In Register Pathophysiologic Mechanisms of Selected Types of Nephrotoxicity Author: Piper Julie Hughes, MD, MS; Chief Editor: Vecihi Batuman, MD, FACP, FASN more... Updated: Dec 18, 2013 Aminoglycoside Nephrotoxicity Aminoglycosides preferentially affect the proximal tubular cells. 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. They exert their main toxic effect within the tubular cell by altering phospholipid metabolism. In addition to their direct effect on cells, aminoglycosides cause renal vasoconstriction. The 2 critical factors in the development of acute kidney injury (AKI) secondary to aminoglycoside nephrotoxicity are dosing and duration of therapy. Aminoglycoside uptake by the tubules is a saturable phenomenon, so uptake is limited after a single dose. Thus, a single daily large dose is preferable to 3 doses per day. One dose per day presumably causes less accumulation in the tubular cells once the saturation point is reached.[1, 2] For further information, go to Acute Renal Failure and Acute Tubular Necrosis. Amphotericin B Nephrotoxicity Amphotericin B binds to sterols in cell membranes, thereby creating pores that compromise membrane integrity and increase membrane permeability. It binds not only to ergosterol in fungal cell walls but also to cholesterol in human cell membranes; this is what accounts for its nephrotoxicity. Characteristic electrolyte abnormalities include wasting of potassium and magnesium secondary to increased permeability of the cell membranes.
    [Show full text]
  • Role of the Furosemide Stress Test in Renal Injury Prognosis
    International Journal of Molecular Sciences Review Role of the Furosemide Stress Test in Renal Injury Prognosis Armando Coca 1 , Carmen Aller 1, Jimmy Reinaldo Sánchez 1, Ana Lucía Valencia 1, 2, 3, , Elena Bustamante-Munguira y and Juan Bustamante-Munguira * y 1 Department of Nephrology, Hospital Clinico Universitario de Valladolid, 47003 Valladolid, Spain; [email protected] (A.C.); [email protected] (C.A.); [email protected] (J.R.S.); [email protected] (A.L.V.) 2 Department of Intensive Care Medicine, Hospital Clinico Universitario de Valladolid, 47003 Valladolid, Spain; [email protected] 3 Department of Cardiac Surgery, Hospital Clinico Universitario de Valladolid, 47003 Valladolid, Spain * Correspondence: [email protected] These authors contributed equally to this work. y Received: 11 April 2020; Accepted: 24 April 2020; Published: 27 April 2020 Abstract: Risk stratification and accurate patient prognosis are pending issues in the management of patients with kidney disease. The furosemide stress test (FST) has been proposed as a low-cost, fast, safe, and easy-to-perform test to assess tubular integrity, especially when compared to novel plasma and urinary biomarkers. However, the findings regarding its clinical use published so far provide insufficient evidence to recommend the generalized application of the test in daily clinical routine. Dosage, timing, and clinical outcomes of the FST proposed thus far have been significantly different, which further accentuates the need for standardization in the application of the test in order to facilitate the comparison of results between series. This review will summarize published research regarding the usefulness of the FST in different settings, providing the reader some insights about the possible implications of FST in clinical decision-making in patients with kidney disease and the challenges that research will have to address in the near future before widely applying the FST.
    [Show full text]
  • Mechanisms of Antibiotic-Induced Nephrotoxicity THOMAS W
    ANNALS OF CLINICAL AND LABORATORY SCIENCE, Vol. 12, No. 1 Copyright © 1982, Institute for Clinical Science, Inc. Mechanisms of Antibiotic-Induced Nephrotoxicity THOMAS W. SEALE, Ph .D. and OWEN M. RENNERT, M.D. Departments of Pediatrics and Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190 ABSTRACT Each of the major classes of clinically useful antibiotics can cause neph­ rotoxicity. Major differences exist among classes, and these are reviewed with regard to the frequency of occurrence of nephrotoxicity, the direct or indirect toxic effects of the drugs, their site(s) of action within the kidney, current views of their pathophysiological effects and observations which provide clues to the biochemical mechanisms underlying their adverse effects on kidney structure and function. Even for a single abnormal kidney function, such as non-oliguric reduction of glomerular filtration rate by gentamicin, the physiological and biochemical mechanisms may be com­ plex. In no instance has the biochemical mechanism underlying antibiotic- induced nephrotoxicity been definitely established. Introduction of antibiotics with relatively low Nephrotoxicity has long been recog­ therapeutic indices and significant neph­ nized as a serious complication resulting rotoxic potential. In addition, some from antibiotic administration. The vast widely employed antibiotics with low po­ array of antibiotic types and derivatives tential for inducing renal disease will in­ available to the clinician and the in­ frequently have significant detrimental creased monitoring for early signs of renal effects on the kidneys of certain patients. impairment have reduced the risk of kid­ These idiosyncratic drug responses may ney damage compared to the early days of reflect intrinsic or environmentally- sulfonamide and neomycin therapy.
    [Show full text]
  • Pathophysiological Aspects of Nephropathy Caused by Non
    UPDATE ARTICLE | ARTIGO DE ATUALIZAÇÃO Pathophysiological aspects of nephropathy caused by non-steroidal anti-inflammatory drugs Aspectos fisiopatológicos da nefropatia por anti-inflamatórios não esteroidais Authors ABSTRACT RESUMO Guillherme Nobre Cavalcanti Lucas1 Non-steroidal anti-inflammatory drugs Os anti-inflamatórios não esteroidais (AI- Ana Carla Carneiro Leitão1 (NSAIDs) are commonly used medica- NEs) são medicamentos comumente utiliza- Renan Lima Alencar1 tions associated with nephrotoxicity, es- dos, associados à nefrotoxicidade, sobretudo Rosa Malena Fagundes Xavier1,2,3 pecially when used chronically. Factors quando utilizados cronicamente. Fatores such as advanced age and comorbidities, como idade avançada e comorbidades, que Elizabeth De Francesco Daher4 which in themselves already lead to a por si só já levam à diminuição da taxa de Geraldo Bezerra da Silva Junior1 decrease in glomerular filtration rate, in- filtração glomerular, aumentam o risco de crease the risk of NSAID-related nephro- nefrotoxicidade dos AINEs. O principal 1 Universidade de Fortaleza, toxicity. The main mechanism of NSAID mecanismo de ação dos AINEs é a inibição Programa de Pós-Graduação action is cyclooxygenase (COX) enzyme da enzima ciclooxigenase (COX), interfer- em Saúde Coletiva, Centro de inhibition, interfering on arachidonic acid indo na conversão do ácido araquidônico em Ciências da Saúde, Fortaleza, conversion into E2 prostaglandins E2, prostaglandinas E2, prostaciclinas e trom- CE, Brasil. prostacyclins and thromboxanes. Within boxanos. Nos rins, as prostaglandinas atuam 2 Universidade do Estado da Bahia, Curso de Farmácia, the kidneys, prostaglandins act as vaso- como vasodilatadoras, aumentando a per- Salvador, BA, Brasil. dilators, increasing renal perfusion. This fusão renal. Essa vasodilatação atua como 3 Universidade Federal da Bahia, vasodilatation is a counter regulation of uma contrarregulação de mecanismos, como Instituto de Saúde Coletiva, mechanisms, such as the renin-angioten- a atuação do sistema renina-angiotensina- Salvador, BA, Brasil.
    [Show full text]
  • Drug-Induced Acute Kidney Injury: a Study from the French Medical Administrative and the French National Pharmacovigilance Databases Using Capture-Recapture Method
    Journal of Clinical Medicine Article Drug-Induced Acute Kidney Injury: A Study from the French Medical Administrative and the French National Pharmacovigilance Databases Using Capture-Recapture Method Anne-Lise Rolland 1 , Anne-Sophie Garnier 2,3, Katy Meunier 1, Guillaume Drablier 4 and Marie Briet 2,4,* 1 Département d’Information Médicale, Centre Hospitalo-Universitaire d’Angers, 49100 Angers, France; [email protected] (A.-L.R.); [email protected] (K.M.) 2 Service de Néphrologie-Dialysis-Transplantation, Centre Hospitalo-Universitaire d’Angers, 49100 Angers, France; [email protected] 3 Laboratoire MitoVasc, INSERM U1083, CNRS UMR 6015, Université d’Angers, 49100 Angers, France 4 Service de Pharmacologie-Toxicologie et Centre Régional de Pharmacovigilance, Centre Hospitalo-Universitaire d’Angers, 49100 Angers, France; [email protected] * Correspondence: [email protected] Abstract: Background: Acute kidney injury (AKI) is a public health concern. Among the pathological situations leading to AKI, drugs are preventable factors but are still under-notified. We aimed to pro- vide an overview of drug-induced AKI (DIAKI) using pharmacovigilance and medical administrative databases Methods: A query of the PMSI database (French Medical Information System Program) of adult inpatient hospital stays between 1 January 2017 and 31 December 2018 was performed using ICD-10 (International Classification of Diseases 10th revision) codes to identify AKI cases which were reviewed by a nephrologist and a pharmacovigilance expert to identify DIAKI cases. In parallel, DIAKIs notified in the French Pharmacovigilance Database (FPVDB) were collected. A capture- Citation: Rolland, A.-L.; Garnier, A.-S.; Meunier, K.; Drablier, G.; Briet, recapture method was performed to estimate the total number of DIAKIs.
    [Show full text]
  • Review of Qualification Data for Biomarkers of Nephrotoxicity Submitted by the Predictive Safety Testing Consortium
    Review of Qualification Data for Biomarkers of Nephrotoxicity Submitted by the Predictive Safety Testing Consortium Biomarker Qualification Review Team Melanie Blank Albert De Felice Federico Goodsaid Patricia Harlow Elizabeth Hausner David Jacobson-Kram William Taylor Aliza Thompson Douglas Throckmorton Shen Xiao Center for Drug Evaluation and Research U.S. Food and Drug Administration January 16, 2009 BQRT Review of PSTC Nephrotoxicity Biomarkers Table of Contents 1. Executive Summary 4 a. Background 4 b. Sources of Data and Major Findings 4 c. BQRT Conclusions 5 d. BQRT Recommendations 5 2. Background 6 a. Overview of the Problem 6 b. The Biomarker Qualification Pilot Process 6 i. Definition of Qualification and of Qualification in Context 6 ii. Overview of Pilot Qualification Process 7 c. Commonly Used Laboratory Animal Species for Nonclinical Safety Assessments of Nephrotoxicity 8 d. Detection of Drug-Induced Nephrotoxicity in Animal Models 8 e. Biomarkers of Drug-Induced Nephrotoxicity Proposed by PSTC 9 f. Context Claims Submitted by PSTC for the Qualification of Proposed Biomarkers of Drug-Induced Nephrotoxicity 12 3. Summary of the Supporting Data Submitted by PSTC for the Qualification of Proposed Biomarkers of Drug-Induced Nephrotoxicity 13 a. Overall Summary of Results 13 b. Summary of Studies Conducted and Biomarkers Measured 16 c. Histopathology Lexicon and Scoring 18 d. Summary Tables of ROC Curves 19 e. Statistical Analysis 20 f. Individual Animal Data 22 g. Recovery Studies 26 h. ROC Analysis of Different Histopathology Lesions 26 4. Reviewer Discussion of Qualification Data 27 a. The Qualification Process 27 b. Analytical Validation 29 c. Correlation between Histopathology and Biomarker Data 35 i.
    [Show full text]
  • Benefits and Risks of Furosemide in Acute Kidney Injury
    Anaesthesia, 2010, 65, pages 283–293 doi:10.1111/j.1365-2044.2009.06228.x ..................................................................................................................................................................................................................... REVIEW ARTICLE Benefits and risks of furosemide in acute kidney injury K. M. Ho1 and B. M. Power2 1 Intensive Care Specialist, Royal Perth Hospital and Clinical Associate Professor, University of Western Australia, Perth, WA, Australia 2 Intensive Care Specialist, Joondalup Hospital, Perth, WA, Australia Summary Furosemide, a potent loop diuretic, is frequently used in different stages of acute kidney injury, but its clinical roles remain uncertain. This review summarises the pharmacology of furosemide, its potential uses and side effects, and the evidence of its efficacy. Furosemide is actively secreted by the proximal tubules into the urine before reaching its site of action at the ascending limb of loop of Henle. It is the urinary concentrations of furosemide that determine its diuretic effect. The severity of acute kidney injury has a significant effect on the diuretic response to furosemide; a good ‘urinary response’ may be considered as a ‘proxy’ for having some residual renal function. The current evidence does not suggest that furosemide can reduce mortality in patients with acute kidney injury. In patients with acute lung injury without haemodynamic instability, furosemide may be useful in achieving fluid balance to facilitate mechanical ventilation
    [Show full text]
  • The Mechanism of Drug Nephrotoxicity and the Methods for Preventing Kidney Damage
    International Journal of Molecular Sciences Review The Mechanism of Drug Nephrotoxicity and the Methods for Preventing Kidney Damage Ewa Kwiatkowska 1,* , Leszek Doma ´nski 1, Violetta Dziedziejko 2 , Anna Kajdy 3, Katarzyna Stefa ´nska 4 and Sebastian Kwiatkowski 5 1 Clinical Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, 70-111 Szczecin, Poland; [email protected] 2 Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, 70-111 Szczecin, Poland; [email protected] 3 Centre of Postgraduate Medical Education, Department of Reproductive Health, St. Sophie’s Obstetrics and Gynecology Hospital, 01-004 Warsaw, Poland; [email protected] 4 Department of Obstetrics Medical, University of Gda´nsk,80-952 Gda´nsk,Poland; [email protected] 5 Department of Obstetrics and Gynecology, Pomeranian Medical University, 70-111 Szczecin, Poland; [email protected] * Correspondence: [email protected]; Tel.: +48-91-466-1196 Abstract: Acute kidney injury (AKI) is a global health challenge of vast proportions, as approx. 13.3% of people worldwide are affected annually. The pathophysiology of AKI is very complex, but its main causes are sepsis, ischemia, and nephrotoxicity. Nephrotoxicity is mainly associated with the use of drugs. Drug-induced AKI accounts for 19–26% of all hospitalized cases. Drug-induced nephrotoxicity develops according to one of the three mechanisms: (1) proximal tubular injury and acute tubular Citation: Kwiatkowska, E.; necrosis (ATN) (a dose-dependent mechanism), where the cause is related to apical contact with Doma´nski,L.; Dziedziejko, V.; Kajdy, drugs or their metabolites, the transport of drugs and their metabolites from the apical surface, and A.; Stefa´nska,K.; Kwiatkowski, S.
    [Show full text]
  • Can Nsaids Be Used Safely for Analgesia in Patients with CKD?
    Kidney360 Publish Ahead of Print, published on September 23, 2020 as doi:10.34067/KID.0004582020 NSAIDs can be used safely for analgesia in patients with CKD: PRO Erin F. Barreto1, 2, Molly A. Feely3 1Department of Pharmacy, Mayo Clinic, Rochester, MN 2Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN 3Center for Palliative Medicine, Mayo Clinic, Rochester, MN Corresponding author: Erin F. Barreto, PharmD, MSc, FCCM 200 1st St SW, Rochester, MN 55905 [email protected] Copyright 2020 by American Society of Nephrology. Overview of NSAID use and safety in kidney disease Nearly 60% of patients with chronic kidney disease (CKD) suffer pain. Of those patients with CKD who have pain, most rate their pain as moderate or severe in intensity. Undermanaged pain is associated with higher rates of mood disorders, maladaptive coping and decreased quality of life for patients with CKD.(1) In general, non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as first-line for analgesia and also act as antipyretics and anti- inflammatory medications. Estimates indicate that 98 million patients annually are prescribed NSAIDs(2), which likely represents only a fraction of total use given widespread non- prescription access. Epidemiologic studies suggest that 70-80% of all NSAID users consume over-the-counter products like ibuprofen or naproxen.(3,4) In the National Health and Nutrition Examination Survey, routine NSAID use was common in patients with CKD and use increased with increasing CKD severity.(3) NSAIDs have well known adverse effects in CKD patients. These risks can broadly be categorized into affecting the kidneys, gastrointestinal (GI) tract, or cardiovascular system.
    [Show full text]
  • Evaluation of Current Amikacin Dosing Recommendations and Development of an Interactive Nomogram: the Role of Albumin
    pharmaceutics Article Evaluation of Current Amikacin Dosing Recommendations and Development of an Interactive Nomogram: The Role of Albumin Jonás Samuel Pérez-Blanco 1,2,† , Eva María Sáez Fernández 1,2,3,† , María Victoria Calvo 1,2 , José M. Lanao 1,2,* and Ana Martín-Suárez 1 1 Department of Pharmaceutical Sciences, Pharmacy Faculty, University of Salamanca, 37007 Salamanca, Spain; [email protected] (J.S.P.-B.); [email protected] (E.M.S.F.); [email protected] (M.V.C.); [email protected] (A.M.-S.) 2 Institute for Biomedical Research of Salamanca (IBSAL), Paseo de San Vicente, 58-182, 37007 Salamanca, Spain 3 Pharmacy Service, University Hospital of Salamanca, Paseo de San Vicente, 58-182, 37007 Salamanca, Spain * Correspondence: [email protected]; Tel.: +34-923294518 † These authors contributed equally to this work. Abstract: This study aimed to evaluate the potential efficacy and safety of the amikacin dosage proposed by the main guidelines and to develop an interactive nomogram, especially focused on the potential impact of albumin on initial dosage recommendation. The probability of target attainment (PTA) for each of the different dosing recommendations was calculated through stochastic simulations based on pharmacokinetic/pharmacodynamic (PKPD) criteria. Large efficacy and safety differences were observed for the evaluated amikacin dosing guidelines together with a significant impact of albumin concentrations on efficacy and safety. For all recommended dosages evaluated, efficacy and safety criteria of amikacin dosage proposed were not achieved simultaneously in most of the Citation: Pérez-Blanco, J.S.; Sáez clinical scenarios evaluated. Furthermore, a significant impact of albumin was identified: The higher Fernández, E.M.; Calvo, M.V.; Lanao, is the albumin, (i) the higher will be the PTA for maximum concentration/minimum inhibitory J.M.; Martín-Suárez, A.
    [Show full text]