AKI is defined as a clinical situation with heterogeneous etiology, clinical presentation, and both renal and patient survival. Its incidence is highly dependent on the study population. For example, Srisawat et al. [9] studied critically ill patients admitted to the ICU and reported that 32% of the study population (n = 15132) developed AKI. Another study reported an incidence of 12.7% [10]. In our study, we decided to evaluate the data of patients with AKI diagnosed by nephrology specialists at emergency clinics, inpatient wards, or ICUs.
Compared with Europe and Asia, Turkey is a crowded country with a population of 81623817 in its 814578 km2 surface area according to the records of the Turkish Statistical Institute [11]. It is divided into seven different geographical areas, each with different characteristics related to climate, flora, and residents. The majority of the population resides in the Western regions, followed by the Mediterranean region, an eastern part of Turkey. There are enough nationwide technical opportunities/personnel for the care of patients with AKI, such as nephrologists, educated nurses and technicians, modern hospitals and ICUs, and dialysis facilities, including those for all types of KRT. Moreover, the social security system covers renal care of patients both in university and government hospitals nationwide. Thus, there is no obstacle in caring for patients with AKI regarding coverage by the social security system.
A sufficiently large number of cases with AKI (n = 776) were included in our study to evaluate the etiologic factors, geographical differences, and outcomes. Unfortunately, we could not conclude on the incidence of AKI, since we did not have data on the number of patients admitted to the related centers during the study period. Further, not all hospitals and nephrologists provided data to the study. Therefore, we could not evaluate the proportion of patients with AKI within the outpatient and inpatient populations. Nevertheless, we were able to evaluate the clinical courses, treatment options, and differences between the geographical regions.
Many disease conditions are known to contribute to the development of AKI. The incidence of AKI may differ according to the features of the studied population and approach of the physician. The nephrological approach in patients at high risks can be lifesaving in this field. Training physicians on how to recognize and evaluate patients at high risks to protect them from developing AKI is important. To clarify the different features among countries, the International Society of Nephrology (ISN) designed the Snapshot Study [12], which was a multinational study including 3664 patients from different countries with varying degrees of income. Hypotension or shock was the most common etiological factor in high-income countries; meanwhile, dehydration was the most common factor in lower-income countries, wherein sepsis and AKI related to pregnancy were more frequent [12]. In a study conducted in Malawi, community-acquired AKI was detected in 12.7% of admissions within a pre-specified period of 3 months. A significant number of patients (43.8%) were seropositive for HIV. The most frequent causes of AKI were reported to be HIV-related sepsis and hypovolemia mostly due to gastroenteritis. Toxins, urinary obstruction, and primary renal parenchymal diseases were less prevalent [10]. Investigators from Karachi studied hospital-acquired AKI and found that the most common causes of AKI were sepsis, gastroenteritis, and surgical and obstetric complications [3]. Another study conducted in Singapore analyzed 422 cases of AKI. The most common etiological factors were prerenal etiologies, followed by sepsis and ischemic acute tubular necrosis [13]. Lombardy et al. [14] studied the causes of AKI in 2864 patients. They reported that AKI was more prevalent during winter (RR: 1.16; 95% CI: 1.05–1.29; p = 0.003), and a higher AKI risk was found to be associated with lower air temperature and higher humidity [14]. In our study, the most frequent etiology of prerenal AKI was dehydration, heart failure, and sepsis. This prompts the necessity of early evaluation and supportive care of patients with symptoms that may cause dehydration. With advances in the treatment options for ischemic heart disease, survival is prolonged, and an increasing number of cardiorenal syndrome cases are observed. There is a need for education among both primary care physicians and patients regarding the use of diuretics, especially their correct indication and dose, to prevent both hypervolemia and dehydration.
Since the primary function of the kidneys is concentration and excretion of toxic metabolites and drugs, the kidneys are the main organ affected by drug toxicity. It has been reported that nephrotoxicity accounts for 8–60% of all AKI cases depending on the population and definition of AKI [15]. Interestingly, the use of nephrotoxic agents was the most prominent etiology of renal AKI in our population (72.1%). This result was found to be true for all parts of the country. Thus, it is important to alert all physicians regarding nephrotoxicity of medications, especially those practicing in ICUs.
Infectious diseases are commonly associated with AKI. Krairoun et al. [16] studied 1716 patients admitted to emergency clinics with suspected infectious disease. Of these patients, 10.8% had AKI, and 12.4% died; 4.2% of those who died had no AKI [16].
Sepsis is also commonly associated and/or confounded with AKI [17]. Deleterious inflammatory events, hypovolemia, and exposure to nephrotoxic agents are some of the many potential causes of AKI seen in patients with sepsis. Infections were among the frequent etiologies of AKI in our study, as in many previous studies, and the proportion of patients with sepsis was quite high. Timely and adequate treatment of infections may prevent the development of AKI.
One of the known major risk factors for AKI is the presence of CKD. Approximately one-third of the patients included in our study had CKD. This necessitates careful evaluation of these patients.
There was some regional variation in the etiology of AKI regarding prerenal and renal factors. Dehydration and heart failure were more frequent in the Marmara-2 region, while sepsis and dehydration were more prevalent in the Southern Anatolia region. This cannot be explained simply by the several possible related factors, such as the change in the population characteristics, including age and sex, climate differences, and predominant population of patients cared for in clinical settings, such as cardiovascular hospitals or cancer centers. Another factor may be related to the physicians. The characteristics of the patients may change if the physician is responsible for inpatient, outpatient, or emergency clinic consultation. This factor also applies to the differences between the causes of hospitalization and comorbidities of patients according to region.
We concluded that the diversity of the type of KRT among the geographical regions in our study may be related to the individual characteristics of the patients and technical facilities or the differences in the practice of the clinicians providing data to the study.
Data on renal and patient survival vary in the literature. Again, the study population, risk factors, and socioeconomic factors may play a role. In one study, the overall mortality rate of patients with AKI admitted to the ICU was reported to be 27%, which was correlated with the severity of AKI [9]. The mortality rate was higher in lower-income countries than in higher-income countries in the ISN Global Snapshot Study [12]. In this study, 22% of patients needed dialysis, and among them, the mortality rate was higher. Age, concomitant organ dysfunction, sepsis, and oliguria were other factors related to increased mortality rates, while the presence of CKD was associated with decreased mortality rates. The mortality rate of patients with prerenal AKI due to hypovolemia was similar to that of patients with prerenal AKI secondary to heart failure or liver cirrhosis. However, in the study by Evans et al. [10], the mortality rate increased with advancing stage of AKI. Age above 40 years, stage of AKI, and history of nephrotoxin exposure were found to increase the risk of mortality related to AKI.
In a study conducted in Singapore, KRT was needed in 27% of patients, and the in-hospital and 6-month mortality rates were reported to be 20.3% and 9.4%, respectively. Stage 3 AKI was associated with higher mortality rates [13]. Another study from India reported that 220 of 1150 patients admitted to a general ward in a year had AKI. The in-hospital mortality rate of patients with and without AKI was reported to be 19.09% and 1.8%, respectively. Hematological malignancies, the need for inotropic agents, and the serum creatinine level at the time of admission were independent predictors of mortality. Underlying CKD and hospital-acquired AKI were not related to mortality [18]. In our study, the mortality rates at the 1st week and 6th month of diagnosis were 8.6% and 24.1%, respectively. This is an alarming finding, necessitating all clinicians to follow up patients in the long term. An increasing stage of AKI was associated with both patient and renal survival, which is common in most reports in the literature. Using the staging system proposed by the KDIGO may help clinicians determine patients at the highest risk.
Besides mortality, AKI is also associated with worse renal outcomes. In a recent study involving 5548 patients receiving anesthesia for the first time, all stages of AKI had been found to be related to progression to CKD [19]. In our study, ESKD developed in 74 (9.5%) patients. Being in the Marmara-1 and Central Anatolian regions and having elevated basal creatinine levels, heart failure, glomerulonephritis, stage 2 AKI, and CKD were found to increase the risk of ESKD; conversely, being in the Marmara-2 and Southern Anatolian regions and having dehydration or postrenal factors as the etiology of AKI were associated with a decreased risk of ESKD.
Regional variations may be related to the different risk factors, etiologies, and clinical practices. Dehydration and postrenal factors seem to cause a potentially reversible AKI. CKD is a well-known risk factor for AKI, as shown in our study. Advanced age, admission to the ICU, diagnosis at the emergency clinic, history of cardiovascular surgery, and presence of stage 3 AKI, the diagnostic criteria of SIRS, sepsis, respiratory diseases, cerebrovascular diseases, hepatological diseases, infectious diseases, cirrhosis, malignancy, and heart failure were related to increased mortality rates in our study. Most of these factors are similar to those in the current literature. In a study from Lithuanian University, 575 cases of severe AKI requiring KRT were analyzed [19]. The lowest mortality rate was noted in patients with postrenal AKI and the highest mortality rate in those with renal causes. Older age, systolic blood pressure below 120 mmHg, multiple organ dysfunction, pH level of < 7.3, oliguria, hepatorenal syndrome, cardiac surgery, and sepsis were associated with very high mortality rates. The AKI risk and mortality rate have been reported to be substantially high in patients with liver cirrhosis [20]. This finding is consistent with our results. Glomerulonephritis as the etiology and underlying CKD were associated with decreased mortality rates. The first association may be attributed to the potential reversibility of the disorder with treatment of glomerulonephritis. The mortality rate was lower in the patients with CKD than in those without and was found to decrease with advancing stage of preexisting CKD, when present. The positive effect of preexisting CKD is an interesting finding that may be speculated to be attributed to the less clinical implication of hyperkalemia in patients with CKD. Moreover, there might be an effect of the population included in the study. As we could not include all patients with AKI admitted to the involved centers, bias might have occurred during evaluation. There might have been patients with advanced CKD and multiple comorbidities with worse prognosis.
Herein, the mortality rate was higher in the patients who needed CKRT than in those who did not. This is an expected finding considering the indications for CKRT, instead of conventional hemodialysis, with the most common one being hemodynamic instability.