Acute kidney injury in Sepsis

Lestariningsih
SubBag Nefrologi / Hipertensi Bag. Penyakit Dalam FK UNDIP / RS. Dr. Kariadi S E M AR A N G

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 function currently 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

Non-Oliguria Risk Oliguria

Injury

Adjusted creat or GFR decrease> 50% or Scr x 2

UO < 0.5/ml/kg/h x 12 hr ??

Failure Loss ESRD

Adjusted creat or GFR UO < .5/ml/kg/h decrease > 75% Scr x 3 or Scr > 4mg% x 24 hr When acute > 0.5mg% Anuria x 12 hrs

ARF ~ earliest time point for provision of RRT

Irreversible ARF or persistent ARF > 4 wks ESRD > 3 months

Specificity

Abrupt (1-7 days) Decreased UO relative to decrease (> 25%) in GFR or the fluid input Scr x 1.5 UO < 0.5/ml/kg/h x 6hr Sustained (> 24 hrs)

Klasifikasi/staging AKI modifikasi RIFLE

Stadium 1. Risk 2. Injury 3. Failure kriteria kreatinin serum kreatinin meningkat > 0,3 mg/dl atau meningkat lebih dari 150-200 % dari awal serum kreatinin meningkat sampai > 200% sampai 300% dari data awal serum kreatinin meningkat > 300%, (serum kreatinin > 4mg/dl dengan peningkatan akut 0,5mg/dl, indikasi untuk renal replacement therapy kriteria urin output < 0,5ml/kg per jam untuk >6jam < 0,5 ml/kg per jam untuk 12 jam <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 ESRD

Persistent renal failure for >4 weeks Persistent renal failure for >3 months
Murray PT, Palevsky PM. Nephrology Self Assesment Program , Vol 6, No 5, Sept 2007

Sepsis Ischemic insult Nephrotoxic insult

Ischemia-reperfusion

Endotoxin release

Complement activation

Pro-inflamatory mediators Oxygen free radicals

+ -

Anti-inflamatory mediators Arachidonic acid metabolities

Nitric oxide
Heat shock proteins Endothelins

Cellular activation (PMN, endothelial cells)

Proteases
Chemokines Platelet activating factor

Urinary KIM-1, NAG

Acute kidney injury

Serum creatinine

Urine output

GFR

Pathogenic mechanism of sepsis related acute kidney injury

Possible pathogenetic mechanisms in ATN.

Ischemia Nephrotoxins
Tubular damage (proximal tubules and ascending thick limb)

(1) Vasoconstriction Renin-angiotensin endothelin PGI2 NO

(2) Obstruction by casts

(3) Tubular backleak

(4) Interstitial inflammation

Intratubular pressure

Tubular fluid flow

(5) ? Direct glomerular effect

GFR

Oliguria

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

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

The potential interventions in sepsis 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 5. Strategies that promote recovery of renal function
Ronco . ASN 2008

Renal Protection

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 ?

Vasopressors and the kidney

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

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- 6hourly 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.

Tight control of blood glucose

Intensive insulin therapy sepsis by 45%
Blood glucose 80-110 mg/dl morbidity and mortality

Mechanism : bacterial phagocytosis and antiapoptotic effect of insulin

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
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) P<0.001 vs alternate day group

Alternate day hemodialysis

3.4+0.5 243+25 1.21+0.09 0.94+0.11 3.0+0.6 104+18 3.5+0.3

Daily hemodialysis
3.3+0.4 248+45 1.19+0.11 0.92+ 0.16 5.8+0,4 60+20 1.2+0.5

Conclusion
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

terima kasih

Management of AKI

Treatment modalities for AKI in ICU

IHD SLED

CRRT