BOOK TRY

Is it possible to fall in love when all you know is hate?

SLOWLY FALLING
FOR THE SCHOOL BULLY

Christopher hates Paul with every fiber of his being.
So why does his heart beat faster whenever
his nemesis is around?

BY KATIE LYNN JOHNSON

KANDUNGAN

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KANDUNGAN

BAB 1
INTRODUCTION

REVIEW & META-ANALYSIS OF Cephalosporin-induced acute kidney Disease

 Introduction

 Acute kidney injury (AKI) ↑ morbidity and mortality1

 One of the causes of AKI is exposure to nephrotoxic drugs
 Antibiotics are reported as one of the most common cause of drug-induced kidney disease2
 Thus, early detection and prevention for antibiotic-induced AKI are vital1
 Acute Kidney Injury: Staging
 AKI vs Acute Kidney Disease (AKD)
 AKI: Clinical consequence
 AKI lead to poor outcomes :
 Drug-induced AKI

 Drug-induced Kidney Disease

 2015 Consensus1

 Time course :

 Sub-acute phenotype in AKI as many drugs manifest biomarker changes outside the

time frame of the acute time period

 Problem Statement & Justification

 Cephalosporins commonly used

 Cefepime ↑ 165% (2011-2014)1

 Potential risk of kidney injury with cephalosporin
 No consolidated information

 Incidence
 Dose-injury relationship
 At-risk population

 Expand knowledge regarding drug-induced kidney disease

 Aim & Objectives

 Aim :

 To review available studies on cephalosporin-induced acute kidney disease (Ceph-AKD)

 Objectives :

 To determine the incidence of Ceph-AKD
 To describe the type of injury and severity of Ceph-AKD
 To describe the potential risk factors for the development of Ceph-AKD
 To calculate the effect size of Ceph-AKD using meta-analysis approach if possible
 Methodology : Search Strategy
 Article will be searched by:
 Electronic databases: PubMed/MEDLINE, Ovid EMBASE, Cochrane Library and Scopus

from inception to March 2019

 Hand searching of reference list of located studies
 Relevant MeSH term and keywords combination using Boolean operators will be use

 Methodology : Study Selection
 All located studies will be imported to a reference manager software, Mendeley
 Inclusion criteria:

 Published studies
 All study designs (with and without comparison group)
 Reported use of cephalosporin in patients’ treatment
 Adults (> 18 years)
 All settings (ward, clinic)
 Exclusion criterion:
 Non-English language

 Methodology: Study Selection



Methodology: Quality of Study Assessment

 Cochrane’s Risk of Bias 2.0 Tool (for RCTs)
 5 domains :
 Risk of bias arising from the randomization process
 Risk of bias due to deviations from the intended interventions
 Missing outcome data
 Risk of bias in measurement of the outcome
 Risk of bias in selection of the reported result


Methodology: Quality of Study Assessment

 Cochrane’s Risk Of Bias In Non-randomized Studies - of Interventions (ROBIN-I tool)
 7 domains :

 Bias due to confounding
 Bias in selection of participants into the study
 Bias in classification of interventions
 Bias due to deviations from intended interventions
 Bias due to missing data
 Bias in measurement of outcomes
 Bias in selection of the reported result
 Data Analysis

 Data will be reported narratively and analytically using meta-analysis (if possible – have at

least 3 studies that can be compared)

 Meta-analysis:
 OR /adjusted OR to estimate the risk for kidney injury/disease where available
 Random effects model to obtain pooled OR
 I2 statistic to quantify the proportion of observed inconsistency
 Publication bias investigated by funnel plots
 All analyses will be performed with Review Manager Software (RevMan Analyses

Version 5.0.4)

 Potential Findings/Implication
 The current study will be able to provide information on:

 incidence
 severity
 type of cephalosporin that commonly reported to induce AKI and
 potential risk factors that contribute the event
 This will provide guide to healthcare professionals in choosing appropriate antibiotic or

management for patients who are at risk for AKI or who have developed drug-induced AKI

 The finding may also be use to conduct future study with appropriate study design
 Potential Findings/Implication
 Appendix : Data Collection Form
 Appendix : Gantt Chart
 References

 Acute Kidney Injury Work Group. 2012. KDIGO Clinical Practice Guideline for Acute Kidney
Injury. Kidney International 2(1): i-iv; 1-138. doi:10.1159/000339789

 Altman, D. G. & Bland, J. M. 2003. Interaction revisited: the difference between two
estimates. BMJ 326(7382): 219. Retrieved from
http://www.bmj.com/content/326/7382/219.abstract

 Awdishu, L. & Mehta, R. L. 2017. The 6R’s of drug induced nephrotoxicity. BMC Nephrology
18(1): 1–12. doi:10.1186/s12882-017-0536-3

 Basile, D. P., Anderson, M. D. & Sutton, T. A. 2012. Pathophysiology of acute kidney injury.
Comprehensive Physiology 2(2): 1303–1353. doi:10.1002/cphy.c110041

 Bellomo, R., Ronco, C., Kellum, J. A., Mehta, R. L. & Palevsky, P. 2004. Acute renal failure –
definition , outcome measures , animal models , fluid therapy and information technology
needs : the Second International Consensus Conference of the Acute Dialysis Quality Initiative
( ADQI ) Group. Critical Care 8(4). doi:10.1186/cc2872

 Chertow, G. M., Burdick, E., Honour, M., Bonventre, J. V & Bates, D. W. 2005. Acute kidney
injury, mortality, length of stay, and costs in hospitalized patients. Journal of the American
Society of Nephrology : JASN 16(11): 3365–70. doi:10.1681/ASN.2004090740

 Coca, S. G., Singanmala, S. & Parikh, C. R. 2012. Chronic Kidney Disease after Acute Kidney
Injury: A Systematic Review and Meta-analysis. Kidney Int. 81(5): 442–448.
doi:10.1038/ki.2011.379.

 Daudon, M. & Jungers, P. 2004. Drug-Induced Renal Calculi: Epidemiology, Prevention and
Management. Drugs 64(3): 245–275. Retrieved from
https://www.scopus.com/inward/record.uri?eid=2-s2.0-
1442357702&doi=10.2165%2F00003495-200464030-
00003&partnerID=40&md5=96c218cd9d873663df238bbd87e070cc

 Decloedt, E. & Maartens, G. 2011. Drug-induced renal injury 29(6): 252–255.
 DerSimonian, R. & Laird, N. 2015. Meta-Analysis in Clinical Trials Revisited. Contemp Clin

Trials 45(0 0): 139–145. doi:10.1016/j.cct.2015.09.002.Meta-Analysis
 Dursun, M., Otunctemur, A. & Ozbek, E. 2015. Kidney Stones and Ceftriaxone. EMJ Urol 3(1):

68–74. doi:10.1080/14672710410001676061

 References

 Goldstein, S. L. 2016. Medication-induced acute kidney injury. Current Opinion in Critical
Care 22(6): 542–545. doi:10.1097/MCC.0000000000000355

 Higgins, J. P. T., Thompson, S. G., Deeks, J. J. & Altman, D. G. 2003. Measuring inconsistency
in meta-analyses. BMJ 327(7414): 557 LP-560. Retrieved from
http://www.bmj.com/content/327/7414/557.abstract

 Higgins, J.P.T., Sterne J.A.C., Savović J., Page M.J., Hróbjartsson A., Boutron I., Reeves B.,
Eldridge S. A revised tool for assessing risk of bias in randomized trials In: Chandler J,
McKenzie J, Boutron I, Welch V (editors). Cochrane Methods. Cochrane Database of
Systematic Reviews 2016, Issue 10 (Suppl 1). dx.doi.org/10.1002/14651858.CD201601.

 Hoste, E. A. J., Bagshaw, S. M., Bellomo, R., Cely, C. M., Colman, R., Cruz, D. N., Edipidis, K., et
al. 2015. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-
EPI study. Intensive Care Medicine 41(8): 1411–1423. doi:10.1007/s00134-015-3934-7

 Hoste, E. A. J. & De Corte, W. 2011. Clinical consequences of acute kidney injury.
Controversies in Acute Kidney Injury 174: 56–64. doi:10.1159/000329236

 Lameire, N. H., Bagga, A., Cruz, D., Maeseneer, J., Endre, Z. & Kellum, J. A. 2013. Acute
kidney injury: an increasing global concern. Lancet 382. doi:10.1016/S0140-
6736(13)60647-9

 Mehta, R. L., Awdishu, L., Davenport, A., Murray, P. T., Macedo, E., Cerda, J., Chakaravarthi,
R., et al. 2015. Phenotype standardization for drug-induced kidney disease. Kidney
international 88(2): 226–34. doi:10.1038/ki.2015.115

 Mehta, R. L., Kellum, J. A., Shah, S. V, Molitoris, B. A., Ronco, C., Warnock, D. G., Levin, A., et
al. 2007. Acute Kidney Injury Network : report of an initiative to improve outcomes in acute
kidney injury. Critical Care 11(2). doi:10.1186/cc5713

 Mehta, R. L., Pascual, M. T., Soroko, S., Savage, B. R., Himmelfarb, J., Ikizler, T. A., Paganini, E.
P., et al. 2004. Spectrum of acute renal failure in the intensive care unit: The PICARD
experience. Kidney International 66(4): 1613–1621. doi:10.1111/j.1523-
1755.2004.00927.x

 Ministry of Health Malaysia. 2017. Malaysian Statistics on Medicines 2011-2014. (C. Chock
& L. Chan, Eds.). Pharmaceutical Services Division, Ministry of Health Malaysia.

 References

 Moher, D., Liberati, A., Tetzlaff, J., Altman, D. G., Altman, D., Antes, G., Atkins, D., et al. 2009.
Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement.
PLoS Medicine 6(7). doi:10.1371/journal.pmed.1000097

 Muriithi, A. K., Leung, N., Valeri, A. M., Cornell, L. D., Sethi, S., Fidler, M. E. & Nasr, S. H.
2014. Biopsy-proven acute interstitial nephritis, 1993-2011: A case series. American Journal
of Kidney Diseases 64(4): 558–566. doi:10.1053/j.ajkd.2014.04.027

 Perazella, M. A. & Markowitz, G. S. 2010. Drug-induced acute interstitial nephritis. Nat Rev
Nephrol 6. doi:10.1038/nrneph.2010.71

 Praga, M. & Gonzalez, E. 2010. Acute interstitial nephritis. Kidney Int 77: 956–961.
doi:10.1038/ki.2010.89

 Raghavan, R. & Eknoyan, G. 2014. Acute interstitial nephritis - a reappraisal and update.
Clinical nephrology 82(3): 149–162. doi:10.5414/CN108386

 Raghavan, R. & Shawar, S. 2017. Mechanisms of Drug-Induced Interstitial Nephritis.
Advances in Chronic Kidney Disease 24(2): 64–71. doi:10.1053/j.ackd.2016.11.004

 Rossert, J. 2001. Drug-induced acute interstitial nephritis. Kidney Int 60.
doi:10.1046/j.1523-1755.2001.060002804.x

 Sawhney, S., Mitchell, M., Marks, A., Fluck, N. & Black, C. 2015. Long-term prognosis after
acute kidney injury (AKI): What is the role of baseline kidney function and recovery? A
systematic review. BMJ Open 5(1). doi:10.1136/bmjopen-2014-006497

 Sterne, J. A. C. & Egger, M. 2001. Funnel plots for detecting bias in meta-analysis. Journal of
Clinical Epidemiology 54(10): 1046–1055. doi:10.1016/S0895-4356(01)00377-8

 Sterne, J. A., Hernán, M. A., Reeves, B. C., Savović, J., Berkman, N. D., Viswanathan, M.,
Henry, D., et al. 2016. ROBINS-I: a tool for assessing risk of bias in non-randomised studies
of interventions. BMJ (Clinical research ed.) 355: i4919. doi:10.1136/bmj.i4919

 Uchino, S. K. J. a. 2005. Acute renal failure in critically ill patients. Jama 294(7): 813–818.
doi:10.4045/tidsskr.10.34549

 Yang, Y., George, K. C., Shang, W.-F., Zeng, R., Ge, S.-W. & Xu, G. 2017. Proton-pump
inhibitors use, and risk of acute kidney injury: a meta-analysis of observational studies. Drug
design, development and therapy 11: 1291–1299. doi:10.2147/DDDT.S130568