Development of a Multivariable Prediction Model for Citrate Accumulation in Liver Transplant Patients Undergoing Continuous Renal Replacement Therapy with Regional Citrate Anticoagulation.

INTRODUCTION: Patients with impaired citrate metabolism may experience citrate accumulation (CA), which causes life-threatening metabolic acidosis and hypocalcemia. CA poses a challenge for clinicians when deciding on the use of regional citrate anticoagulation (RCA) for patients with liver dysfunction. This study aimed to develop a prediction model integrating multiple clinical variables to assess the risk of CA in liver transplant patients. METHODS: This single-center prospective cohort study included postoperative liver transplant patients who underwent continuous renal replacement therapy (CRRT) with RCA. The study end point was CA. A prediction model was developed using a generalized linear mixed-effect model based on the Akaike information criterion. The predictive values were assessed using the receiver operating characteristic curve and bootstrap resampling (times = 500) to estimate the area under the curve (AUC) and the corresponding 95% confidence interval (CI). A nomogram was used to visualize the model. RESULTS: This study included 32 patients who underwent 133 CRRT sessions with RCA. CA occurred in 46 CRRT sessions. The model included lactate, norepinephrine >0.1 µg/kg/min, alanine aminotransferase, total bilirubin, and standard bicarbonate, which were tested before starting each CRRT session and body mass index, diabetes mellitus, and chronic kidney disease as predictors. The AUC of the model was 0.867 (95% CI 0.786-0.921), which was significantly higher than that of the single predictor (p < 0.05). A nomogram visualized the prediction model. CONCLUSIONS: The prediction model integrating multiple clinical variables showed a good predictive value for CA. A nomogram visualized the model for easy application in clinical practice.

RPB5-Mediating Protein Promotes Cholangiocarcinoma Tumorigenesis and Drug Resistance by Competing With NRF2 for KEAP1 Binding.

BACKGROUND AND AIMS: Cancer cell survival depends on the balance between reactive oxygen species production and scavenging, which is regulated primarily by NRF2 during tumorigenesis. Here, we demonstrate that deletion of RBP5-mediating protein (RMP) in an autonomous mouse model of intrahepatic cholangiocarcinoma (ICC) delays tumor progression. APPROACH AND RESULTS: RMP-overexpressing tumor cells exhibited enhanced tolerance to oxidative stress and apoptosis. Mechanistically, RMP competes with NRF2 for binding to the Kelch domain of KEAP1 (Kelch-like ECH-associated protein 1) through the E**E motif, leading to decreased NRF2 degradation via ubiquitination, thus increasing NRF2 nuclear translocation and downstream transactivation of antioxidant genes. This RMP-KEAP1-NRF2 axis promotes ICC tumorigenesis, metastasis, and drug resistance. Consistent with these findings, the RMP level in human ICC is positively correlated with the protein level of NRF2 and is associated with poor prognosis. CONCLUSION: These findings reveal that RMP is involved in the oxidative stress defense program and could be exploited for targeted cancer therapies.

Derivation and validation of plasma endostatin for predicting renal recovery from acute kidney injury: a prospective validation study.

BACKGROUND: Acute kidney injury (AKI) is associated with high morbidity and mortality in surgical patients. Nonrecovery from AKI may increase mortality and early risk stratification seems key to improving clinical outcomes. The aim of the current study was to explore and validate the value of endostatin for predicting failure to recover from AKI. METHODS: We conducted a prospective cohort study of 198 patients without known chronic kidney disease who underwent noncardiac major surgery and developed new-onset AKI in the first 48 h after admission to the ICU. The biomarkers of plasma endostatin, neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C were detected immediately after AKI diagnosis. The primary endpoint was nonrecovery from AKI (within 7 days). Cutoff values of the biomarkers for predicting nonrecovery were determined in a derivation cohort (105 AKI patients). Predictive accuracy was then analyzed in a validation cohort (93 AKI patients). RESULTS: Seventy-six of 198 (38.4%) patients failed to recover from AKI onset, with 41 in the derivation cohort and 35 in the validation cohort. Compared with NGAL and cystatin C, endostatin showed a better prediction for nonrecovery, with an area under the receiver operating characteristic curve (AUC) of 0.776 (95% confidence interval (CI) 0.654-0.892, p < 0.001) and an optimal cutoff value of 63.7 ng/ml. The predictive ability for nonrecovery was greatly improved by the prediction model combining endostatin with clinical risk factors of Sequential Organ Failure Assessment (SOFA) score and AKI classification, with an AUC of 0.887 (95% CI 0.766-0.958, p < 0.001). The value of the endostatin-clinical risk prediction model was superior to the NGAL-clinical risk and cystatin C-clinical risk prediction models in predicting failure to recover from AKI, which was supported by net reclassification improvement and integrated discrimination improvement. Further, the endostatin-clinical risk prediction model achieved sensitivity and specificity of 94.6% (76.8-99.1) and 72.7% (57.2-85.0), respectively, when validated in the validation cohort. CONCLUSION: Plasma endostatin shows a useful value for predicting failure to recover from AKI. The predictive ability can be greatly improved when endostatin is combined with the SOFA score and AKI classification.

Diagnostic value of urinary tissue inhibitor of metalloproteinase-2 and insulin-like growth factor binding protein 7 for acute kidney injury: a meta-analysis.

BACKGROUND: Tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7), inducers of G1 cell cycle arrest, are two recently discovered good biomarkers for early diagnosis of acute kidney injury (AKI). To obtain a more robust performance measurement, the present meta-analysis was performed, pooling existing studies. METHODS: Literature in the MEDLINE (via PubMed), Ovid, Embase, and Cochrane Library databases was systematically searched from inception to 12 October 2016. Studies that met the set inclusion and exclusion criteria were identified by two independent investigators. The diagnostic value of urinary [TIMP-2] × [IGFBP7] for AKI was evaluated by pooled sensitivity, specificity, likelihood ratio (LR), diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) curve analyses. The causes of heterogeneity were explored by sensitivity and subgroup analyses. RESULTS: A total of nine published and eligible studies assessing 1886 cases were included in this meta-analysis. Early diagnostic value of urinary [TIMP-2] × [IGFBP7] for AKI was assessed using a random-effects model. Pooled sensitivity and specificity with corresponding 95% CIs were 0.83 (95% CI 0.79-0.87, heterogeneity I 2 = 68.8%) and 0.55 (95% CI 0.52-0.57, I 2 = 92.9%), respectively. Pooled positive LR, negative LR, and DOR were 2.37 (95% CI 1.87-2.99, I 2 = 82.6%), 0.30 (95% CI 0.21-0.41, I 2 = 43.4%), and 9.92 (95% CI 6.09-16.18, I 2 = 38.5%), respectively. The AUC estimated by SROC was 0.846 (SE 0.027) with a Q* value of 0.777 (SE 0.026). Sensitivity analysis indicated that one study significantly affected the stability of pooled results. Subgroup analysis showed that population setting and AKI threshold were the key factors causing heterogeneity in pooled sensitivity and specificity. CONCLUSIONS: On the basis of recent evidence, urinary [TIMP-2] × [IGFBP7] is an effective predictive factor of AKI. TRIAL REGISTRATION: PROSPERO registration number: CRD42016051186 . Registered on 10 November 2016.

Prognostic value of cell cycle arrest biomarkers in patients at high risk for acute kidney injury: A systematic review and meta-analysis.

Urinary tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7) are G1 cell cycle arrest biomarkers. This systematic review aimed to evaluate the prognostic value of urinary [TIMP-2]·[IGFBP7] in patients at high risk for AKI. The MEDLINE (via PubMed), Ovid, EMBASE and Cochrane Library databases were systematically searched from inception to December 25, 2016. Original clinical studies which met the eligibility criteria were included in this study. The prognostic accuracy of urinary [TIMP-2]·[IGFBP7] for assessing the need for renal replacement therapy (RRT) and mortality was evaluated by pooled sensitivity, specificity, diagnostic odds ratio, and summary receiver operating characteristic curves. A total of four prospective cohort studies evaluating 277 patients were included. The estimated area under the receiver operating characteristic curve (AUC) of urinary [TIMP-2]·[IGFBP7] for predicting the need for RRT in patients at high risk for AKI was 0.915 (standard error [SE] = 0.040). Pooled sensitivity and specificity with corresponding 95% confidence intervals (CI) were 0.69 (95% CI 0.53-0.82) and 0.81 (95% CI 0.75-0.86), respectively. Urinary [TIMP-2]·[IGFBP7] for mortality prediction in patients at high risk for AKI was assessed by qualitative description. Based on the above data, urinary [TIMP-2]·[IGFBP7] performs well in predicting the need for RRT and mortality in patients at high risk for AKI. However, further meta-analyses are warranted as more data become available.

Expression and Prognostic Role of FHIT, Fibronectin, and PTEN in Hepatocellular Carcinoma.

BACKGROUND: Fragile histidine triad (FHIT), fibronectin (FN), and phosphatase and tensin homology deleted on chromosome ten (PTEN) are widely reported as having abnormal expression in malignant tumors. The role of FHIT, fibronectin, PTEN expression in patients with hepatocellular carcinoma (HCC) has not been characterized. Our study aims to investigate the expression of FHIT, fibronectin, and PTEN in human HCC and their relationship with clinicopathological features and prognosis of HCC. METHODS: Immunohistochemistry was used to detect expression of FHIT, FN, and PTEN in tumor tissues from 138 HCC patients. The correlation between their expression and clinicopathological features and prognosis were analyzed. RESULTS: FHIT, fibronectin, and PTEN proteins have different expressions between HCC and adjacent nontumor tissue (χ2 = 5.968, 7.380, 4.962; p < 0.05), which are expressed differently in the groups of different tumor stage, grade, tumor size, tumor number, lymph node metastasis, HBV infection, and cirrhosis in the background of nontumor sections (p < 0.05). In the FHIT and fibronectin positive expression group, the cumulative survival times were shorter than those in the negative expression groups (χ2 = 4.443, 9.867; p < 0.05), and in the PTEN positive expression group the cumulative survival times were longer than in the negative expression group (χ2 = 4.199; p < 0.05). CONCLUSIONS: FHIT, fibronectin, and PTEN were abnormally expressed in HCC cells, which have stimulative or suppressive effects on HCC carcinogenesis and progression. FHIT and fibronectin can be used as negative makers for prognosis and PTEN as a positive one.

Postoperative plasma presepsin as a biomarker of postoperative infectious complications in different surgical departments: A meta-analysis and systematic review.

BACKGROUND: High rates of postoperative infection persist after different surgical procedures, encompassing surgical site infections (SSIs), remote infections, sepsis, and septic shock. Our aim was to assess presepsin's diagnostic accuracy for postoperative infections in patients across surgical procedures. METHOD: We conducted a comprehensive search in seven databases, extracting data independently. Using STATA 14.0, we calculated pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and Under the receiver operator curve and 95 â€‹% confidence interval (AUC, 95 â€‹% CI) as primary outcomes, with secondary outcomes involving sensitivity and specificity in subgroup analyses. RESULTS: This meta-analysis of 14 studies (1891 cases) evaluated presepsin's diagnostic value for postoperative infectious complications. Results include sensitivity of 77 â€‹% (70-83), specificity of 81 â€‹% (71-88), DOR of 14 (8-26), AUC of 84 (80-87), PLR of 4 (3-6), and NLR of 0.28 (0.21-0.38). Presepsin exhibits promise as a diagnostic tool for postoperative infections. CONCLUSION: In summary, compared to conventional markers like C-reactive protein (CRP) and procalcitonin (PCT), presepsin demonstrated superior sensitivity and specificity for detecting postoperative infectious complications across various surgical procedures.

Research Progress of Drug Delivery Systems Targeting the Kidneys.

Chronic kidney disease (CKD) affects more than 10% of the global population, and its incidence is increasing, partially due to an increase in the prevalence of disease risk factors. Acute kidney injury (AKI) is an independent risk factor for CKD and end-stage renal disease (ESRD). The pathogenic mechanisms of CKD provide several potential targets for its treatment. However, due to off-target effects, conventional drugs for CKD typically require high doses to achieve adequate therapeutic effects, leading to long-term organ toxicity. Therefore, ideal treatments that completely cure the different types of kidney disease are rarely available. Several approaches for the drug targeting of the kidneys have been explored in drug delivery system research. Nanotechnology-based drug delivery systems have multiple merits, including good biocompatibility, suitable degradability, the ability to target lesion sites, and fewer non-specific systemic effects. In this review, the development, potential, and limitations of low-molecular-weight protein-lysozymes, polymer nanomaterials, and lipid-based nanocarriers as drug delivery platforms for treating AKI and CKD are summarized.

Brassinosteroids accelerate recovery of photosynthetic apparatus from cold stress by balancing the electron partitioning, carboxylation and redox homeostasis in cucumber.

The aim of this study was to examine the role of brassinosteroids (BRs) in protecting the photosynthetic apparatus from cold-induced damage in cucumber (Cucumis sativus) plants. Recovery at both high light (HL) and low light (LL) after a cooling at 10/7°C induced irreversible inhibition of CO2 assimilation, photoinhibition at photosystem I (PSI) and inhibition of enzyme activities of Calvin cycle and ascorbate (AsA)-reduced glutathione (GSH) cycle, followed by accumulation of H2 O2 and malondialdehyde. However, cold-induced photoinhibition at PSII was fully recovered at LL but not at HL. Meanwhile, recovery at HL increased electron flux to O2 -dependent alternative pathway [Ja(O2 -dependent)]. Foliar application of 24-epibrassinolide (EBR) accelerated recovery from photoinhibition of PSII but not of PSI. EBR also significantly increased CO2 assimilation, activity of Calvin cycle enzymes and electron flux to carbon reduction [Je(PCR)], with a concomitant decrease in Ja(O2 -dependent); meanwhile EBR increased the activity of enzymes in AsA-GSH cycle and cellular redox states. However, the positive effect of EBR on plant recovery was observed only at HL, but not LL. These results indicate that BR accelerates the recovery of photosynthetic apparatus at HL by activation of enzymes in Calvin cycle and increasing the antioxidant capacity, which in turn mitigate the photooxidative stress and the inhibition of plant growth during the recovery.

Plant-soil feedbacks and soil sickness: from mechanisms to application in agriculture.

Negative plant-soil feedbacks play an important role in soil sickness, which is one of the factors limiting the sustainable development of intensive agriculture. Various factors, such as the buildup of pests in the soil, disorder in physico-chemical soil properties, autotoxicity, and other unknown factors may contribute to soil sickness. A range of autotoxins have been identified, and these exhibit their allelopathic potential by influencing cell division, water and ion uptake, dark respiration, ATP synthesis, redox homeostasis, gene expression, and defense responses. Meanwhile, there are great interspecific and intraspecific differences in the uptake and accumulation of autotoxins, which contribute to the specific differences in growth in response to different autotoxins. Importantly, the autotoxins also influence soil microbes and vice versa, leading to an increased or decreased degree of soil sickness. In many cases, autotoxins may enhance soilborne diseases by predisposing the roots to infection by soilborne pathogens through a direct biochemical and physiological effect. Some approaches, such as screening for low autotoxic potential and disease-resistant genotypes, proper rotation and intercropping, proper soil and plant residue management, adoption of resistant plant species as rootstocks, introduction of beneficial microbes, physical removal of phytotoxins, and soil sterilization, are proposed. We discuss the challenges that we are facing and possible approaches to these.

[Effects of early goal-directed diuresis therapy on the outcomes of critical ill patients].

OBJECTIVE: To evaluate the effects of early goal-directed diuresis therapy on the outcomes of critical ill patients. METHODS: A total of 56 critical patients enrolled received an injection of furosemide 5-40 mg under a precondition of stable hemodynamics. They were divided into two groups:standard group [Central venous pressure (CVP) decreased below 8 mm Hg] (n = 30) and control group (if not) (n = 26) depending on the goal of CVP.And the differences of survival rate, intensive care unit (ICU) days and ventilation days after diuresis therapy were compared between two groups. RESULTS: The survival rate of standard group was significantly higher than that of control group (96.7% vs 84.6%, P < 0.05) while the ICU days (4.4 ± 3.6 days) and ventilation days (1.2 ± 1.1 days) after diuresis therapy of standard group were significantly shorter than that of control group (12.5 ± 11.7 and 9.8 ± 9.6 days, P < 0.05). CONCLUSION: Early goal-directed diuresis therapy can improve the prognosis of critical ill patients.

Endoplasmic Reticulum Stress in Systemic Lupus Erythematosus and Lupus Nephritis: Potential Therapeutic Target.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease. Approximately one-third to two-thirds of the patients with SLE progress to lupus nephritis (LN). The pathogenesis of SLE and LN has not yet been fully elucidated, and effective treatment for both conditions is lacking. The endoplasmic reticulum (ER) is the largest intracellular organelle and is a site of protein synthesis, lipid metabolism, and calcium storage. Under stress, the function of ER is disrupted, and the accumulation of unfolded or misfolded proteins occurs in ER, resulting in an ER stress (ERS) response. ERS is involved in the dysfunction of B cells, macrophages, T cells, dendritic cells, neutrophils, and other immune cells, causing immune system disorders, such as SLE. In addition, ERS is also involved in renal resident cell injury and contributes to the progression of LN. The molecular chaperones, autophagy, and proteasome degradation pathways inhibit ERS and restore ER homeostasis to improve the dysfunction of immune cells and renal resident cell injury. This may be a therapeutic strategy for SLE and LN. In this review, we summarize advances in this field.

Diagnostic Accuracy of Procalcitonin for Infection After Adult Liver Transplantation: A Meta-Analysis and Systematic Review.

Background: Post-operative infection remains a major cause of morbidity and mortality in adults early after liver transplantation (LT). Procalcitonin (PCT) may be a good test method for early diagnosis of post-operative infection and determining its severity. This study was performed to assess the diagnostic accuracy of PCT as a biomarker for infection after LT. Patients and Methods: A meta-analysis and systematic review was conducted for studies reporting diagnostic performance of PCT for infection in adults after LT. Observational studies were evaluated for their reporting of diagnostic accuracy, relevance, and quality. Results: Ten eligible studies assessing 730 patients were included in this meta-analysis and systematic review summarizing the diagnostic value of PCT for post-operative infection in adult liver transplantation. Pooled sensitivity and specificity with corresponding 95% confidence interval were 69% (95% confidence interval [CI], 54-81; heterogeneity I2 = 82.4%) and 88% (95% CI, 82-92; I2 = 52.7%), respectively. The diagnostic odd ratio (DOR) was 16 (95% CI, 10-25; I2 = 76.4%). The summary receiver operator characteristic (SROC) of PCT for post-operative infection was 0.88. There was a wide range of variability in the cutoff values, ranging from 0.22 to 42.80 ng/mL. Heterogeneity was reduced by excluding studies that focused on pediatric LT recipients. Conclusions: Procalcitonin is a moderately accurate diagnostic marker for post-operative infection in adult LT. Additionally, the diagnostic performance can be improved by combining it with other inflammatory biomarkers. This article provides the research direction for post-operative infection control.

Predictive Value of Perioperative Cardiac Troponin I in Patients Undergone Liver Transplantation: A Retrospective Cohort Study.

Objective: To examine the change rule and clinical significance of cardiac troponin I (cTnI) in the perioperative period of liver transplantation in adults, as well as its association with 28-day mortality. Methods: This was a retrospective cohort study: patients who underwent elective orthotopic liver transplantation (OLT) in Beijing Chao-Yang Hospital between June 2015 and June 2020 were selected, and plasma cTnI values were collected through the electronic medical record system within 7 days after surgery. Furthermore, the baseline clinical data of these patients were collected, and the change curve of cTnI values following liver transplantation was plotted. Using univariate and multivariate logistic regression models, the relationship between the level of postoperative cTnI and short-term mortality was investigated. The primary study endpoint was mortality within 28 days after surgery. Results: We included 414 patients who had undergone liver transplantation in this study, 48 of whom died within 28 days after surgery. cTnI, a specific marker of myocardial injury, could predict that the postoperative cardiovascular complications were higher in the death group and significantly affect the short-term prognosis of patients; however, its prognostic cut-off value was approximately 0.545 ng/mL (13×URL), indicating that a minor elevation of cTnI after liver transplantation did not significantly affect the prognosis. Moreover, a comparison of the baseline data and postoperative ICU management scores of the two groups revealed that diabetes, maximum value of cTnI >0.545 ng/mL within 7 days, and the need for postoperative renal replacement therapy (RRT) were independent prognostic factors of death within 28 days after liver transplantation. Conclusion: Within 7 days after surgery, an increase in cTnI to the maximum value of 0.545 ng/mL (13×URL) could have a significant impact on the short-term prognosis of patients. Diabetes and postoperative RRT were two independent prognostic factors for liver transplantation perioperative mortality.

Research progress on endoplasmic reticulum homeostasis in kidney diseases.

The endoplasmic reticulum (ER) plays important roles in biosynthetic and metabolic processes, including protein and lipid synthesis, Ca2+ homeostasis regulation, and subcellular organelle crosstalk. Dysregulation of ER homeostasis can cause toxic protein accumulation, lipid accumulation, and Ca2+ homeostasis disturbance, leading to cell injury and even death. Accumulating evidence indicates that the dysregulation of ER homeostasis promotes the onset and progression of kidney diseases. However, maintaining ER homeostasis through unfolded protein response, ER-associated protein degradation, autophagy or ER-phagy, and crosstalk with other organelles may be potential therapeutic strategies for kidney disorders. In this review, we summarize the recent research progress on the relationship and molecular mechanisms of ER dysfunction in kidney pathologies. In addition, the endogenous protective strategies for ER homeostasis and their potential application for kidney diseases have been discussed.

Asiatic acid alleviates cisplatin-induced renal fibrosis in tumor-bearing mice by improving the TFEB-mediated autophagy-lysosome pathway.

Nephrotoxicity is a major side effect of cisplatin treatment of solid tumors in the clinical setting. Long-term low-dose cisplatin administration causes renal fibrosis and inflammation. However, few specific medicines with clinical application value have been developed to reduce or treat the nephrotoxic side effects of cisplatin without affecting its tumor-killing effect. The present study analyzed the potential reno-protective effect and mechanism of asiatic acid (AA) in long-term cisplatin-treated nude mice suffering from tumors. AA treatment significantly attenuated renal injury, inflammation, and fibrosis induced by long-term cisplatin injection in tumor-bearing mice. AA administration notably suppressed tubular necroptosis and improved the autophagy-lysosome pathway disruption caused by chronic cisplatin treatment in tumor-transplanted nude mice and HK-2 cells. AA promoted transcription factor EB (TFEB)-mediated lysosome biogenesis and reduced the accumulation of damaged lysosomes, resulting in enhanced autophagy flux. Mechanistically, AA increased TFEB expression by rebalancing Smad7/Smad3, whereas siRNA inhibition of Smad7 or TFEB abolished the effect of AA on autophagy flux in HK-2 cells. In addition, AA treatment did not weaken, but actually enhanced the anti-tumor effect of cisplatin, as evidenced by the promoted tumor apoptosis and inhibited proliferation in nude mice. In summary, AA alleviates cisplatin-induced renal fibrosis in tumor-bearing mice by improving the TFEB-mediated autophagy-lysosome pathway.

Analysis of urinary C-C motif chemokine ligand 14 (CCL14) and first-generation urinary biomarkers for predicting renal recovery from acute kidney injury: a prospective exploratory study.

BACKGROUND: Acute kidney injury (AKI) is a frequent syndrome in the intensive care unit (ICU). AKI patients with kidney function recovery have better short-term and long-term prognoses compared with those with non-recovery. Numerous studies focus on biomarkers to distinguish them. To better understand the predictive performance of urinary biomarkers of renal recovery in patients with AKI, we evaluated C-C motif chemokine ligand 14 (CCL14) and two first-generation biomarkers (cell cycle arrest biomarkers and neutrophil gelatinase-associated lipocalin) in two ICU settings. METHODS: We performed a prospective study to analyze urinary biomarkers for predicting renal recovery from AKI. Patients who developed AKI after ICU admission were enrolled and urinary biomarkers including tissue inhibitor of metalloproteinase-2 (TIMP-2), insulin-like growth factor-binding protein 7 (IGFBP7), CCL14, and neutrophil gelatinase-associated lipocalin (NGAL) were detected on the day of AKI diagnosis. The primary endpoint was non-recovery from AKI within 7 days. The individual discriminative ability of CCL14, [TIMP-2] × [IGFBP7] and NGAL to predict renal non-recovery were evaluated by the area under receiver operating characteristics curve (AUC). RESULTS: Of 164 AKI patients, 64 (39.0%) failed to recover from AKI onset. CCL14 showed a fair prediction ability for renal non-recovery with an AUC of 0.71 (95% CI 0.63-0.77, p < 0.001). [TIMP-2] × [IGFBP7] showed the best prediction for renal non-recovery with an AUC of 0.78 (95% CI 0.71-0.84, p < 0.001). However, NGAL had no use in predicting non-recovery with an AUC of 0.53 (95% CI 0.45-0.60, p = 0.562). A two-parameter model (non-renal SOFA score and AKI stage) predicted renal non-recovery with an AUC of 0.77 (95% CI 0.77-0.83, p = 0.004). When [TIMP-2] × [IGFBP7] was combined with the clinical factors, the AUC was significantly improved to 0.82 (95% CI 0.74-0.87, p = 0.049). CONCLUSIONS: Urinary CCL14 and [TIMP-2] × [IGFBP7] were fair predictors of renal non-recovery from AKI. Combing urinary [TIMP-2] × [IGFBP7] with a clinical model consisting of non-renal SOFA score and AKI stage enhanced the predictive power for renal non-recovery. Urinary CCL14 showed no significant advantage in predicting renal non-recovery compared to [TIMP-2] × [IGFBP7].

[Value of power Doppler ultrasound to evaluate acute kidney injury].

OBJECTIVE: To explore the value of power Doppler ultrasound (PDU) in the evaluation of acute kidney injury(AKI). METHODS: Renal blood flow of 40 AKI cases was monitored by power Doppler ultrasound and 4-level semiquantitative PDU score method employed. All cases were divided into 3 groups by PDU score. AKI stage and duration were compared. And the co-variables of death and (continuous renal replacement therapy) CRRT days (> 3) were also analyzed by Logistic regression analysis. RESULTS: A total of 40 AKI case were recruited. The 3-score group (n = 13)has lower mortality in intensive care unit and at 28 days than the 2-score group (n = 15) and the 1-score group (n = 12). The number of stage-3 AKI in the 3-score group was less than that in the 2-score and 1-score groups (n = 1, 4, 9 correspondingly, χ(2) = 16.103, degree of freedom = 4, P = 0.003). The number of persistent AKI in the 3-score group was less than that in the 2-score and 1-score groups (n = 3, 9, 10 correspondingly, P < 0.05). Age, APACHEII score and PDU score (< 3) were closely correlated with death while age, APACHEII score, level of serum creatinine and PDU score (< 3) with CRRT days (> 3) (P < 0.05). CONCLUSION: PDU may be used to monitor renal hemodynamics in AKI patients and its score helps clinicians to evaluate the severity and prognosis of AKI.

Calprotectin as a diagnostic marker for sepsis: A meta-analysis.

Introduction: Sepsis is a life-threatening condition, and biomarkers are needed to diagnose sepsis fast and accurately. We aimed to perform this meta-analysis to investigate the diagnostic value of calprotectin on sepsis in critically ill patients. Methods: The investigators searched MEDLINE, Embase, Web of Science and Cochrane Library. Studies were included if they assessed the diagnostic accuracy of serum calprotectin for sepsis in intensive care unit (ICU). We estimated its diagnostic value and explored the source of heterogeneity. The bivariate model and the hierarchical summary receiver operating characteristic (HSROC) curve were used in the meta-analysis. Results: Six records assessing 821 patients were included in this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio (PLR), and diagnostic odds ratio (DOR) were separately as 0.77, 0.85, 5.20, 0.27, respectively. The Fagan's nomogram showed post-test probabilities of 91% and 35% for positive and negative outcomes, respectively. Subgroup analysis indicated that sepsis definition could be a possible source of heterogeneity, but there's no sufficient data to investigate sepsis-3 definition. Sensitivity analysis suggested that two studies could affect the stability of pooled results. Conclusion: On the basis of our meta-analysis, calprotectin is a helpful marker for early diagnosis of sepsis on ICU admission.

Metformin improves renal injury of MRL/lpr lupus-prone mice via the AMPK/STAT3 pathway.

OBJECTIVE: Lupus nephritis (LN) is a major complication and cause of death among patients with SLE. This research used in vivo and in vitro experiments to explore the therapeutic potential of metformin in kidney injury from LN-induced inflammation. METHODS: In vivo study, 8-week-old MRL/MpJ-Faslpr/J (MRL/lpr) mice were randomly divided into two groups (n=12 each): daily administration of 0.3 mg/mL metformin in drinking water and control (water only). Body weight and urinary samples were measured biweekly. Mice were sacrificed after 8-week treatment to harvest serum, lymph nodes, spleen and kidneys. In vitro study, human kidney-2 (HK-2) cells were pretreated with 1 mM metformin for 1 hour and then stimulated with 20 µg/mL lipopolysaccharides (LPS) or 10 ng/mL tumour necrosis factor-α (TNF-α) for another 48 hours. Protein was collected for subsequent analysis. RESULTS: We found that metformin administration improved renal function in MRL/lpr lupus-prone mice, measured by decreased urea nitrogen and urinary proteins. Metformin reduced immunoglobulin G and complement C3 deposition in glomeruli. The treatment also downregulated systemic and renal inflammation, as seen in decreased renal infiltration of F4/80-positive macrophages and reduced splenic and renal MCP-1 (monocyte chemoattractant protein-1) and TNF-α, and renal IL-1ß (interleukin 1ß) expression. Metformin administration decreased renal expression of necroptosis markers p-RIPK1 (phosphorylated receptor-interacting protein kinase 1) and p-MLKL, along with tubular injury marker KIM-1 (kidney injury molecule-1) in lupus mice. In addition, metformin alleviated the necroptosis of HK-2 cells stimulated by LPS and TNF-α, evidencing by a decrease in the expression of necroptosis markers p-RIPK1, p-RIPK3 and p-MLKL, and the inflammasome-related markers NLRP3 (NLR family pyrin domain containing 3), ASC (apoptosis-associated speck-like protein containing a CARD), caspase-1. Mechanistically, metformin treatment upregulated p-AMPK (phosphorylated AMP-activated protein kinase) and downregulated p-STAT3 (phosphorylated signal transducer and activator of transcription 3) expression in the kidneys. Moreover, AMPKα2 knockdown abolished the protective effects of metformin in vitro. CONCLUSIONS: Metformin alleviated kidney injury in LN though suppressing renal necroptosis and inflammation via the AMPK/STAT3 pathway.