Evaluation Of New Acute Kidney Injury Biomarkers In ICU

PRESENTER :Dr.Manjunathan MODERATOR:

To Note
This study was undertaken to evaluate the RELIABILITY of new acute kidney injury biomarkers Evaluation is necessary to confirm their reliability before their translation to clinical use

AKI
Acute kidney injury : Defined as a 50% increase from the baseline creatinine value ,which is creatinine value taken 3 months before admission Study Design : prospective observational cohort study Study Duration : Dec 2008 May 2009

 Study Setting : single study centre 15 bed medical surgical ICU at a tokoyo university hospital

Total patients : 339 adults >20 yrs age critically ill patients pt with end stage renal disease & renal transplant are excluded

Urinary biomarkers
1.L-Type fatty acid binding protein (L-FABP) 2.neutrophil gelatinase associated lipocalin (NGAL) 3.interleutin 18 4.N-acetyl beta D glucosaminidase (NAG) 5.albumin

Following clinical variables were evaluated

Age and gender Admission type : medical /surgery Diabetes Contrast exposure preceding 48 hrs Basline creatinine value Creatinine at admission APACHE II(acute physiology and chronic health evaluation II) Sepsis 14 day in hospital

Urinary biomarkers measurement

Within 12 hrs of icu Then frozen at -80 degree C within 1 hr of collection L FABP ,NGAL ,IL 18 mesaured using enzyme linked immunosorbent assay kits Urinary NAG ,albumin measured using 4-hpnag substrate method & immunonephelometry

Statistical analysis
Data expressed in median Continous variables were compared using turkey kramer method Categorical variables wrer compared using pearson chisquare test To identify best predictors of AKI occurance in ICU & 14 day hospital mortality ,the independent relationship using multiple logistic regression analysis

Biomarkers for AKI detection and prediction

NON AKI (TOTAL -208) L-FATTY ACID BINDING PROTEIN NEUTROPHIL GELATINASE ASSOCIATED LIPOCALCIN INTERLEUKIN 18 N- ACETYL BETA D GLUCOSAMINIDASE ALBUMIN 7.4 15.6 60.0 8.7 3.2 AKI (TOTAL-131) 42.5 ( increased) 61.8 (increased) 192.3 (increased) 13.5 ( increased) 8.0 (increased )

Urinary markers and AKI

5 urinary markers increased in AKI than non AKI L-FABP ,NGAL,IL 18 dynamic range much greater than NAG,ALBUMIN ROC (receiver operating characteristic curve) ANALYSIS for detecting AKI revealed that area under the curve for L-FABP was significantly higher than others

AKI occurance after ICU admission

Newly diagnosed AKI : defined as no AKI dignosis was made at ICU admission but serum creatinine increase to RIFLE(risk,injury,failue,loss,end stage kidney disease) criteria or renal replacement therapy was started within one week All biomarkers were significantly higher in AKI than newly diagnosed AKI

 L-FABP ,NGAL,IL 18 ,ALBUMIN showed good AUC-ROC valves for detecting established AKI L-FABP ,NGAL,IL 18, ALBUMIN were significantly increased in newly diagnosed AKI compared to NON-AKI ROC curve shows that LFABP was better able to establish this later onset AKI than other biomarkers were.

AKI and severity

Five urinary markers were compared with severity of AKI in which urinary LFABP can reflect the AKI severity All biomarkers in patients with AKI with sepsis showed highest values

Urinary biomarkers and mortality

339 ICU patients -14 died in hospital within 2 weeks .their serum creatinine value significantly higher than surviors But ,LFABP,NGAL,IL 18 values remarkably elevated in non surviors than serum creatinine Single measurement of these biomarkers predicted mortality with almost same AUCROC as that of APACHE II score ,which requires an initial 24 hrs observation period

AKI biomarkers and 14 day mortality

SURVIOR (TOTAL-325) L-FATTY ACID BINDING PROTEIN NEUTROPHIL GELATINASE ASSOCIATED LIPOCALCIN 10.6 22.I NON-SURVIORS (TOTAL14) 264 (INCREASED) 514.5 (INCREASED)

INTERLEUKIN 18
N ACETYL BETA D GLUCOSAMINADASE ALBUMIN SERUM CREATININE APACHE II

75.3
10.3 4.3 0.89 11.0

493.9 (INCREASED)
20.7 ( INCREASED) 13.7 (INCREASED) 1.30 (INCREASED) 26.0 (INCREASED )

 To identify the best combination of five urinary markers multiple logistic regression analysis is used L-FABP &NGAL combination good

AKI and creatinine

AKI diagnosed using sr.creatinine has been recognised as LATE and INACCURATE Serum creatinine value was influenced by non renal factors Sepsis decreases creatinine production Several clinical reports say low serum creatinine levels are at risk for mortality & length of ICU stay

conclusion
Because of under estimation of kidney injury determined using serum creatinine ,new urinary biomarkers might be able to PREDICT THE MORTALITY accelerated by AKI BETTER OR EARLIER than serum creatinine