Clinicopathological features of kidney injury in patients receiving immune checkpoint inhibitors (ICPi) combined with anti-vascular endothelial growth factor (anti-VEGF) therapy.

BACKGROUND: Immune checkpoint inhibitor (ICPi) combined with anti-vascular endothelial growth factor (VEGF) therapy has increasingly become a promising strategy in various malignancies. However, the combination might be associated with increased risk of nephrotoxicity. METHODS: We retrospectively recruited patients who suffered kidney injury and received renal biopsy after anti-VEGF/ICPi mono- or combination therapy and divided them into three groups: anti-VEGF monotherapy, ICPi monotherapy and combination therapy. Clinical and histopathological features of three groups were analysed. All patients were followed-up for 3 months after biopsy, with or without glucocorticoid treatment, and renal outcome were compared. RESULTS: A total of 46 patients were enrolled. Eighteen patients received anti-VEGF monotherapy, 12 received ICPi monotherapy and 16 received combined treatment of anti-VEGF and ICPi. Proteinuria level of anti-VEGF group, ICPi group and combination group were 4.07±3.17 g/day, 0.60±0.61 g/day and 2.05±2.50 g/day, respectively (p=0.002). The peak serum creatinine level of combination group (1.75±0.77 mg/dL) was also in between ICPi group (2.79±0.90 mg/dL) and anti-VEGF group (1.34±0.60 mg/dL) (p<0.001). Multiple histopathological patterns involving glomerulus, tubulointerstitium and vessel existed in the majority of cases in combination group (68.8%). Renal complete and partial recovery rate of combination therapy were also in between monotherapy (57.1% vs 40.0% in anti-VEGF group, 100.0% in ICPi group, respectively). CONCLUSIONS: Kidney injury in patients treated with combination therapy of ICPi and anti-VEGF shows hybrid pathological patterns and intermediate clinical features compared with monotherapy. Cohorts with larger sample and better design, as well as basic research, are needed to elucidate the mechanism of 'protection' effect of combination anti-cancer therapy to renal function.

Weekend effect on the incidence and outcomes of cardiac surgery associated - acute kidney injury.

BACKGROUND: The effects of surgical day (workdays or weekends) on occurrence and outcome of cardiac surgery associated -acute kidney injury (CSA-AKI) remains unclear. This study aimed to compare the incidence and short-term outcomes of CSA-AKI in patients undergoing surgery on workdays and weekends. MATERIALS AND METHODS: Patients who underwent cardiac surgery from July 2020 to December 2020 were retrospectively enrolled in this study. These patients were divided into a weekend group and workday group. The primary endpoint was the incidence of CSA-AKI. The secondary endpoints included renal function recovery and in-hospital mortality. The logistic regression model was used to explore the risk factors for CSA-AKI. Stratification analysis was performed to estimate the association between CSA-AKI and weekend surgery stratified by emergency surgery. RESULTS: A total of 1974 patients undergoing cardiac surgery were enrolled. The incidence of CSA-AKI in the weekend group was significantly higher than that in the workday group (42.8% vs. 34.7%, P = 0.038). Further analysis of patients with CSA-AKI showed that there was no difference in renal function recovery between the workday AKI group and weekend AKI group. There was no difference in in-hospital mortality between the weekend group and workday group (3.6% vs. 2.4%, P = 0.327); however, the in-hospital mortality of the weekend AKI group was significantly higher than that of the workday AKI group (8.5% vs. 2.9%, P = 0.014). Weekend surgery and emergency surgery were independent risk factors for CSA-AKI. The multiplicative model showed an interaction between weekend surgery and emergency surgery; weekend surgery was related to an increased risk of AKI among patients undergoing emergency surgery [adjusted OR (95% CI): 1.96 (1.012-8.128)]. CONCLUSIONS: The incidence of CSA-AKI in patients undergoing cardiac surgery on weekends was significantly higher compared to that in patients undergoing cardiac surgery on workdays. Weekend surgery did not affect the in-hospital mortality of all patients but significantly increased the mortality of AKI patients. Weekend surgery and emergency surgery were independent risk factors for CSA-AKI. Weekend emergency surgery significantly increased the risk of CSA-AKI.

Phosphoproteome Profiling of uEVs Reveals p-AQP2 and p-GSK3ß as Potential Markers for Diabetic Nephropathy.

Diabetic nephropathy (DN) contributes to increased morbidity and mortality among patients with diabetes and presents a considerable global health challenge. However, reliable biomarkers of DN have not yet been established. Phosphorylated proteins are crucial for disease progression. However, their diagnostic potential remains unexplored. In this study, we used ultra-high-sensitivity quantitative phosphoproteomics to identify phosphoproteins in urinary extracellular vesicles (uEVs) as potential biomarkers of DN. We detected 233 phosphopeptides within the uEVs, with 47 phosphoproteins exhibiting significant alterations in patients with DN compared to those in patients with diabetes. From these phosphoproteins, we selected phosphorylated aquaporin-2 (p-AQP2[S256]) and phosphorylated glycogen synthase kinase-3ß (p-GSK3ß[Y216]) for validation, as they were significantly overrepresented in pathway analyses and previously implicated in DN pathogenesis. Both phosphoproteins were successfully confirmed through Phos-tag western blotting in uEVs and immunohistochemistry staining in kidney sections, suggesting that phosphoprotein alterations in uEVs reflect corresponding changes within the kidney and their potential as candidate biomarkers for DN. Our research proposes the utilization of phosphoproteins in uEVs as a liquid biopsy, presenting a highly feasible diagnostic tool for kidney disease.

Urinary N-Acetyl-Beta-D-Glucosaminidase levels predict immunoglobulin a nephropathy remission status.

BACKGROUND: Tubulointerstitial lesions play a pivotal role in the progression of IgA nephropathy (IgAN). Elevated N-acetyl-beta-D-glucosaminidase (NAG) in urine is released from damaged proximal tubular epithelial cells (PTEC) and may serve as a biomarker of renal progression in diseases with tubulointerstitial involvement. METHODS: We evaluated the predictive value of urinary NAG (uNAG) for disease progression in 213 biopsy-proven primary IgAN patients from January 2018 to December 2019 at Zhongshan Hospital, Fudan University. We compared the results with those of serum cystatin C (sCysC). RESULTS: Increased uNAG and sCysC levels were associated with worse clinical and histological manifestations. Only uNAG level was independently associated with remission status after adjustment. Patients with high uNAG levels (> 22.32 U/g Cr) had a 4.32-fold greater risk of disease progression. The combination of baseline uNAG and clinical data may achieve satisfactory risk prediction in IgAN patients with relatively preserved renal function (eGFR ≥ 60 ml/min/1.73 m2, area under the curve [AUC] 0.760). CONCLUSION: Our results suggest that uNAG is a promising biomarker for predicting IgAN remission status.

An L-arginine-functionalized pillar[5]arene-based supramolecular photosensitizer for synergistically enhanced cancer therapeutic effectiveness.

An L-arginine-functionalized pillar[5]arene-based supramolecular photosensitizer LAP5⊃NBSPD was constructed by host-guest interactions, which could self-assemble into nano-micelles to achieve effective delivery and selective release of LAP5 and NBS in cancer cells. In vitro studies revealed that LAP5⊃NBSPD NPs exhibited excellent cancer cell membrane disruption and ROS generation properties, which provides a novel route for synergistically enhanced cancer therapeutic effectiveness.

Three-in-one self-assembled metallo-nanophotosensitizers for photodynamic/chemodynamic/chemo multimodal synergistic cancer therapy.

A three-in-one self-assembled metallo-nanophotosensitizer system (NLCD) was constructed by cooperative coordination of amphiphilic L-arginine-modified photosensitizer NBS-L-Arg and DOX in the presence of Cu2+via the synergy of coordination, hydrophobic, and π-π stacking interactions. The resulting NLCD NPs possessed uniform size, well-defined nanosphere structure, and GSH-responsive ability. In vitro studies exhibited that NLCD NPs integrating photodynamic/chemodynamic/chemo multimodal therapy achieved an enhanced therapeutic effect.

Covalently bridged pillararene-based polymers: structures, synthesis, and applications.

Covalently bridged pillararene-based polymers (CBPPs) are a special class of macrocycle-based polymers in which multiple pillararene monomers are attached to the polymer structures by covalent bonds. Owing to the unique molecular structures including the connection components or the spatial structures, CBPPs have become increasingly popular in applications ranging from environmental science to biomedical science. In this review, CBPPs are divided into three types (linear polymers, grafted polymers, and cross-linked polymers) according to their structural characteristics and described from the perspective of synthesis methods comprehensively. In addition, the applications of CBPPs are presented, including selective adsorption and separation, fluorescence sensing and detection, construction of supramolecular gels, anticancer drug delivery, artificial light-harvesting, catalysis, and others. Finally, the current challenging issues and comprehensive prospects of CBPPs are discussed.

Construction and validation of a novel ten miRNA-pair based signature for the prognosis of clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most predominate pathological subtype of renal cell carcinoma, causing a recurrence or metastasis rate as high as 20% to 40% after operation, for which effective prognostic signature is urgently needed. METHODS: The mRNA and miRNA profiles of ccRCC specimens were collected from the Cancer Genome Atlas. MiRNA-pair risk score (miPRS) for each miRNA pair was generated as a signature and validated by univariate and multivariate Cox proportional hazards regression analysis. Functional enrichment was performed, and immune cells infiltration, as well as tumor mutation burden (TMB), and immunophenoscore (IPS) were evaluated between high and low miPRS groups. Target gene-prediction and differentially expressed gene-analysis were performed based on databases of miRDB, miRTarBase, and TargetScan. Multivariate Cox proportional hazards regression analysis was adopted to establish the prognostic model and Kaplan-Meier survival analysis was performed. FINDINGS: A novel 10 miRNA-pair based signature was established. Area under the time-dependent receiver operating curve proved the performance of the signature in the training, validation, and testing cohorts. Higher TMB, as well as the higher CTLA4-negative PD1-negative IPS, were discovered in high miPRS patients. A prognostic model was built based on miPRS (1 year-, 5 year-, 10 year- ROC-AUC=0.92, 0.84, 0.82, respectively). INTERPRETATION: The model based on miPRS is a novel and valid tool for predicting the prognosis of ccRCC. FUNDING: This study was supported by research grants from the China National Natural Scientific Foundation (81903972, 82002018, and 82170752) and Shanghai Sailing Program (19YF1406700 and 20YF1406000).

Cystatin C-based estimated GFR performs best in identifying individuals with poorer survival in an unselected Chinese population: results from the China Health and Retirement Longitudinal Study (CHARLS).

Background: The decline in estimated glomerular filtration rate (eGFR) has been reported as a risk factor for mortality. However, it remains unclear which eGFR equation is most useful in predicting death in the general Chinese population. Methods: The association was examined between eGFR and all-cause mortality using data from the China Health and Retirement Longitudinal Study. Participants with complete data in 2011 and survival follow-up in 2013, 2015 and 2018 were included and analyzed in three separate cohorts, which included 8160, 8154 and 8020 participants, respectively. Logistic regression analyses, receiver operating characteristic curve, continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were computed to compare the discriminative power of eGFR derived by abbreviated Modification of Diet in Renal Disease (MDRD), Chinese coefficient-modified MDRD (MDRD-CN), Japanese coefficient-modified MDRD (MDRD-JPN), CKD-EPIcr, Japanese coefficient-modified CKD-EPIcr (CKD-EPIcr-JPN), CKD-EPIcys, CKD-EPIcr-cys, CKD-EPIcr fit without race and CKD-EPIcr-cys fit without race. Results: A decreased eGFR (<60 ml/min/1.73 m2) was significantly associated with increased mortality at 2 years no matter which eGFR equation was used (odds ratio ranged between 2.02 and 4.94, all P < 0.001). The association remained significant after adjusting multiple covariates when MDRD-CN, CKD-EPIcys or CKD-EPIcr-cys fit without race was used. CKD-EPIcys showed the highest discriminative power for mortality (area under the curve 0.744 ± 0.40) and outperformed other equations (all P < 0.001) except for CKD-EPIcr-cys. The overall risk classification was also improved when the CKD-EPIcys equation was adopted as indicated by continuous NRI and IDI. Similar results were observed at 4 and 7 years. Conclusions: A decline in eGFR by all equations could predict poorer survival, among which the CKD-EPIcys equation showed the best discriminative power.

The effect of triglycerides to high-density lipoprotein cholesterol ratio on the reduction of renal function: findings from China health and retirement longitudinal study (CHARLS).

BACKGROUND: Previous studies show that abnormal lipoprotein metabolism can increase the prevalence of chronic kidney disease (CKD). This study prospectively investigated the association of triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio and renal dysfunction in the Chinese population. METHODS: This longitudinal cohort research examined 7,316 participants (age range: 22-93) from the China Health and Retirement Longitudinal Study (CHARLS), including 6,560 individuals with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 (normal renal function, NRF) group and 756 with eGFR < 60 mL/min/1.73 m2 (impaired renal function, IRF) group. In NRF group, reduction in renal function was defined as eGFR < 60 mL/min/1.73 m2 at exit visit and in IRF group, it was defined as decline in eGFR category, average eGFR decline > 5 mL/min/1.73 m2 per year or > 30 % decrease in eGFR from baseline. RESULTS: The study results showed that TG/HDL-C ratio was positively associated with the risk of renal function decline in the NRF group (OR 1.30, 95 %CI 1.03-1.65, P = 0.03) and the IRF group (OR 1.90, 95 %CI 1.21-3.23, P = 0.02) when adjusting for age, gender, obesity, diabetes, hypertension, waist circumference, drinking, smoking, history of heart disease and stroke, low-density lipoprotein cholesterol and eGFR category. Analysis of the IRF group indicated that relative to the group of TG/HDL-C < 1.60, the group of TG/HDL-C ≥ 2.97 had an increased risk for the decline of eGFR category (OR 1.89, 95 %CI 1.12-3.21, P = 0.02) and > 30 % decline in eGFR (OR 2.56, 95 %CI 1.05-6.38, P = 0.04). CONCLUSIONS: The high TG/HDL-C ratio was an independent risk factor for declining renal function in the Chinese population.

Pillar[5]arene-based supramolecular photosensitizer for enhanced hypoxic-tumor therapeutic effectiveness.

A galactose-targeting supramolecular photosensitizer system DOX@GP5⊃NBSPD was constructed based on a host-guest inclusion complex. The supramolecular system could achieve efficient delivery of DOX/NBS and selective release under GSH stimulation. In vitro studies revealed that this supramolecular DOX/NBS co-delivery system exhibited high ROS production and excellent cancer cell damage capability in a hypoxic environment. This strategy can therefore achieve enhanced hypoxic-tumor therapeutic effectiveness by chemo-photodynamic combination.

A Multiepitope Peptide, rOmp22, Encapsulated in Chitosan-PLGA Nanoparticles as a Candidate Vaccine Against Acinetobacter baumannii Infection.

BACKGROUND: The development of vaccines is a promising and cost-effective strategy to prevent emerging multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) infections. The purpose of this study was to prepare a multiepitope peptide nanovaccine and evaluate its immunogenicity and protective effect in BALB/c mice. METHODS: The B-cell and T-cell epitopes of Omp22 from A. baumannii were predicted using bioinformatics methods and identified by immunological experiments. The optimal epitopes were conjugated in series by 6-aminocaproic acid and chemically synthesized multiepitope polypeptide rOmp22. Then, rOmp22 was encapsulated by chitosan (CS) and poly (lactic-co-glycolic) acid (PLGA) to prepare CS-PLGA-rOmp22 nanoparticles (NPs). The immunogenicity and immunoprotective efficacy of the vaccine were evaluated in BALB/c mice. RESULTS: CS-PLGA-rOmp22 NPs were small (mean size of 272.83 nm) with apparently spherical structures, positively charged (4.39 mV) and nontoxic to A549 cells. A high encapsulation efficiency (54.94%) and a continuous slow release pattern were achieved. Compared with nonencapsulated rOmp22, CS-PLGA-rOmp22 immunized BALB/c mice induced higher levels of rOmp22-specific IgG in serum and IFN-γ in splenocyte supernatant. Additionally, lung injury and bacterial burdens in the lung and blood were suppressed, and potent protection (57.14%-83.3%) against acute lethal intratracheal A. baumannii challenge was observed in BALB/c mice vaccinated with CS-PLGA-rOmp22. CONCLUSION: CS-PLGA-rOmp22 NPs elicited specific IgG antibodies, Th1 cellular immunity and protection against acute lethal intratracheal A. baumannii challenge. Our results indicate that this nanovaccine is a desirable candidate for preventing A. baumannii infection.

Urinary Soluble CD163 Levels Predict IgA Nephropathy Remission Status.

Noninvasive biomarkers of disease activity are needed to predict disease remission status in patients with IgA nephropathy (IgAN). Soluble CD163 (sCD163), shed by monocytes and macrophages, is a potential biomarker in diseases associated with excessive macrophage activation. We investigated the association of urinary sCD163 (u-sCD163) with histopathological activity and clinical manifestations in 349 patients with biopsy-diagnosed IgAN. U-sCD163 was measured via enzyme-linked immunosorbent assay. In patients with IgAN, higher u-sCD163 levels were associated with histological lesions of greater severity, as well as more proteinuria and poorer renal function. Additionally, u-sCD163 was correlated with infiltration of tubulointerstitial CD163+ macrophages. High u-sCD163 levels (>3.57 ng/mg Cr) were associated with a 2.66-fold greater risk for IgAN remission failure in adjusted analyses. Adding u-sCD163 levels to the model containing clinical data at biopsy and MEST-C score significantly improved the risk prediction of IgAN remission status (AUC 0.788). Together, our results suggest that u-sCD163 may be a useful noninvasive biomarker to evaluate disease severity and remission status of IgAN.

A GSH-Responsive Nanoprodrug System Based on Self-Assembly of Lactose Modified Camptothecin for Targeted Drug Delivery and Combination Chemotherapy.

BACKGROUND: Conventional chemotherapy using small molecular antitumor drugs suffers from several limitations, for instance poor water solubility, high toxicity, and lack of specificity. However, prodrugs constructed by covalent modification of anticancer drugs can overcome these limitations, which are able to release its active form after entering the tumor tissues by specific stimulus response. METHODS: A GSH-responsive glyco-nanoprodrug system has been constructed by self-assembled of amphiphilic lactosemodified camptothecin prodrug molecular (Lac-SS-CPT) for targeting drug delivery and combination therapy. RESULTS: Using HL7702 cells as experimental models, the cytotoxic effects of Lac-SS-CPT were investigated to 10-30 µmol/L for 48 hours. Notably, the cell viability of Lac-SS-CPT to HL7702 cells was higher compared with free CPT which indicated that Lac-SS-CPT can reduce side-effects. Simultaneously, we have evaluated the anticancer efficiency of doxorubicin hydrochloride (DOX)-loaded Lac-SS-CPT glyco-nanoprodrug system (Lac-SS-CPT@DOX), where Lac-SS-CPT@DOX and free DOX incubated with HpeG2 cells and HL7702 cells for 24, 48, and 72 hours, respectively. It turned out that Lac-SS-CPT@DOX encapsulated anticancer drug (DOX) could decrease DOX side-effect on HL7702 cells and increase DOX anticancer efficiency. More importantly, the CPT and DOX were released from Lac-SS-CPT@DOX in HepG2 cells where a higher GSH concentration exists. Moreover, combination therapy efficiency was evaluated, where free DOX and Lac-SS-CPT@DOX incubated with DOX-resistance HepG2 cells (HepG2-ADR cells), respectively. CONCLUSION: The results revealed that the Lac-SS-CPT@DOX could enhance the cytotoxicity of DOX for HepG2-ADR cells and provided a new idea for designing an advanced nano-prodrug system toward combination therapy.

Prediction models for acute kidney injury in patients with gastrointestinal cancers: a real-world study based on Bayesian networks.

BACKGROUND: This study attempts to establish a Bayesian networks (BNs) based model for inferring the risk of AKI in gastrointestinal cancer (GI) patients, and to compare its predictive capacity with other machine learning (ML) models. METHODS: From 1 October 2014 to 30 September 2015, we recruited 6495 inpatients with GI cancers in a tertiary hospital in eastern China. Data on demographics, clinical and laboratory indicators were retrospectively extracted from the electronic medical record system. Predictors of AKI were selected in gLASSO regression, and further incorporated into BNs analysis. RESULTS: The incidences of AKI in patients with esophagus, stomach, and intestine cancer were 20.5%, 13.9%, and 12.5%, respectively. Through gLASSO, 11 predictors were screened out, including diabetes, cancer category, anti-tumor treatment, ALT, serum creatinine, estimated glomerular filtration rate (eGFR), serum uric acid (SUA), hypoalbuminemia, anemia, abnormal sodium, and potassium. BNs model revealed that cancer category, treatment, eGFR, and hypoalbuminemia had direct connections with AKI. Diabetes and SUA were indirectly linked to AKI through eGFR, and anemia created connections with AKI through affecting album level. Compared with other ML models, BNs model maintained a higher AUC value in both the internal and external validation (AUC: 0.823/0.790). CONCLUSION: BNs model not only delineates the qualitative and quantitative relationship between AKI and its associated factors but shows the more robust generalizability in AKI prediction.

Hydrogen sulfide attenuates renal fibrosis by inducing TET-dependent DNA demethylation on Klotho promoter.

Hypoxia is a key pathogenetic characteristic of chronic kidney disease (CKD). Klotho has renoprotective effect and its expression is commonly suppressed in CKD patients. We showed that chronic hypoxia in unilateral ureteral obstruction model mice is associated with renal Klotho promoter methylation and expression silencing. Administration of low-dose of sodium hydrosulfide (NaHS) effectively ameliorated renal tubulointerstitial fibrosis in the mouse model by demethylating Klotho promoter and restoring its expression. Mechanistically, hypoxia microenvironment in CKD reduced cellular oxygen availability and Fe2+ concentration, and led to impaired activity of ten-eleven translocation (TET), which is critical in maintaining Klotho promoter demethylation status. NaHS treatment greatly improved hypoxia condition, restored TET activity, reversed DNA methylation, and thus, increased Klotho expression. Our results strongly suggested that correcting hypoxia condition to restore TET activity could be a promising therapeutic strategy against CKD.

A supramolecular nanoprodrug based on a boronate ester linked curcumin complexing with water-soluble pillar[5]arene for synergistic chemotherapies.

A supramolecular nanoprodrug based on the host-guest complexation of water-soluble pillar[5]arene (WP5) and a boronate ester linked curcumin (Cur) was constructed, which had dual-responsiveness towards pH and GSH, allowing the drug to be selectively released in hepatoma cells. In vitro studies revealed that the Dox-loaded WP5G-Cur nanoprodrug achieved co-delivery of Dox/Cur. The anti-cancer efficiency could be enhanced through synergistic chemotherapies of Dox/Cur.

Volume-associated hemodynamic variables for prediction of cardiac surgery-associated acute kidney injury.

BACKGROUND: Delayed diagnosis of acute kidney injury (AKI) is common because the changes in renal function markers often lag injury. We aimed to find optimal non-invasive hemodynamic variables for the prediction of postoperative AKI and AKI renal replacement therapy (RRT). METHODS: The data were collected from 1,180 patients who underwent cardiac surgery in our hospital between March 2015 and Feb 2016. Postoperative central venous pressure (CVP), mean arterial pressure (MAP), heart rate, PaO2, and PaCO2 on ICU admission and daily fluid input and output (calculated as 24 h PFO) were monitored and compared between AKI vs. non-AKI and RRT vs non-RRT cases. RESULTS: The AKI and AKI-RRT incidences were 36.7% (n = 433) and 1.2% (n = 14). Low cardiac output syndromes (LCOSs) occurred significantly more in AKI and RRT than in non-AKI or non-RRT groups (13.2% vs. 3.9%, P < 0.01; 42.9% vs. 7.1%, P < 0.01). CVP on ICU admission was significantly higher in AKI and RRT than in non-AKI and non-RRT groups (11.5 vs. 9.0 mmHg, P < 0.01; 13.3 vs. 9.9 mmHg, P < 0.01). 24 h PFO in AKI and RRT cases were significantly higher than in non-AKI or non-RRT patients (1.6% vs. 0.9%, P < 0.01; 3.9% vs. 0.8%, P < 0.01). The areas under the ROC curves to predict postoperative AKI by CVP on ICU admission (> 11 mmHg) + LCOS + 24 h PFO (> 5%) and to predict AKI-RRT by CVP on ICU admission (> 13 mmHg) + LCOS + 24 h PFO (> 5%) were 0.763 and 0.886, respectively. CONCLUSION: The volume-associated hemodynamic variables, including CVP on ICU admission, LCOS, and 24 h PFO after surgery could predict postoperative AKI and AKI-RRT.

Application of group LASSO regression based Bayesian networks in risk factors exploration and disease prediction for acute kidney injury in hospitalized patients with hematologic malignancies.

BACKGROUND: Patients who were diagnosed with hematologic malignancies (HM) had a higher risk of acute kidney injury (AKI). This study applies the Bayesian networks (BNs) to investigate the interrelationships between AKI and its risk factors among HM patients, and to evaluate the predictive and inferential ability of BNs model in different clinical settings. METHODS: During 2014 and 2015, a total of 2501 inpatients with HM were recruited in this retrospective study conducted in a tertiary hospital, Shanghai of China. Patients' demographics, medical history, clinical and laboratory records on admission were extracted from the electronic medical records. Candidate predictors of AKI were screened in the group-LASSO (gLASSO) regression, and then they were incorporated into BNs analysis for further interrelationship modeling and disease prediction. RESULTS: Of 2395 eligible patients with HM, 370 episodes were diagnosed with AKI (15.4%). Patients with multiple myeloma (24.1%) and leukemia (23.9%) had higher incidences of AKI, followed by lymphoma (13.4%). Screened by the gLASSO regression, variables as age, gender, diabetes, HM category, anti-tumor treatment, hemoglobin, serum creatinine (SCr), the estimated glomerular filtration rate (eGFR), serum uric acid, serum sodium and potassium level were found with significant associations with the occurrence of AKI. Through BNs analysis, age, hemoglobin, eGFR, serum sodium and potassium had directed connections with AKI. HM category and anti-tumor treatment were indirectly linked to AKI via hemoglobin and eGFR, and diabetes was connected with AKI by affecting eGFR level. BNs inferences concluded that when poor eGFR, anemia and hyponatremia occurred simultaneously, the patients' probability of AKI was up to 78.5%. The area under the receiver operating characteristic curve (AUC) of BNs model was 0.835, higher than that in the logistic score model (0.763). It also showed a robust performance in 10-fold cross-validation (AUC: 0.812). CONCLUSION: Bayesian networks can provide a novel perspective to reveal the intrinsic connections between AKI and its risk factors in HM patients. The BNs predictive model could help us to calculate the probability of AKI at the individual level, and follow the tide of e-alert and big-data realize the early detection of AKI.