This study evaluated the diagnostic value of presepsin, PCT and CRP levels for sepsis in patients with CKD undergoing hemodialysis or not. Presepsin levels were increased in patients with CKD with or without sepsis or hemodialysis compared with the controls, and were the highest in patients with CKD and sepsis undergoing hemodialysis. Presepsin levels were similar between patients with CKD with sepsis and no hemodialysis, and patients with normal renal function and sepsis, but these levels were lower than those in patients with CKD without sepsis undergoing hemodialysis. Presepsin, PCT and CRP levels had a diagnostic value for sepsis; however, presepsin was a better predictor of sepsis than PCT or CRP in patients with CKD not undergoing hemodialysis. Presepsin levels had a limited diagnostic value for sepsis in patients with CKD undergoing hemodialysis. In CKD complicated with sepsis, presepsin levels were significantly correlated with CRP level, SOFA score, partial pressure of oxygen and body temperature; there was no correlation between presepsin levels and these indicators in CKD without sepsis.
Kidney disease and some other systemic diseases can lead to a progressive decline in GFR and renal insufficiency. Diseases complicated by infection can result in septic shock. Sepsis is one of the main causes of death in the end stage of many diseases, so the early diagnosis and differential diagnosis of sepsis have attracted increasing attention. Currently, PCT, CRP and WBC count are widely used in the clinical diagnosis of sepsis, but their predictive value has certain limitations. Many studies have found that bacterial infections characterized by an SIRS can induce PCT release, and PCT is positively correlated with the severity of sepsis [21–23]. One study in patients with acute SIRS and suspected infection reported that elevated PCT concentrations were an indicator of sepsis in newly admitted, critically ill patients [21]. CRP is an acute phase protein synthesized by the liver during infection and other inflammatory processes, which plays an important role in immune response[24]. When CRP concentration exceeds 40–100 mg/l it can predict the presence of severe infection or sepsis [25]. However, many non-infectious factors, such as severe trauma, can lead to an increase in CRP. Accordingly, previous studies have shown that CRP has a moderate performance for predicting sepsis in critically ill patients with SIRS or in patients in the emergency department, and that CRP was inferior to PCT and interleukin-6 [26].
Presepsin is derived from the soluble CD14 subtype produced following infection. Presepsin is often used as a marker of sepsis, since presepsin is a glycoprotein produced during bacterial phagocytosis [27]. In addition, analyses have shown that changes in presepsin levels have a predictive value for the prognosis and mortality of patients with sepsis [28]. However, it is well known that changes in presepsin levels are affected by renal function, so there is controversy about predicting or evaluating changes in renal function or chronic kidney disease based on presepsin [15]. Previous studies have shown that presepsin has potential as a novel biomarker for the early diagnosis of sepsis [14]. Studies have confirmed that presepsin levels are affected by kidney function. When renal dysfunction occurs, presepsin can be detected at a higher level than normal. Presepsin levels increase with a decrease in glomerular filtration rate [29, 30] and presepsin levels increase significantly in patients with CKD undergoing hemodialysis [1]. The present study indicated that presepsin levels were increased in patients with CKD with or without sepsis or hemodialysis compared with the controls, and were the highest in patients with CKD and sepsis undergoing hemodialysis. This is consistent with the findings of Nagata et al [1]. ROC curve analysis showed that presepsin had a higher diagnostic value for sepsis in patients with CKD and no hemodialysis compared with patients with CKD undergoing hemodialysis.
ROC curve analysis showed that the diagnostic value of presepsin for sepsis was limited in patients with CKD undergoing hemodialysis. Presepsin is a 13 KD protein that can be filtered by the glomeruli and absorbed and catabolized by the proximal tubules. Therefore, presepsin levels in patients with CKD undergoing hemodialysis may be associated with its molecular weight and flow elimination characteristics. In patients with AKI, presepsin may "adhere" to the hyperabsorbent membrane during continuous renal replacement therapy [31]. Such a mechanism may also exist during hemodialysis. Alternatively, a metabolite of presepsin may be formed during hemodialysis treatment, decreasing the clearance rate of presepsin, and affecting detectable levels. Furthermore, increased presepsin levels in patients undergoing hemodialysis might be associated with the microinflammatory state. Presepsin is a soluble fragment of CD14 that is released in the phagocytosis process following bacterial infection [32, 33]. Endotoxin and dialysis products can enter the human blood circulation through dialysis membranes in patients undergoing long-term hemodialysis, and incompatibility of dialysis membranes can lead to microinflammation [34].
In patients with CKD undergoing hemodialysis, presepsin predicted sepsis at a cut-off value of 3,076 pg/ml, with a sensitivity and specificity of 30.5 and 99.2%, respectively. It is well known that when hemodialysis is performed, the solute is removed mainly by the diffusion effect caused by the difference in solute concentration between the two sides of the semipermeable membrane, and its clearance rate is inversely proportional to the solute molecular weight. It has a high clearance rate for small molecular substances, such as urea and creatinine, but a poor clearance rate for middle molecular substances, such as β2 microglobulin, cytokines and complement factor D fragments [35–38]. Presepsin is a small molecule substance metabolized in the kidney, so it has a high clearance rate by hemodialysis, which is why it has a high specificity but a low sensitivity. The sensitivity of presepsin in the identification of sepsis was low, and the rate of missed diagnoses was high, so its diagnostic value was limited. Until the effect of hemodialysis on presepsin levels in patients with CKD is better understood, caution should be taken when using presepsin in the diagnosis of sepsis in this patient population. In the present study, multivariate linear regression analysis showed that presepsin levels were significantly correlated with CRP level, SOFA score, partial pressure of oxygen and body temperature in CKD complicated with sepsis; there was no correlation between presepsin and these indicators in CKD without sepsis. These indicators, relevant test results, and clinical symptoms and signs should be combined with judgment in a comprehensive analysis when diagnosing sepsis in patients with CKD undergoing hemodialysis.
Finally, it should be stated that, venous blood was collected on days 1, 3 and 7 from admission, and statistical analysis showed that no significant statistical difference was observed in the presepsin value of the 3-day samples. Therefore, the sampled blood from all 3 days was included in the blood sample for statistical analysis. No significant statistical difference was identified in the presepsin value of the 3-day samples; this lack of significance may be associated with some clinical interventions that occured following admission, as well as individual differences in different clinical types of patients, which can affect the level of presepsin.
This study had several limitations. First, it was a single-center study. Secondly, the patients included in the present study did not receive the same treatments, so there may be unpredictable confounding factors affecting the outcomes. Thirdly, the sample size was relatively small, and while the study had clear inclusion criteria, selection bias cannot be completely excluded. Fourthly, the study concluded that presepsin levels have a better diagnostic value for sepsis in patients without hemodialysis than in those with hemodialysis; however, sepsis is most severe in patients in need of hemodialysis. Finally, patients diagnosed with CKD were not staged. Further studies are needed to resolve these issues.
In conclusion, based on the above results and discussion, we can draw the following conclusions: First, CKD, hemodialysis and sepsis can all lead to elevated plasma presepsin levels. Secondly, plasma presepsin, PCT and CRP all have a diagnostic value for sepsis in CKD patients without hemodialysis treatment, but the diagnostic value of presepsin is greater. In addition, presepsin was significantly correlated with PCT, CRP, SOFA score and body temperature change in CKD patients with sepsis. However, there was no correlation between presepsin and the above indexes in CKLD without sepsis. Finally, it was found that the diagnostic value of presepsin in CKD patients with sepsis on hemodialysis is limited. At this time, plasma presepsin should be used with caution in the diagnosis of sepsis, and it and it is advisable that it be used in combination with combined with PCT, SOFA score, body temperature change, clinical symptoms and signs for comprehensive judgment.