Multiple studies have proven the detrimental impact of AKI on ICU patients, unfortunately their etiology and mechanism remain unclear. In ICU, a variety of conditions related to their reasons of admission such as infection, trauma, and other problems could prompt the induction of AKI or worsen any pre-existing condition of AKI.(1) Therefore, this stressed out the important to study epidemiology of each countries, especially in the countries, like Indonesia, where resources were limited and might have different risk factors for the AKI development. AKI has been reported to occur in 20–50% of patients in ICUs around the world.(8) In Indonesia, at Central Army Hospital of Gatot Soebroto, almost half of ICU patients, 43% suffered from AKI. Thus, indicating that AKI is also a common problem in Indonesian ICU (Fig. 1). This high incidence of AKI may reflect the problem of public health issues and socioeconomic factors affect the epidemiology of AKI in low resource settings.(9)
Among 373 patients in ICU suffered from AKI, 181 patients (48.5%) belong to stage III of the KDIGO criteria for AKI. Early diagnosis for AKI in ICU patients proved to be challenging, no wonder the number of patients with severe AKI in our center is high and might require extensive studies. Contrary to the results of most published studies, our center has higher proportion of AKI stage III compare to AKI stage I or II (Fig. 1). Recently, a published study in Australia reported that 37.1% patients on ICU who developed AKI, categorized as follows: AKI stage I 18.1%; stage II 10.1%; and stage III 8.9%.(10) Meanwhile, our data correspond to the data from less developed area. Recently, Srisawat et al reported the data from Thai ICU and showed the incidence of AKI stage 3 (28.9%) was the most common followed by stage 2 (16.4%) and stage 1 (7.5%).(11) The investigators showed that most of AKI patients have reached AKI stage 3 at the time of ICU admission and might reflect the delayed ICU admission and delayed AKI recognition as the main explanation.
In our center, based on multivariate analysis using logistic regression, the significant factors contribute toward the severity of AKI were male, patients with CKD and malignancy, higher APACHE II score, and vasopressor usage (Table 4).
The mean of patients age with AKI in our center is 58 years old (± 15 years old), and one published study in Malaysia which showed similar result of AKI severity, with more proportion of AKI Stage 3 (56%) compare to AKI stage 1 (18%) and AKI stage 2 (25%), has similar mean of AKI patients’ age with our center, 53 years old (± 16 years old).(12) But, there is no explanation on the association between age and AKI severity. Age might contribute as a risk factor of AKI occurrence in different races and countries. The causes not only because the kidney undergoes age dependent structural and functional alterations over time but also because of the comorbidities that accumulate with age.(13) One experimental study using rats showed that aged rats exhibited reduced antioxidant potential and increased oxidative stress after ischemia-reperfusion, compare to young rats.(14) This study showed that the total plasma antioxidant potential (AOP) of aged rats was lower than that of young rats regardless of whether they underwent ischemia-reperfusion. In addition, renal tissue 8-OHdG levels, which contributes to the destruction of kidney were increased in aged rats after reperfusion injury. Elderly patients have an increased risk for non-recovery of renal function after acute ischemia and a heightened susceptibility to AKI.(15)
The two most comorbidities of AKI in our study was hypertension and diabetes mellitus, with the number of patients admitted with those conditions were 147 and 145 patients respectively. This study is comparable to previous study in 2013 showed that diabetes was associated with a 2.8 fold increased risk of developing AKI.(16) The mechanism by which diabetes increases the severity of AKI has not yet been well established, but a great deal of research supports the connection between obesity, inflammation, and insulin resistance.(17) Inflammatory cytokines such as tumor necrosis factor-〈(TNF-〈) and interleukin-6 (IL-6) are produced by adipocytes and have been shown to cause insulin resistance.(18)
History of hypertension in patients also contributed to the increased risk of AKI incidences (OR, 1.13; 95% Cl, 1.02–1.05). Hypertension is commonly found in patients with AKI and vice versa due to several mechanism with inter-related complications, such as balance disorders of vascular active substances, renin-angiotensin system activation, changes in inflammatory factors, and increases in active oxygen species.(19) Inflammation causes changes in endothelial function and further increasing the arterial stiffness, oxidative stress and increased circulating angiotensin II levels caused by inflammation will also reduce the availability of nitric oxide (NO) and worsen the vascular damage. Thus, the combination of hypertension, increased angiotensin II levels and oxidative stress initiates events will also lead to the damage of the renal system.(20)
In this study, 9.47 times more likely to have CKD as their comorbidities. In recent years, studies in different regions have found that CKD is a strong risk factor for the development of AKI, mainly in septic patients. Currently, CKD is found in 30% of patients who develop AKI in the intensive care unit (ICU).(21) It is noteworthy that CKD was the variable with the highest percentage of association, which makes it a strong predictor for the development of AKI in critically ill patients.
This study confirmed that almost a half population (49.6%) of patients with AKI needed mechanical ventilation, while less than a fifth (17.3%) among non-AKI patients required the use of mechanical ventilation. Compared with ventilated non-AKI patients, ventilated AKI patients had a higher APACHE and three days SOFA score. This study result might support current view that AKI in ICU is a prominent risk factor contributes to the worsening of patients’ health conditions, more specifically in low-risk AKI-RRT patients.(22) Based on the study conducted by Vieira, et al shows that renal dysfunction has serious consequence in the duration of mechanical ventilation and weaning from mechanical ventilation. The median duration of mechanical ventilation use in AKI patients was 3 days longer than non-AKI patients (10 vs 7 days).(23) The underlying mechanism that may contribute to the use of mechanical ventilation in AKI patients because patients experienced severe acute respiratory insufficiency, which will increase the intrathoracic pressure to reach acceptable gas exchange to compensate these changes. This will eventually result in renal dysfunction such as renal tubular apoptosis.(22)
There are 92 patients (24.6%) AKI patients required RRT(AKI-RRT), this result might validate the importance of RRT in ICU settings, despite certain challenges such as availability of modalities and understaffing of nephrologist.(24) It is important to remember that AKI is a case with a staggering amount of mortality rates, especially for critically ill patients in ICU setting.(25)
At our center, like most hospitals in developing country, IHD is the most commonly used method (66 procedures, 71.7%). On the other hand, a study using online questionnaire responded by members of European Society of Intensive Care Medicine from 50 countries, showed that half of the intensivists, preferred the use of CRRT compare to IHD. The reasons for preferring CRRT were the perception of better hemodynamic stability, better therapeutic effect resulting from cytokine removal and easier fluid balance control.(26)
A cohort study done by Mandelbaum, et al. to measure the outcome of critically ill patients with AKI shown that the rate of hospital mortality and ICU mortality are both worse in patients with AKI at any given stage compared to in-hospital mortality rate in non-AKI patients, shown as follow: rate of mortality in non-AKI patients were 6.25%, AKI stage I 13.87%, AKI stage II 16.42%, and AKI stage III 33.76%. The ICU mortality rate is also higher in AKI patients as follow non-AKI 4.54%, AKI stage I 10.06%, AKI stage II 13.15%, and AKI stage III 30.48%.(27) A significant survival differences is shown by Kaplan-Meier survival curves according to the presence of AKI, where the curve for AKI patients survival is steeper compare to non-AKI patients. This represents worse survival rate in patients with AKI compare to non-AKI.(28) With previous published studies clearly emphasized the worse outcome in AKI patients compare to non-AKI patients, we are certain that it is important to prevent AKI from happening or to manage AKI at earlier stage. This will be beneficial to decrease the healthcare burden and bring betterment towards patients’ overall survival rate.
We believe that identification the risk factor of AKI will provide the opportunity to develop the predictability score for AKI prevention and finally improve AKI outcome. Another key strength was the availability of data to permit the detailed analysis of risk factors of AKI between mild (AKI stage 1/2) and severe AKI (AKI stage 3), something that has received little attention. Another strength was that our AKI criteria were from KDIGO which employs both the information from creatinine and urine output data. This research will be a reference research for other studies of AKI patients in ICU in other hospitals, especially in Indonesia. However, this reference will improve the completeness of epidemiological data and risk factors for AKI patients in Indonesia.
Our study did have limitation. We collected data only in ICU patients in Gatot Soebroto Hospital. So our patient sample may not truly represent the incidence of AKI in all hospitalized ICU patients in all over Indonesia.