Fracture Management in Chronic Kidney Disease: Challenges and Considerations for Orthopedic Surgeons.

Orthopedic surgeons treating fractures need to consider comorbidities, including chronic kidney disease (CKD), which affects millions worldwide. CKD patients are at elevated risk of fractures due to osteoporosis, especially in advanced stages. In addition, fractures in CKD patients pose challenges due to impaired bone healing and increased post-fracture complications including surgical site infection and nonunion. In this article, we will discuss factors that must be considered when treating fractures in CKD patients. Perioperative management includes careful adjustment of hemodialysis schedules, selection of anesthetic methods, and addressing bleeding tendencies. Tourniquet usage for fractures in limbs with arteriovenous fistulae should be cautious. Pain medication should be administered carefully, with opioids like hydromorphone preferred over nonsteroidal anti-inflammatory drugs. Medical management after fractures should address underlying factors and include physical rehabilitation to reduce the risk of subsequent fractures. A comprehensive approach to fracture management in CKD patients can improve outcomes.

The effect of renal function on the pharmacokinetics and pharmacodynamics of enavogliflozin, a potent and selective sodium-glucose cotransporter-2 inhibitor, in type 2 diabetes.

AIMS: To explore the effect of renal function on the pharmacokinetic (PK) and pharmacodynamic (PD) profile and safety of enavogliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes mellitus (T2DM). METHODS: An open-label, two-part clinical trial was conducted in T2DM patients, stratified by renal function: Group 1, normal renal function; Group 2, mild renal impairment (RI); Group 3, moderate RI; and Group 4, severe RI. In Part A, Groups 2 and 4 received enavogliflozin 0.5 mg once. In Part B, Groups 1 and 3 received enavogliflozin 0.5 mg once daily for 7 days. Serial blood and timed urine samples were collected to analyse the PK and PD characteristics of enavogliflozin. Pearson's correlation coefficients were calculated to assess the correlations between PK or PD parameters and creatinine clearance (CrCL). RESULTS: A total of 21 patients completed the study as planned. The area under the curve (AUC) for enavogliflozin was not significantly correlated with CrCL, although the maximum concentration slightly decreased as renal function decreased. By contrast, daily urinary glucose excretion (UGE) was positively correlated with CrCL after both single- (r = 0.7866, p < 0.0001) and multiple-dose administration (r = 0.6606, p = 0.0438). CONCLUSIONS: Systemic exposure to oral enavogliflozin 0.5 mg was similar among the patients with T2DM regardless of their renal function levels. However, the glucosuric effect of enavogliflozin decreased with RI. Considering the UGE observed and approved therapeutic use of other SGLT2 inhibitors, the efficacy of enavogliflozin with regard to glycaemic control could be explored in patients with mild and moderate RI (estimated glomerular filtration rate ≥30 or ≥45 mL/min/1.73 m2) in a subsequent larger study.

Engineering Two-Dimensional Nodal Semimetals in Functionalized Biphenylene by Fluorine Adatoms.

We propose a band engineering scheme on the biphenylene network, a newly synthesized carbon allotrope. We illustrate that the electronic structure of the biphenylene network can be significantly altered by controlling conditions affecting the symmetry and destructive interference of wave functions through periodic fluorination. First, we investigate the mechanism for the appearance of a type-II Dirac fermion in a pristine biphenylene network. We show that the essential ingredients are mirror symmetries and stabilization of the compact localized eigenstates via destructive interference. While the former is used for the band-crossing point along high symmetry lines, the latter induces highly inclined Dirac dispersions. Subsequently, we demonstrate the transformation of the biphenylene network's type-II Dirac semimetal phase into various Dirac phases such as type-I Dirac, gapped type-II Dirac, and nodal line semimetals through the deliberate disruption of mirror symmetry or modulation of destructive interference by varying the concentration of fluorine atoms.

Development of Drug Efficacy Testing Platform for Glomerulonephritis.

We developed a 3D glomeruli tissue chip for glomerulonephritis (GN) testing, featuring a gravity-driven glomerular filtration barrier (GFB) with human podocytes and endothelial cells with a bidirectional flow in the bottom channel. Using puromycin-induced GN, we observed decreased cell viability, increased albumin permeability, and reduced WT1 and nephrin compared to the normal GFB. Tacrolimus restored cell viability, reduced albumin permeability, and increased WT1 expression. Using serum from five membranous nephropathy (MN) patients, we created MN models using a GFB-mimicking chip. A notable decline in cell viability was observed in the serum-induced MN1 and MN2 models. However, tacrolimus restored it. Albumin permeability was reduced in the MN1, MN2, and MN5 models by tacrolimus treatment. MN1 displayed the best clinical response to tacrolimus, exhibiting increased expression of WT1 in chip-based evaluations after tacrolimus treatment. We successfully evaluated the efficacy of tacrolimus using puromycin-induced and serum-induced GN models on a chip that mimicked the structure and function of the GFB. The GFB-mimicking chip holds promise as a personalized platform for assessing drug efficacy using patient serum samples.

Antibiotic-induced intestinal microbiota depletion can attenuate the acute kidney injury to chronic kidney disease transition via NADPH oxidase 2 and trimethylamine-N-oxide inhibition.

Intestinal microbiota and their metabolites affect systemic inflammation and kidney disease outcomes. Here, we investigated the key metabolites associated with the acute kidney injury (AKI)-to chronic kidney disease (CKD) transition and the effect of antibiotic-induced microbiota depletion (AIMD) on this transition. In 61 patients with AKI, 59 plasma metabolites were assessed to determine the risk of AKI-to-CKD transition. An AKI-to-CKD transition murine model was established four weeks after unilateral ischemia-reperfusion injury (IRI) to determine the effects of AIMD on the gut microbiome, metabolites, and pathological responses related to CKD transition. Human proximal tubular epithelial cells were challenged with CKD transition-related metabolites, and inhibitory effects of NADPH oxidase 2 (NOX2) signals were tested. Based on clinical metabolomics, plasma trimethylamine N-oxide (TMAO) was associated with a significantly increased risk for AKI-to-CKD transition [adjusted odds ratio 4.389 (95% confidence interval 1.106-17.416)]. In vivo, AIMD inhibited a unilateral IRI-induced increase in TMAO, along with a decrease in apoptosis, inflammation, and fibrosis. The expression of NOX2 and oxidative stress decreased after AIMD. In vitro, TMAO induced fibrosis with NOX2 activation and oxidative stress. NOX2 inhibition successfully attenuated apoptosis, inflammation, and fibrosis with suppression of G2/M arrest. NOX2 inhibition (in vivo) showed improvement in pathological changes with a decrease in oxidative stress without changes in TMAO levels. Thus, TMAO is a key metabolite associated with the AKI-to-CKD transition, and NOX2 activation was identified as a key regulator of TMAO-related AKI-to-CKD transition both in vivo and in vitro.

Sodium Intake Estimation in Hospital Patients Using AI-Based Imaging: Prospective Pilot Study.

BACKGROUND: Measurement of sodium intake in hospitalized patients is critical for their care. In this study, artificial intelligence (AI)-based imaging was performed to determine sodium intake in these patients. OBJECTIVE: The applicability of a diet management system was evaluated using AI-based imaging to assess the sodium content of diets prescribed for hospitalized patients. METHODS: Based on the information on the already investigated nutrients and quantity of food, consumed sodium was analyzed through photographs obtained before and after a meal. We used a hybrid model that first leveraged the capabilities of the You Only Look Once, version 4 (YOLOv4) architecture for the detection of food and dish areas in images. Following this initial detection, 2 distinct approaches were adopted for further classification: a custom ResNet-101 model and a hyperspectral imaging-based technique. These methodologies focused on accurate classification and estimation of the food quantity and sodium amount, respectively. The 24-hour urine sodium (UNa) value was measured as a reference for evaluating the sodium intake. RESULTS: Results were analyzed using complete data from 25 participants out of the total 54 enrolled individuals. The median sodium intake calculated by the AI algorithm (AI-Na) was determined to be 2022.7 mg per day/person (adjusted by administered fluids). A significant correlation was observed between AI-Na and 24-hour UNa, while there was a notable disparity between them. A regression analysis, considering patient characteristics (eg, gender, age, renal function, the use of diuretics, and administered fluids) yielded a formula accounting for the interaction between AI-Na and 24-hour UNa. Consequently, it was concluded that AI-Na holds clinical significance in estimating salt intake for hospitalized patients using images without the need for 24-hour UNa measurements. The degree of correlation between AI-Na and 24-hour UNa was found to vary depending on the use of diuretics. CONCLUSIONS: This study highlights the potential of AI-based imaging for determining sodium intake in hospitalized patients.

Long-term exposure to high perceived temperature and risk of mortality among patients with chronic kidney disease.

Health risks due to climate change are emerging, particularly from high-temperature exposure. The perceived temperature is an equivalent temperature based on the complete heat budget model of the human body. Therefore, we aimed to analyze the effect of perceived temperature on overall mortality among patients with chronic kidney disease. In total, 32,870 patients with chronic kidney disease in Seoul participated in this retrospective study (2001-2018) at three medical centers. The perceived temperature during the summer season was calculated using meteorological factors, including the air temperature near the automated weather station, dew point temperature, wind velocity, and total cloud amount. We assessed the association between perceived temperature using Kriging spatial interpolation and mortality in patients with CKD in the time-varying Cox proportional hazards model that was adjusted for sex, age, body mass index, hypertension, diabetes mellitus, estimated glomerular filtration rate, smoking, alcohol consumption, and educational level. During the 6.14 ± 3.96 years of follow-up, 3863 deaths were recorded. In multivariable analysis, the average level of perceived temperature and maximum level of perceived temperature demonstrated an increased risk of overall mortality among patients with chronic kidney disease. The concordance index for mortality of perceived temperature was higher than temperature, discomfort index, and heat index. When stratified by age, diabetes mellitus, and estimated glomerular filtration rate, patients with chronic kidney disease with young age (age <65 years) showed higher hazard ratio for mortality (interaction P = 0.049). Moreover, the risk of death in the winter and spring seasons was more significant compared to that of the summer and autumn seasons. Therefore, long-term exposure to high perceived temperature during summer increases the risk of mortality among patients with chronic kidney disease.

Comparison between characteristics of immunoglobulin M nephropathy and other glomerular diseases.

Background: Immunoglobulin M (IgM) nephropathy (IgMN) is characterized by the IgM deposition in the kidney's mesangium. We assessed the impact of electron-dense deposits (EDDs) on IgMN and compared it to other kidney diseases. Methods: We enrolled 63 adult patients with IgMN who underwent renal biopsy from May 2003 to June 2017. We compared clinicopathological features of IgMN based on EDD presence; compared characteristics to 91 minimal change disease (MCD), 103 focal segmental glomerulosclerosis (FSGS), and 469 immunoglobulin A nephropathy (IgAN) patients. Renal events were defined as a >50% decrease in estimated glomerular filtration rate (eGFR), eGFR of <15 mL/min/1.73 m2, or end-stage renal disease development. Results: IgMN patients with EDDs had increased mesangial cellularity, matrix accumulation, prominent immunofluorescent staining, and more diffuse podocyte effacement than those without EDD. Clinical characteristics and renal outcomes did not differ significantly based on EDD presence. During 79.5 ± 58.8 months of follow-up, renal events developed in 46.2% and 46.0% of IgMN cases with and without EDD. IgMN (46.0%) and FSGS cases (40.8%) had similar frequencies of renal events and higher frequency than MCD (18.7%) or IgAN cases (26.4%). IgMN cases had more severe manifestations than MCD and IgAN; higher blood pressure, lower proteinuria, and eGFR levels at biopsy than MCD cases; higher blood pressure, proteinuria, frequency of acute kidney injury, and lower eGFR levels. Conclusion: Clinical characteristics of IgMN did not differ based on EDD presence. Therefore, IgMN should be defined based on IF findings. IgMN shared clinical characteristics with FSGS but had more severe than MCD and IgAN.

Long-term ozone exposure and mortality in patients with chronic kidney disease: a large cohort study.

BACKGROUND: Epidemiologic studies on the effects of long-term exposure to ozone (O3) have shown inconclusive results. It is unclear whether to O3 has an effect on chronic kidney disease (CKD). We investigated the effects of O3 on mortality and renal outcome in CKD. METHODS: We included 61,073 participants and applied Cox proportional hazards models to examine the effects of ozone on the risk of end-stage renal disease (ESRD) and mortality in a two-pollutants model adjusted for socioeconomic status. We calculated the concentration of ozone exposure one year before enrollment and used inverse distance weighting (IDW) for interpolation, where the exposure was evenly distributed. RESULTS: In the single pollutant model, O3 was significantly associated with an increased risk of ESRD and all-cause mortality. Based on the O3 concentration from IDW interpolation, this moving O3 average was significantly associated with an increased risk of ESRD and all-cause mortality. In a two-pollutants model, even after we adjusted for other measured pollutants, nitrogen dioxide did not attenuate the result for O3. The hazard ratio (HR) value for the district-level assessment is 1.025 with a 95% confidence interval (CI) of 1.014-1.035, while for the point-level assessment, the HR value is 1.04 with a 95% CI of 1.035-1.045. The impact of ozone on ESRD, hazard ratio (HR) values are, 1.049(95%CI: 1.044-1.054) at the district unit and 1.04 (95%CI: 1.031-1.05) at the individual address of the exposure assessment. The ozone hazard ratio for all-cause mortality was 1.012 (95% confidence interval: 1.008-1.017) for administrative districts and 1.04 (95% confidence interval: 1.031-1.05) for individual addresses. CONCLUSIONS: This study suggests that long-term ambient O3 increases the risk of ESRD and mortality in CKD. The strategy to decrease O3 emissions will substantially benefit health and the environment.

Impact of metformin on cardiovascular and kidney outcome based on kidney function status in type 2 diabetic patients: a multicentric, retrospective cohort study.

Metformin is the primary treatment for type 2 diabetes mellitus (T2DM) due to its effectiveness in improving clinical outcomes in patients with preserved renal function, however, the evidence on the effectiveness of metformin in various renal functions is lacking. We performed a retrospective, multicenter, observational study used data of patients with T2DM obtained from three tertiary hospitals' databases. Patients given metformin within run-in periods and with at least one additional prescription formed the metformin cohort. A control cohort comprised those prescribed oral hypoglycemic agents other than metformin and never subsequently received a metformin prescription within observation period. For patients without diabetic nephropathy (DN), the outcomes included events of DN, major adverse cardiovascular events (MACE), and major adverse kidney events (MAKE). After 1:1 propensity matching, 1994 individuals each were selected for the metformin and control cohorts among T2DM patients without baseline DN. The incidence rate ratios (IRR) for DN, MACEs, and MAKEs between cohorts were 1.06 (95% CI 0.96-1.17), 0.76 (0.64-0.92), and 0.45 (0.33-0.62), respectively. In cohorts with renal function of CKD 3A, 3B, and 4, summarized IRRs of MACEs and MAKEs were 0.70 (0.57-0.87) and 0.39 (0.35-0.43) in CKD 3A, 0.83 (0.74-0.93) and 0.44 (0.40-0.48) in CKD 3B, and 0.71 (0.60-0.85) and 0.45 (0.39-0.51) in CKD 4. Our research indicates that metformin use in T2DM patients across various renal functions consistently correlates with a decreased risk of overt DN, MACE, and MAKE.

Routine Ureteral Stenting in Kidney Transplant Reduces Postoperative Hydronephrosis and Percutaneous Ureteral Interventions: A Single-Center Experience.

OBJECTIVES: The effect of routine ureteral stenting on postoperative hydronephrosis and percutaneous ureteral intervention in kidney transplant remains unknown. This study aimed to evaluate the effects of routine ureteral stenting on hydronephrosis and percutaneous ureteral intervention and the cost benefit of ureteral stenting in kidney transplant. MATERIALS AND METHODS: We retrospectively analyzed patients who underwent kidney transplant at a tertiary institution between 2005 and 2021. We adopted a ureteral stentingprotocol in2017, anda comparisonwas performed with previous patients without stents. RESULTS: In total, 539 patients underwent kidney transplant(271 with stents [51.3%], 268 without stents [49.7%]). Hydronephrosis was detected in 16 cases (5.9%) and 30 cases (11.2%) of groups with and without stents,respectively (P = .041). Among patients with hydronephrosis, the number of patients who underwent percutaneous ureteral intervention was significantly lower in the stent group than in the nostent group (1 [6.25%] vs 10 [33.33%]; P= .014).Twenty patients (3.71%) experienced major urologic complications (19 [7.1%] in the no-stent group, and 1 [0.4%] in the stent group; P = .001). No significant differences between the groups were shown in the incidence of urinary tract infections within 3 months of transplant (24 [8.9%] vs 22 [8.2%]; P = .846). No differences were shown between the groups in ureterovesical anastomosis time (24.4 vs 24.03 min; P = .699) or 1-year graft survival (97% vs 97.8%; P = .803). The healthcare cost was significantly lower in the stent group than in the no-stent group by $1702.05 ($15000.89 vs $16702.95; P < .001). CONCLUSIONS: Routine ureteral stenting in kidney transplant significantly decreased the incidence of postoperative hydronephrosis and percutaneous ureteral intervention. Stenting did notlead to increased urinary tract infections and was cost-effective.

Efficacy of Mesenchymal-Stromal-Cell-Derived Extracellular Vesicles in Ameliorating Cisplatin Nephrotoxicity, as Modeled Using Three-Dimensional, Gravity-Driven, Two-Layer Tubule-on-a-Chip (3D-MOTIVE Chip).

Mesenchymal stromal cell (MSC)-derived extracellular vesicles (EVs) are known to have a therapeutic effect on nephrotoxicity. As animal models require significant time and resources to evaluate drug effects, there is a need for a new experimental technique that can accurately predict drug effects in humans. We evaluated the therapeutic effect of MSC-derived EVs in cisplatin nephrotoxicity using a three-dimensional, gravity-driven, two-layer tubule-on-a-chip (3D-MOTIVE chip). In the 3D-MOTIVE chip, 10 µM cisplatin decreased the number of attached cells compared to the vehicle. Conversely, annexin V and reactive oxygen species (ROS) were increased. Cell viability was increased 2.8-fold and 2.5-fold after treatment with EVs at 4 and 8 µg/mL, respectively, compared to the cisplatin-induced nephrotoxicity group. Cell attachment was increased 2.25-fold by treatment with 4 µg/mL EVs and 2.02-fold by 8 µg/mL EVs. Annexin V and ROS levels were decreased compared to those in the cisplatin-induced nephrotoxicity group. There were no significant differences in annexin V and ROS levels according to EV concentration. In sum, we created a cisplatin-induced nephrotoxicity model on a 3D-MOTIVE chip and found that MSC-derived EVs could restore cell viability. Thus, MSC-derived EVs may have the potential to ameliorate cisplatin-induced nephrotoxicity.

Requirements for Trustworthy Artificial Intelligence and its Application in Healthcare.

OBJECTIVES: Artificial intelligence (AI) technologies are developing very rapidly in the medical field, but have yet to be actively used in actual clinical settings. Ensuring reliability is essential to disseminating technologies, necessitating a wide range of research and subsequent social consensus on requirements for trustworthy AI. METHODS: This review divided the requirements for trustworthy medical AI into explainability, fairness, privacy protection, and robustness, investigated research trends in the literature on AI in healthcare, and explored the criteria for trustworthy AI in the medical field. RESULTS: Explainability provides a basis for determining whether healthcare providers would refer to the output of an AI model, which requires the further development of explainable AI technology, evaluation methods, and user interfaces. For AI fairness, the primary task is to identify evaluation metrics optimized for the medical field. As for privacy and robustness, further development of technologies is needed, especially in defending training data or AI algorithms against adversarial attacks. CONCLUSIONS: In the future, detailed standards need to be established according to the issues that medical AI would solve or the clinical field where medical AI would be used. Furthermore, these criteria should be reflected in AI-related regulations, such as AI development guidelines and approval processes for medical devices.

Prostaglandin F2α analogue, bimatoprost ameliorates colistin-induced nephrotoxicity.

Colistin (polymyxin E) is an antibiotic that is effective against multidrug-resistant gram-negative bacteria. However, the high incidence of nephrotoxicity caused by colistin limits its clinical use. To identify compounds that might ameliorate colistin-induced nephrotoxicity, we obtained 1707 compounds from the Korea Chemical Bank and used a high-content screening (HCS) imaging-based assay. In this way, we found that bimatoprost (one of prostaglandin F2α analogue) ameliorated colistin-induced nephrotoxicity. To further assess the effects of bimatoprost on colistin-induced nephrotoxicity, we used in vitro and in vivo models. In cultured human proximal tubular cells (HK-2), colistin induced dose-dependent cytotoxicity. The number of terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells, indicative of apoptosis, was higher in colistin-treated cells, but this effect of colistin was ameliorated by cotreatment with bimatoprost. The generation of reactive oxygen species, assessed using 2,7-dichlorodihydrofluorescein diacetate, was less marked in cells treated with both colistin and bimatoprost than in those treated with colistin alone. Female C57BL/6 mice (n = 10 per group) that were intraperitoneally injected with colistin (10 mg/kg/12 hr) for 14 days showed high blood urea nitrogen and serum creatinine concentrations that were reduced by the coadministration of bimatoprost (0.5 mg/kg/12 hr). In addition, kidney injury molecule-1 (KIM1) and Neutrophil gelatinase-associated lipocalin (NGAL) expression also reduced by bimatoprost administration. Further investigation in tubuloid and kidney organoids also showed that bimatoprost attenuated the nephrotoxicity by colistin, showing dose-dependent reducing effect of KIM1 expression. In this study, we have identified bimatoprost, prostaglandin F2α analogue as a drug that ameliorates colistin-induced nephrotoxicity.

Electronic alert outpatient protocol improves the quality of care for the risk of postcontrast acute kidney injury following computed tomography.

BACKGROUND: Prevention and diagnosis of postcontrast acute kidney injury (AKI) after contrast-enhanced computed tomography is burdensome in outpatient department. We investigated whether an electronic alert system could improve prevention and diagnosis of postcontrast AKI. METHODS: In March 2018, we launched an electronic alert system that automatically identifies patients with a baseline estimated glomerular filtration rate of <45 mL/min/1.73 m2, provides a prescription of fluid regimen, and recommends a follow-up for serum creatinine measurement. Participants prescribed contrast-enhanced computed tomography at outpatient department before and after the launch of the system were categorized as historical and alert group, respectively. Propensity for the surveillance of postcontrast AKI was compared using logistic regression. Risks of AKI, admission, mortality, and renal replacement therapy were analyzed. RESULTS: The historical and alert groups included 289 and 309 participants, respectively. The alert group was more likely to be men and take diuretics. The most frequent volume of prophylactic fluid in historical and alert group was 1,000 and 750 mL, respectively. Follow-up for AKI was more common in the alert group (adjusted odds ratio, 6.00; p < 0.001). Among them, incidence of postcontrast AKI was not statistically different. The two groups did not differ in risks of admission, mortality, or renal replacement therapy. CONCLUSION: The electronic alert system could assist in the detection of high-risk patients, prevention with reduced fluid volume, and proper diagnosis of postcontrast AKI, while limiting the prescribing clinicians' burden. Whether the system can improve long-term outcomes remains unclear.

Comparison of the performance of currently used estimated glomerular filtration rate equations with 24-hour urine creatinine clearance: sample analysis of randomised controlled trial participants.

OBJECTIVE: There are several equations for estimating the glomerular filtration rate (GFR), and each method has its limitations. We compared various estimated GFR (eGFR) equations with 24 hours urine creatinine clearance (24u-CCr). DESIGN: Sample analysis of randomised controlled trial participants. SETTING AND PARTICIPANTS: We compared the mean 24u-CCr values measured 2-3 times for 211 patients with eGFR values calculated using the following equations: isotope dilution mass spectrometry-Modification of Diet in Renal Disease (IDMS-MDRD) equation, Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation, equations for Koreans (KOR-IDMS-MDRD and KOR-CKD-EPI) and full age spectrum equation. OUTCOME MEASURES: Performance of various creatinine-based eGFR equations, including those with Korean coefficients, compared with the results of the 24u-CCr. RESULTS: IDMS-MDRD showed the best overall correlation with the 24u-CCr (R=0.949, p<0.001), and KOR-CKD-EPI showed the best agreement in terms of the intraclass correlation coefficient (ICC, 0.969, 95% CI 0.959 to 0.976, p<0.001). In subgroup analysis, IDMS-MDRD-GFR showed the highest ICCs in CKD stages 1 and 3 (ICC 0.872 in stage 1 and 0.927 in CKD stage 3, all p<0.001). KOR-CKD-EPI showed the highest ICC in CKD stage 2 (ICC 0.854, p<0.001). Overall, the accuracy of CKD-EPI (2021) was the highest at P15 (15%) and P30 (30%) (P15: 65.4 and P30: 97.6). In addition, CKD-EPI (2021) showed the highest P30 accuracy in CKD stage 1 (98.7), whereas KOR-IDMS-MDRD showed the highest P30 accuracy in CKD stages 2 and 3 (98.8 and 98.2, respectively). CONCLUSIONS: The IDMS-MDRD equation showed the best correlation and overall good agreement with the 24u-CCr; however, the accuracy was low. The most accurate measurements were obtained using the CKD-EPI (2021) equation in CKD stage 1 and the KOR-IDMS-MDRD equation in CKD stages 2-3; nevertheless, the CKD-EPI (2021) equation showed the best overall accuracy. TRIAL REGISTRATION NUMBER: NCT01552954.

Application of microphysiologic system to assess neutrophil extracellular trap in xenotransplantation.

Transplantation of organs, cells, or tissues from one species to another, known as xenotransplantation, has the potential to alleviate organ donor shortages and enhance the success of organ transplantation. However, the possibility of immunological rejection by the recipient is one of the biggest difficulties associated with xenotransplantation. The creation of neutrophil extracellular traps (NETs), also known as NETosis, is hypothesized as a mechanism of rejection. Innovations in microfluidics and co-culturing techniques have provided access to several classes of microengineered model systems in experimental models, connecting animal research and traditional in vitro methods such as organoids, microphysiological systems, and organs-on-chip. To achieve this goal, we established a perfusable 3D Xeno vessel chip using a porcine aortic endothelial cell line and examined how NETs grow when isolated human and primate neutrophils were used. Neutrophils from both humans and monkeys displayed the usual NETosis phases, including nuclear decondensation, enlargement, and rounding of DNA, occupying the entire cytoplasm, and discharge of fragmented DNA after cell membrane rupture. Using confocal fluorescence imaging of DNA and citrullinated histone colocalization and DNA histone complex formation in supernatants from xeno vessel chips, we confirmed NETs generation by human and monkey neutrophils when cocultured in a xeno-vessel chip.

Artificial intelligence-assisted repurposing of lubiprostone alleviates tubulointerstitial fibrosis.

Tubulointerstitial fibrosis (TIF) is the most prominent cause which leads to chronic kidney disease (CKD) and end-stage renal failure. Despite extensive research, there have been many clinical trial failures, and there is currently no effective treatment to cure renal fibrosis. This demonstrates the necessity of more effective therapies and better preclinical models to screen potential drugs for TIF. In this study, we investigated the antifibrotic effect of the machine learning-based repurposed drug, lubiprostone, validated through an advanced proximal tubule on a chip system and in vivo UUO mice model. Lubiprostone significantly downregulated TIF biomarkers including connective tissue growth factor (CTGF), extracellular matrix deposition (Fibronectin and collagen), transforming growth factor (TGF-ß) downstream signaling markers especially, Smad-2/3, matrix metalloproteinase (MMP2/9), plasminogen activator inhibitor-1 (PAI-1), EMT and JAK/STAT-3 pathway expression in the proximal tubule on a chip model and UUO model compared to the conventional 2D culture. These findings suggest that the proximal tubule on a chip model is a more physiologically relevant model for studying and identifying potential biomarkers for fibrosis compared to conventional in vitro 2D culture and alternative of an animal model. In conclusion, the high throughput Proximal tubule-on-chip system shows improved in vivo-like function and indicates the potential utility for renal fibrosis drug screening. Additionally, repurposed Lubiprostone shows an effective potency to treat TIF via inhibiting 3 major profibrotic signaling pathways such as TGFß/Smad, JAK/STAT, and epithelial-mesenchymal transition (EMT), and restores kidney function.

Outcomes of minimal change disease without nephrotic range proteinuria.

Minimal change disease (MCD) is characterized by edema and nephrotic range proteinuria (NS). However, the fate of MCD without nephrotic proteinuria requires elucidation. We retrospectively reviewed 79 adults diagnosed with primary MCD at their initial renal biopsy at a tertiary hospital between May 2003 and June 2017. Clinicopathologic features were compared between patients with and without NS. The frequency of flaring to nephrotic proteinuria and renal outcomes were assessed during follow-up. There were 20 and 59 patients in the Non-NS and NS groups, respectively. The Non-NS group had a lower frequency of acute kidney injury (AKI) during the follow-up period [5.0% vs. 59.3%, p <0.001]. The response rate to steroid treatment was 100% in the Non-NS group and 92.3% in the NS group (p = 1.000). Except for one patient, the Non-NS group was treated with steroids when their proteinuria increased to a nephrotic level. There were no differences in the frequency of the first relapse or the number of relapses among patients with initial remission from nephrotic range proteinuria. At the final visit, the complete remission rate was 73.4%. The estimated glomerular filtration rate during follow-up was significantly better in the NS group than the Non-NS group, given the higher rates of AKI at renal biopsy. The rates of renal events, end-stage renal disease, and mortality did not differ between the groups. Adult MCD patients with nephrotic and non-nephrotic range proteinuria showed similar outcomes. Accordingly, this population must be carefully managed, regardless of the amount of proteinuria at renal biopsy.