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Pediatric AKI
Measurement of kidney function in children with AKI.
After 2 years of age, renal growth results in a GFR eui!alent to that
of adults, when ad"usted for #ody surface area.$$%,$$& 'he older
(chwart) euation$$*,$2+ for estimating GFR in children is no longer
!alid.$2$ (chwart) et al.$$&,$22 de!eloed an udated !ersion of
their eGFR euation for children with -K /aged $0$1 years, using
an isotoe3dilution mass sectrometry tracea#le creatinine assay.
'his 45edside (chwart) euation6 has #een !alidated in a non3-K
oulation.$27 An e8amle of its use is gi!en in 'a#le 9.
i:erent methodologies for measurement of creatinine reuire
method3seci;c age3standardi)ed reference ranges in children. 'he
lack of seci;city of e
call on -linical -hemistry societies and la#oratories to work with their
ediatricians to introduce these ranges. 'his will facilitate the
introduction of AKI alerts for children. 'he use of eGFR estimated #y
the re!ised (chwart) formula to detect AKI in children needs further
'a#le 9 ? An e8amle of ediatric AKI in a %3year3old child
with length /height of $2+ cm
Premor#id /#aseline AKI -hange
@eight $2+cm @eight $2+cm
-r + mmolBl 3 -r 1% mmolBl 77C Rise
/+.%mgBdl /+.%1mgBdl
eGFRD && mlBmin er
$.%7m2
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eGFR 1 mlBmin er
$.%7m2
2C FallE
A##re!iations AKI, acute kidney in"ury -r, creatinine eGFR,
estimated glomerular
;ltration rate.
eGFR is calculated using the re!ised or 5edside (chwart)
euation,$$&,$22,$27 which
ad"usts the estimated GFR to a standard /adult #ody si)e of $.%7m2.
Hote, the
reduction in eGFR with AKI is 2C00that is, RIFJ stage R, while the
increase in
creatinine /-r is $77C00that is, less than the reuired increase in -r
to #e classi;ed
as RIFJ stage R. 'hus, the change in kidney function in one child
may #e
classi;ed di:erently, if either GFR or creatinine alone is used.$2 'his
is inherent
with the use of #oth creatinine and GFR changes within the same
de;nition /that
is, within RIFJ or RIFJ.
'he original (chwart) euation$$*,$2+ /using a modi;ed
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study. 'he studies of GFR estimation in children do not include
neonates. 'he RIFJ de;nition of AKI in children. Pediatric AKI is
mainly an issue for children in critical care. A ediatric modi;cation of
the RIFJ de;nition /RIFJ was de!eloed$21
using the original (chwart) euation$$* to calculate 4estimated
creatinine clearance6 or eGFR. 'he KIGL guidelines7 refer to RIFJ
for the de;nition of AKI in children, and the latter remains the one in
use for children aged o!er $ month. Further work is needed #efore
RIFJ can #e recommended for neonates. 'he RIFJ de;nition was
su#seuently con;rmed to #e of !alue.$2% It stages AKI #y the fall in
eGFR, rise in
creatinine, or decrease in urine outut /'a#le . aitelli et al.$2&
found that the use of change in eGFR, with the original (chwart)
formula, resulted in a higher re!alence of AKI diagnosis, comared
with that using change in creatinine in ediatric inatients. A change
in eGFR may result in di:erent staging comared with the increase in
creatinine in the same atient /'a#le 9. 'his de;nition reuires a
comarison with eGFR measured in the re!ious 7 months.$21 If no
creatinine result is a!aila#le in that time eriod, imutation is
ermitted assuming a re!iously normal GFR of $++ mlBmin er
$.%7m2 and using the atient6s height. 'he likelihood of a child who
de!elos AKI
ha!ing undiagnosed -K is !ery low /unlike adults, "ustifying the
assumtion of a re!iously normal eGFR. (chneider et al.9$ used the
RIFJ classi;cation #ased on
serum creatinine alone and found it to #e !alid in their ediatric
intensi!e care unit oulation. 'he use of serum creatinine, and not
eGFR, has one ad!antage accurate
measurement of height is necessary to calculate eGFR using the
(chwart) formula, and this can #e diNcult in sick, !entilated atients.
'here are few u#lished studies using RIFJ, and there is !ariation
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in #oth the reorted incidence of AKI$2* and the e8act methodology
for de;ning AKI.$2&
He!ertheless, the studies do show a correlation #etween ad!erse
outcomes and increasingly se!ere AKI /a#o!e. A study of an
automated electronic inter!ention to reduce e8osure to
nehroto8ins, com#ined with RIFJ detection of AKI, suggests that
AKI can #e reduced in non3critically ill children.$7+
5iomarkerswhere are we in racticeO
'he issue of no!el #iomarkers was not within the scoe of the recent
HI-J guideline.2 AKI #iomarkers are #roadly di!ided into functional or
structural /indicating in"ury or damage #iomarkers.$7$0$79 'here is
much e8ectation that they will #e incororated into de;nitions of AKI
as well as routine clinical ractice. @owe!er, some degree of caution
is warranted.$7 arious o#stacles e8ist to the widesread routine
alication of #iomarkers,99,$710$7& including
Q oorer erformance when the timing of renal insult/s is
unknown$7%
Q reduced erformance in the resence of common confounding
comor#idities, esecially -K and sesis$7*0$97
Q ina#ility to relia#ly detect AKI at the le!el of the indi!idual,
esecially in the resence of heterogeneous causes, -K, and
comor#idities$7*,$9$,$92,$99
Q ina#ility of #iomarkers to determine the seci;c etiology of AKI.$79
It has #een suggested that AKI should #e designated a 4Kidney
attack6,$9 analogous to heart attack, and that a 4renal troonin6 may
#e used to detect AKI earlier in its course, similar to the use of
cardiac troonin in the detection of myocardial infarction.
=nfortunately, the analogy #etween the two conditions #reaks down
when inter!entions are considered. Myocardial infarction has seci;c
treatments. J!en if a #iomarker relia#ly shows early AKI, there are
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currently no seci;c theraies for ischemic or setic tu#ular in"ury.
'here ha!e #een conicting results regarding the
a#ility of #iomarkers to imro!e on the redicti!e !alue of clinical
factors.$71,$910$9* A large study of #iomarkers after the timed
insult of cardiac surgery found a modest increase in the redicti!e
ower for outcomes with their use.$9% A study of two urine
#iomarkers of cell cycle arrest showed moderate imro!ement in the
rediction of the de!eloment of stage 2 or 7 AKI.$9* Another recent
study found limited a#ility to distinguish #etween AKI cases and
controls in intensi!e care.$+ emonstrating the cost e:ecti!eness of
#iomarker use in addition to creatinine and urine outut monitoring
resents a challenge. 'he atient6s general management would #e
otimi)ed as art of any study. Hew #iomarkers will need to
demonstrate 4added !alue6, o!er and a#o!e otimal atient care and
use of traditional AKI markers. In future, the earlier detection of AKI
with #iomarker/s may allow a targeted aroach to the use of no!el
theraies.
-LH-=(ILH(
A uni!ersal de;nition of AKI is crucial for its identi;cation and
management. It is !ital for translation of re!entati!e and
theraeutic research into ractice for this condition,
which is common in aging societies. 'he new de;nitions of AKI ha!e
already re!olutioni)ed #oth research and routine clinical ractice.
>e recommend that future modi;cations are #ased on thorough
e!aluation. Research should now e8tend to e!aluation of their
ractical imlementation in di!erse clinical settings and their
oerational erformance in rosecti!e studies on AKI clinical
inter!entions. e;nitions should now e!ol!e on the #asis of e!idence,
rather than oinion or consensus.2 'he high cost of AKI to an
indi!idual6s health and to health3care systems means that this ;eld
should #e a riority for health3care research.
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I(-L(=RJ
'he !iews e8ressed in this u#lication are those of the authors and
not necessarily those of the Institute. r Lstermann has recei!ed
seaker honoraria from Fresenius, Gilead, and Alere and has taken
art in educational meetings sonsored #y Fresenius. All the other
authors declared no cometing interests.
A-KHL>JGMJH'(
'his work was undertaken #y the a#o!e mem#ers of the AKI
Guideline de!eloment grou, of the Hational -linical Guideline
-entre, which recei!ed funding from the Hational Institute for @ealth
and -are J8cellence.