Enhanced visible-light photocatalytic activity of N-doped C/Na2Ti6O13/TiO2 hollow spheres for efficient dye degradation.

Doping and hybridization with other semiconductors are highly effective ways to address the limitations, including their weak response to visible light and significant recombination of photogenerated carriers. In addition, the assisted carbon on the catalyst surface and the structural design have the advantage of being catalytically active. Herein, visible-light-active N-doped C/Na2Ti6O13/TiO2 hollow spheres (denoted as N-C/NTO/TiO2 HS) were successfully prepared using a facile two-step method and evaluated for methylene blue (MB) aqueous solution degradation under visible-light irradiation. The as-obtained N-C/NTO/TiO2 HS demonstrated improved photocatalytic efficiency (94 %) and pseudo-first-order kinetic degradation rate (0.023 min-1). Moreover, after three cycles of testing, N-C/NTO/TiO2 HS showed a 91 % degradation rate in its photostability. The enhanced photocatalytic performance was attributed to the combined effects of N-doping, carbon species on the surface, and the coupling of TiO2 and Na2Ti6O13 using morphology engineering. Finally, based on the experimental results, a possible photocatalytic mechanism was proposed. This study provides a rational approach toward the development of high-performance titanate-based photocatalysts for solar energy-assisted wastewater treatment.

Polymer Micropatches as B-Cell Engagers.

B cells, despite their several unique functionalities, remain largely untapped for use as an adoptive cell therapy and are limited to in vitro use for antibody production. B cells can be easily sourced, they possess excellent lymphoid-homing capabilities, and they can act as antigen-presenting cells (APCs), offering an alternative to dendritic cells (DCs), which have shown limited efficacy in the clinical setting. Soluble factors such as IL-4 and anti-CD40 antibody can enhance the activation, survival, and antigen-presenting capabilities of B cells; however, it is difficult to attain sufficiently high concentrations of these biologics to stimulate B cells in vivo. Micropatches as Cell Engagers (MACE) are polymeric microparticles, surface functionalized with anti-CD40 and anti-IgM, which can attach to B cells and simultaneously engage multiple B-cell receptors (BCR) and CD40 receptors. Stimulation of these receptors through MACE, unlike free antibodies, enhanced the display of costimulatory molecules on the B-cell surface, increased B-cell viability, and improved antigen presentation by B cells to T cells in vitro. B-cell activation by MACE further synergized with soluble IL-4 and anti-CD40. MACE also elicited T-cell chemokine secretion by B cells. Upon intravenous adoptive transfer, MACE-bound B cells homed to the spleen and lymph nodes, key sites for antigen presentation to T cells. Adoptive transfer of MACE-B cells pulsed with the CD4+ and CD8+ epitopes of ovalbumin significantly delayed tumor progression in a murine subcutaneous EG7-OVA tumor model, demonstrating the functional benefit conferred to B cells by MACE.

Pharmacokinetic Modeling of Bepotastine for Determination of Optimal Dosage Regimen in Pediatric Patients with Allergic Rhinitis or Urticaria.

Bepotastine, a second-generation antihistamine for allergic rhinitis and urticaria, is widely used in all age groups but lacks appropriate dosing guidelines for pediatric patients, leading to off-label prescriptions. We conducted this study to propose an optimal dosing regimen for pediatric patients based on population pharmacokinetic (popPK) and physiologically based pharmacokinetic (PBPK) models using data from two previous trials. A popPK model was built using NONMEM software. A one-compartment model with first-order absorption and absorption lag time described our data well, with body weight incorporated as the only covariate. A PBPK model was developed using PK-Sim software version 10, and the model well predicted the drug concentrations obtained from pediatric patients. Furthermore, the final PBPK model showed good concordance with the known properties of bepotastine. Appropriate pediatric doses for different weight and age groups were proposed based on the simulations. Discrepancies in recommended doses from the two models were likely due to the incorporation of age-dependent physiological factors in the PBPK model. In conclusion, our study is the first to suggest an optimal oral dosing regimen of bepotastine in pediatric patients using both approaches. This is expected to foster safer and more productive use of the drug.

A population pharmacokinetic model of methotrexate in Korean patients with haematologic malignancy.

AIMS: This study was conducted to develop a population pharmacokinetic (PK) model of methotrexate in Korean patients with haematologic malignancy, identify factors affecting methotrexate PK, and propose an optimal dosage regimen for the Korean population. METHODS: Data were retrospectively collected from 188 patients with acute leukaemia or non-Hodgkin's lymphoma who were admitted to Severance Hospital during the period from November 2005 to January 2016. Using demographic factors and laboratory results as potential covariates for PK parameters, model development was performed using NONMEM and optimal dosing regimens were developed using the final PK model. RESULTS: A two-compartment model incorporating body weight via allometry best described the data, yielding typical parameter values of 25.09 L for central volume of distribution ( V 1 ), 17.65 L for peripheral volume of distribution ( V 2 ), 12.89 L/h for clearance (CL) and 0.655 L/h for inter-compartmental clearance in a 50 kg patient. Covariate analyses showed that, at the weight of 50 kg, CL decreased by 0.11 L/h for each 1-year increase in age above 14 years old and decreased 0.8-fold when serum creatinine level doubled, indicating the importance of age-specific dose individualization in methotrexate treatment. Volume of distribution at steady state derived from PK parameters (= V 1 + V 2 ) was 0.85 L/kg, which was similar to those in the Western or Chinese populations. Optimal doses simulated from the final model successfully produced the PK measures close to the target chosen. CONCLUSIONS: The population PK model and optimal dosage regimens developed in this study can be used as a basis to achieve precision dosing in Korean patients with haematologic malignancy.

Induction of Fatty Acid Oxidation Underlies DNA Damage-Induced Cell Death and Ameliorates Obesity-Driven Chemoresistance.

The DNA damage response is essential for preserving genome integrity and eliminating damaged cells. Although cellular metabolism plays a central role in cell fate decision between proliferation, survival, or death, the metabolic response to DNA damage remains largely obscure. Here, this work shows that DNA damage induces fatty acid oxidation (FAO), which is required for DNA damage-induced cell death. Mechanistically, FAO induction increases cellular acetyl-CoA levels and promotes N-alpha-acetylation of caspase-2, leading to cell death. Whereas chemotherapy increases FAO related genes through peroxisome proliferator-activated receptor α (PPARα), accelerated hypoxia-inducible factor-1α stabilization by tumor cells in obese mice impedes the upregulation of FAO, which contributes to its chemoresistance. Finally, this work finds that improving FAO by PPARα activation ameliorates obesity-driven chemoresistance and enhances the outcomes of chemotherapy in obese mice. These findings reveal the shift toward FAO induction is an important metabolic response to DNA damage and may provide effective therapeutic strategies for cancer patients with obesity.

Model-informed precision dosing in vancomycin treatment.

Introduction: While vancomycin remains a widely prescribed antibiotic, it can cause ototoxicity and nephrotoxicity, both of which are concentration-associated. Overtreatment can occur when the treatment lasts for an unnecessarily long time. Using a model-informed precision dosing scheme, this study aims to develop a population pharmacokinetic (PK) and pharmacodynamic (PD) model for vancomycin to determine the optimal dosage regimen and treatment duration in order to avoid drug-induced toxicity. Methods: The data were obtained from electronic medical records of 542 patients, including 40 children, and were analyzed using NONMEM software. For PK, vancomycin concentrations were described with a two-compartment model incorporating allometry scaling. Results and discussion: This revealed that systemic clearance decreased with creatinine and blood urea nitrogen levels, history of diabetes and renal diseases, and further decreased in women. On the other hand, the central volume of distribution increased with age. For PD, C-reactive protein (CRP) plasma concentrations were described by transit compartments and were found to decrease with the presence of pneumonia. Simulations demonstrated that, given the model informed optimal doses, peak and trough concentrations as well as the area under the concentration-time curve remained within the therapeutic range, even at doses smaller than routine doses, for most patients. Additionally, CRP levels decreased more rapidly with the higher dose starting from 10 days after treatment initiation. The developed R Shiny application efficiently visualized the time courses of vancomycin and CRP concentrations, indicating its applicability in designing optimal treatment schemes simply based on visual inspection.

Unveiling the enigma of Brain-resident immune cells.

The immune system has been extensively studied in traditional immune hubs like the spleen and lymph nodes. However, recent advances in immunology highlight unique immune cell characteristics across anatomical compartments. In this study, we challenged conventional thinking by uncovering distinct immune cell populations within the brain parenchyma, separate from those in the blood, meninges, and choroid plexus, with unique transcriptional profiles. Brain-resident immune cells are not derived from maternal immune cells, and age-related changes, with an increase in CD8 + T cells in aged mice, are noted. Alzheimer's disease (AD) alters microglia's interaction with brain-resident immune cells, emphasizing immune-brain dynamics. Furthermore, we reveal dynamic immune cell interactions and essential cytokine roles in brain homeostasis, with stable cytokine expression but emerging signaling pathways in AD. In summary, this study advances our understanding of brain-resident immune cells in both normal and pathological conditions.

Lrig1-expression confers suppressive function to CD4+ cells and is essential for averting autoimmunity via the Smad2/3/Foxp3 axis.

Regulatory T cells (Treg) are CD4+ T cells with immune-suppressive function, which is defined by Foxp3 expression. However, the molecular determinants defining the suppressive population of T cells have yet to be discovered. Here we report that the cell surface protein Lrig1 is enriched in suppressive T cells and controls their suppressive behaviors. Within CD4+ T cells, Treg cells express the highest levels of Lrig1, and the expression level is further increasing with activation. The Lrig1+ subpopulation from T helper (Th) 17 cells showed higher suppressive activity than the Lrig1- subpopulation. Lrig1-deficiency impairs the suppressive function of Treg cells, while Lrig1-deficient naïve T cells normally differentiate into other T cell subsets. Adoptive transfer of CD4+Lrig1+ T cells alleviates autoimmune symptoms in colitis and lupus nephritis mouse models. A monoclonal anti-Lrig1 antibody significantly improves the symptoms of experimental autoimmune encephalomyelitis. In conclusion, Lrig1 is an important regulator of suppressive T cell function and an exploitable target for treating autoimmune conditions.

Defective N-glycosylation in tumor-infiltrating CD8+ T cells impairs IFN-γ-mediated effector function.

T cell-mediated antitumor immunity is modulated, in part, by N-glycosylation. However, the interplay between N-glycosylation and the loss of effector function in exhausted T cells has not yet been fully investigated. Here, we delineated the impact of N-glycosylation on the exhaustion of tumor-infiltrating lymphocytes in a murine colon adenocarcinoma model, focusing on the IFN-γ-mediated immune response. We found that exhausted CD8+ T cells downregulated the oligosaccharyltransferase complex, which is indispensable for N-glycan transfer. Concordant N-glycosylation deficiency in tumor-infiltrating lymphocytes leads to loss of antitumor immunity. Complementing the oligosaccharyltransferase complex restored IFN-γ production and alleviated CD8+ T cell exhaustion, resulting in reduced tumor growth. Thus, aberrant glycosylation induced in the tumor microenvironment incapacitates effector CD8+ T cells. Our findings provide insights into CD8+ T cell exhaustion by incorporating N-glycosylation to understand the characteristic loss of IFN-γ, opening new opportunities to amend the glycosylation status in cancer immunotherapies.

Development of a population pharmacokinetic model and optimal dosing regimen of leflunomide in Korean population.

PURPOSE: Leflunomide is an immunosuppressive drug indicated for the treatment of rheumatoid arthritis (RA). While the pharmacokinetics (PK) of its active metabolite A771726 reportedly show large interindividual variability, no efficient dose individualization strategy is currently available. The goal of this work was to develop a population PK model for A771726 and propose an optimal individualized dosing strategy. METHODS: A771726 plasma concentration data were collected from 50 healthy male volunteers participating in two leflunomide PK studies given a single oral dose of 40 mg. Concentrations were elevated in low body weight (WT) subjects and showed multiple peaks. Thus, A771726 PK modeling was conducted incorporating allometry scaling and enterohepatic circulation (EHC). For dose optimization, simulating a set of 1000 virtual subjects from the developed model and dividing the subjects into 5 groups with WT of 50, 60, 70, 80, 90 kg, respectively, the optimal dose was explored that achieves the drug concentration most similar to the target, which was defined as the concentration for the 70 kg subject treated with the current standard dosage regimen (the loading dose of 100 mg QD for 3 days, followed by the maintenance dose of 20 mg QD). RESULTS: The data were best described by a two compartment model with first order absorption incorporating EHC with the bile released into the intestine. None of the covariates tested was found to be significant other than WT used in allometry. Simulation showed that the optimal loading dose increased by 15 mg for every 10 kg increment in WT while the optimal maintenance dose was 15 and 25 mg for 50 and 90 kg groups, respectively, and the same (= 20 mg) for the others. Large concentration differences from the target observed in low and high WT groups disappeared when optimal doses were given. CONCLUSIONS: This work demonstrates the importance of a population PK model-based dose optimization approach in maintaining drug therapeutic concentrations in leflunomide treatment.

Effect of Rifampicin on the Pharmacokinetics of Evogliptin in Healthy Volunteers.

Purpose: Evogliptin (DA-1229) is a novel, potent, and selective dipeptidyl peptidase 4 (DPP-4) inhibitor for treating type 2 diabetes mellitus. This study investigates the effect of rifampicin on evogliptin pharmacokinetics. Patients and Methods: An open-label, crossover, one-sequence study was conducted on 12 healthy subjects. Reference baseline pharmacokinetic samples were collected on day 1 after the subjects were administered a single dose of 5 mg evogliptin. After a washout period, the subjects were administered 600 mg rifampicin once daily for 10 days, from days 8 to 17, for full induction of hepatic enzyme activity. On day 17, single doses of evogliptin (5 mg) were administered along with rifampicin (600 mg). The test pharmacokinetic samples were collected with a sampling schedule identical to that used for the reference. Results: Maximum concentration (Cmax) and area under the plasma drug concentration-time curve (AUC0-96h) of evogliptin with and without co-administration of rifampicin were compared. Reference and test Cmax and AUC0-96h values of evogliptin were 4.70 ng/mL vs 4.86 ng/mL and 153.97 ng∙h/mL vs 58.83 ng∙h/mL, respectively. All adverse events were mild in intensity and considered unrelated to evogliptin administration. Conclusion: Rifampicin decreased the AUC0-96h of evogliptin by 61.8% without significantly affecting Cmax. The mechanism underlying the decrease in AUC0-96h is thought to be the induction of cytochrome P450 (CYP), especially 3A, by rifampicin. The adverse events, none of which were serious, were not significantly altered by the concomitant administration of evogliptin and rifampicin. Nevertheless, it would be prudent that evogliptin dosing should be carefully considered when co-administered with CYP3A inducers.

A Pharmacometric Model to Predict Chemotherapy-Induced Myelosuppression and Associated Risk Factors in Non-Small Cell Lung Cancer.

Chemotherapy often induces severe neutropenia due to the myelosuppressive effect. While predictive pharmacokinetic (PK)/pharmacodynamic (PD) models of absolute neutrophil count (ANC) after anticancer drug administrations have been developed, their deployments to routine clinics have been limited due to the unavailability of PK data and sparseness of PD (or ANC) data. Here, we sought to develop a model describing temporal changes of ANC in non-small cell lung cancer patients receiving (i) combined chemotherapy of paclitaxel and cisplatin and (ii) granulocyte colony stimulating factor (G-CSF) treatment when needed, under such limited circumstances. Maturation of myelocytes into blood neutrophils was described by transit compartments with negative feedback. The K-PD model was employed for drug effects with drug concentration unavailable and the constant model for G-CSF effects. The fitted model exhibited reasonable goodness of fit and parameter estimates. Covariate analyses revealed that ANC decreased in those without diabetes mellitus and female patients. Using the final model obtained, an R Shiny web-based application was developed, which can visualize predicted ANC profiles and associated risk of severe neutropenia for a new patient. Our model and application can be used as a supportive tool to identify patients at the risk of grade 4 neutropenia early and suggest dose reduction.

Synergistic Effects of Fluorine and WO3 Nanoparticles on the Surface of TiO2 Hollow Spheres for Enhanced Photocatalytic Activity under Visible Light Irradiation.

TiO2 is an attractive catalyst for the photocatalytic degradation of organic pollutants. However, owing to its large band gap, it can only be activated by ultraviolet (UV) light, which constitutes a small portion of solar energy. Therefore, there has been significant interest in extending its light absorption range from UV to visible light. In this study, fluorinated TiO2 hollow spheres (FTHSs) were prepared via a rapid and simple wet chemical process using ammonium hexafluorotitanate, and then FTHS/WO3 heterostructures with different weight ratios of the FTHS and WO3 nanoparticles were synthesized via a simple wet impregnation method. The formation of the hybrid structure was confirmed by various characterization techniques. The photocatalytic activity of the synthesized photocatalysts in the photodegradation of rhodamine B, a model pollutant, was evaluated under visible light irradiation. The FTHS/WO3 heterostructures exhibited significantly improved photocatalytic activity compared to the bare FTHS or WO3 nanoparticles. The photodegradation efficiency of the FTHS/WO3 heterostructure in the present study was up to 0.0581 min-1. Detailed mechanisms that lead to the enhanced photocatalytic activity of the heterostructures are discussed. In addition, comparative experiments reveal that the photodegradation efficiency of the FTHS/WO3 heterostructure under visible light irradiation is superior to that of the P25/WO3 heterostructure prepared from the commercially available TiO2 catalyst (P25) via the same impregnation method.

Quantifying intracellular trafficking of silica-coated magnetic nanoparticles in live single cells by site-specific direct stochastic optical reconstruction microscopy.

BACKGROUND: Nanoparticles have been used for biomedical applications, including drug delivery, diagnosis, and imaging based on their unique properties derived from small size and large surface-to-volume ratio. However, concerns regarding unexpected toxicity due to the localization of nanoparticles in the cells are growing. Herein, we quantified the number of cell-internalized nanoparticles and monitored their cellular localization, which are critical factors for biomedical applications of nanoparticles. METHODS: This study investigates the intracellular trafficking of silica-coated magnetic nanoparticles containing rhodamine B isothiocyanate dye [MNPs@SiO2(RITC)] in various live single cells, such as HEK293, NIH3T3, and RAW 264.7 cells, using site-specific direct stochastic optical reconstruction microscopy (dSTORM). The time-dependent subdiffraction-limit spatial resolution of the dSTORM method allowed intracellular site-specific quantification and tracking of MNPs@SiO2(RITC). RESULTS: The MNPs@SiO2(RITC) were observed to be highly internalized in RAW 264.7 cells, compared to the HEK293 and NIH3T3 cells undergoing single-particle analysis. In addition, MNPs@SiO2(RITC) were internalized within the nuclei of RAW 264.7 and HEK293 cells but were not detected in the nuclei of NIH3T3 cells. Moreover, because of the treatment of the MNPs@SiO2(RITC), more micronuclei were detected in RAW 264.7 cells than in other cells. CONCLUSION: The sensitive and quantitative evaluations of MNPs@SiO2(RITC) at specific sites in three different cells using a combination of dSTORM, transcriptomics, and molecular biology were performed. These findings highlight the quantitative differences in the uptake efficiency of MNPs@SiO2(RITC) and ultra-sensitivity, varying according to the cell types as ascertained by subdiffraction-limit super-resolution microscopy.

The use of real-world data in drug repurposing.

Drug repurposing, or repositioning, is to identify new uses for existing drugs. Significantly reducing the costs and time-to-market of a medication, drug repurposing has been an alternative tool to accelerate drug development process. On the other hand, 'real world data (RWD)' has been also increasingly used to support drug development process owing to its better representing actual pattern of drug treatment and outcome in real world. In the healthcare domain, RWD refers to data collected from sources other than traditional clinical trials; for example, in electronic health records or claims and billing data. With the enactment of the 21st Century Cures Act, which encourages the use of RWD in drug development and repurposing as well, such increasing trend in RWD use will be expedited. In this context, this review provides an overview of recent progresses in the area of drug repurposing where RWD was used by firstly introducing the increasing trend and regulatory change in the use of RWD in drug development, secondly reviewing published works using RWD in drug repurposing, classifying them in the repurposing strategy, and lastly addressing limitations and advantages of RWDs.

Effects of SLCO1B1 and SLCO1B3 Genetic Polymorphisms on Valsartan Pharmacokinetics in Healthy Korean Volunteers.

Purpose: This study aimed to examine OATP1B1 (SLCO1B1) and OATP1B3 (SLCO1B3) on the pharmacokinetics of valsartan. Twenty-five subjects were genotyped for 16 single-nucleotide polymorphisms of the SLCO1B1 and SLCO1B3 genes. Methods: After a single dose of 160 mg of valsartan was orally administered to healthy male volunteers, drug concentrations were assayed up to 48 h. The 25 subjects were genotyped for 16 single-nucleotide polymorphisms (SNPs) of the SLCO1B1 and SLCO1B3 genes. Subjects were classified into groups according to their SLCO1B1*1B haplotype; 23 subjects were carriers of SLCO1B1*1B and two subjects were included in the reference group with SLCO1B1*1A/*1A. Alternations of the splicing factor-binding site pattern caused by the given mutation were evaluated with the Human Splicing Finder (HSF) 3.1. Results: The subjects who carried SLCO1B1*1B showed a 2.3-fold higher clearance than those without the *1B haplotype. Mean Cmax and AUCinf were reduced by 45% and 54%, respectively, in the SLCO1B1*1B genotype group compared to the reference group with the *1A/*1A genotype (p < 0.01). The carriers of the rs4149153 T allele of SLCO1B3 had a 27% lower mean Cmax and a 1.5-fold higher Vd compared to homozygotic CC carriers (p < 0.05). In a combined analysis of SLCO1B1 and SLCO1B3, subjects not carrying SLCO1B1 *1B and carrying SLCO1B3 rs4149153 T allele showed a 1.6-fold higher clearance than those with the other genotypes, whereas mean Cmax and AUClast were reduced by 35% and 42%, respectively (p < 0.05), in the subjects. HSF 3.1 analysis showed that rs4149153 could cause alterations of the acceptor splice site (TAAATACTAAAGAC to TAAATATTAAAGAC) with scoring change (from 72.57 to 71.92, difference = -0.9). Conclusion: It was found that plasma exposure to valsartan is significantly decreased in SLCO1B1*1B carriers and carriers of the rs4149153 T allele of SLCO1B3, possibly as a result of increased hepatic uptake.

Population Pharmacokinetics of Primaquine in the Korean Population.

While primaquine has long been used for malaria treatment, treatment failure is common. This study aims to develop a population pharmacokinetic model of primaquine and its metabolite, carboxyprimaquine, and examine factors influencing pharmacokinetic variability. The data was obtained from a clinical study in 24 Korean subjects randomly assigned to normal and obese groups. The participants received primaquine 15 mg daily for 4 days and blood samples were collected at day 4. Pharmacokinetic modeling was performed with NONMEM and using simulations; the influences of doses and covariates on drug exposure were examined. A minimal physiology-based pharmacokinetic model connected with a liver compartment comprehensively described the data, with CYP450 mediated clearance being positively correlated with the body weight and CYP2D6 activity score (p < 0.05). In the simulation, while the weight-normalized area under drug concentration for primaquine in the obese group decreased by 29% at the current recommended dose of 15 mg, it became similar to the normal weight group at a weight-normalized dose of 3.5 mg/kg. This study has demonstrated that the body weight and CYP2D6 activity score significantly influence the pharmacokinetics of primaquine. The developed model is expected to be used as a basis for optimal malaria treatment in Korean patients.

Predicting the longitudinal changes of levodopa dose requirements in Parkinson's disease using item response theory assessment of real-world Unified Parkinson's Disease Rating Scale.

Item response theory (IRT) has been recently adopted to successfully characterize the progression of Parkinson's disease using serial Unified Parkinson's Disease Rating Scale (UPDRS) measurements. However, it has yet to be applied in predicting the longitudinal changes of levodopa dose requirements in the real-world setting. Here we use IRT to extract two latent variables that represent tremor and non-tremor-related symptoms from baseline assessments of UPDRS Part III scores. We show that relative magnitudes of the two latent variables are strong predictors of the progressive increase of levodopa equivalent dose (LED). Retrospectively collected item-level UPDRS Part III scores and longitudinal records of prescribed medication doses of 128 patients with de novo PD extracted from the electronic medical records were used for model building. Supplementary analysis based on a subset of 36 patients with at least three serial assessments of UPDRS Part III scores suggested that the two latent variables progress at significantly different rates. A web application was developed to facilitate the use of our model in making individualized predictions of future LED and disease progression.

Development of a risk scoring system for predicting acute kidney injury after minimally invasive partial and radical nephrectomy: a retrospective study.

BACKGROUND: Acute kidney injury after partial or radical nephrectomy remains an unsolved problem even when using minimally invasive techniques. We aimed to identify risk factors for acute kidney injury (AKI) after minimally invasive nephrectomy and to develop a clinical risk scoring system. METHODS: Medical records of 1762 patients who underwent minimally invasive laparoscopic or robot-assisted laparoscopic partial (n = 1009) or radical (n = 753) nephrectomy from December 2005 to November 2018 were reviewed. Candidate risk factors were screened using univariate analysis and ranked using linear discriminant analysis; top ranking factors were incorporated into a multivariate logistic regression model. Then, the final clinical scoring system was created based on the estimated odds ratios. RESULTS: The incidence of acute kidney injury after partial or radical nephrectomy was 20.3 and 61.6%, respectively. Risk factors incorporated into the scoring system included: size of the parenchymal mass removed (3 < parenchymal mass ≤ 4 cm, 1 point; 4 < parenchymal mass ≤ 6 cm, 3 points; parenchymal mass > 6 cm, 5 points), male sex (2 points), diabetes mellitus (1 point), warm ischemia time ≥ 25 min (1 point), and immediate postoperative neutrophil count ≥ 12,000 µl-1 (1 point) in patients with partial nephrectomy, and sex (male, 10 points; female, 7 points) in patients with radical nephrectomy. For risk scores of 0-4, 5-6, 7, 8-9, and 10 points, the probabilities of acute kidney injury were approximately 10, 20, 40, 60, and 80%, respectively. The predictive accuracy of the scoring system was 0.827 (95% CI 0.789-0.865). CONCLUSION: Our risk scoring system could help clinicians identify those at risk of acute kidney injury after minimally invasive partial or radical nephrectomy, thereby optimizing postoperative management.