Dual Immunoglobulin Domain-Containing Cell Adhesion Molecule Increases Early in Renal Tubular Cell Injury and Plays Anti-Inflammatory Role.

Dual immunoglobulin domain-containing cell adhesion molecule (DICAM) is a type I transmembrane protein that presents in various cells including renal tubular cells. This study evaluated the expression and protective role of DICAM in renal tubular cell injury. HK-2 cells were incubated and treated with lipopolysaccharide (LPS, 30 µg/mL) or hydrogen peroxide (H2O2, 100 µM) for 24 h. To investigate the effect of the gene silencing of DICAM, small interfering RNA of DICAM was used. Additionally, to explain its role in cellular response to injury, DICAM was overexpressed using an adenoviral vector. DICAM protein expression levels significantly increased following treatment with LPS or H2O2 in HK-2 cells. In response to oxidative stress, DICAM showed an earlier increase (2-4 h following treatment) than neutrophil gelatinase-associated lipocalin (NGAL) (24 h following treatment). DICAM gene silencing increased the protein expression of inflammation-related markers, including IL-1ß, TNF-α, NOX4, integrin ß1, and integrin ß3, in H2O2-induced HK-2 cell injury. Likewise, in the LPS-induced HK-2 cell injury, DICAM knockdown led to a decrease in occludin levels and an increase in integrin ß3, IL-1ß, and IL-6 levels. Furthermore, DICAM overexpression followed by LPS-induced HK-2 cell injury resulted in an increase in occludin levels and a decrease in integrin ß1, integrin ß3, TNF-α, IL-1ß, and IL-6 levels, suggesting an alleviating effect on inflammatory responses. DICAM was elevated in the early stage of regular tubular cell injury and may protect against renal tubular injury through its anti-inflammatory properties. DICAM has a potential as an early diagnostic marker and therapeutic target for renal cell injury.

Anuria after kidney transplantation diagnosed as early recurrence of focal segmental glomerulosclerosis combined with acute calcineurin inhibitor nephrotoxicity: a case report and literature review.

BACKGROUND: Primary focal segmental glomerulosclerosis (FSGS) is a glomerular disease that sometimes recurs in patients after kidney transplantation (KT) and increases the risk of graft loss. Proteinuria is a common early sign of recurrent FSGS, but an abrupt decrease in urine volume is rare. Herein, we report a patient with early recurrence of FSGS with anuria following KT. CASE PRESENTATION: A 55-year-old man with end-stage kidney disease caused by primary FSGS experienced anuria on postoperative day 2 following deceased donor KT. Laboratory results revealed that serum tacrolimus trough levels were consistently elevated at the time of anuria. At first, we considered acute calcineurin inhibitor (CNI) nephrotoxicity based on graft biopsy on light microscopy, laboratory findings, and clinical courses. However, the allograft function did not recover even after discontinuation of CNI, and recurrent FSGS was diagnosed 2 weeks later on electron microscopy. A total of 13 sessions of plasmapheresis and two administrations of rituximab (375 mg/m2) were required to treat recurrent FSGS. The patient achieved a partial response, and the spot urine protein-to-creatinine ratio decreased from 15.5 g/g creatinine to 5.2 g/g creatinine. At 5 months following KT, the serum creatinine level was stable at 1.15 mg/dL. CONCLUSIONS: These findings highlight that anuria can occur in cases of early recurrence of FSGS combined with acute CNI nephrotoxicity.

Efficacy of Integrated Risk Score Using Omics-Based Biomarkers for the Prediction of Acute Rejection in Kidney Transplantation: A Randomized Prospective Pilot Study.

Acute rejection (AR) is critical for long-term graft survival in kidney transplant recipients (KTRs). This study aimed to evaluate the efficacy of the integrated risk score of omics-based biomarkers in predicting AR in KTRs. This prospective, randomized, controlled, multicenter, pilot study enrolled 40 patients who recently underwent high-immunologic-risk kidney transplantation (KT). Five omics biomarkers were measured, namely, blood mRNA (three-gene signature), urinary exosomal miRNA (three-gene signature), urinary mRNA (six-gene signature), and two urinary exosomal proteins (hemopexin and tetraspanin-1) at 2 weeks and every 4 weeks after KT for 1 year. An integrated risk score was generated by summing each biomarker up. The biomarker group was informed about the integrated risk scores and used to adjust immunosuppression, but not the control group. The outcomes were graft function and frequency of graft biopsy. Sixteen patients in the biomarker group and nineteen in the control group completed the study. The mean estimated glomerular filtration rate after KT did not differ between the groups. Graft biopsy was performed in two patients (12.5%) and nine (47.4%) in the biomarker and control groups, respectively, with the proportion being significantly lower in the biomarker group (p = 0.027). One patient (6.3%) in the biomarker group and two (10.5%) in the control group were diagnosed with AR, and the AR incidence did not differ between the groups. The tacrolimus trough level was significantly lower in the biomarker group than in the control group at 1 year after KT (p = 0.006). Integrated omics biomarker monitoring may help prevent unnecessary or high-complication-risk biopsy and enables tailored immunosuppression by predicting the risk of AR in KTRs.

Factors Associated with Acute Kidney Injury Occurrence and Prognosis in Rhabdomyolysis at the Emergency Department.

Background and Objectives: This study aimed to analyze patients with rhabdomyolysis who presented to emergency departments and identify their distribution of related disease and prognostic factors. Materials and Methods: A retrospective cohort study was conducted on patients with rhabdomyolysis who presented to emergency departments over a 10-year period. Patient data, including patients' demographic variables (sex and age), mode of arrival, final diagnosis, statin use, rhabdomyolysis trigger factors, and levels of serum creatine phosphokinase (CPK), myoglobin, creatinine, sodium, potassium, phosphate, calcium, and lactate, were analyzed. Univariate and multivariate logistic regression analyses were conducted to identify the predictive factors of acute kidney injury (AKI). Results: Among the patients, 268 (65.6%) were found to have trigger factors without underlying diseases. Furthermore, 115 (28.2%) patients developed AKI. This comprehensive study sheds light on the diverse factors influencing the occurrence of AKI in rhabdomyolysis and provides insights into AKI predictive markers. Furthermore, we analyzed the cases by dividing them into six groups: occurrence of AKI, occurrence of infection, and simple or complex rhabdomyolysis. CPK time course was found to be important in clinical prognosis, such as AKI occurrence, dialysis or not, and mortality. Conclusions: Age, statin use, elevated creatinine and lactate levels, and initial serum CPK level emerged as significant predictors of AKI. CPK time course was also found to be an important factor in predicting the clinical outcomes of patients with rhabdomyolysis.

Using early health economic modeling to inform medical innovation development: a soft robotic sock in poststroke patients in Singapore.

OBJECTIVES: Based on a real-world collaboration with innovators in applying early health economic modeling, we aimed to offer practical steps that health technology assessment (HTA) researchers and innovators can follow and promote the usage of early HTA among research and development (R&D) communities. METHODS: The HTA researcher was approached by the innovator to carry out an early HTA ahead of the first clinical trial of the technology, a soft robotic sock for poststroke patients. Early health economic modeling was selected to understand the potential value of the technology and to help uncover the information gap. Threshold analysis was used to identify the target product profiles. Value-of-information analysis was conducted to understand the uncertainties and the need for further research. RESULTS: Based on the expected price and clinical effectiveness by the innovator, the new technology was found to be cost-saving compared to the current practice. Risk reduction in deep vein thrombosis and ankle contracture, the incidence rate of ankle contracture, the compliance rate of the new technology, and utility scores were found to have high impacts on the value-for-money of the new technology. The value of information was low if the new technology can achieve the expected clinical effectiveness. A list of parameters was recommended for data collection in the impending clinical trial. CONCLUSIONS: This work, based on a real-world collaboration, has illustrated that early health economic modeling can inform medical innovation development. We provided practical steps in order to achieve more efficient R&D investment in medical innovation moving forward.

A Clinical Perspective on Bespoke Sensing Mechanisms for Remote Monitoring and Rehabilitation of Neurological Diseases: Scoping Review.

Neurological diseases including stroke and neurodegenerative disorders cause a hefty burden on the healthcare system. Survivors experience significant impairment in mobility and daily activities, which requires extensive rehabilitative interventions to assist them to regain lost skills and restore independence. The advent of remote rehabilitation architecture and enabling technology mandates the elaboration of sensing mechanisms tailored to individual clinical needs. This study aims to review current trends in the application of sensing mechanisms in remote monitoring and rehabilitation in neurological diseases, and to provide clinical insights to develop bespoke sensing mechanisms. A systematic search was performed using the PubMED database to identify 16 papers published for the period between 2018 to 2022. Teleceptive sensors (56%) were utilized more often than wearable proximate sensors (50%). The most commonly used modality was infrared (38%) and acceleration force (38%), followed by RGB color, EMG, light and temperature, and radio signal. The strategy adopted to improve the sensing mechanism included a multimodal sensor, the application of multiple sensors, sensor fusion, and machine learning. Most of the stroke studies utilized biofeedback control systems (78%) while the majority of studies for neurodegenerative disorders used sensors for remote monitoring (57%). Functional assessment tools that the sensing mechanism may emulate to produce clinically valid information were proposed and factors affecting user adoption were described. Lastly, the limitations and directions for further development were discussed.

A Critical Review on Factors Affecting the User Adoption of Wearable and Soft Robotics.

In recent years, the advent of soft robotics has changed the landscape of wearable technologies. Soft robots are highly compliant and malleable, thus ensuring safe human-machine interactions. To date, a wide variety of actuation mechanisms have been studied and adopted into a multitude of soft wearables for use in clinical practice, such as assistive devices and rehabilitation modalities. Much research effort has been put into improving their technical performance and establishing the ideal indications for which rigid exoskeletons would play a limited role. However, despite having achieved many feats over the past decade, soft wearable technologies have not been extensively investigated from the perspective of user adoption. Most scholarly reviews of soft wearables have focused on the perspective of service providers such as developers, manufacturers, or clinicians, but few have scrutinized the factors affecting adoption and user experience. Hence, this would pose a good opportunity to gain insight into the current practice of soft robotics from a user's perspective. This review aims to provide a broad overview of the different types of soft wearables and identify the factors that hinder the adoption of soft robotics. In this paper, a systematic literature search using terms such as "soft", "robot", "wearable", and "exoskeleton" was conducted according to PRISMA guidelines to include peer-reviewed publications between 2012 and 2022. The soft robotics were classified according to their actuation mechanisms into motor-driven tendon cables, pneumatics, hydraulics, shape memory alloys, and polyvinyl chloride muscles, and their pros and cons were discussed. The identified factors affecting user adoption include design, availability of materials, durability, modeling and control, artificial intelligence augmentation, standardized evaluation criteria, public perception related to perceived utility, ease of use, and aesthetics. The critical areas for improvement and future research directions to increase adoption of soft wearables have also been highlighted.

Renal Sarcoidosis-like Reaction Induced by PD-1 Inhibitor Treatment in Non-Small Cell Lung Cancer: A Case Report and Literature Review.

Monoclonal antibodies directed against immune checkpoint proteins have been widely used to treat various cancers and have resulted in favorable clinical outcomes. Despite these beneficial properties, immune checkpoint inhibitors (ICIs) can induce side effects called immune-related adverse events, including sarcoidosis-like reactions (SLR) across multiple organs. Here, we report a case of renal SLR after ICI treatment, and we review the related literature. A 66-year-old Korean patient with non-small cell lung cancer was referred to the nephrology clinic for renal failure after the 14th pembrolizumab treatment dose. A renal biopsy revealed multiple epithelioid cell granulomas, with several lymphoid aggregates in the renal interstitium and a moderate degree of inflammatory cell infiltration in the tubulointerstitium. A moderate dose of steroid therapy was initiated, and the serum creatinine level partially recovered after four weeks of treatment. Judicious monitoring of renal SLR is, therefore, required during ICI therapy, and a timely diagnosis by renal biopsy and appropriate treatment are important.

Recurrent C3 Glomerulonephritis along with BK-Virus-Associated Nephropathy after Kidney Transplantation: A Case Report.

C3 glomerulonephritis (C3GN) is a rare cause of end-stage kidney disease and frequently recurrent in allografts following kidney transplantation (KT). Herein, we describe the case of a kidney transplant recipient who developed recurrent C3GN along with BK-virus-associated nephropathy (BKVAN) following KT. A 33-year-old man diagnosed with membranoproliferative glomerulonephritis 17 years ago underwent preemptive KT with a donor kidney from his aunt. Proteinuria gradually increased after 3 months following KT, and graft biopsy was performed 30 months after KT. Histopathological examination revealed recurrent C3GN. The dosages of triple immunosuppressive maintenance therapy agents were increased. Subsequently, serum C3 levels recovered to normal levels. However, at 33 months following KT, the BK viral load increased and graft function gradually deteriorated; a second graft biopsy was performed at 46 months following KT, which revealed BKVAN and decreased C3GN activity. The dosages of immunosuppressive agents were decreased; subsequently, BKVAN improved and graft function was maintained with normal serum C3 levels at 49 months following KT. This case indicates that C3GN is highly prone to recurrence following KT and that immunosuppressive therapy for C3GN increases the risk of BKVAN.

Declining trend of preemptive kidney transplantation and impact of pretransplant dialysis: a Korean nationwide prospective cohort study.

We evaluated the temporal trend of preemptive kidney transplantation (KT) and the effect of pretransplant dialysis duration on post-transplant outcomes. This was a nationwide cohort study of the first-time 3392 living donor KT (LDKT) recipients (2014-2019). The annual changes in proportion of preemptive KT, factors associated with preemptive KT, and post-transplant outcomes were analyzed. Preemptive KT was performed in 816 (24.1%) patients. Annual trend analysis revealed gradual decrease in preemptive KT over time (P = 0.042). Among the underlying causes of preemptive KT, the proportion of diabetes increased and that of glomerulonephritis decreased during the study period. Glomerulonephritis as the primary renal disease was a predictor of preemptive KT. Patients with pretransplant dialysis >6 months showed increased graft failure risk than preemptive KT in the subdistribution of hazard model for competing risk (adjusted hazard ratio [aHR], 2.53; 95% confidence interval [CI], 1.09-5.87; P = 0.031) and in propensity score-matched analysis (aHR, 2.45; 95% CI, 1.02-5.92; P = 0.034); however, pretransplant dialysis ≤6 months showed comparable graft survival with preemptive KT in both analyses. Preemptive KT declined over successive years, associated with an increase in diabetes and a decrease in glomerulonephritis as underlying causes of KT. Short period of dialysis less than 6 months does not affect graft survival compared with preemptive KT; however, longer dialysis decreases graft survival.

New-onset Nephrotic Syndrome after Janssen COVID-19 Vaccination: a Case Report and Literature Review.

Various coronavirus disease 2019 (COVID-19) vaccines are being developed, which show practical preventive effects. Here, we report a 51-year-old healthy man with nephrotic syndrome secondary to minimal change disease (MCD) after Ad26.COV.2 (Janssen) vaccination. He had no comorbid disease and received Ad26.COV.2 on April 13, 2021. Seven days after vaccination, he developed edema and foamy urine. Edema rapidly aggravated with decreased urine volume. He was admitted to the hospital 28 days after vaccination, and his body weight increased by 21 kg after vaccination. His serum creatinine level was 1.54 mg/dL, and 24-h urinary protein excretion was 8.6 g/day. Kidney biopsy revealed no abnormality in the glomeruli and interstitium of the cortex and medulla under the light microscope. Electron microscopy revealed diffuse effacement of the podocyte foot processes, thus, he was diagnosed with MCD. High-dose steroid therapy was applied, and his kidney function improved three days after steroid therapy. Three weeks after steroid use, his serum creatinine decreased to 0.95 mg/dL, and spot urine protein-to-creatine decreased to 0.2 g/g. This case highlights the risk of new-onset nephrotic syndrome secondary to MCD after vectored COVID-19 vaccination. Although the pathogenesis is uncertain, clinicians need to be careful about adverse renal effects of COVID-19 vaccines.

Paricalcitol Improves Hypoxia-Induced and TGF-ß1-Induced Injury in Kidney Pericytes.

Recently, the role of kidney pericytes in kidney fibrosis has been investigated. This study aims to evaluate the effect of paricalcitol on hypoxia-induced and TGF-ß1-induced injury in kidney pericytes. The primary cultured pericytes were pretreated with paricalcitol (20 ng/mL) for 90 min before inducing injury, and then they were exposed to TGF-ß1 (5 ng/mL) or hypoxia (1% O2 and 5% CO2). TGF-ß1 increased α-SMA and other fibrosis markers but reduced PDGFRß expression in pericytes, whereas paricalcitol reversed the changes. Paricalcitol inhibited the TGF-ß1-induced cell migration of pericytes. Hypoxia increased TGF-ß1, α-SMA and other fibrosis markers but reduced PDGFRß expression in pericyte, whereas paricalcitol reversed them. Hypoxia activated the HIF-1α and downstream molecules including prolyl hydroxylase 3 and glucose transporter-1, whereas paricalcitol attenuated the activation of the HIF-1α-dependent molecules and TGF-ß1/Smad signaling pathways in hypoxic pericytes. The gene silencing of HIF-1α vanished the hypoxia-induced TGF-ß1, α-SMA upregulation, and PDGFRß downregulation. The effect of paricalcitol on the HIF-1α-dependent changes of fibrosis markers was not significant after the gene silencing of HIF-1α. In addition, hypoxia aggravated the oxidative stress in pericytes, whereas paricalcitol reversed the oxidative stress by increasing the antioxidant enzymes in an HIF-1α-independent manner. In conclusion, paricalcitol improved the phenotype changes of pericyte to myofibroblast in TGF-ß1-stimulated pericytes. In addition, paricalcitol improved the expression of fibrosis markers in hypoxia-exposed pericytes both in an HIF-1α-dependent and independent manner.

Critical Tetramine Poisoning after Sea Snail Ingestion in a Patient on Peritoneal Dialysis: A Case Report.

Tetramine in gastropods can cause poisoning symptoms with various side effects. Most of these symptoms are mild and spontaneously resolved due to the rapid excretion of tetramine through the kidneys; however, patients with kidney dysfunction can present severe symptoms. A 48-year-old woman with end-stage kidney disease due to diabetic nephropathy and undergoing peritoneal dialysis (PD) visited our emergency department (ED) with complaints of general weakness, vomiting, and shortness of breath after ingesting some sea snails. On ED arrival, she was in a respiratory failure state; therefore, invasive mechanical ventilation was immediately initiated. Chest radiography showed diffuse severe pulmonary edema and her vital signs fluctuated; thus, continuous renal replacement therapy (CRRT) was initiated at the intensive care unit to treat tetramine intoxication and control volume status. Her condition gradually improved, and she was successfully weaned from mechanical ventilation on the 5th day of admission and moved to the general ward on the 10th day. CRRT was switched to PD. She fully recovered and was discharged on the 15th day of admission. Therefore, clinicians should explain the risk associated with gastropod ingestion to patients with kidney dysfunction and recognize that the clinical course of tetramine toxicity can be critical.

Renoprotective Effects of Alpha-1 Antitrypsin against Tacrolimus-Induced Renal Injury.

The protective effects of alpha-1 antitrypsin (AAT) in tacrolimus (TAC)-induced renal injury was evaluated in a rat model. The TAC group rats were subcutaneously injected with 2 mg/kg TAC every day for four weeks. The TAC with AAT group was cotreated with daily subcutaneous injections of TAC and intraperitoneal injections of AAT (80 mg/kg) for four weeks. The effects of AAT on TAC-induced renal injury were evaluated using serum biochemistry, histopathology, and Western blotting. The TAC injection significantly increased renal interstitial fibrosis, inflammation, and apoptosis as compared to the control treatment. The histopathological examination showed that cotreatment of TAC and AAT attenuated interstitial fibrosis (collagen, fibronectin, and α-SMA staining), and α-SMA expression in Western blotting was also decreased. Immunohistochemical staining for inflammation (osteopontin and ED-1 staining) revealed improved interstitial inflammation in the TAC with AAT group compared to that in the TAC group. The TAC treatment increased renal apoptosis compared to the control treatment, based on the results of increased immunohistochemical staining of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), increased caspase-3 activity, and lower Bcl-2 to Bad expression ratio. However, AAT cotreatment significantly changed these markers and consequently showed decreased apoptosis. AAT protects against TAC-induced renal injury via antifibrotic, anti-inflammatory, and antiapoptotic effects.

Functional connectivity of brain associated with passive range of motion exercise: Proprioceptive input promoting motor activation?

Soft robotics have come to the forefront of devices available for rehabilitation following stroke; however, objective evaluation of the specific brain changes following rehabilitation with these devices is lacking. In this study, we utilized functional Magnetic Resonance Imaging (fMRI) and dynamic causal modeling (DCM) to characterize the activation of brain areas with a MRI compatible glove actuator compared to the conventional manual therapy. Thirteen healthy volunteers engaged in a motor-visual fMRI task under four different conditions namely active movement, manual passive movement, passive movement using a glove actuator, and crude tactile stimulation. Brain activity following each task clearly identified the somatosensory motor area (SMA) as a major hub orchestrating activity between the primary motor (M1) and sensory (S1) cortex. During the glove-induced passive movement, activity in the motor-somatosensory areas was reduced, but there were significant increases in motor cortical activity compared to manual passive movement. We estimated the modulatory signaling from within a defined sensorimotor network (SMA, M1, and S1), through DCM and highlighted a dual-gating of sensorimotor inputs to the SMA. Proprioceptive signaling from S1 to the SMA reflected positive coupling for the manually assisted condition, while M1 activity was positively coupled to the SMA during the glove condition. Importantly, both the S1 and M1 were shown to influence each other's connections with the SMA, with inhibitory nonlinear modulation by the M1 on the S1-SMA connection, and similarly S1 gated the M1-SMA connection. The work is one of the first to have applied effective connectivity to examine sensorimotor activity ensued by manual or robotic passive range of motion exercise, crude tactile stimulation, and voluntary movements to provide a basis for the mechanism by which soft actuators can alter brain activity.

Reliability and reproducibility of interapical distance assessment of the lateral deviation of vertebrae in scoliosis.

[Purpose] The purpose of this study was to investigate the interobserver reliability and intraobserver reproducibility of interapical distance (IAD) and to analyze its correlation with the Cobb angle (CA). [Subjects and Methods] IAD, a handy tool for assessment of the lateral deviation of vertebrae with a metric scale, was defined as the horizontal distance between one apical vertebra and its counterpart, the opposite apical vertebra in the case of a double curve and the farthest vertebra in the case of a single curve. Fifty full-length, standing anteroposterior radiographs of "idiopathic scoliosis" were reviewed. Three investigators independently measure the CA and IAD at the same time and remeasured the IAD on the same radiograph a week later. [Results] There was no interobserver difference (reliability) in the measurement of IAD or statistical differences in intraobserver reproducibility for each observer. IAD was well correlated with the CA for each observer (r=0.765, r=0.737, and r=0.764). [Conclusion] IAD is useful when assessing lateral deviation in scoliosis and may be a reliable and reproducible index that is well correlated with the CA, and it can be used as a supplementary measure to describe the overall derangement of scoliosis in the coronal plane.

Successful treatment of recurrent focal segmental glomerulosclerosis with a low dose rituximab in a kidney transplant recipient.

Recurrence of focal segmental glomerulosclerosis (FSGS) is a major therapeutic challenge in kidney transplantation (KT). Although intensive plasmapheresis and high-dose rituximab have been introduced to treat recurrent FSGS, the most effective dosage and regimen of rituximab have not been determined. Herein we reported the first case of successful treatment of recurrent FSGS with a low-dose rituximab. The patient showed marked proteinuria (3.5 g/d) and oliguria 2 d after KT. Two courses of plasmapheresis and immunoglobulin were applied to the patient, however, nephrotic range proteinuria persisted and creatinine level increased to 3.56 mg/dL. Five months post-transplant, the patient received injection with only one dose of rituximab 100 mg, without further plasmapheresis, which resulted in immediate reduction of serum creatinine and full remission of proteinuria during the following 18 months. This case suggested that recurrent FSGS, which frequently relapses after plasmapheresis, could be treated successfully with a low-dose rituximab even without plasmapheresis.

Autophagy caused by oxidative stress promotes TGF-ß1-induced epithelial-to-mesenchymal transition in human peritoneal mesothelial cells.

Epithelial-to-mesenchymal transition (EMT) is one of the main causes of peritoneal fibrosis. However, the pathophysiological mechanisms of EMT, specifically its relationship with autophagy, are still unknown. This study aimed to evaluate the role of autophagy in transforming growth factor-beta 1 (TGF-ß1)-induced EMT in human peritoneal mesothelial cells (HPMCs). Primary cultured HPMCs were treated with TGF-ß1 (2 and 5 ng/mL) and changes in autophagy markers and the relationship between autophagy and EMT were evaluated. We also identified changes in EMT- and autophagy-related signaling pathways after autophagy and NADPH oxidase 4 (NOX4) inhibition. TGF-ß1 increased the generation of NOX4 and reactive oxygen species (ROS) in HPMCs, resulting in mitochondrial damage. Treatment with GKT137831 (20 µM), a NOX1/4 inhibitor, reduced ROS in the mitochondria of HPMC cells and reduced TGF-ß1-induced mitochondrial damage. Additionally, the indirect inhibition of autophagy by GKT137831 (20 µM) downregulated TGF-ß1-induced EMT, whereas direct inhibition of autophagy using 3-methyladenine (3-MA) (2 mM) or autophagy-related gene 5 (ATG5) gene silencing decreased the TGF-ß1-induced EMT in HPMCs. The suppressor of mothers against decapentaplegic 2/3 (Smad2/3), autophagy-related phosphoinositide 3-kinase (PI3K) class III, and protein kinase B (Akt) pathways, and mitogen-activated protein kinase (MAPK) signaling pathways, such as extracellular signal-regulated kinase (ERK) and P38, were involved in TGF-ß1-induced EMT. Autophagy and NOX4 inhibition suppressed the activation of these signaling pathways. Direct inhibition of autophagy and its indirect inhibition through the reduction of mitochondrial damage by upstream NOX4 inhibition reduced EMT in HPMCs. These results suggest that autophagy could serve as a therapeutic target for the prevention of peritoneal fibrosis in patients undergoing peritoneal dialysis.

Association between systemic inflammation biomarkers and mortality in patients with sepsis-associated acute kidney injury receiving intensive care and continuous kidney replacement therapy: results from the RENERGY (REsearches for NEphRology and epidemioloGY) study.

Background: Identifying risk factors and improving prognostication for mortality among patients with sepsis-associated acute kidney injury (AKI) undergoing continuous kidney replacement therapy (CKRT) is important in improving the adverse prognosis of this patient population. This study aimed to compare the prognostic value of existing systemic inflammation biomarkers and determine the optimal systemic inflammation biomarker in patients with sepsis-associated AKI receiving CKRT. Methods: This multi-center, retrospective, observational cohort study included 1,500 patients with sepsis-associated AKI treated with intensive care and CKRT. The main predictor was a panel of 13 different systemic inflammation biomarkers. The primary outcome was 28-day mortality after CKRT initiation. Secondary outcomes included 90-day mortality after CKRT initiation, CKRT duration, kidney replacement therapy dependence at discharge, and lengths of intensive care unit (ICU) and hospital stays. Results: When added to the widely accepted Acute Physiology and Chronic Health Evaluation II score, platelet-to-albumin ratio (PAR) and neutrophil-platelet score (NPS) had the highest improvements in prognostication of 28-day mortality, where the corresponding increases in C-statistic were 0.01 (95% confidence interval [CI], 0.00-0.02) and 0.02 (95% CI, 0.01-0.03). Similar findings were observed for 90-day mortality. The 28- and 90-day mortality rates were significantly lower for the higher PAR and NPS quartiles. These associations remained significant even after adjustment for potential confounding variables in multivariable Cox proportional hazards models. Conclusion: Of the available systemic inflammation biomarkers, the addition of PAR or NPS to conventional ICU prediction models improved the prognostication of patients with sepsis-associated AKI receiving intensive care and CKRT.

Severe Acute Kidney Injury Associated with Transformation of Chronic Myelomonocytic Leukemia into Acute Myeloid Leukemia: A Case Report.

Chronic myelomonocytic leukemia (CMML) is a rare hematologic disorder that infrequently causes acute kidney injury (AKI). CMML can transform into acute myeloid leukemia (AML), which can be accompanied by a deterioration in kidney function. However, severe AKI due to extramedullary manifestations of AML is rare. Herein, we present the case of a 67-year-old male patient with CMML that transformed into AML with severe AKI necessitating hemodialysis. The cause of the AKI was the AML transformation. The patient, with stable kidney function after chemotherapy for CMML, presented with a sudden decline in kidney function. Hemodialysis was initiated because of severe AKI, and histopathologic evaluation of the kidney biopsy specimen revealed severe, diffuse mixed inflammatory cell infiltrates in the interstitium and c-kit-immunopositive myeloblast-like cells. A bone marrow biopsy was performed because of the kidney biopsy findings suggesting that leukemic infiltration led to the diagnosis of AML. The patient received chemotherapy for AML, and his kidney function recovered. As illustrated in this case, severe AKI can develop as an early extramedullary manifestation during transformation from CMML to AML. Therefore, in patients with CMML and rapidly declining renal function, transformation into AML should be considered and histopathologically confirmed by kidney biopsy.