PERIOPERATIVE

 AKI:  EPIDEMIOLOGY  AND  

PREVENTION  
dr.  Jevelin  Sinuraya  SpAn-­‐KIC  
 Incidence  of  AKI  
•  Approximately  7%  of  all  hospitalized  paLent  (65%  
of  intensive  care  admission)  
•  20%  of  acutely  ill  paLent  developed  AKI  
•  Pre  renal  and  acute  tubular  necrosis  (ATN)  
accounts  for  75%  of  the  cases  of  AKI  
Mortality:  
•  5-­‐16%  in  uncomplicated  AKI  
•  50-­‐70%  in  AKI  secondary  to  other  organ  failure,  
infecLons  
•  >50%  in  dialysis  requiring  AKI  
THE  FUTURE  
•  Hou  et  al,  1983  found  4.9%  of  hospitalised  pts  
developed  AKI.  AKI  defined  as  a  relaLve  increase  in  
sCr  of  0.5,  1.0  or  1.5  mg/dl  depending  on  the  baseline  
sCr.  
•  Major  causes  of  hospital  acquired  AKI:  
–  decreased  renal  perfusion  (42%),    
–  major  surgery  (18%),    
–  contrast  nephropathy  (12%),    
–  aminoglycosides  (7%).  
•  In-­‐hospital  mortality  rate  25%,  higher  with  more  
significant  degrees  of  AKI  
•  Nash  et  al,  2002  using  same  AKI  defining  criteria  at  a  
different  insLtuLon,  reported  frequency  of  AKI  in  
hospitalised  pts  had  increased  to  7.2%.  
•  In-­‐hospital  mortality  rate  was  19.4%.    
•  Major  causes  were:  
–  decreased  renal  perfusion  (39%),    
–  nephrotoxin  administraOon  (16%),    
–  contrast  administraOon  (11%),    
–  major  surgery  (9%)  
CONCEPTUAL  MODEL  FOR  AKI  
LATE  MARKER  
AFTER  RENAL  
INJURY  

DIAGNOSE  
AKI  BEFORE  
CREATININE  
RISE  

Clin  J  Am  Soc  Nephrol  2008;  3:  864–868  with  permission  from  
American  Society  of  Nephrology  
Causes  of  AKI  have  been  divided  into  
three  groups  
Pathogenic  mechanisms  of  sepsis-­‐related  acute  kidney  
injury  
Systemic  inflamaOon  
Ischemic Insult lipopolysaccharide/endotoxin   Sepsis
direct-­‐indirect  
(cytokine)
hypoxia  
oxidaOe  stress  
Hemodynamic changes toxicity  
Toxins
hypoperfusion exogenous
endothelial  
global and/or regional heme proteins
dysfuncOon  
ishemia-reperfusion antibiotics, contras media
nitric  oxide  
microtrombus vasopressor
Renal cell injury

Sublethal injury Apoptosis and necrosis

Renal cell repair and regeneration Cell loss

Ronco, Clin J Am Soc Nephrol. 2008

Who  is  a  risk?  
PREVENTION  OF  ACUTE  KIDNEY   INJURY  
THEY  WILL  ANSWER:  
1.  TO  CORRECT  FLUID  DEPLETION  
2.  TO  REVERSE  HIPOTENSION  
3.  TO  AVOID  NEPHROTOXIC  DRUGS  
 Volume  expansion  
RecommendaLons    
1.    We  recommend  controlled  fluid  resuscita0on  in  volume  depleLon,  while,  
however,  avoiding  volume  overload  (Grade  1C).  
2.    We  recommend  against  the  use  of  starches  (Grade1A)  as  harm  has  been  
shown  and  suggest  not  using    gelaLne  or  dextrans  for  fluid  resuscitaLon  
(Grad  2C).  
3.    We  recommend  correc0on  of  hypovolaemia/dehydra0on  using  isotonic  
crystalloids  in  paLents  receiving  intravascular  contrast  media  (Grade  1B).  
4.    We  recommend  regular  monitoring  of  chloride  levels  and  acid–base  status  
in  situaLons  where  chloriderich  soluLons  are  used  (BPS).  
5.    We  suggest  the  use  of  balanced  crystalloids  for  large  volume  resuscitaLon          
(Grade  2C).    
6.  We  suggest  using  human  serum  albumin  if  a  colloid  is  deemed  necessary  
for  the  treatment  of  paLents  with  sepLc  shock  (Grade  2C).  
7.    We  suggest  prophylac0c  volume  expansion  with  crystalloids  to  prevent  AKI  
by  certain  drugs  (specified  below)  .    
8.    We  suggest  not  delaying  urgent  contrast-­‐enhanced    invesLgaLons  or  
intervenLons  for  potenLal  preventaLve  measures  .  
 DiureOcs  
RecommendaLons  
1.  We  recommend  against  loop  diure0cs  given  
solely  for  the  prevenLon  of  acute  kidney  
injury  (Grade  1B).  
2.  We  suggest  using  diure0cs  to  control  or  avoid  
fluid  overload  in  paLents  that  are  diureLc-­‐
responsive  (Grade  2D).  
 Vasopressors  
RecommendaLons  
1.    We  recommend  0tra0ng  vasopressors  to  a  mean  arterial  pressure  (MAP)  
of   65–70   mmHg   (Grade   1B)   rather   than   a   higher   MAP   target                    
(80–85   mmHg)   in   paLents   with   sepLc   shock.   However,   for   paLents   with  
chronic   hypertension   we   recommend   aiming   for   a   higher   target                    
(80–85  mmHg)  for  renal  protecLon  in  sepLc  shock  (Grade  1C).  
2.    We  recommend  lowering  systolic  pressure  to  140–190  mmHg  rather  than  
to   110–139   mmHg   in   paLents   with   acute   cerebral   haemorrhage   with  
severe  admission  hypertension  (Grade  1C).  
3.    If  vasopressors  are  needed  for  treatment  of  hypotension,  we  recommend  
norepinephrine   (along   with   correc0on   of   hypovolaemia)   as   the   first-­‐choice  
vasopressor   to   protect   kidney   funcLon   (Grade   1B)   and   suggest  
vasopressin  in  paLents  with  vasoplegic  shock  amer  cardiac  surgery  (Grade  
2C).  
4.     We   suggest   individualizing   target   pressure   when   premorbid   blood  
pressure  is  available  .  
 Use  of  vasodilators  
RecommendaLons  
1.  We  recommend  against  low-­‐dose  dopamine  for  protec0on  
against  AKI  (Grade  1A).    
2.  We  recommend  not  using  levosimendan  for  renal  
protecLon  in  paLents  with  sepsis  (Grade  1B)  and  
recommend  against  its  use  for  renal  protec0on  in  cardiac  
surgery  paLents  with  poor  preoperaLve  lem  ventricular  
funcLon  or  needing  postoperaLve  haemodynamic  support  
(Grade  1B).  
3.  We  suggest  not  using  fenoldopam  or  natriure0c  pep0des  
for  renal  protecLon  in  criLcally  ill  or  cardiovascular  surgery  
paLents  at  risk  of  AKI  (Grade  2B).  
 SedaOon  
 RecommendaLons  
  O n   t h e   b a s i s   o f   c u r r e n t   d a t a   n o  
recommendaLon   can   be   given,   although   it  
appears   that   shorter   sedaLon   using   propofol  
or   dexmedetomidine   may   have   several  
advantages,  possibly  reducing  the  rate  of  AKI.  
 Hormonal  manipulaOon  
 
RecommendaLons  
1.  We  suggest  targe0ng  a  blood  glucose  level  at  
least  below  180  mg/dL  (10  mmol/l)  for  the  
prevenLon  of  hyperglycaemic  kidney  damage  
in  the  general  ICU  populaLon  (Grade  2B).    
2.  We  suggest  not  using  erythropoie0n  (Grade  
2B)  or  steroids  (Grade  2B)  for  prevenLon  of  
acute  kidney  injury.  
 Metabolic  intervenOons  
RecommendaLons    
1.  We  recommend  not  using  high-­‐dose  IV  selenium  
for  renal  protecLon  in  criLcally  ill  paLents  (1B).    
2.  We  suggest  not  using  N-­‐acetylcysteine  to  prevent  
contrast-­‐associated  AKI  in  criLcally  ill  paLents  
because  of  conflicLng  results  and  possible  
adverse  effects  (Grade  2B).  
3.  We  suggest  that  all  pa0ents  with  or  at  risk  of  
acute  kidney  injury  have  adequate  nutriLonal  
support  preferably  through  the  enteral  route.  
 StaOns  
RecommendaLons  
1.  We  recommend  against  the  periopera0ve  use  
of  high  dose  staLns  to  prevent  postoperaLve  
AKI  in  cardiac  surgery  (Grade  1A).  
2.  We  suggest  the  short-­‐term  use  of  atorvasta0n  
or  rosuvastaLn  to  prevent  contrast-­‐associated  
AKI  in  high-­‐risk  paLents  undergoing  coronary  
contrast  angiography  (Grade  2B).  
 AKI  care  bundles  
RecommendaLons  
1.  We  suggest  using  the  KDIGO  
recommenda0ons  to  reduce  the  incidence  of  
AKI  amer  cardiac  surgery(Grade  2C).  
2.  The  use  of  AKI  care  bundles  outside  the  
intensive  care  unit  has  some  benefits,  
including  the  potenLal  to  improve  the  
outcome  of  AKI  .  
 ak AKI  Care  Bundle  
CREATININ    1.5X/U  <0.5  IN  
6  HOURS  

EMERGENCY  
RESUSCITATION  
DIAGNOSE  

SEPSIS/ OBSTRUCTI PRIMARY  

HIPOPERFUS TOXICITY   ON   RENAL  
ION   DISEASE  

GENERAL  SUPPORTIVE  CARE  AND  ESCALATION  

FOLLOW    UP  
 Drugs  interfering  with  renal  perfusion  
 
•  These  include  those  medicaLons  interfering  with  
renal  autoregulaLon  (ACEi/ARBs,  NSAIDs)  and  
those  medicaLons  with  the  potenLal  to  reduce  
blood  pressure.    
•  AnLhypertensive  medicaLons  (including  
diureLcs)  should  be  withheld  in  paLents  with  
both  absolute  (SBP  <  90  mmHg)  and  relaLve  (SBP  
<  120  mmHg)  hypotension.    
•  PaLents  treated  with  beta  blockers  need  careful  
consideraLon  of  the  risk  /  benefit  of  temporary  
cessaLon.  
 Drugs  requiring  dose  reduc0on  or  cessa0on  
 
•  All   medicaLons   that   are   metabolized   and  
excreted   by   the   kidneys   should   be   dose  
adjusted   for   an   assumed   eGFR   of   <   10   mL/
min/1.73m2.   Such   drugs   include   fracLonated  
heparins,   opiates,   penicillin-­‐based   anLbioLcs,  
sulphonylurea-­‐based   hypoglycaemic   agents,  
and   aciclovir.   Although   mepormin   is   not  
specifically   nephrotoxic,   it   will   accumulate   in  
renal   failure   and   is   associated   with   life  
threatening  lacLc  acidosis.  
 Drugs  requiring  close  monitoring  
 
•  These   include   warfarin   and   aminoglycosides.  
Gentamicin   in   parLcular   demands   careful  
consideraLon.   It   should   not   be   withheld  
where   there   is   a   clear   benefit   to   its   use   (life  
threatening   sepsis).   If   used,   the   daily   trough  
level  should  be  <  1  mg/L  .  
 Drugs  aggrava0ng  hyperkalemia  
 
•  All   drugs   which   block   renal   excreLon   of  
potassium   (trimethoprin   and   potassium  
sparing   diureLcs   (spironolactone,   amiloride)  
should   be   stopped.   In   addiLon,   both   beta-­‐
blockers   and   digoxin   can   inhibit   the   sodium   /  
potassium   ATPase   pumps   which   move  
potassium   inside   cells.   The   presence   of   these  
drugs   can   render   the   paLent   resistant   to  
insulin/glucose  treatment  of  hyperkalaemia.  
 Case  1:  
 
  A  78  year  old  woman  is  admiqed  to  the  ward  with  a  lem  iliac  
fossa   pain   and   a   clinical   surgical   supicion   of   acute  
diverLculiLs.  She  has  a  background  of  CKD  (eGFR  35  mL/  min/
1.73m2),   hypertension   treated   with   perindopril   and   type   2  
diabetes  treated  with  mepormin.  One  week  before  admission  
she   developed   dysuria   and   was   empirically   prescribed  
trimethoprim.   Despite   a   poor   oral   intake   during   the   week   she  
conLnued  to  take  all  of  her  medicaLon.  On  admission  she  was  
febrile  (38  C),  hypotensive  (BP  80/50  mmHg),  and  heart  rate  
120   bpm.   Oxygen   saturaLon   was   96%   on   room   air.   Urine  
output  was  5  –  10  mL/hr.  
  InvesLgaLons   reveal;   stage   3   AKI   (creaLnine   480   umol/L),  
hyperkalaemia   –   Potassium   7.1mmol/L,   acidaemia   (pH   7.25)  
with   a   high   anion   gap   metabolic   acidosis,   elevated   plasma  
lactate   (8   mmol/L),   CRP   235.   She   was   treated   with   IV  
Tazocin®   /   gentamicin   and   insulin/glucose   for   her  
hyperkalaemia.  
     Over   the   next   24   hr   despite   6   L   of   Hartmann’s  
soluLon   she   remained   hypotensive   and   oliguric.  
Her   serum   creaLnine   rose   to   650   umol/L.   She  
became   increasingly   hypoxic   with   radiological  
evidence   of   pulmonary   oedema   and   was  
transferred   to   ICU   for   mechanical   venLlaLon,  
vasopressor   support   and   dialysis.   A   CT   scan   of  
abdomen   demonstrated   a   perforated   sigmoid  
diverLculum   with   generalized   peritoniLs.   She  
underwent  a  lem  hemicolectomy  but  2  days  later  
whilst  sLll  vasopressor  dependent  in  ICU  suffered  
a  cardiac  arrest  from  which  she  did  not  recover.  
 Learning  points:  
 
 PREVENTION:  This  lady  was  at  extremely  high  risk  
of  developing  AKI  in  the  community.  She  has  pre-­‐
exisLng   CKD,   is   elderly   with   significant   co-­‐
morbidity   and   is   treated   with   an   ACEi.   Such  
paLents   should   be   idenLfied   with   from   the   GP  
register,   provided   with   a   Kidney   Care   Card   and  
counseled   to   temporarily   stop   potenLally  
nephrotoxic   drugs   (including   mepormin)   during  
periods   of   poor   oral   intake.   In   addiLon,  
trimethoprim   should   be   used   with   cauLon   in  
paLents   with   Stage   4/5   CKD   due   to   its   potenLal  
to  cause  hyperkalaemia.  
  Treatment:  It  is  essenLal  to  restore  an  effecLve  blood  
pressure   within   the   first   4   hr   of   hospital   admission.  
Failure   to   achieve   an   adequate   BP   (MAP   >   65   mmHg)  
despite   an   iniLal   rapid   infusion   of   up   to   2   L   of  
crystalloid   is   a   marker   of   illness   severity.   In   the  
absence   of   obvious   fluid   /   blood   loss   or   cardiogenic  
shock,   such   paLents   should   be   regarded   as   being   in  
sepLc  shock  and  should  be  referred  to  the  CriLcal  Care  
team  for  consideraLon  of  vasopressor  therapy.  In  this  
case   addiLonal   fluids   failed   to   restore   an   effecLve  
perfusion   pressure,   failed   to   improve   renal   funcLon  
and   contributed   to   the   development   of   pulmonary  
oedema.   Finally   this   case   demonstrates   the   high  
mortality  associated  with  AKI  where  the  renal  insult  is  
simply  a  talisman  for  serious  underlying  pathology.  
THANK YOU  
Spectrum diagnoctic AKI
Four subgroup
Prognostic in AKI
KDIGO-­‐AKI  GUIDELINES  
•  Assembled  experts  in  
nephrology,  criLcal  care  
medicine,internal  
medicine,  pediatrics,  
cardiology,  radiology,  
infecLous  diseases  and  
epidemiology  
biomarkers  
Tradisional  vs  biomarkers  of  AKI  
  
 
 
THE  FUTURE  
prerenal  

renal  

postrenal  
                                                                                                  N  Engl  J  Med  2012;367:124-­‐34  
 
Acute  kidney  injury:  new  studies.                                              
52  
Intensive  Care  Med  (2013)  39:569-­‐571  
 Acute  kidney  injury:  new  studies.                                              
53  
Intensive  Care  Med  (2013)  39:569-­‐571  
  
 
 
 
 
 
 

Acute  kidney  injury:  new  studies.                                              

55  
Intensive  Care  Med  (2013)  39:569-­‐571  
                                      
                                                                                                 N  Engl  J  Med  2012;367:1901-­‐11.  

Acute  kidney  injury:  new  studies.                                              

56  
Intensive  Care  Med  (2013)  39:569-­‐571  
 Acute  kidney  injury:  new  studies.                                              
57  
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 Acute  kidney  injury:  new  studies.                                              
58  
Intensive  Care  Med  (2013)  39:569-­‐571  
there  was  no  significant  difference  in  the  rate  of    
death  at  28  days  bet  ween  paLents  who  received  
dopamine  and  those  who  received  
norepinephrine.    

more  arrhythmic    
more  arrhythmic     signif  icant  increase  in  the  rate  
of  death    
Monitoring  hemodynamic  and  
infecLon  
Tanggal     18/11/2013                    19/11/2013                          20/11/2013  
Hari                    1                  2   KumulaOf                3   KumulaOf  
Berat  badan   80  kg   80  kg   80  kg   80  kg  
Total  intake   1786cc   2171cc   3957cc   2185  cc   6142  cc  
PRC   -­‐   -­‐   -­‐  
TC   -­‐   -­‐   -­‐-­‐  
FFP   -­‐   -­‐   -­‐  
Total  output  tanpa  IWL   3400  cc   4430  cc   7830    cc   5300  cc   13130  cc  

Balance  kumulaOve   -­‐1614  cc   -­‐3873  cc   -­‐5487cc   -­‐5404  cc   -­‐10974  cc  

%Fluid  Overload/%FO   -­‐4.8%   -­‐6,8%   -­‐6.7%   -­‐13,7%  

(Target  <10%)  
CVP   14-­‐23  mmHg   11-­‐23   11-­‐12  mmHg  
LASIX  DRIP/JAM   5  mg/jam   10  mg/jam   15  mg/jam   2  mg/jam   17  mg/jam  

ANTIBIOTIK   Meropenem   Mero   Mero    

+  amikasin   +  amikasin  
Hb/Ht   12/36,9   11,3/34,2   -­‐  
LEUKOSIT   18,490   15.600   13,6  00  (↓)  
TROMBOSIT   95000   87000   133000  (↑)  
ALBUMIN   2,7   >0.3  
3,3   mg/dl  .  AKI   -­‐   <0.3  mg/dl  .    No-­‐AKI  
GULA  DARAH   133   130   -­‐  
PCT   -­‐   18,77   -­‐  
LACTATE   3   1.9   1,3  
UREUM/CREATININ   43/0,96   71/1,97   44/1,2  
KALIUM   -­‐   5,3   4,41  
Na/Cl   -­‐   144/107   144/103  
CO2  Gap   <6   -­‐   <6  
Saturasi  Vena   69,8%   -­‐   51,8%  
NT-­‐Pro  BNP   4439   -­‐   425  
 Prognosis  
•  Pre  renal  and  Post  renal  beqer  prognosis  
•  Kidneys  may  recover  even  amer  dialysis  
requiring  AKI  
•   10%  of  cases  requiring  dialysis  develop  CKD  
 Conclusions  
•  AKI  complicates  5-­‐15%  of  hospitalisaLons,  is  
associated  with  increased  mortality,  increased  
hospital  stay,  excess  hospital  costs  and  is  an  
increased  risk  for  CKD  
•  New  classificaLons:  RIFLE,  AKIN  staging  
•  Dopamine  doesn’t  work  
•  Strategies  to  prevent  and  treat  AKI  in  various  
clinical  scenarios  
 Conclusions  and  summary  
•  Prompt  resuscitaLon  of  the  circulaLon  with  
fluids,  vasopressors  and  inotropes  remains  the  
cornerstone  in  the  prevenLon  of  AKI.  
•  Volume  expansion  with  isotonic  crystalloids  is  
only  recommended  in  states  of  true  and  
suspected  hypovolaemia.  
•  Uncontrolled  volume  expansion  and  the  use  
of  starches  and  dextrans  should  be  avoided.  
•  norepinephrine,  and  Ltrated  individually  with  
a  target  MAP  of  65–70  mmHg  being  adequate  
in  most  individuals  without  pre-­‐exisLng  
chronic  hypertension.  
•  DiureLcs  should  not  be  used  for  prevenLon  of  
AKI  alone  but  may  benefit  the  kidney  by  
relieving  renal  congesLon.  
 Secondary  prevenLon  of  AKI  
•  The  goal  is  to  prevent  secondary  primary  
insults  and  to  alter  the  nature  of  the  primary  
renal  injury  
•  The  major  targets  are:  
 Blood  pressure  
 Cardiac  output  
 Intravascular  volume  
 Renal  blood  flow  
 
•  There  is  insufficient  evidence  to  recommend  
physiological  targets  (MAP,  cardiac  output,  filling  
pressures)  that  will  ensure  adequate  renal  perfusion  
•  Extreme  hypotension  should  be  avoided  
(sBP<80mmHg)  
•  When  vasopressor  agents  are  required  to  reverse  
systemic  vasodilaLon  norepinephrine  is  the  drug  of  
choice  
•  Drugs  should  not  be  used  to  induce  renal  
vasodilaLon  
 Minimising  iatrogenic  AKI  
•  Iatrogenic  AKI  is  not  always  preventable  
 
•  Incidence  varies  between  1-­‐3%  
 
•  Drug  nephrotoxicity    is  the  main  cause  
accounLng  for  20-­‐60%  of  all  cases  
•  Need  for  educaLon,  increased  vigilance  and  earlier  
intervenLon  
•  Insufficient  knowledge  of:  
–  Presence  of  risk  factors  for  nephrotoxicity  
–  AlternaLve  therapies  for  drugs  with  potenLal  
nephrotoxicity  
–  Appropriate  drug  dosing  
–  Appropriate  assessment  of  kidney  funcLon  before  and  at  
intervals  during  treatment  
–  Earlier  idenLficaLon  of  AKI  (  new  biomarkers  eg  CystaLn  C)  
–  PreventaLve  measures  for  nephrotoxicity