In this study, we found that the Cr/Alb ratio is a novel but promising, easy-to-measure, reproducible, non-invasive prognostic score that can be used for the prediction of the effect of debridement in AP patients.
AP is an emergency gastrointestinal condition, characterized by a rapid onset and poor prognoses, with mortality values of up to 40%[19]. As AP often causes severe systemic inflammation and necrosis in the abdomen, debridement plays an important role in its treatment. However, the effect of surgery is not satisfactory owing to the complexity of pancreatic or peri-pancreatic infections, multiple organ attack, and violent systemic inflammation, due to which a large proportion of patients experience numerous post-operative complications, re-operation or even death. Therefore, it is important to evaluate patients’ prognoses before surgery. Previous studies showed that CRP, Cr, and Alb had definite implications for systemic inflammatory response-related conditions such as AP[20, 21]; however, their predictive value, when used alone, is not satisfactory. Therefore, some studies combined those parameters for an enhanced prediction effect[14, 22].
In our study, of all the admission and pre-operation Cr/Alb and CRP/Alb values, the admission Cr/Alb showed the best performance in several analyses, including the distribution analysis and correlation analysis, and had the best predictive value. An admission Cr/Alb cut-off ≥ 3.43 could predict worse prognoses in AP patients, including a more severe heart rate and respiratory rate, impaired levels of blood urea nitrogen, Cr, Alb, white blood cells and platelets, APACHE II score, post-operative electrolyte disorders, respiratory failure, hemorrhage, shock, renal failure, re-operation rate, and mortality. In the logistic regression analysis, the admission Cr/Alb was independently correlated with the APACHE II score, renal failure and re-operation. About the diagnosis value of Cr/Alb, it is basically satisfying in predicting the outcomes of the AP debridement. In predicting the re-operation, the sensitivity, specificity, and AUC of the admission Cr/Alb reached 86.3%, 61.7%, and 0.724, respectively. And the variables of APACHE II were 82.6%, 58.3%, and 0.716, respectively. In the assessment of perioperative mortality, the sensitivity, specificity, and AUC of admission Cr/Alb were 73.4%, 81.3%, and 0.794, respectively. And those of APACHE II were 50.9%, 92.3% and 0.713, respectively. Above all, our research suggests that the admission Cr/Alb has the potential to predict AP-related prognoses as a simpler alternative to the APACHE II score.
The development of AP is often accompanied by systemic inflammation, sepsis, and multiple organ failure. Therefore, the prognoses of AP are closely related to the severity of inflammation, nutrition intake, negative nitrogen balance, and functional reserve[23]. Of the various tests, CRP, Cr and Alb are the most relevant examinations. CRP is synthesized by the liver and responds to inflammation within a few hours[24]. Owing to its short half-life and high sensitivity, it is often used for the detection and assessment of inflammation[7, 25, 26]. Alb is a negative acute phase reactant synthesized by the liver, and its expression decreases during inflammatory reactions. In previous studies, Alb was shown to be related negatively to the severity of inflammation, disease prognoses, and mortality in AP[20, 27]. Cr is an amino acid derivative produced by the metabolism of muscle tissues. It is filtered through the kidney and its levels are raised significantly in systemic inflammatory diseases[28]. An increase in the Cr level 48 hours after admission is considered a marker of pancreatic necrosis, hypovolemia and renal insufficiency[11]. According to Wilkman et al.[29], increased Cr levels are independent risk factors for 90-day mortality in AP patients. Lipinski et al.[10] also reported that higher Cr values at admission and after 48 hours were associated with a higher incidence of mortality.
In complicated disease like AP, a single biomarker usually could not provide accurate prognostic effect. As a result, more and more combinations of biomarkers were being applied recently. In AP, the most frequently used values were CRP/Alb, Neutrophil-lymphocyte ratio (NLR), Platelet-lymphocyte ratio (PLR), etc., which exceeded excellent diagnostic values in the assessment of AP. Suppiah et al. [30] discovered that the elevation of NLR at the first 48 hours of admission was significantly associated with severe acute pancreatitis as a result of neutrophilia and lymphopenia during the systemic inflammatory response. The sensitivity and specificity of NLR to predict SAP achieved 63-90% and 50-57% respectively. PLR also showed good application value for mortality prediction with sensitivity of 73.3% and specificity of 99.22%. Furtherly, it was found that the combination of PLR and NLR had the highest AUC in evaluating the prognosis of AP, with similar predictive value among other scoring systems[31]. Besides, Kaplan et al.[14] discovered that the CRP/Alb ratio could predict the mortality of AP patients with sensitivity of 92.1% and specificity of 58.0%, while this ratio was also positively corelated with Ranson score, Atlanta classification etc. As mentioned above, those predictors reflected the severity of inflammatory status outstandingly. However, surgical intervention of AP means higher requirements for the surgical tolerance, higher risk of complications and mortality. Merely inflammatory factors might not be enough. Therefore, our study used Cr and Alb to focus mainly on the evaluation of surgical outcomes.
In our study, Cr/Alb showed better performance than CRP/Alb. CRP level fluctuations are more intensive in AP and may lead to measurement-related difficulties and inaccuracies in severity evaluation. In comparison, Cr level trends are more stable, lending them more credibility for use as predictors. Cr also has the ability to reflect the pancreatic necrosis, protein decomposition metabolism and renal function. In pancreatic necrosis, a large amount of toxic substances and inflammatory factors would be released and directly attacking the kidney, leading to aggravated renal injury[12]. And the process in turn weakens the renal clearance ability and resulting in decreased surgical tolerance. Besides, Alb reflects a body’s protein reserve more accurately. Several studies have given possible mechanistic explanations, (i) the inflammatory response produced by AP increases catabolism and tissue consumption; (ii) AP releases a large number of inflammatory factors such as interleukin-1, and interleukin-6 leads to a decrease in albumin biosynthesis in liver; (iii) during the stress response, vascular permeability increases and albumin penetration into the tissue space[32, 33]. In summary, Cr and Alb could assess the degree of inflammatory response, catabolism, and fundamental status. In AP patients with weaker status, serum albumin tends to decrease because of the impaired hepatic synthesis function, albumin exudation and increased consumption; and creatinine tends to increase because of the renal injury and pancreatic necrosis. The combination of the two markers could indicate the severity and prognosis of AP debridement more reliably and accurately.
This study is the first to compare admission and preoperative Cr/Alb and CRP/Alb values in the assessment of AP debridement. AP is a highly inflammatory and catabolic state that often leads to malnutrition. These features increase the risk of re-operation and mortality in debridement. Therefore, our study focused on surgical tolerance by examining the reserve capacity and nutritional status in contrast to previous studies that focused on severity of systemic inflammatory response. Patients with poor surgical tolerance usually face higher risk of re-operation and mortality, which requires more prudence in surgical decision-making. For surgeons, our study provides a simpler and more feasible tool for the evaluation of the basic state of AP patients before surgery-related decision-making. For ward managers, the Cr/Alb value could aid in the identification of high-risk patients in advance and remind medical staff to strengthen the degree of ward care targeted at those patients. As the Cr/Alb value could distinguish mild AP from its severe form, our results can be used by hospitals and health policymakers in the formulation of more efficient gradient treatment strategies for AP.
Our study has several limitations. First, its retrospective design may have led to a certain selection bias. Second, the study included only 140 cases enrolled from a single center, leading to insufficient reliability. Third, this study focused only on AP patients with debridement. In the future, we will include patients with non-surgical treatment for further investigation.
In conclusion, as a clinical scoring system with high accuracy and simplicity, the admission Cr/Alb value was superior in the assessment of the severity of AP with debridement. With the confirmation of our results in larger-scale investigations in the future, Cr/Alb has the potential to improve the quality of the AP risk scoring system and prognostic prediction.