**3. Etiology and risk factors for AKI**

Early detection of AKI in ICU is crucial to perform early intervention and prevent further complications, thus it may be lifesaving to determine the risk factors for the impairment of the renal function.

The Program to Improve Care in Acute Renal Disease (PICARD) is prospective observational extensive cohort study, which was done in USA from 1999 to 2001 (Mehta,

2011). The choice of estimation technique used to obtain the baseline creatinine value has a marked effect on the prevalence of AKI, severity of disease, and mortality risk associated with various stages of AKI. When premorbid renal function is not known ADQI group has recommended back- estimation of the baseline serum creatinine level value using the MDRD formula. In a study, involving 4,863 hospitalized patents, investigators studied the performance of these three potential surrogates for the baseline serum creatinine level and they concluded that all three surrogates resulted in bidirectional misclassification of AKI. Although the use of serum creatinine level at admission found to be more specific in this study, this parameter had the lowest

Subgroup analysis of data from the Beginning and Ending Supportive Therapy for the Kidney (BEST) study also compared observed baseline serum creatinine levels with MDRD back estimated values to determine the RIFLE class. They found that MDRD back estimated serum creatinine value performed reasonably well for the determination of the RIFLE categories when premorbid renal function was near normal, but should be cautiously used

As a conclusion investigators should make every effort to find out true baseline creatinine level before using any estimated values. An appropriate baseline serum creatinine value should express normal renal function of patients, such as outpatients serum creatinine level measured within the past year (prefereably in the past 3 months). When an outpatient serum creatinine level is not available, serum creatinine level on admission to hospital or ICU could be used as a second choice. However, use of admission serum creatinine level is

*Which classification is better RIFLE or AKIN?* Based on the studies to compare these two classifications; AKIN did not seem to show any improvement in the sensitivity and predictive ability of the definition and classification of AKI. Acute Physiology Score (SAPS)3 database in 2009 re-evaluated and compared the performance of the RIFLE and AKIN criteria (Joannidis, 2009). They concluded that RIFLE seems to be more sensitive for diagnosing AKI and to have a greater ability then AKIN criteria to predict the mortality. These data confirm that neither classification offers clear advantage over the other; and both systems still have some limitations. Similarly Bagshaw et al. compared AKIN classification and RIFLE criteria in 120,123 critically ill patients during the first 24 hours after admission to the ICU (Bagshaw, 2008). They concluded that AKIN classification did not improve the sensitivity and predictive ability of RIFLE criteria for the definition and classification of AKI in the first 24 hours in ICU. Based on these large database studies there is no evidence about superiority of any of these classifications. Both criteria can be used for the evaluation of critically ill patients, as long as the clinician is aware of the

Early detection of AKI in ICU is crucial to perform early intervention and prevent further complications, thus it may be lifesaving to determine the risk factors for the impairment of

The Program to Improve Care in Acute Renal Disease (PICARD) is prospective observational extensive cohort study, which was done in USA from 1999 to 2001 (Mehta,

sensitivity (38.9%) for diagnosis of AKI (Siew, 2010).

in patients with suspected CKD (Bagshaw, 2009).

limitations mentioned above.

the renal function.

**3. Etiology and risk factors for AKI** 

specific but insensitive, and may underestimate the incidence of AKI.

2004). This study revealed that, etiology of AKI was ATN (acute tubular necrosis) in 50% of cases with no specific determined cause. The next most common etiologies included nephrotoxin administration (26%), cardiac disease (20%) including myocardial infarction, cardiogenic shock, and congestive heart failure, ATN from hypotension (12%), sepsis (19%), unresolved prerenal factors (16%) and liver disease (11%). They found that predictors of mortality using proportional hazards Cox regression at the day of diagnosis of ARF were age, BUN, liver failure. At the day of consultation; age, Log urine output, creatinine (<2mg/dl), BUN, liver failure, ARDS (acute respiratory distress syndrome) and platelet count were related to mortality. When the day renal replacement therapy started, the predictive factors for survival were found as age, platelet count, liver failure, sepsis or septic shock. Oliguria, sepsis, respiratory failure, and hepatic failure would be consistently associated with mortality in AKI (Chertow, 2006).

The largest cohort with most participant of AKI to date was the Beginning and Ending Supportive Therapy for Kidney (BEST) study (Uchino, 2005). Out of 29.269 critically ill patients, there were 1.738 (5.7%) patients with AKI. The most common cause of AKI was septic shock (47.5 %), followed by major surgery (34%), cardiogenic shock (27%), hypovolemia (26%) and nephrotoxin administration (19%). In-hospital mortality varied from 50.5% to 76.8% between centers. A multivariate logistic regression model to identify independent correlates of in-hospital mortality yielded several previously identified risk factors, including delayed diagnosis of AKI, age, sepsis, and known disease severity score that included BUN and urine output, which are consistent with the previous studies.

Based on the previous reports; most common and complicated cause of AKI in ICU was found as sepsis and its prevalence have been reported to be 9-40% (Brivet, 1996 & Liano, 1998 & Bellomo,2008). Therefore, we prospectively evaluated 257 patients with sepsis or systemic inflammatory response syndrome who were admitted to the surgical and medical ICU during 12 months in 2001 to determine the risk factors for acute renal failure (ARF) development (Yegenaga, 2004). In this study, ARF was defined as serum creatinine level >2 mg/dL, based on this definition out of 257, twentynine (11%) patients were diagnosed as ARF. Mortality rate was 72% in patient with sepsis and ARF and in those with sepsis without ARF this rate was found as low as to 24 %. Multivariate logistic regression analysis of data showed that older age (OR:1.1, CI:1.03- 1.13) serum bilirubin >1.5 (OR:9.7, CI:1.65-60.3), higher baseline serum creatinine level (OR:1.02,CI:1.007-1.04), and higher central venous pressure (CVP) (OR:1.5,CI:1.26-1.80) were predictive for the development of ARF (Yegenaga, 2004). It was mandatory to evaluate fluid status of these patients, since it was found that CVP is an independent risk factor for the development of AKI (Van Biesen & Yegenaga, 2004). And subgroup analysis of these patients revealed that higher colloid fluid loading for the first 3 days (2037±1681vs 1116±1220, p<0.03) and lower diuresis (1347±649vs1849±916mL, p=0.005) was associated with poor outcomes and in addition interestingly the fraction of inspired oxygen (FiO2) needed to be increased significantly on the second day of sepsis in the ARF group but remained unchanged in non ARF group. These patients developed ARF despite further fluid loading and in addition, respiratory function deteriorated. Against the classical knowledge; this study brought up the idea that in critically ill patient fluid loading should be performed in cautious. It is more likely that in dehydrated patients fluid loading can prevent ARF development but in critical ill patients

Evaluation of Acute Kidney Injury in Intensive Care Unit 179

findings may not be clear. The earliest sign of ischemic or nephrotoxic AKI may not be decreasing in GFR level, therefore in this particular condition biomarkers should be able to identify tubular injury even before GFR falls and increasing in serum SCr level. Furthermore early identification of kidney injury will be critical for future developments in treatment or

Several more biomarkers of AKI have been introduced recently, Neutrophil Gelatinase-Associated Lipocaline (NGAL) also known as Lipocalin-2 or siderocalin is one of the best studied biomarker of AKI to date. And it is rapidly up-regulated in the blood and in urine post-AKI. It was reported that; even though Cystatin C seems to be a better marker for AKI then SCr, Urine NGAL is superior to Cystatin C for earlier detection of AKI. In fact, cystatin C is mainly a marker of clearance, and its serum concentration may increase only after the GFR begins to decrease. Unlikely, NGAL which is rapidly induced in kidney tubule cells in response to ischemic injury, and its appearance in urine and serum is independent of the

Another promising biomarker is KIM-1, a type-1 transmembrane glycoprotein that is highly expressed in proximal tubule cells after ischemic and nephrotoxic injury. In a study with patient undergoing cardiac surgery, urine KIM-1 levels peaked 12 hours after injury in AKI and predicted the need for dialysis or mortality in hospitalised patients. KIM-1 seems to be more specific to ischemic and nephrotoxic kidney injury than NGAL and it is not significantly affected by chronic kidney disease or urinary tract infection (Liangos, 2007). A pro-inflamatory cytokine IL-18 was also reported to be up-regulated and easily detected in the urine of animals with ischemic AKI. In a study, urine IL-18 levels were found markedly increased in patient with AKI but not in the patients with urinary tract infection, chronic kidney disease, nephritic syndrome, and prerenal failure. Urinary IL-18 showed sensitivty > 90% and specifity>95% for the diagnosis of AKI (Parikh, 2008). Both urine IL-18 and NGAL were found as sequential predictive biomarkers of AKI in children undergoing cardiac surgery. The patients in whom AKI developed 2-3 days after surgery, urine NGAL peaked at 25 fold within 2 hours and declined 6 hours after surgery, whereas urine IL-18

Since AKI increases mortality rate and significantly worsens patients' outcome, it is important to determine the patient with risk for AKI in ICU. The consensus has been achieved for the definition of AKI. This definition focuses on the association of hospital mortality, instead of renal failure requiring dialysis or clinical syndrome defined by pathology. Every patient who is admitted to the ICU should be evaluated and categorized based on the creatinine level. Furthermore, close follow-up of renal function is crucial. Recently introduced biomarkers can be used for early diagnosis of AKI even before SCr level starts to increase. During treatment of these patients intensivist should be alert against fluid overload which is described as an

Kellum JA. Acute kidney injury. Crit Care Med 2008;36 (Suppl 4): S141-145.

GFR but is highly predictive of a subsequent decline in GFR (Mishra, 2003).

levels peaked 12 hours after surgery (Parikh, 2006).

independent risk factor to develop AKI.

**5. Conclusion** 

**6. References** 

prevention of AKI (Cruz, 2010).

with sepsis it might bring more risk for ARF and also to increase the mortality rate (Payen, 2008).

A similar study was designed previously for the Turkish ICU population of two tertiary hospitals, and RIFLE criteria were used for the definition of AKI (Yegenaga, 2010). In this Turkish ICU population, AKI incidence was 56,8% including Risk of RIFLE, and mortality rate was 65% in AKI and and it was found 35% in non AKI group. In this study it was observed that mortality rate was correlated well with the severity of RIFLE criteria; in the risk group 56%, in injury 68%, and in failure it was found as 72%. Multivariate logistic regression revealed that unlike the previous study age and serum bilirubin level were not significant anymore, but SOFA score (OR: 1.49, CI:1.085-2.205, p=0.045), baseline serum creatinine level (OR: 1.87,CI:1.391-2.520, p<0.001), and every 1 liter of extra positive fluid balance (OR: 1.56, CI:1.029-2.373, p=0.036) were independent risk factors for AKI. This study also brought up the importance of fluid overload in critically ill patients with sepsis; despite more vasopressor use and more fluid resuscitation, kidney damage starts very early and that is difficult to reverse. Previously in this particular population fluid loading was known as early intervention, but based on the observation in this and in some other recent reports fluid therapy should be performed cautiously. It is claimed that fluid overload may increase intra-abdominal pressure, leading to abdominal compartment syndrome, which has been recently recognized as an important cause of AKI in critically ill patients (Schrier, 2004). Furthermore fluid overload has been demonstrated to cause other organ failure in addition to kidney in ICU patients (Malbraina, 2005); for example impairment of cardiac function, worsens the lung injury (Essen, 2002).
