OVERVIEW • Pathophysiology sepsis AKI • Diagnosis sepsis AKI • Biomarker AKI- NGAL INTRODUCTION • Sepsis risk factor for AKI • Acute Kidney Injury (AKI) high morbidity and mortality
Crit.care Med.2008 April:36(4):1297-1303
EPIDEMIOLOGY • Incidence AKI up to 20% (ICU) mortality rate 25-80%. • The Beginning and Ending Supportive Therapy (BEST) study in 23 country sepsis cause AKI (47,5%)
Blood Purif, 2012;33:131-7
PATHOPHYSIOLOGY OF SEPSIS AKI
www:cjasn.asnjournal.org PATHOPHYSIOLOGY OF SEPSIS AKI
• Current clinical practice serum creatinin (RIFFLE)
• Creatinin unreliable & insensitive early acute change • Neutrophil Gelatinase Associated Lipocalin (NGAL) sensitive, specific and predictive early biomarker for AKI
Crit Care Med,2008 April:36(4):1297-1303
RIFFLE CRITERIA FOR AKI Neutrophil Gelatinase Associated Lipocalin
• NGAL is a 25-kD protein, small molecule of 178 amino
acid superfamily of lipocalin • NGAL important role in host defense, reducing apoptosis and proliferation of renal tubules. • In stress condition (infection, inflammation, ischemic, neoplasm) the NGAL level will increase
Ann Intern Med.2008 June 3;148(11)
Clin J Am Soc Neprol 3;531-44 Pacificbiomarker2012 Figure . Possible mechanisms for increased urinary (NGAL) levels in proteinuric diseases. (A) Under physiological conditions, almost totally reabs in tubular by megalin transporter (B) In proteinuric diseases damage glomerular, NGAL ↑ (C) Megalin reabs ↓ cause by damage tubular (megalin located) (D) Injured tubular cells NGAL↑ defence mech against oxidative stress
. Journal of Medical Research and Science.2012;1:30-6
NGAL as Biomarker AKI
• Reference value for uNGAL in pediatric (25 healthy newborns &
308 children pediatric normal ( mean 10.2 ng/mL, median 4.6 ng/mL, range 0.2-146.7 ng/mL; p<0.0001). • uNGAL values for neonates ( mean 44.2 ng/mL, median 30.3 ng/mL, range 5.2-137.4 ng/mL)
Clin Chem Lab Med. 2013 May;51(5):
• Observation Jan-Maret 2014 on 29 sepsis children in RSCM Jakarta and RS. Wahidin Makassar (sepsis 17, shock sepsis 12) showed: • Urine NGAL according to severity of illness: PELOD score <10 (N:14) median 26,31 (2,64-678,42), score 10- 20 (N:9) median 485,66 (81,58-5999,84), score > 20 (N:6) median 2209,8 (3,2 – 6353) THERAPY
• Renal Replacement Therapy
• Non dialysis: 1. Hydration and volume loading 2. Maintaining renal perfusion pressure 3. Low dose dopamine no benefit 4. Loop diuretic controversy 5. Osmotic diuretic-manitol risk of AKI↑
Rajapakse et.al SLJCC.vol 1 no 1
Clin J Am Soc Neprol 3;533-44 PROGNOSIS
• AKI higher risk of death than without AKI.
• Increased risk of death rises incrementally with the severity of AKI
Nat Rev Nephrol.April 2011;7(4):209-217
CONCLUSION
• AKI is common and serious problem
• The diagnosis of AKI is often delayed • Preventive and therapeutic measures are delayed due to lack of early biomarker