Dwi Lestari Partiningrum

Nephrology and Hypertension Division,

p
Internal Medicine Department
Medical Faculty Diponegoro University/ Kariadi Hospital
 “A NEW CONCEPT THAT STILL
MOVES and CHANGES”

Dwi Lestari
 DEFINITION and CLASIFICATION
of AKI

ETIOLOGY and DIAGNOSIS of AKI

MANAGEMENT off AKI

Dwi Lestari
 DEFINITION and CLASIFICATION
AKI

Dwi Lestari
 Acute Renal Failure

Acute Kidney Injury

Dwi Lestari
 Acute Kidney Injury (AKI)
digunakan oleh
Acute Dialysis Quantitative Initiative (ADQI), (2002), 
menggantikan definisi
Acute Renal Failure (Gagal Ginjal Akut).

Di Indonesia, definisi AKI telah digunakan secara

resmi oleh PERNEFRI. 
PERNEFRI  
:
Gangguan Ginjal Akut
(GGA = GgGA)

Dwi Lestari
  Acute renal failure occurs in 5-20% of
critically ill patients with a mortality of 28-90%

 Conclusion :
- We have no idea what ARF is!
 At least 30 definitions of ARF are in use

Dwi Lestari
 Definisi GGA  berdasarkan beberapa penelitian

Penelitian Definisi
dde Medonca
M d dkk (2000)4 , P i k t SCr
Peningkatan SC sebesar
b 0 5 mg/dl
0,5 /dl dalam
d l waktu
kt 48 jam
j
Tepel dkk (2000) 6

B i t dkk (1996) 10
Brivet Kenaikan
K ik SCr
SC > 2.0
2 0 mg/dl
/dl = (“GGA”)
Kenaikan SCr >3.5 mg/dl dan /atau kenaikan BUN > 100 mg/dl
(“GGA berat”)

Agrawal dan Swartz (2000) 2 Kenaikan SCr > 0,5 mg/dl/hari disertai produksi urin < 400 cc/hari
Disebut GGA berat (”complete renal shutdown)

Ricci dkk (2006) 8 Kenaikan SCr bervariasi antara 1,5 – 10 mg/dl

( meta-analisis) Penurunan produksi urin bervariasi antara 0-900 cc/hari
Pen r nan LFG sebesar > 50 % disertai penurunan
Penurunan pen r nan
produksi urin berlangsung beberapa jam sampai beberapa hari

Keterangan :  Scr= Serum Creatinin.  BUN = Blood Urea Nitrogen.  LFG = Laju Filtrasi glomeruli

Dwi Lestari
Dwi Lestari
  Elevation in serum creatinin is the current gold
standard,
t d d b butt thi
this is
i problematic
bl ti
 Normal serum creatinin varies widely with age,
gender, diet, muscle mass, muscle metabolism,
medications, hydration status
 In AKI, serum creatinin can take several days to
reach a new steady state

Dwi Lestari
Dwi Lestari
 2,5

2,0

1,5
,

1,0
,

0,5

0,0
1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002

Source: National Center for Health Statistics, National Hospital Discharge Survey
Dwi Lestari
 5,0%

4 0%
4,0% 3 7%
3,7%

3,0% 2,8%
2,3%
2,0%
1 3%
1,3%
1,0%
1,0% 0,7%
0,4%
, 0 3%
0,3%
0 2%
0,2% 0,1% 0 2%
0,2%
0,0%
0,0%
0-44 45-64 65-74 75+
Age (yr)
Dwi Lestari 1982 1992 2002
 GFR criteria Urine output criteria
Abrupt (1-7 days)
Decreased UO relative to
decrease (> 25%) in GFR
Risk Or Scr x 1.5
the fluid input
High Sensitivity
UO < 0.5/ml/kg/h x 6hr
Sustained (> 24 hrs)
Adjusted creat or UO < 0.5/ml/kg/h
Injury GFR decrease> 50% x 12 hr ??
or Scr x 2

Adjusted creat or GFR UO < .5/ml/kg/h

decrease > 75%
Failure x 24 hr High
g Specificity
p y
Scr x 3 or Scr > 4mg%
When acute > 0.5mg% A
Anuria
i x 12 h
hrs

Loss Irreversible ARF or

persistent ARF > 4 wks
ESRD > 3 months
ESRD
Dwi Lestari
Dwi Lestari
Dwi Lestari
Dwi Lestari
 ETIOLOGY or COMMON
CAUSES OF AKI

Dwi Lestari
  Ischemia (60%): cardiovascular disease, cardiac
surgery, abdominal surgery, shock, sepsis
 Nephrotoxins (30%): antibiotics, contrast,
chemotherapy, anti-rejection, NSAIDs

These causes also frequently lead to

sub-clinical renal injury,
j y a vastlyy
underestimated problem

Dwi Lestari
 Acute Renal Failure

Prerenal Intrinsic renal Postrenal

Causes Causes Causes

Interstitial
Tubular Acute
nephritis
h iti
necrosis Glomerulonephritis +
(10% of cases)
vasculitis
(5% of cases)

Ischemia Toxins
(50% of cases) (35% of cases)
Dwi Lestari
 Rapidly reversible decrease
In GFR caused by renal
Hypo perfusion.

Causes 50% of ARF

Acute Tubuler Necrosis

(ATN) is an abrupt
Decrease of GFR caused
By tubular damage from:
- renal hypo perfusion
- nephrotoxic injury
- Tubulo-interstitial nephritis
Rapidly reversible decrease
In GFR caused by obstruction
In renal or Uretero -
Uretheral - vesico urinary
(OBSTRUCTIVE UROPATHY)

Dwi Lestari
  pre‐renal
akibat terjadinya penurunan renal blood flow pada :
‐ penurunan volume cairan tubuh
(contoh:sepsis, perdarahan,dehidrasi,diuretik, intake kurang)
‐ penurunan volume darah efektif
(contoh:gagal jantung, sindroma nefrotik,sirosis,dll))
‐ pengaruh obat‐obatan
(contoh:ACE‐I,NSAID,dll).

 renal (intrinsik)
akibat terjadinya gangguan (injury) pada :
‐ tubulus (nekrosis tubuler akut)
(contoh:toksin, kontras, obat‐obatan, mioglobin)
‐ glomerulus
(contoh: RPGN,SLE, Wageners, pasca‐streptokokus)
‐ vaskuler
(contoh: penyakit mikrovaskuler dan makrovaskuler)
‐ interstitial 
(contoh: pielonefritis, penyakit auto‐imun, alergi obat)

 post‐renalal
Akibat terjadinya sumbatan total ataupun parsial
(akibat batu, tumor, prostat, dll) 
pada : ginjal,  saluran kemih (ureter), ckantung kemih dan uretra   

Dwi Lestari
 PATHOPHYSIOLOGY OF AKI

Dwi Lestari
 Blood flow
4.2 ml/min/g Macula densa PO2,
~ 50
Cortical labyrinths mm Hg

Medullary rays
PO2,,
Outer ~ 10-20
medulla mm Hg
Blood flow
1.9 ml/min/g

Inner
medulla

Medullary tick
ascending limbs
Cortex

Renal vein Renal artery

Dwi Lestari Brezis & Seymour, The New Engl. J. of Med., 332,647-655, 1995.
 Congestive
Volume depletion heart failure Sepsis

+ -
Angiotensin II
Renal vasoconstriction Nitric oxide
+
Ad
Adrenergic
i nerves and d decreased
d d -
+ glomerular Prostaglandins
Antidiuretic hormone ultrafiltration coefficient

Decreased glomerular
Tubuloglomerular feedback filtration rate

Dwi Lestari Blantz, KI, 53, 512-523, 1998.

 Possible
oss b e pathogenetic
pat oge et c mechanisms
ec a s s in ATN.
Tubular damage
Ischemia (proximal tubules and
Nephrotoxins ascending thick limb)

(1) (2) (3) (4)

Vasoconstriction Ob t ti
Obstruction Tubular Interstitial
Renin-angiotensin by casts backleak inflammation
endothelin
PGI2
NO Intratubular Tubular
pressure
p fluid flow

(5)
? Direct glomerular GFR Oliguria
effect
Dwi Lestari
 Sepsis
Ischemic insult
Nephrotoxic insult

Ischemia-reperfusion Endotoxin release Complement activation

Pro-inflamatory + Anti-inflamatory
mediators mediators
-
Oxygen free radicals Arachidonic acid
metabolities

Nitric oxide Cellular activation Proteases

Heat shock proteins (PMN, endothelial cells…) Chemokines

Endothelins Platelet activating factor

 Urinary KIM-1, NAG Acute kidney injury  Serum creatinine

 Urine output  GFR

Dwi Lestari Pathogenic mechanism of sepsis related acute kidney injury

 Loss of cellular polarity and
t b l obstruction
tubular b t ti ini ischemic
i h i ARF

Dwi Lestari
 Analyze biology by time zone with adequate
and precission clock

We can identify different milestones along the timeline of AKI. Injury begins
inducing molecular modifications subsequently evolving into cellular damage.
Cells start to produce biomarkers of injury and only later does the clinical
picture of the syndrome develop with typical sign and symptoms
Dwi Lestari
Dwi Lestari
 ALGORITMA UNTUK MENEGAKKAN DIAGNOSIS GgGA

MEMENUHI KRITERIA DIAGNOSIS

GANGGUAN GINJAL AKUT (GgGA)

LANGKAH 1 YA TIDAK

GgGA Observasi
24-48 jam

LANGKAH 2 DIAGNOSIS
ETIOLOGI GgGA TIDAK

DIAGNOSIS KLINIK & BUKAN

LANGKAH 3 TAHAPAN GgGA GgGA
Gejala & Komplikasi

LANGKAH 4 PEMERIKSAAN
PENUNJANG

Dwi Lestari
 The p
potential interventions in sepsis
p related AKI

1. Effective prevention/protection strategies for the

kidney in patient at risk
2. Early recognition and attenuation of renal
damaged
3. Pathophysiology driven pharmacology support
4 Efficient extracorporeal blood purification therapy
4.
5. Strategies that promote recovery of renal function

Ronco . ASN 2008

Dwi Lestari
 Renal
e a Protection
otect o

•
Renal protection, there is damage before any symptom
•
MAP 65 mmHg
MAP> H
•
CVP 8-12 mmHg (no ventilator)
12-15 mmHg (ventilator)
•
Urine > 0
0,5ml/BW/hour
5ml/BW/hour
•
SaO2 >70%
•
Koloid ,albumin ?

Dwi Lestari
LANGKAH 1
Mengenal kondisi klinis yang dihadapi
- Menentukan diagnosis GgGA secara dini dan benar .
- Menentukan etiologi GGA
- Mengetahui komplikasi yang menyertai GgGA
(komplikasi penyakit dasar maupun komplikasi GgGA)

LANGKAH 2
Pada tahap mana GgGA yang dihadapi ? Risk –Injury- Failure
Pemilihan jenis pengobatan yang tepat waktu,
waktu sangat tergantung pada tahap
mana GgGA yang kita hadapi

LANGKAH 3
Memilih jenis pengobatan yang tepat
S
Secara i besar
garis b d 2 jjenis
ada i pengobatan
b t untuk
t kG GA yaitu
GgGA, it tterapii
konservatif dan terapi pengganti ginjal. Dwi Lestari
 1. Gangguan keseimbangan cairan tubuh dan
elektrolit (retensi Natrium, edema)
2. Gangguan keseimbangan elektrolit (terutama
hiperkalemia)
3. Asidosis metabolik
4. Gagal Jantung
5. Gagal Nafas
6. Azotemia

Dwi Lestari
 Tujuan terapi konservatif adalah :
• Mencegah
M h memburuknya
b k f l ginjal
faal i j l secara progresif
if
• Meringankan keluhan-keluhan akibat akumulasi toksin azotemia
• Mempertahankan dan memperbaiki metabolisme secara optimal
• Memelihara keseimbangan cairan dan elektrolit

Beberapa prinsip terapi konservatif :

• Hati-hati pemberian obat yang bersifat nefrotoksik
• Hindari keadaan yang menyababkan deplesi volume cairan ekstraseluler dan
hipotensi
• Hindari gangguan keseimbangan elektrolit dan asidosis metabolik
• Hindari instrumentasi ((kateterisasi dan sistoskopi)
p ) tanpa
p indikasi medis yyang
g kuat
• Hindari pemeriksaan radiologi dengan media kontras tanpa indikasi medis yang
kuat
• Kendalikan hipertensi sistemik dan tekanan intraglomerular
• Kendalikan keadaan hiperglikemia dan infeksi saluran kemih (ISK)
• Diet protein yang proporsional

Dwi Lestari
 Best cure is to prevent

 Have a high index of suspicion for 
reversible factors ‐ volume depletion, 
p ,
decreasing cardiac function, sepsis, 
urinary tract obstruction
 Be sure patient is well‐hydrated when 
exposing patient to nephrotoxic
i   ti t t   h t i drugs
d

Dwi Lestari