Acute kidney injury (AKI) is a common complication of acute pancreatitis (AP) and usually occurs after the failure of the other organs. However, the kidney is the first failed organ in about 8.9% of AP patients [10] .A propensity score matching (PSM) analysis revealed that AKI was independently associated with a higher mortality rate in AP patients [11].Therefore, early prediction of the risk of developing AKI in acute pancreatitis may help lower the mortality rate of the disease. According to some previous studies, procalcitonin[6], systemic immune-inflammatory index (SII)[7], serum cystatin C [12], increased serum chloride and chloride exposure [13], and serum and urinary NGAL [14] were shown to predict AKI in AP. However, these studies had limitations such as being single-center studies or employing a small sample size. Qu et al. used a machine learning model to study the early occurrence of AKI in AP patients with 26 variables. They demonstrated that the XGBoost model had an excellent ability to predict the development of AKI in AP patients. However, the study had a small sample size and lacked clinical utility [5]. To the best of our knowledge, no study has revealed a clinically useful model for predicting the risk of developing AKI in AP patients [15].
The MIMIC database contains a large amount of data on clinical diagnosis and treatment of critically ill patients, thus providing data for scientific research. In this study, we constructed a nomogram to predict the early occurrence of AKI in AP patients using data from the MIMIC database. A total of 56 risk factors were identified as potential predictors for developing AKI in AP patients. However, a preliminary screen using all-subsets regression identified only seven predictors, including age, race, total bilirubin, activated partial thromboplastin time, need for mechanical ventilation, use of vasoactive drugs, and sepsis as the potential predictors for AKI in AP patients. Moreover, the multivariate logistic regression analysis showed that the seven predictors were independent risk factors for developing AKI in AP patients, consistent with previous analysis. The constructed nomogram had a good predicting ability, was based on a large sample size obtained from the MIMIC database, and had a good clinical utility.
An increase in age is associated with a declining renal function.Patients with acute pancreatitis show a higher incidence rate of developing AKI associated with deterioration of physiological functioning with age [16]. In addition, age is a known predictor of AP severity and mortality [17]. For example, older patients have a higher risk of developing systemic complications, such as multiple organ failure [18]. In contrast, a multicenter prospective study in Spain reported that age was not associated with organ failure. However, age > 85 years was associated with a higher likelihood of 30-day mortality [19]. Other study did not show any significant correlation between age and AP [20]. Kong et al. reported that age could not independently predict mortality in AP. However, multivariate logistic regression analysis showed that respiratory, cardiovascular, and renal failure were independent prognostic factors for mortality in AP [21].
The risk of developing kidney diseases varies amongst different ethnicities. For example, African Americans have a 2–4 times higher risk of developing chronic kidney disease (CKD) or end-stage renal disease (ESRD) than Caucasians. In addition, African Americans have a higher risk of developing AKI than Caucasians.This differences may be attributed to differences in economic conditions, social status, and genetics between African Americans and Caucasians. However, the present study revealed that caucasians with acute pancreatitis were more likely to develop AKI than African Americans,possibly due to their diet and a higher basal metabolic rate [22].
Furthermore, the present study identified hyperbilirubinemia as an independent risk factor for the early development of AKI in AP patients.Hyperbilirubinemia may induce the formation of reactive oxygen species in mitochondria, damaging the tubular epithelial cells and exacerbating ischemic reperfusion kidney injury [23, 24]. Bilirubin is a potent antioxidant. Previous studies have shown that the pathogenesis of AP is closely related to oxidative stress [25, 26]. An elevated bilirubin level is an independent risk factor for the development of AKI [27]. Moreover, studies have shown that serum bilirubin is associated with the prognosis of AP patients [28, 29]. Shi et al. predicted the prognosis of acute pancreatitis using the albumin-bilirubin (ALBI) score. They demonstrated that the dead had higher total bilirubin levels than recovered patients [28]. According to Xu et al., total serum bilirubin was one of the independent predictors of SAP and inpatient mortality in AP patients [29]. Moreover, Popa et al. reported that dead AP patients with multi-organ dysfunction syndrome showed elevated bilirubin levels [30].
Microcirculatory dysfunction is associated with AP progression. In addition, coagulation disorders may be related to AP severity. These processes could be caused or exacerbated by ischemic reperfusion injury and the development of oxygen-derived radicals [31]. Moreover, coagulation dysfunction is an independent risk factor for acute kidney injury[32]. In addition, a prolonged APTT has a predictive value in sepsis-associated AKI [33, 34]. However, only a few studies have evaluated the predictive value of coagulation parameters in determining mortality and organ failure in AP patients. The present study revealed that an APTT value greater than 20 was associated with a poorer prognosis. According to Liu et al., differences in APTT values and thrombin time (TT) values were risk factors for organ failure in AP patients [35]. An increase in APTT by five seconds was shown to increase the risk of organ failure by about two times, consistent with the present study.
Furthermore, previous studies have shown that mechanical ventilation is a risk factor for AKI [36, 37]. The present study found that the use of mechanical ventilation was a predictor of AKI in AP, consistent with a previous study by Shi et al. [38]. Studies have shown that acute respiratory failure due to acute pancreatitis necessitates the use of mechanical ventilation in patients admitted to the ICU. The use of mechanical ventilation can lead to acute lung injury, thus worsening hypoxia, cause vasoconstriction, decreased renal perfusion, and a decreased glomerular filtration rate. In addition, mechanical ventilation increases intrathoracic pressure, lower venous return and the mean arterial pressure, which may cause prerenal hypoperfusion and lead to acute renal injury [39, 40].
The present study demonstrated that the use of vasoactive drugs was a predictor of AKI in AP. Consistent with this finding, a previous study revealed that the need for MV, the use of vasopressor agents, and RRT were risk factors for higher mortality in AP patients [41]. Critically ill patients require higher doses of vasopressor agents to help regulate blood pressure.
Up to one-third of patients with necrotizing pancreatitis develop necrotic infection [42]. The incidence of SAP is biphasic and is closely related to the early and persistent presence of organ or multi-organ dysfunction in the first week of the disease course. Clinical sepsis caused by multiple organ failure syndrome (MOFS) due to infectious necrosis occurs later in the first week [43]. A prospective study revealed that the most important independent predictors of AP mortality were persistent organ failure and infectious pancreatic necrosis complicated by multidrug-resistant organisms [44]. The extent of necrosis has been correlated with organ failure and mortality, this may be associated with further complications of the pancreas and extrapancreatic necrosis, which could predispose the patient to infections, pseudoaneurysms, and intestinal fistulas. In addition, unsaturated fatty acids could worsen systemic inflammation and organ failure.
Currently, the APACHE II, BISAP, and Ranson scores are clinically used to predict the prognosis of AP patients in the ICU. These scoring systems have been validated by external data sets. The prediction performance of these scores varies greatly. Different scores have different advantages and disadvantages. The APACHE II score contains several variables and is more complex. On the other hand, the Ranson score requires recalculation and lacks continuity. The BISAP scoring index is simple. However, the pleural exudation needs to be evaluated and the score has a poor predictive ability. In addition, the above socre mainly used in SAP patients. This study used seven predictors of AKI in AP patients to construct a nomogram. The nomogram showed good degree of differentiation and calibration in the training and validation cohorts. The ROC curve area of the APACHE II, BISAP, and Ranson scores in the training and validation cohorts were lower than that of the nomogram. In addition to validating the APACHE II score in the validation cohort(This may be related to the sample size of the validation set, and further sample size verification is required in the future), the AUC between the nomogram and the scores showed statistically significant differences. Compared with the above scoring system, the variables of the nomogram can be simply obtained and are easy to calculate. Further, the nomogram can be used to stratify the risk of AKI in AP patients admitted to the ICU, thus guiding physicians to offer targeted management.
AKI is a common complication of AP, associated with a high case fatality rate. Therefore, the findings of this study are clinically useful in improving the awareness of AKI and detecting AP patients with a high risk of developing AKI. Furthermore, this study included commonly measured variables in the predictive model. This study offers clinicians a novel predictive tool for predicting the risk of the early development of AKI in AP patients. Moreover, this study can guide clinicians in optimizing treatment modalities in AP patients.
However, this study had some limitations. First, this study was a retrospective, and single-centered. Therefore, future studies should be conducted prospectively in multiple centers to improve clinical utility and external validation, respectively. In addition, the nomogram did not include novel biomarkers or imaging results, which could hinder the performance of the model.The model did not include other factors, such as intra-abdominal hypertension and abdominal compartment syndrome that could potentially affect the development of AKI in AP. Third, the sample size of this study is not large, and only internal verification is used to evaluate the accuracy and effectiveness of the model. Future studies should employ large sample sizes, including more variables.