Pediatric AKI

8/18/2019 Pediatric AKI

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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.

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Pediatric AKI