acute kidney injury (aki) dr lestariningsih

Acute kidney injury in Sepsis

SubBag Nefrologi / Hipertensi

Bag. Penyakit Dalam FK UNDIP / RS. Dr. Kariadi

S E M AR A N G

Lestariningsih

Critical ill patient potentially AKI

AKI in ICU 5 –25% Mortality AKI 40-80%

Definition and diagnostic criteria for AKI

An abrupt (within 48 hr) reduction in kidney functioncurrently defined as an absolute increase in serum creatinine of either >0,3 mg/dl (25 umol/L) or presentage increase of >50% or reduction in OUP (documented oliguria of < 0,5 ml / kg per h for > 6hr )

Mehta RL. Nephrology Self Ass-vol 6, No 5, Sept 2007

More than different definitions of acute renal failure have been used in the literature

RIFLE criteria for Acute Renal Dysfunction

Risk

Injury

Failure

Loss

ESRD

Abrupt (1-7 days) decrease (> 25%) in GFR orScr x 1.5Sustained (> 24 hrs)

ARF ~ earliest time point for provision of RRT

Irreversible ARF or persistent ARF > 4 wks

ESRD > 3 months

Non-Oliguria Oliguria

UO < .5/ml/kg/hx 24 hrAnuria x 12 hrs

UO < 0.5/ml/kg/hx 12 hr ??

Decreased UO relative to the fluid inputUO < 0.5/ml/kg/h x 6hr

Adjusted creat or GFR decrease> 50% orScr x 2

Adjusted creat or GFR decrease > 75%Scr x 3 or Scr > 4mg%When acute > 0.5mg%

Spec

ific

ity

Klasifikasi/staging AKI modifikasi RIFLE

Stadium kriteria kreatinin kriteria urin output

1.

Risk

serum kreatinin meningkat > 0,3 mg/dl atau meningkat lebih dari 150-200 % dari awal

< 0,5ml/kg per jam untuk >6jam

2.

Injury

serum kreatinin meningkat sampai > 200% sampai 300% dari data awal

< 0,5 ml/kg per jam untuk 12 jam

3.

Failure

serum kreatinin meningkat > 300%, (serum kreatinin > 4mg/dl dengan peningkatan akut 0,5mg/dl, indikasi untuk renal replacement therapy

<0,3 ml/kg per jam x 24 jam atau anuria x 12 jam

Mehta RL. Nephrology Self Assesment Program , Vol 6, No 5, Sept 2007

Loss Persistent renal failure for >4 weeks

ESRD Persistent renal failure for >3 months

Murray PT, Palevsky PM. Nephrology Self Assesment Program , Vol 6, No 5, Sept 2007

SepsisIschemic insult

Nephrotoxic insult

Complement activationEndotoxin releaseIschemia-reperfusion

Cellular activation(PMN, endothelial cells…)

Arachidonic acid metabolities

Proteases

Chemokines

Platelet activating factor

Serum creatinine

Oxygen free radicals

Nitric oxide

Heat shock proteins

Endothelins

Acute kidney injury Urinary KIM-1, NAG

Urine output GFR

Anti-inflamatorymediators

Pro-inflamatorymediators -

+

Pathogenic mechanism of sepsis related acute kidney injury

(1)Vasoconstriction

Renin-angiotensinendothelin

PGI2NO

(2)Obstruction

by casts

(3)Tubularbackleak

IschemiaNephrotoxins

Tubular damage(proximal tubules andascending thick limb)

(5)? Direct glomerular

effectGFR Oliguria

Tubularfluid flow

Intratubularpressure

Possible pathogenetic mechanisms in ATN.

(4)Interstitial

inflammation

Effects of ischemia on renal tubules in the pathogenesis of ischemic AKI

Schrier et al, J Clin Invest 2004, 114:5-14

Hemodynamic mechanism of ATN

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

Analyze biology by time zone with adequate and precission clock

The potential interventions in sepsis related AKI

1. Effective prevention/protection strategies for the kidney

in patient at risk2. Early recognition and attenuation of renal

damaged3. Pathophysiology driven pharmacology support4. Efficient extracorporeal blood purification therapy5. Strategies that promote recovery of renal function

Ronco . ASN 2008

Renal protection, there is damage before any symptom

MAP> 65 mmHg

CVP 8-12 mmHg (no ventilator)

12-15 mmHg (ventilator)

Urine > 0,5ml/BW/hour

SaO2 >70%

Koloid ,albumin ?

Renal Protection

•

•

•

•

•

•

Vasopressor therapy should be started early and not as a last resort in moribund patients. In a retrospective analysis of patient requiring NE, both the degree of organ dysfunction (SOFA score) and time to administer NE are associated with worse outcome

In conclusion, NE can be used to restore blood pressure without jeopardizing the renal function in fluid-resuscitated patients with distributive shock. Whether other vasopressors offer advantages over NE should be further investigated

M.Schetz, Blood Purification 20:243-251,2002

Vasopressors and the kidney

Loop diuretics in ARF: a double-blind randomized controlled trial

• Over 3 years, 278 oliguric patients were assessed as potential ARF. Twenty five percent recovered with simple rehydration.

• Ninety six patients were enrolled in the study. Study patients received i.v. dopamine 2 microgram/kg per min for 3 days ; mannitol i.v., 100 ml 6-hourly for 3 days, and randomized medication - i.v. torasemide 3 mg/kg, furosemide 3 mg/kg, or placebo- 6- hourly for 21 days or until renal recovery,dialysis, or death.

• Apache II scores were similar in the three groups.

Shilliday IR et al. Nephrol Dial Transplant 11: 1684, 1996.

Intensive insulin therapy sepsis by 45%

Blood glucose 80-110 mg/dl morbidity and mortality

Mechanism : bacterial phagocytosis and antiapoptotic effect of insulin

Tight control of blood glucose

Effect of control of mean blood glucose in ICU patients

Van den Berghe et al Crit Care Med2003, 31:359-366

Other therapy

- Ventilator ; low tidal volume

- Dietary nutrition

- N-acetil cystein

- Eritropoietin

- Stem cell

Treatment parameters in IHD dose study

Characteristic Alternate day hemodialysis

Daily hemodialysis

Duration of session (hr)

Blood flow rate ml/mnt

Dose (Kt/V)

Prescribed

Delivered

Weekly delivered

Time averaged BUN (mg/dl)

UF volume (L/session)

3.4+0.5

243+25

1.21+0.09

0.94+0.11

3.0+0.6

104+18

3.5+0.3

3.3+0.4

248+45

1.19+0.11

0.92+ 0.16

5.8+0,4

60+20

1.2+0.5

P<0.001 vs alternate day group

• AKI is a new terminology, which is identically to ARF type ATN ?

• AKI sepsis, RIFLE modified

• Early detection of AKI by biomarker

• Management

– Early detection

– Blood glucose control 80-110mg/dl

– Renal perfusion (MAP>70mmHg, CVP 8-12/12-15 mmHg, diuresis >0.5cc/BW/hour,SaO2 >70%

– Ventilator low TV, nutrition, Erithropoeitin, stem cell

– Extracorporeal therapy, CRRT, SLED

Conclusion

terima kasihterima kasih

Management of AKI

CRRTSLED

IHD

Treatment modalities for AKI in ICU