Correspondence

with secondary (eg, prescription 3 Csete J, Kamarulzaman A, Kazatchkine M, et al. my view, health professionals should
Public health and international drug policy.
drug monitoring programmes) and Lancet 2016; 387: 1427–80.
leave defending unethical conduct
tertiary (eg, harm reduction or opioid 4 Wood E. Stopping the opioid epidemic means by multinational industries that
addiction treatment) opioid addiction smarter prescribing. The Globe and Mail produce addictive products to the
(Toronto). July 26, 2017. https://www.
prevention strategies.2 theglobeandmail.com/opinion/stopping-the- lawyers, lobbyists, and public relations
Moreover, although the argument opioid-epidemic-means-smarter-prescribing/ professionals such industries employ.
article35813548/ (accessed Jan 2, 2018).
that the advocacy against the war I declare no competing interests.
5 Clarke TC, Norris T, Schiller JS. Early release of
on drugs has fuelled the overdose selected estimates based on data from the
Keith Humphreys
epidemic might seem attractive, 2016 national health interview survey.
knh@stanford.edu
Atlanta, GA: National Center for Health
it fails to acknowledge that supply Statistics, 2017.
Department of Psychiatry and Behavioral Sciences,
reduction efforts led by enforcement 6 Centers for Disease Control and Prevention. and School of Law, Stanford University, Stanford,
agencies have only created more Multiple cause of death data. 2016. https://
CA 94305, USA; and Veterans Affairs Palo Alto
wonder.cdc.gov/mcd.html (accessed
potent, cheaper, and more toxic drugs.3 Aug 8, 2017). Health Care System, Palo Alto, CA, USA
The current synthetic opioid crisis 1 Humphreys K. Avoiding globalisation of the
prescription opioid epidemic. Lancet 2017;
indeed is a natural consequence of Author’s reply 390: 437–39.
similar prohibition efforts suppressing I agree with Mohammad Karamouzian 2 Lembke A, Humphreys K, Newmark J. Weighing
the availability of traditional illicit and Thomas Kerr that “restricting the risks and benefits of chronic opioid therapy.
Am Fam Physician 2016; 93: 982–90.
opioids (eg, heroin and opium).3,4 access to prescription opioids for 3 Frank JW, Lovejoy TI, Becker WC, et al. Patient
Lastly, although blaming physicians opioid-naive populations should be outcomes in dose reduction of discontinuation
and pharmaceutical companies for included in the primary strategies” in of long-term opioid therapy: a systematic
review. Ann Intern Med 2017; 167: 181–91.
the opioid crisis is convenient, it does response to the epidemic of opioid 4 Strang JS, Babor T, Caulkins J, Foxcroft D,
not acknowledge many potent root overdose and addiction, as discussed Fischer B, Humphreys K. Drug policy and the
public good: evidence for effective
causes of the crisis. For example, along in my Comment.1 Karamouzian and interventions. Lancet 2012; 378: 71–83.
with the increased use of prescription Kerr are also correct to note that 5 US District Court for the Western District of
opioids, the use of alcohol and other people currently taking opioids will Virginia. Case decision, case no. 1: 07CR00029.
July 23, 2007. http://www.vawd.uscourts.gov/
psychiatric medications have also require different clinical and policy opinions/jones/107cr00029.pdf (accessed
increased since 1999. 5,6 Indeed, strategies. For example, some people Sept 10, 2017).
many doctors have been prescribing with chronic pain conditions will
more of these medications because need to remain on their medication
of increased individual demand for indefinitely because the net costs and The definition of acute
treatment of unmet mental and benefits of doing so are favourable.2
physical health needs, an increase that Other people’s opioid medication
kidney injury
could be attributed in part to major use can be carefully tapered down, We read with interest the Comment
sociodemographic and economic which is supported by findings in The Lancet by Jon Barasch and
changes in the USA since the late 1990s. from a systematic review3 showing colleagues (Feb 25, 2017, p 779)1 with
We declare no competing interests. reduced pain, improved function, and its controversial title “Acute kidney
enhanced quality of life. injury: a problem of definition”.
Mohammad Karamouzian,
*Thomas Kerr However, other patients would We appreciate the opportunity to
uhri-tk@cfenet.ubc.ca benefit from ceasing opioid use but clarify what is written in the Kidney
will have difficulty doing so because of Disease Improving Global Outcomes
British Columbia Centre on Substance Use, St Paul’s
Hospital, Vancouver, BC V6Z 1Y6, Canada (MK, TK); addiction. I agree with Karamouzian (KDIGO) clinical practice guideline
School of Population and Public Health, University and Kerr that a range of treatments on acute kidney injury (AKI),2 in the
of British Columbia, Vancouver, BC, Canada (MK); should be offered to such individuals, hope that clinicians will read beyond
HIV/STI Surveillance Research Center, and WHO
Collaborating Center for HIV Surveillance, Institute the most effective of which are the headlines. The guideline clearly
for Futures Studies in Health, Kerman University of opioid substitution therapies—eg, states that AKI is a clinical diagnosis
Medical Sciences, Kerman, Iran (MK); and British buprenorphine maintenance.4 and stresses the importance of clini­
Columbia Centre for Excellence in HIV/AIDS (TK)
and Department of Medicine, University of British
I must, however, object to cal judgment: “While the definitions
Columbia (TK), St Paul’s Hospital, Vancouver, Karamouzian and Kerr’s effort to and classification system discussed
BC, Canada minimise the pharmaceutical industry’s in Chapter 2.1 provide a frame­
1 Humphreys K. Avoiding globalisation of the responsibility for the prescription work for the clinical diagnosis
prescription opioid epidemic. Lancet 2017;
390: 437–39.
opioid epidemic, particularly given of AKI, they should not be inter­
2 Kolodny A, Courtwright DT, Hwang CS, et al. The that the manufacturer of OxyContin preted to replace or to exclude clinical
prescription opioid and heroin crisis: a public has already confessed to grossly judgment”.2 Barasch and colleagues1
health approach to an epidemic of addiction.
Ann Rev Public Health 2015; 36: 559–74. irresponsible behaviour in court.5 In might have overlooked that before

202 www.thelancet.com Vol 391 January 20, 2018

the establishment of the international not invalidate the initial observation 3 Liu KD, Vijayan A, Rosner MH, Shi J, Chawla LS,
Kellum JA. Clinical adjudication in acute
consensus criteria for AKI, no less than that ST-elevation myocardial kidney injury studies: findings from the
30 biochemical definitions existed infarction has worse outcomes. More pivotal TIMP-2*IGFBP7 biomarker study.
for acute renal failure (the term used advanced stages of AKI have worse Nephrol Dial Transplant 2016; published online
June 23. DOI:10.1093/ndt/gfw238.
for AKI at the time). Although this prognoses; this observation has been 4 Coca SG, King JT, Rosenthal RA, Perkal MF,
absence in standardisation might validated in more than 1 million Parikh CR. The duration of postoperative acute
be advantageous in experimental patients. Finally, the assumption that kidney injury is an additional parameter
predicting long-term survival in diabetic
models of AKI, in which several transient AKI is due to an inadequate veterans. Kidney Int 2010; 78: 926–33.
definitions can be chosen for data circulating volume is refuted by 5 Kellum JA, Sileanu FE, Murugan R, Lucko N,
Shaw AD, Clermont G. Classifying AKI by urine
analysis, it represented a major the authors’ own opinions about output versus serum creatinine
impediment in clinical research. subclinical AKI—injury to the kidney level. J Am Soc Nephrol 2015; 26: 2231–38.
The KDIGO criteria now form the can exist without any change in serum 6 Kellum JA, Sileanu FE, Bihorac A, Hoste EAJ,
Chawla LS. Recovery after acute kidney injury.
basis of, and have been validated creatinine, so how can the duration of Am J Respir Crit Care Med 2016; published
in, hundreds of epidemiological changes in serum creatinine indicate online Sept 16. DOI:10.1164/rccm.201604-
0799OC.
studies and several clinical trials. New the extent of renal injury?
7 Kellum JA. Why are patients still getting
diagnostics and therapeutics require We hope that Barasch and and dying from acute kidney injury?
regulatory approval on the basis colleagues1 are not nostalgic for a Curr Opin Crit Care 2016; 22: 513–19.
of these criteria, which, however, time when acute renal dysfunction
do not stand in isolation. For clini­ was evaluated according to Authors’ reply
cal studies evaluating diagnostics the classification of prerenal, We thank John A Kellum and Norbert
and therapeutics, clinical adjudication intrarenal, and post-renal causes. Lameire for their letter in response
of AKI is always preferred,3 and for Unfortunately, AKI evaluation is not to our Comment.1 An acute increase
clinical practice, clinical judgment this simple. Sepsis, cardiac surgery, in serum creatinine (sCr) is caused
remains essential. liver disease, and trauma can all by direct injury to kidney cells
AKI should be evaluated in real time, alter kidney function that affects (ie, pathophysiological processes

101dalmatians/from iStock
which forms part of the complexity in multiple intrarenal and extrarenal resulting from ischaemia, sepsis,
practice. Barasch and colleagues1 make systems. These clinical syndromes medications, metals, or enzymes)
a valid point that the duration of AKI are not synonymous with the or a compromise in cardiovascular
is also important in its evaluation, but simple laboratory models of volume homoeostasis (ie, substantial volume
is not more important than severity depletion or renal artery clamping. The depletion,2 congestive heart failure,3
as they claim—adjusted hazard ratios authors are correct in that advanced or portal hypertension4). Hence, we
are similar for both stage 3 AKI and diagnostics will be used in the future appreciate that an acute rise in sCr can
AKI that has persisted over 7 days to sub-classify AKI, not into the indicate several pathophysiological
or more.4 This relationship between outmoded constructs of prerenal and processes with worsened patient
severity, duration, and outcome renal phenotypes of AKI but instead population outcomes.5,6 As a result, the
is even more complex when both into more precise phenotypes that concentration of, or the change in sCr
oliguria and creatinine,5 or relapses can be specifically targeted with cannot diagnose the type, severity, or
in AKI are considered. 6 However, therapeutics. The problem is not with presence of renal injury. For example,
duration is not a usable criterion in the definition of AKI, but the fact an increase in sCr due to obstruction
the real-time evaluation of AKI and that the syndromes causing AKI are has very different pathophysiological
is in fact a component of most med­ considered as one disease7 and on implications than an equivalent
ical conditions because persistent this point we agree with the authors increase in sCr caused by sepsis.
dysfunction is the opposite of completely. Around 60% of patients who are
recovery. On average, an ST-elevation JAK and NL were co-chairs for KDIGO AKI Guideline. admitted to hospital with an increased
myocardial infarction is more fatal sCr concentration normalise their sCr
*John A Kellum, Norbert Lameire
than a non-ST-elevation myocardial kellum@pitt.edu
concentration within 1 to 2 days;6,7 do
infarction. However, some patients do these patients really have the same
Department of Critical Care Medicine, University of
not recover after a non-ST-elevation Pittsburgh, Pittsburgh, PA 15213, USA
cellular events as those with persistent
myocardial infarction and a patient 1 Barasch J, Zager R, Bonventre JV. Acute kidney
elevation of sCr concentration,
recovering from an ST-elevation injury: a problem of definition. Lancet 2017; especially given that the molecular
myocardial infarction will have a 389: 779–81. and cellular responses to different
2 KDIGO AKIWG. Kidney Disease: Improving
better prognosis than a patient with Global Outcomes (KDIGO) clinical practice
stimuli show variable and sometimes
non-recovering non-ST-elevation guideline for acute kidney injury. limited overlap?7 Acute changes in sCr
myo­cardial infarction. This fact does Kidney Int Suppl 2012; 2: 1–141. concentration cannot predict biopsy

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