**1. Introduction**

Acute Kidney Injury is a syndrome that consists of several clinical conditions, due to sudden kidney dysfunction (within a few hours to several days) that causes retention of residual nitrogen (urea-creatinine) and non-nitrogenous metabolism, with or without oligouria, and is affected by some underlying disease. The most common causes of AKI in patients with critical illness are sepsis and septic shock, accounting for more than 50% of AKI cases in the ICU. The incidence of sepsis and AKI in critical patients increases gradually and both shows poor prognosis. In various epidemiological studies, it is said that AKI occurs in 11-60% of sepsis patients, 23% of severe sepsis patients and 51 – 64% in septic shock patients [1, 2]. Sepsis is one of the causes of Acute Kidney Injury (AKI) in critically ill patients treated in the ICU known as Sepsis-Associated AKI (SA-AKI). The morbidity and mortality

rate of SA-AKI is still quite high even though the development of supportive care technology has progressed. A good understanding of SA-AKI is expected to increase alertness and make appropriate decisions in initiating management so as to provide better outcomes for patients with SA-AKI in the ICU.

By definition, Sepsis is a life-threatening condition of organ dysfunction due to an uncontrolled body's response to a systemic infection. Meanwhile, septic shock is part of sepsis with higher mortality characterized by hypotension requiring vasoactive therapy to maintain an average arterial pressure of at least 65 mmHg and serum lactate above 2 mmol/L despite adequate fluid resuscitation with a mortality rate of>40% [2]. Organ dysfunction caused by inflammatory response can be used to distinguish infections with sepsis, using Sequential Organ Failure Assessment (SOFA) scoring where a minimum of 2 points is the most recent associated with a mortality rate of 10% [3–5]. Critically ill patients with sepsis when patients are undergoing treatment in the Intensive Care Unit (ICU) may experience organ failure, especially in the respiratory system (43%) and the renal system (36%) [6, 7].

## **2. Literature review**

#### **2.1 Definition**

According to the latest definition, sepsis is characterized by suspicion or evidence of infection plus clinical signs and laboratory findings that indicate organ dysfunction (based on the SOFA/Sequential Organ Failure Assessment score) due to an immune response to the infection. The heart, liver, lungs and kidneys are organs that are often affected during this process [2]. For a longtime sepsis has been known as a cause of morbidity and mortality; the consensually agreed upon definition of sepsis has only been around for the last few decades [3]. The first consensual definition defined sepsis as a continuous physiological and serological disorder that causes progressive organ failure.

The consensual definition of Sepsis-3 is the response to the limitations of the old definition, where SIRS and severe sepsis are removed. Sepsis is defined as life-threatening organ dysfunction due to the body's uncontrolled response to infection. Organ dysfunction can be identified by a condition of acute changes associated with infection with at least 2 points on a Sequential Organ Failure Assessment (SOFA score), increasing the mortality rate by 10% [2]. The determination of the sepsis diagnosis in patients with infection can use the quick SOFA score, where two of the three criteria can meet the criteria of sepsis. Meanwhile, septic shock is sepsis with hypotension that requires a vasopressor to maintain a minimum MAP of 65 mmHg and serum lactate above 2 mmol/L despite adequate fluid resuscitation; this condition has a mortality rate of 40% [4]. Based on the European Society of Intensive Care Medicine and the Society of Critical Care Medicine's Third International Consensus Definition for Sepsis and Septic Shock in 2016, sepsis is defined as life-threatening organ dysfunction caused by dysregulation of the body's response to infection. So, the criteria for sepsis must also include the three elements, namely, infection, body response and organ dysfunction. The criterion for the diagnosis of sepsis is established through a SOFA (Sequential/Sepsis-related Organ Failure Assessment) score ≥ 2 [5].

Given the significantly high mortality rates, AKI as one of the most frequent complications of sepsis is considered an important issue in clinical practice and especially for hospitalized patients treated in the ICU. This may be due to the limited understanding of the pathogenesis of SA-AKI sepsis, the lack of ability to assess kidney function in early diagnosis of AKI, and the absence of specific treatments other than supportive care [3].

#### *Sepsis Associated Acute Kidney Injury DOI: http://dx.doi.org/10.5772/intechopen.97609*

AKI is characterized by a sudden decline in kidney function for several hours to days, resulting in the accumulation of creatinine, urea and other waste products. The latest definition was formulated in the consensus of Kidney Disease: Improving Global Outcome (KDIGO) in 2012, where the AKI was established if it met the criteria: an increase in serum creatinine levels ≥0.3 mg/dL (26.5 μmol/L) within 48 hours, an increase in serum creatinine at least 1.5 times the baseline value within the previous 7 days, or urine volume ≤ 0.5 ml/kg body weight for 6 hours [6].

The initial definition of AKI was the result of the international consensus of the Acute Dialysis Quality Initiative (ADQI) in 2004 that produced RIFLE (Risk, Injury, Failure, Loss, End stage Kidney disease) criteria based on an assessment of increased serum creatinine, decreased Glumerular Filtration Rate (GFR) urine production, loss if AKI lasts >4 weeks and end stage Kidney disease if AKI continues >3 months [7]. Then in 2007, the Acute Kidney Injury Network (AKIN), an international nephrological network or community in the USA and Europe, issued a more specific measure on RIFLE criteria focusing on the condition of the injury, i.e. Risk, Injury, and Failure were changed into stages (stage 1, stage 2, stage 3); Loss and end stage Kidney disease was eliminated; and an increase in serum creatinine of 0.3 mg/dL within 48 hours was added [8].

In 2012, the KDIGO issued clinical guidelines for the management of AKI and made a classification of AKI by combining RIFLE and AKIN criteria. This KDIGO-based classification defines AKI based on an increase in serum creatinine of 0.3 mg/dL within 48 hours or an increase of 1.5 x serum creatinine from baseline or urine production <0.5 ml/kg/hour for 6-12 hours. Baseline serum creatinine is the examination value obtained in the last 7 days. KDIGO also introduced the definition of Acute Kidney Disease (AKD), where an increase in serum creatinine >7 days and < 3 months. This condition occurs due to injury to the kidney and it can also occur slowly, different from AKI with a significant decrease in kidney function occurring within 7 days after the cause of injury to the kidney [9].

In patients who meet both the criteria for sepsis and AKI, it is called SA-AKI [10, 11]. Sepsis can be associated with >50% of AKI cases, and > 60% of sepsis patients can experience AKI. SA-AKI can also be interpreted as AKI which is caused or worsened by sepsis, so that it can be classified as a different condition in AKI which is usually caused by nephrotoxic regimens and ischemic conditions. The inflammatory response is more prominent in SA-AKI compared to nephrotoxic and ischemic AKI [12, 13]. SA-AKI is a clinical syndrome due to acute damage to organ function and damage. It is related to long-term adverse outcomes depending on the severity of the underlying organ damage. In general, SA-AKI should be considered a syndrome, characterized by fulfilling the criteria for sepsis and AKI [6].
