Presepsin and platelet to lymphocyte ratio predict the progression of septic subclinical acute kidney injury to septic acute kidney injury and the prognosis of subclinical septic acute kidney injury patients: a pilot study

This study aimed to determine whether presepsin can predict the progression of septic subclinical acute kidney injury (AKI) to septic AKI among intensive care unit (ICU) patients. Presepsin values were measured immediately after ICU admission (baseline) and on Days 2, 3, and 5 after ICU admission. Glasgow Prognostic Score, neutrophil to lymphocyte ratio, platelet to lymphocyte ratio (PLR), Prognostic Index, and Prognostic Nutritional Index were measured at baseline. Presepsin values and these indices were compared between septic AKI and septic subclinical AKI patients. There were 38 septic AKI patients and 21 septic subclinical AKI patients. Receiver operating characteristic curve analyses revealed the following cut-off values for AKI (relative to subclinical AKI): 708.0 (pg/ml) for presepsin on Day 1 (AUC, 0.69; sensitivity, 82%; specificity, 52%), 1283.0 (pg/ml) for presepsin on Day 2 (AUC, 0.69; sensitivity, 55%; specificity, 80%), and 368.66 for PLR (AUC, 0.67; sensitivity, 71%; specificity, 62%). Multivariate logistic regression analyses revealed PLR to be a predictor of septic subclinical AKI (odds ratio, 1.0023; 95% confidence interval, 1.0000-1.0046; p=0.046). Presepsin and PLR predicted the progression of septic subclinical AKI to septic AKI and the prognosis of subclinical septic AKI patients.

Non-invasive Early Prediction of Septic Acute Kidney Injury by Doppler-Based Renal Resistive Indexes Combined With Echocardiographic Parameters: An Experimental Study

Non-invasive early prediction of septic acute kidney injury (S-AKI) is still urgent and challenging. Increased Doppler-based renal resistive index (RRI) has been shown to be associated with S-AKI, but its clinical use is limited, which may be explained by the complex effects of systemic circulation. Echocardiogram allows non-invasive assessment of systemic circulation, which may provide an effective supplement to RRI. To find the value of RRI combined with echocardiographic parameters in the non-invasive early prediction of S-AKI, we designed this experiment with repeated measurements of ultrasonographic parameters in the early stage of sepsis (3, 6, 12, and 24 h) in cecum ligation and puncture (CLP) rats (divided into AKI and non-AKI groups at 24 h based on serum creatinine), with sham-operated group serving as controls. Our results found that RRI alone could not effectively predict S-AKI, but when combined with echocardiographic parameters (heart rate, left ventricular end-diastolic internal diameter, and left ventricular end-systolic internal diameter), the predictive value was significantly improved, especially in the early stage of sepsis (3 h, AUC: 0.948, 95% CI 0.839–0.992, P < 0.001), and far earlier than the conventional renal function indicators (serum creatinine and blood urea nitrogen), which only significantly elevated at 24 h. Our method showed novel advances and potential in the early detection of S-AKI.

Maresin conjugates in tissue regeneration-1 suppresses ferroptosis in septic acute kidney injury

Background Ferroptosis is unique among different types of regulated cell death and closely related to organ injury. Whether ferroptosis occurs in sepsis-associated acute kidney injury (SA-AKI) is not clear. Nuclear factor-erythroid-2-related factor 2 (Nrf2) is crucial to the regulation of ferroptosis. We and others have shown that Maresin conjugates in tissue regeneration 1 (MCTR1) or other members of specialized pro-resolving mediators (SPMs) can actively regulate inflammation resolution and protect organs against injury in inflammatory diseases by activating the Nrf2 signaling. The aim of this study was to determine whether ferroptosis occurs in SA-AKI. Furthermore, we investigated the potential role and mechanism of MCTR1 in the regulation of ferroptosis in SA-AKI, which mainly focus on the Nrf2 signaling. Results We demonstrated for the first time that ferroptosis is present in SA-AKI. Moreover, MCTR1 effectively suppressed ferroptosis in SA-AKI. Meanwhile, MCTR1 upregulated the expression of Nrf2 in the kidney of septic mice. Nrf2 inhibitor ML-385 reversed MCTR1-regulated ferroptosis and AKI, implying that Nrf2 is involved in the inhibitory effects of MCTR1 on ferroptosis in SA-AKI. Further, MCTR1 inhibited ferroptosis and elevated the expression of Nrf2 in LPS-induced HK-2 cells. However, Nrf2 siRNA offset the effect of MCTR1 on ferroptosis. Finally, we observed that MCTR1 ameliorates multi-organ injury and improves survival in animal models of sepsis. Conclusions These data demonstrate that MCTR1 suppresses ferroptosis in SA-AKI through the Nrf2 signaling. Our study enriches the pathophysiological mechanism of SA-AKI and provides new therapeutic ideas and potential intervention targets for SA-AKI.

PREDICTORS IN-HOSPITAL MORTALITY OF SEPTIC VS NON-SEPTIC ACUTE KIDNEY INJURY PATIENTS: AN OBSERVATIONAL COHORT STUDY

Background: To compare the predictors In-hospital mortality of patients with septic Acute Kidney Injury (S-AKI) and non-septic AKI (NS-AKI). Methods: a cohort study of critically ill patients with AKI admitted to the emergency room at a tertiary hospital from January to June 2019. The primary outcome was hospital mortality. Results: There were 116 patients who met the inclusion criteria. Compared with NS-AKI, patients with S-AKI had significantly lower mean MAP, median eGFR, and urine output. (UO). S-AKI had higher mortality and vasopressor requirements and had a lower renal recovery than NS-AKI (63.2% vs 31.4%, p=0.001; 30.8% vs 13.7%, p=0.031, and 36.9% vs 60.8%, p=0.011, respectively). AKI stage 3 and vasopressor requirements were dependent risk factors for both S-AKI and NS-AKI mortality. Meanwhile, SOFA score > 7 and the need for dialysis are dependent and independent risk factors for mortality in S-AKI. Worsening and/or persistence in UO, serum urea and creatinine levels at 48 h after admission were predictors of mortality in S-AKI and NS-AKI. Improvement in UO in surviving patients was more pronounced in S-AKI than in NS-AKI (50% vs 17.1%, p=0.007). The surviving S-AKI patients had a longer hospital stay than surviving NS-AKI [8 (6-14.5) vs 5 (4 – 8), p=0.004]. S-AKI have higher mortality and vasopressor requirements and have lower renal recovery than NS-AKI. Conclusion: S-AKI have higher mortality and vasopressor requirements and a lower renal recovery than NS-AKI. Independent predictors of mortality in S-AKI were high SOFA scores and the need for dialysis.

Impact of Cumulative Fluid Balance During Continuous Renal Replacement Therapy on Mortality in Patients With Septic Acute Kidney Injury: A Retrospective Cohort Study

Background: The clinicians often use continuous renal replacement therapy (CRRT) for the fluid management of patients with septic acute kidney injury (AKI). However, there is limited knowledge of the effects of changes in fluid balance (FB) on CRRT and its association with outcomes in patients with septic AKI.Objective: This study aimed to determine the association of cumulative FB (CFB) during treatment with 28-day all-cause mortality in the patients with septic AKI who require CRRT.Methods: This retrospective observational study examined patients who received CRRT due to septic AKI in a mixed intensive care unit (ICU) of a tertiary teaching hospital between January 2015 and December 2018. The patients were divided into three groups—negative FB, even FB, and positive FB—based on the CFB during CRRT. The primary outcome was 28-day all-cause mortality.Results: We examined 227 eligible patients and the mean age was 62.4 ± 18.3 years. The even FB group had a significantly lower 28-day mortality (43.0%, p = 0.007) than the positive FB group (72.7%) and the negative FB group (54.8%). The unadjusted and adjusted Cox regression models indicated that the positive FB group had an increased risk for 28-day all-cause mortality relative to the even FB group. A restricted cubic splines model indicated a J-shaped association between the CFB and 28-day all-cause mortality in the unadjusted model.Conclusion: Among the critically ill patients with septic AKI who require CRRT, those with positive FB had a higher mortality rate than those with even FB.

Clinical and economic assessment of the therapy of acute kidney injury in sepsis with continuous combined methods of renal replacement therapy

Objective: complex assessment of clinical and economic effectiveness as well as saving of the state budget assets within the therapy of patients with sepsis/septic shock based on different technologies of blood purification.Methods. Evaluation of direct and indirect costs of the eight blood purifcation methods. The target population includes adult patients 18+ with septic acute kidney injury. The study was conducted in compliance with acting Standards on Clinical Economic Studies used in the Russian Federation.The study methods included evaluation of existing randomized clinical studies and trials with data from network meta-analyses and systematic reviews of the target technologies. The direct medical and indirect non-medical costs were calculated and analyzed in respect of cost-effectiveness and budget impact analyses.Results. Direct and indirect costs were calculated for the sorption devices oXiris (Baxter International Inc.), Toraymyxin (Toray Medical Co.), Alteco LPS Adsorber (Alteco Medical AB), Toxipak (POKARD NPF), Desepta.LPS (BIOTECH M NPP), CytoSorb (CytoSorbents Inc.), HA330 (Jafron Biomedical Co.), Desepta (BIOTECH M NPP) for two time-horizons: 1-year period and 5-years period with discounting. For both periods, the use of oXiris hemoflter results in the least economic burden for the state budget.Conclusion. The use of blood purifcation in septic patients therapy is associated with considerable direct and indirect fnancial expenses, the amount of which and consequential budget saving depend on the technology of blood purifcation applied. The actual tariff compensation policy evidently demands revising.