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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.

Introduction: We hypothesize that remote patient monitoring (RPM) for automated peritoneal dialysis (APD) and feedback could enhance patient self-management and improve outcomes. The aim of this study was to evaluate the efficacy of RPM-APD compared to traditional APD (T-APD) without RPM. Methods: In this multicenter, randomized controlled trial, patients on APD were randomized to T-APD (n = 29) or RPM-APD (n = 28) at 12 weeks and followed until 25 weeks. Health-related quality of life (HRQOL), patient and medical staff satisfaction with RPM-APD, and dialysis-related outcomes were compared between the 2 groups. Results: We found no significant differences in HRQOL scores at the time of enrollment and randomization between RPM-APD and T-APD. At the end of the study, the RPM-APD group showed better HRQOL for the sleep domain (p = 0.049) than the T-APD group and the T-APD group showed better HRQOL for the sexual function domain (p = 0.030) than the RPM-APD group. However, we found no significant interactions between the time and groups in terms of HRQOL. Different HRQOL domains significantly improved over time in patients undergoing RPM-APD (effects of kidney disease, p = 0.025) and T-APD (burden of kidney disease, p = 0.029; physical component summary, p = 0.048). Though medical staff satisfaction with RPM-APD was neutral, most patients were quite satisfied with RPM-APD (median score 82; possible total score 105 on 21 5-item scales) and the rating scores were maintained during the study period. We found no significant differences in dialysis adherence, accuracy, adequacy, overhydration status, blood pressure, or the number of unplanned visits between the 2 groups. Discussion/Conclusion: Although HRQOL and dialysis-related outcomes were comparable between RPM-APD and T-APD, RPM-APD was positive in terms of patient satisfaction. Further long-term and large-scale studies will be required to determine the efficacy of RPM-APD. Trial Registration: CRIS identifier: KCT0003390, registered on December 14, 2018 – retrospectively registered, https://cris.nih.go.kr/cris/search/search_result_st01.jsp?seq=12348.

Donor-recipient age difference (DRAD) is one of the reasons why patients on kidney waiting lists refuse to receive the offered organ. However, its impact on deceased donor kidney transplantation (DDKT) outcomes is still controversial.One hundred fifty-three kidney transplant recipients (KTRs) who received their first-time DDKT were enrolled. The KTRs were divided into groups by DRAD: group 1 (n = 74) (DRAD 0) and group 2 (n = 79) (DRAD ≥ 0). The KTRs in group 2 were divided into 3 subgroups: DRAD 0 to 10 (n = 35), 10 to 20 (n = 32), and ≥ 20 (n = 12). The outcome measures included estimated glomerular filtration rate (eGFR), delayed graft function (DGF), acute rejection (AR), and graft and patient survival.There were no significant differences in clinical outcomes between group 1 and 2 except eGFR until 5 years after DDKT. Among the subgroups of group 2, DGF, AR, patient survival, and eGFR until 5 years showed no significant differences. However, graft survival was significantly different (P = .015); in addition, in the DRAD ≥ 20 subgroup, graft survival decreased compared with that in the DRAD 10 to 20 subgroup and DRAD 0 to 10 subgroup (P = .020, P = .012, respectively). In a multivariate Cox proportional hazards analysis, the DRAD ≥ 20 subgroup showed a higher risk for graft failure than the DRAD 0 to 10 subgroup.Although donors were of the same age or older than recipients, DDKT showed acceptable graft outcomes. However, because donors over 20 years older than recipients showed a decreased graft survival, it might be important to consider this point in donor-recipient matching of DDKT.

Objective: This randomized controlled feasibility study investigates the ability for clinical application of the Brain-Computer Interface-based Soft Robotic Glove (BCI-SRG) incorporating activities of daily living (ADL)-oriented tasks for stroke rehabilitation. Methods: Eleven recruited chronic stroke patients were randomized into BCI-SRG or Soft Robotic Glove (SRG) group. Each group underwent 120-minute intervention per session comprising 30-minute standard arm therapy and 90-minute experimental therapy (BCI-SRG or SRG). To perform ADL tasks, BCI-SRG group used motor imagery-BCI and SRG, while SRG group used SRG without motor imagery-BCI. Both groups received 18 sessions of intervention over 6 weeks. Fugl-Meyer Motor Assessment (FMA) and Action Research Arm Test (ARAT) scores were measured at baseline (week 0), post- intervention (week 6), and follow-ups (week 12 and 24). In total, 10/11 patients completed the study with 5 in each group and 1 dropped out. Results: Though there were no significant intergroup differences for FMA and ARAT during 6-week intervention, the improvement of FMA and ARAT seemed to sustain beyond 6-week intervention for BCI-SRG group, as compared with SRG control. Incidentally, all BCI-SRG subjects reported a sense of vivid movement of the stroke-impaired upper limb and 3/5 had this phenomenon persisting beyond intervention while none of SRG did. Conclusion : BCI-SRG suggested probable trends of sustained functional improvements with peculiar kinesthetic experience outlasting active intervention in chronic stroke despite the dire need for large-scale investigations to verify statistical significance. Significance: Addition of BCI to soft robotic training for ADL-oriented stroke rehabilitation holds promise for sustained improvements as well as elicited perception of motor movements.

Herein, we report a rare case of severe respiratory syncytial virus pneumonia after kidney transplant in a 46-year-old woman. The patient was diagnosed with end-stage renal disease and underwent living-donor kidney transplant. Direct flow cytometry crossmatch testing yielded positive results, and desensitization treatment with rituximab, plasmapheresis, and im-munoglobulin was performed before transplant. There were no complications. Five days after discharge, the patient was readmitted with a 2-day history of fever and diagnosed with bilateral pneumonia. The patient was placed on mechanical ventilation and given renal replacement therapy. Respiratory syncytial virus in the bronchial washings was detected via polymerase chain reaction. Broad-spectrum antibiotics, intravenous methylprednisolone, and immunoglobulin were admin-istered. Over-immunosuppression strategies, such as desensitization therapy, may result in severe respiratory syncytial virus pneumonia, even in kidney transplant recipients.

Background Human leukocyte antigen (HLA) molecules are cell-bound but can be identified in a soluble form. These soluble HLA (sHLA) molecules have an immunomodulatory function. We investigated whether natural sHLA in donor serum can neutralize donor-specific HLA alloantibodies (DSAs) in recipient serum. Methods Neutralizing effects of donor serum on DSAs in recipient serum were measured using inhibition assay principle of flow cytometric crossmatch (FCXM), performed using sera from 143 kidney transplant recipients and their donors. The adding of donor serum to recipient serum yielded lower mean fluorescence intensity (MFI) ratios (test/control) than when diluent was added [Roswell Park Memorial Institute (RPMI) or third-party serum], which was presumed to be caused by the neutralizing effects of sHLA. Results In the recipient group with class I DSAs alone (N=14), donor serum addition to recipient serum resulted in lower T cell MFI ratios [2.25 (1.31‒32.51)] than those observed on RPMI addition [3.04 (1.33‒125.39), P0.05 for both. Conclusion Using inhibition FCXM, we verified that natural sHLA class I in donor serum neutralizes DSAs in recipient serum. However, no neutralizing effects of sHLA class II were revealed in this study. These potentially beneficial effects of sHLA infused via blood-derived products should be considered when desensitizing highly HLA-sensitized patients.

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-β1-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-β1 (5 ng/mL) or hypoxia (1% O2 and 5% CO2). TGF-β1 increased α-SMA and other fibrosis markers but reduced PDGFRβ expression in pericytes, whereas paricalcitol reversed the changes. Paricalcitol inhibited the TGF-β1-induced cell migration of pericytes. Hypoxia increased TGF-β1, α-SMA and other fibrosis markers but reduced PDGFRβ 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-β1/Smad signaling pathways in hypoxic pericytes. The gene silencing of HIF-1α vanished the hypoxia-induced TGF-β1, α-SMA upregulation, and PDGFRβ 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-β1-stimulated pericytes. In addition, paricalcitol improved the expression of fibrosis markers in hypoxia-exposed pericytes both in an HIF-1α-dependent and independent manner.

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., Graphical Abstract

Background α1-Antitrypsin (AAT) is an important protein in the anti-inflammatory response that functions to regulate the activity of serine proteinases. We aimed to evaluate the protective effect of AAT on ischemia-reperfusion injury (IRI) in a mouse model. Methods We investigated the effects of AAT in a C57BL/6 mouse model of IRI by dividing them into 4 groups: normal control, sham operated, ischemia-reperfusion (IR), and IR after AAT pretreatment (IR-AAT). In the IR-AAT group, mice were pretreated with AAT (80 mg/kg/d) for 3 days before renal ischemia was induced by clamping the bilateral renal vascular pedicles for 30 minutes. At 24 hours after IRI, biochemistry, histology, inflammatory cytokines, and apoptosis were assayed. Results Blood urea nitrogen and serum creatinine levels were significantly lower in the IR-AAT group than in the IR group. Neutrophil gelatinase-associated lipocalin and kidney injury molecule 1 protein levels were significantly lower in the IR-AAT group than in the IR group. In addition, there were fewer tubular injuries and less interstitial fibrosis in the IR-AAT group than in the IR group, and the expression levels of transforming growth factor β, interleukin 1β, and interleukin 6 were significantly lower in the IR-AAT group than in the IR group. When compared with the IR group, there were fewer terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay–positive cells, lower caspase 3 activity and B-cell lymphoma 2-associated X protein (Bax), and higher B-cell lymphoma 2 (Bcl–2) in the IR-AAT group. Conclusions α1-Antitrypsin preserved renal function, attenuated tubular injuries and interstitial fibrosis, and inhibited inflammation and apoptosis after renal IRI. Our results suggest that AAT has protective effects against renal IRI by inhibiting inflammatory and apoptosis pathways.

Background Compared to tacrolimus, cyclosporine increases cardiovascular risk. Furthermore, tacrolimus has a negative effect on glucose metabolism compared to cyclosporine. This study investigated the effect of the conversion from cyclosporine to tacrolimus for immunosuppressive therapy on glucose metabolism and cardiovascular risk profiles in long-term stable kidney transplant recipients (KTRs). Methods In this prospective, open-label, single-arm study, 36 KTRs were enrolled; 3 were excluded. Patients were evaluated for glucose metabolism and cardiovascular risk factors at baseline, 3, and 6 months after conversion of medication. Serial changes were analyzed by repeated analysis of variance. Results The mean duration from transplantation was 12.6 ± 4.0 years and baseline serum creatinine levels were 1.10 ± .23 mg/dL. After conversion, fasting plasma glucose levels increased sequentially from 101.7 ± 18.5 to 107.4 ± 21.3 mg/dL (P = .007), and glycated hemoglobin levels increased from 5.7 ± .8 to 6.0 ± 1.2% (P = .016). Among cardiovascular risk factors, fibrinogen levels were decreased (P = .015), but other factors, including blood pressure and lipid profile, did not change (all P > .05). There was no change in renal function, including serum creatinine (P = .611) and urine protein-to-creatinine ratio (P = .092). Body mass index levels were decreased (P = .037) and body weight tended to decrease (P = .063). Conclusions Switching immunosuppressant therapy to tacrolimus has an apparent negative effect on glucose metabolism and imparts an unclear advantage on cardiovascular risk profiles for long-term stable KTRs.

Background There is a high risk of fracture after kidney transplantation (KT). Recipients of KT are susceptible to persistent hyperparathyroidism and other disorders of bone and mineral metabolism. However, the risk factors for fractures after KT remain uncertain. The aim of the present study was to investigate the risk factors for fracture after KT. Methods A total of 941 recipients of KT were enrolled from a multicenter observational cohort study in Korea from 2012 to 2016. The biochemical markers were measured at the time of KT, then annually for 5 years following KT. All fracture events were recorded. A Cox proportional hazards analysis was performed to calculate hazard ratios (HR) for the association of risk factors with fractures. Results Twenty-two fractures had occurred in 20 patients during the study period. Baseline and serial changes of mineral and bone biochemical markers were similar between fracture and nonfracture patient groups. Among the total study population, 104 patients were diagnosed with osteoporosis and 422 patients were diagnosed with osteopenia in a pretransplant bone mineral density test. In a multivariate Cox analysis, pretransplant osteoporosis (HR = 11.76; 95% confidence interval [CI], 2.28-60.69; P = .003) and pretransplant osteopenia (HR = 5.21; 95% CI, 1.15-23.57; P = .032) were independent risk factors for fracture in recipients of KT. Conclusions Pretransplant osteoporosis and osteopenia were independent risk factors for fracture after KT. More careful monitoring of bone mineral density before and after KT might be beneficial to predict the risk for fracture after KT.

Background : Cardiovascular diseases of chronic dialysis patients are often undertreated because of their higher surgical risk. This study aimed to assess mortality and morbidity after open heart surgery in chronic dialysis patients compared to those with normal renal function and identify risk factors for postoperative outcomes. Methods : We retrospectively analyzed 2,432 patients who underwent open heart surgery from 2002 to 2017 and collected data from 116 patients (38 patients on dialysis and 78 age-, sex-, and diabetes mellitus status-matched control patients with normal kidney function). We assessed comorbidities, New York Heart Association (NYHA) class, laboratory data, surgical methods, and postoperative outcomes. Results : The dialysis group had more comorbidities, higher NYHA classes, and greater need for urgent surgeries compared to the control group. They exhibited significantly higher postoperative mortality (18.4% vs. 2.6%, P = 0.005) and more overall complications (65.8% vs. 25.6%, P < 0.001). Dialysis itself significantly increased relative risk for in-hospital mortality after adjustment. EuroSCORE II was not as useful as in the general population. Multivariate logistic regression analysis demonstrated that total (adjusted odds ratio [AOR], 10.7; P = 0.029) and in-hospital death risk (AOR, 14.7; P = 0.033), the durations of postoperative hospitalization (AOR, 4.6; P = 0.034), CRRT (AOR 36.8; P = 0.004), and ventilator use (AOR, 7.6; P = 0.022) were significantly increased in the dialysis group. Conclusion : The dialysis group exhibited a higher risk for mortality and overcall complications after open heart surgery compared to the patients with normal renal function. Therefore, the benefit of surgical treatment must be balanced against potential risks.

Hepcidin's relationships with other variables are unclear. We evaluated associations of serum hepcidin with clinical parameters in ESRD patients. Ninety-nine incident dialysis patients, including 57 on peritoneal dialysis (PD) and 42 on HD, were prospectively followed for 6 months. Serum hepcidin levels significantly increased during initial 6 months of dialysis. In the multivariate regression model, independent predictors of serum hepcidin levels in ESRD patients before maintenance dialysis were interleukin-6, ferritin, phosphate, iron, and aspartate transaminase. Six months after initiating dialysis, serum hepcidin levels were independently predicted by ferritin, total iron binding capacity (TIBC), and aspartate transaminase in all patients, whereas by ferritin and TIBC in PD patients, and ferritin, TIBC, and 24-h urine volume in HD patients. Serum hepcidin levels are differentially associated with anemia parameters in PD compared with HD patients. Urine volume was an independent predictor of hepcidin levels in early HD patients.

Background and objective: Immobility of the lower extremity due to medical conditions such as stroke can lead to medical complications such as deep vein thrombosis or ankle contracture, and thereafter prolonged recovery process of the patients. In this preliminary clinical study, we aimed to examine the effect of a novel soft robotic sock device, capable of providing assisted ankle exercise, in improving blood flow in the lower limb to prevent the complication of strokes such as deep vein thrombosis and joint contracture. Methods: Stroke patients were recruited (n = 17) to compare patients using the conventional pneumatic compression device with our robotic sock device on separate days. The primary outcome was to compare the venous flow profile of the superficial femoral vein in terms of the time average mean velocity and volumetric flow. The secondary outcome was to identify the ankle joint range of motion with the assistance of the device. Results: We noted improvements in the venous profile at the early phase of the device use, though its efficacy seemed to drop with time, as compared to the IPC device, where there was a significant improvement in the venous profile. The ankle joint dorsiflexion-plantarflexion range of motion assisted by the device was 11.5±6.3°. Conclusion and clinical impact: The current version of our sock device appears to be capable of improving venous blood flow in the early phase of device use and assisting with ankle joint exercise. The insights from this preliminary clinical study will serve as the basis for further improvement of the device and subsequent conduct of a longitudinal clinical trial. Funding: National Health Innovation Centre Singapore (NHIC) grant, R-172-000-391-511, MOE AcRF Tier 1 R-397-000-301-114., In this preliminary clinical study, we tested the effect of a novel soft robotic sock device, capable of providing assisted ankle exercise, in improving blood flow in the lower limb for the prevention of complications of stroke such as deep vein thrombosis and joint contracture. The results of the clinical trial show that the sock device improves venous blood flow in the early phase of device use and assists with ankle joint exercise.

Background. ML171 is a potent nicotinamide adenine dinucleotide phosphate oxidase (NOX) inhibitor with isoform selectivity only for NOX1. This study is aimed at investigating the safety of ML171 after a single intraperitoneal (IP) injection in mice. Methods. The toxicity of a single dose of ML171 was evaluated in 6-week-old Institute of Cancer Research (ICR) mice in a good laboratory practice (GLP) laboratory. Twenty-five mice of each sex were assigned to five groups: negative control, vehicle control, and 125, 250, and 500 mg/kg of ML171. All mice were acclimatized for one week before beginning the study. Mice received an IP injection of ML171 or vehicle. The general condition and mortality of the animals were observed. The mice were sacrificed to evaluate histopathology 14 days after the administration of ML171 or vehicle. Results. Bodyweights were not significantly different in any group. Three males and one female died due to ML171 administration in the 500 mg/kg dose group. Autopsies of the surviving mice did not reveal any significant abnormalities after the injection of 125 mg/kg of ML171. However, the anterior lobe edge of the liver was thickened and adhesions between the liver and adjacent organs were observed in mice treated with 250 or 500 mg/kg of ML171. In addition, hypertrophy of centrilobular hepatocytes and inflammatory cell infiltration were observed after injection of 250 and 500 mg/kg of ML171. Conclusion. Our results indicate that the lethal IP injection dose of ML171 is 500 mg/kg for both males and females. Mortality were not observed for lower doses of ML171. The safe dose of single IP ML171 in ICR mice was 250 mg/kg or less. Further studies are needed to confirm the safety of ML171 in the human body.

Gait patterns of Cerebral Palsy (CP) patients have been used for cluster and classification analysis. Diplegia is the paralysis of one or more body parts which may be caused by CP and may come in various forms. Current clinical practice in gait issue diagnosis relies heavily on observation and is prone to human error. Following previous studies, the effectiveness of introducing modern machine learning techniques and processes in improving the classification accuracy on gait video data was investigated. This paper proposes a novel feature engineering approach by transforming the original video into overlapping sub-clips which not only maintains important features but also reduces training time. Multiple machine learning models have been constructed to examine their individual performances before ensembling them to improve overall performance. The ensemble architecture consists of two stages, a probabilistic-based aggregator and normalizer and a performance-weighted ensemble. Finally, the model classification accuracy was able to achieve over 95%, a marked improvement from the results obtained by the models applied on similar dataset from literature. Hence, this highlights the effectiveness of the proposed method in classification of gait patterns and potentially changing current clinical practice in gait-related diagnosis.

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 &alpha, SMA staining), and &alpha, 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.

The association between angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin II receptor blocker (ARB) and the risk of mortality in hospitalized patients with severe coronavirus disease 2019 (COVID-19) was investigated. This retrospective cohort study was performed in all hospitalized patients with COVID-19 in tertiary hospitals in Daegu, Korea. Patients were classified based on whether they received ACE-I or ARB before COVID-19 diagnosis. The analysis of the primary outcome, in-hospital mortality, was performed using the Cox proportional hazards regression model. Of 130 patients with COVID-19, 30 (23.1%) who received ACE-I or ARB exhibited an increased risk of in-hospital mortality (adjusted hazard ratio, 2.20; 95% confidence interval [CI], 1.10–4.38; P = 0.025). ACE-I or ARB was also associated with severe complications, such as acute respiratory distress syndrome (ARDS) (adjusted odds ratio [aOR], 2.58; 95% CI, 1.02–6.51; P = 0.045) and acute kidney injury (AKI) (aOR, 3.06; 95% CI, 1.15–8.15; P = 0.026). Among the patients with ACE-I or ARB therapy, 8 patients (26.7%) used high equivalent doses of ACE-I or ARB and they had higher in-hospital mortality and an increased risk of ARDS and AKI (all, P

The response to erythropoiesis stimulating agents (ESAs) is affected by inflammation linked to middle molecules in hemodialysis (HD) patients. We evaluated the effect of a medium cut-off (MCO) dialyzer on ESA resistance in maintenance HD patients. Forty-nine patients who underwent high-flux HD were randomly allocated to the MCO or high-flux group. The primary outcome was the changes of erythropoietin resistance index (ERI; U/kg/wk/g/dL) between baseline and 12 weeks. The MCO group showed significant decrease in the ESA dose, weight-adjusted ESA dose, and ERI compared to the high-flux group at 12 weeks (p p p p

The outcome of coronavirus disease 2019 (COVID-19) is associated with organ damage, however, the information about the relationship between acute kidney injury (AKI) and COVID-19 is still rare. We evaluated the clinical features and prognosis of COVID-19 patients with AKI according to the AKI severity. Medical data of hospitalized COVID-19 patients in two university-based hospitals during an outbreak in Daegu, South Korea, were retrospectively analyzed. AKI and its severity were defined according to the Acute Kidney Injury Network. Of the 164 hospitalized patients with COVID-19, 30 patients (18.3%) had AKI, 14, 4, and 12 patients had stage 1, 2, and 3, respectively. The median age was significantly higher in AKI patients than in non-AKI patients (75.5 vs. 67.0 years, p = 0.005). There were 17 deaths (56.7%) among AKI patients, 4 (28.6%), 1 (25.0%), and 12 (100.0%), respectively. In-hospital mortality was higher in AKI patients than in non-AKI patients (56.7% vs. 20.8%, p &lt, 0.001). After adjusting for potential confounding factors, stage 3 AKI was associated with higher mortality than either non-AKI or stage 1 AKI (hazard ratio (HR) = 3.62 (95% confidence interval (CI) = 1.75&ndash, 7.48), p = 0.001, HR = 15.65 (95% CI = 2.43&ndash, 100.64), p = 0.004). Among the AKI patients, acute respiratory distress syndrome and low serum albumin on admission were considered independent risk factors for stage 3 AKI (both p &lt, 0.05). Five patients with stage 3 AKI underwent dialysis and eventually died. In conclusion, COVID-19 patients with severe AKI had fatal outcomes.

Background and Aims Idiopathic membranous nephropathy (iMN) is a leading cause of nephrotic syndrome and one of the major causes of end-stage renal disease (ESRD). Various factors can affect renal and patient outcome in patients with iMN. In this study, we analyzed the predictors of renal and patient survival in patients with iMN. Method We analyzed 1,776 patients diagnosed with iMN in Korean GlomeruloNEphritis STudy (KoGNET), a retrospective database of patients with renal biopsy from 1979 to 2018 from 18 centers in Korea. Student t-test for continuous variables and Chi-square test for categorical variables were performed for analyses. Cox proportional hazard regression was used to determine risk factors affecting renal and patient survival. Results The mean age of patients was 53.0 ± 14.7 years old and 1,075 (60.5%) were male. At the time of renal biopsy, 755 (46.0%) and 266 (16.2%) had hypertension and diabetes, respectively. Serum albumin level was 2.7 ± 0.8 g/dL and 871 (49.0%) had nephrotic range of proteinuria. When analyzed by dividing over 65 and under, the hemoglobin and serum albumin level were lower, more patients showed nephrotic ranged proteinuria, and higher prevalence of comorbidities such as hypertension, diabetes, coronary heart disease and cerebrovascular disease in the group over 65 than in the group under 65. Median duration of follow-up was 88.0 (38.0 – 115.1) months. Complete or partial remission rates were 48.5%, 63.8%, and 68.0% at 6 months, 12months after biopsy, and last follow-up, respectively. In Cox proportional hazard regression, high hemoglobin [HR 0.66 (0.47 – 0.93), p=0.017], high serum albumin level [HR 0.41 (0.18 – 0.94), p=0.034], and high estimated GFR by CKD-EPI equation [HR 0.94 (0.91 – 0.96), p Conclusion High hemoglobin and serum albumin, and good renal function at biopsy were good predictors for renal survival. Older age and hypertension at biopsy were poor prognostic factors for patient survival in iMN patients. Prognostic information of outcomes in this study might be helpful to optimize management in iMN patients.

Background and Aims Little is known regarding the safe fixed dose of mycophenolic acid (MPA) for preventing biopsy-proven acute rejection (BPAR) in kidney transplant recipients (KTRs). We investigated the correlation of MPA trough concentration (MPA C0) and dose with renal transplant outcomes and adverse events. Method This study included 79 consecutive KTRs who received MPA with tacrolimus (TAC) and corticosteroids. The MPA C0 of all the enrolled KTRs was measured, which was determined monthly by using particle-enhanced turbidimetric inhibition immunoassay for 12 months, and clinical data were collected at each time point. The clinical endpoints included BPAR, any cytopenia, and BK or cytomegalovirus infections. Results No differences in MPA C0 and dose were observed between KTRs with or without BPAR or viral infections under statistically comparable TAC concentrations. MPA C0 was significantly higher in patients with leukopenia (P = 0.021) and anemia (P = 0.002) compared with those without cytopenia. The MPA dose was significantly higher in patients with thrombocytopenia (P = 0.002) compared with those without thrombocytopenia. MPA C0 ≥ 3.5 µg/mL was an independent risk factor for leukopenia (adjusted odds ratio [AOR] 3.80, 95% confidence interval [CI] 1.24–11.64, P = 0.019) and anemia (AOR 5.90, 95% CI 1.27–27.51, P = 0.024). An MPA dose greater than the mean value of 1188.8 mg/day was an independent risk factor for thrombocytopenia (AOR 3.83, 95% CI 1.15–12.78, P = 0.029). However, an MPA dose less than the mean value of 1137.3 mg/day did not increase the risk of BPAR. Conclusion Either a higher MPA C0 or dose was associated with an increased risk of cytopenia, but neither a lower MPA C0 nor dose was associated with BPAR within the first year of transplantation. Hence, a reduced MPA dose with TAC and corticosteroids might be safe in terms of reducing hematologic abnormalities without causing rejection.

Medium cut-off (MCO) dialyzers help remove larger middle molecules associated with symptoms related to the accumulation of uremic retention solutes. We investigated the effect of an MCO dialyzer on the improvement of quality of life (QOL) in maintenance hemodialysis (HD) patients. Forty-nine HD patients with high-flux dialysis were randomly assigned to either an MCO (Theranova 400, Baxter) or a high-flux (FX CorDiax 80 or 60, Fresenius Medical Care) dialyzer and completed the study. QOL was assessed at baseline and after 12 weeks of treatment using the Kidney Disease Quality of Life Short Form-36, and pruritus was assessed using a questionnaire and visual analog scale. The reduction ratios of middle molecules were also evaluated. Laboratory markers, including serum albumin, did not differ between the two groups after 12 weeks. Removals of kappa and lambda free light chains were greater for MCO dialyzer than high-flux dialyzer. The MCO group had higher scores than the high-flux group in the domains of physical functioning and physical role (75.2 ± 20.8 vs. 59.8 ± 30.1, P = 0.042; 61.5 ± 37.6 vs. 39.0 ± 39.6, P = 0.047, respectively), and the MCO group had lower mean scores for morning pruritus distribution and the frequency of scratching during sleep (1.29 ± 0.46 vs. 1.64 ± 0.64, P = 0.034; 0.25 ± 0.53 vs. 1.00 ± 1.47, P = 0.023, respectively). MCO dialyzers may improve patient-reported outcomes, particularly the physical components of QOL and uremic pruritus, in patients with high-flux dialyzers.

Background:The alpha-1 antitrypsin (AAT) protein has an important role in the anti-inflammatory and apoptotic response. AAT inhibits not only serine proteases but also cysteine and aspartic proteases. Apoptosis results from the sequential activation of cysteine proteases of the caspase family. This study aimed to evaluate the effect of AAT on formaldehyde-induced apoptosis of human peritoneal mesothelial cells (HPMCs).Methods:HPMCs were cultured and treated with formaldehyde (250 µM) to induce apoptosis. In the AAT group, the cultured HPMCs were pretreated with AAT (2 mg/mL) for 1 h before formaldehyde treatment. We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays to determine cell viability, and flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assays to detect apoptosis. The MTT assays were used to find optimal concentrations of formaldehyde and AAT. We measured caspase-3 activity and used Western blotting to estimate Bcl-2 and Bad expression.Results:Flow cytometry and TUNEL assays revealed that formaldehyde exposure significantly increased apoptosis compared with the control treatment, but pretreatment with AAT significantly inhibited this effect. Compared with the control, caspase-3 activity was significantly increased and the ratio of Bcl-2 to Bad expression significantly decreased following treatment with formaldehyde. However, caspase-3 activity was significantly lower and the Bcl-2 to Bad expression ratio higher in the AAT group than in the formaldehyde-only group.Conclusion:AAT inhibits formaldehyde-induced apoptosis of HPMCs via a caspase-mediated pathway. These data support a potential use for AAT as a therapeutic agent for the inhibition of peritoneal cell apoptosis during peritoneal dialysis.

Patients with advanced chronic kidney disease (CKD) or who are on hemodialysis (HD) could have increased susceptibility to the 2019 coronavirus disease (COVID-19) given their pre-existing comorbidities, older age, compromised immune system, and regular visits to populated outpatient dialysis centers. This study included 14 consecutive patients on HD or with advanced CKD who initiated HD after being diagnosed with laboratory-confirmed COVID-19 from February to April 2020 in hospitals throughout Daegu, South Korea. The included patients, 42.9% of whom were men, had a mean age of 63.5 years. Four patients had a history of contact with a patient suffering from COVID-19. The most common symptom was cough (50.0%), followed by dyspnea (35.7%). The mean time from symptom onset to diagnosis and admission was 2.6 and 3.5 days, respectively. Patients exhibited lymphopenia and elevated inflammatory markers, including C-reactive protein and ferritin. Chest radiography findings showed pulmonary infiltration in 10 patients. All patients underwent regular HD in a negative pressure room and received antiviral agents. Four patients received mechanical ventilation and continuous renal replacement therapy at a median duration of 14.0 and 8.5 days, respectively. One patient underwent extracorporeal membrane oxygenation for three days. Among the 14 patients included, two died due to acute respiratory distress syndrome, nine were discharged from the hospital, and three remained hospitalized. Despite the high-risk conditions associated with worse outcomes, patients on HD did not exhibit extremely poor overall COVID-19 outcomes perhaps due to early diagnosis, prompt hospitalization, and antiviral therapy.

IntroductionCrescentic glomerulonephritis (CrGN) is a histologic feature of severe glomerular injury, clinically characterized by a rapid decline of renal function when not treated in a timely fashion. Factors associated with CrGN prognosis have not been thoroughly investigated. This study investigated the prognostic predictors of renal outcomes associated with CrGN, such as the histopathologic classification of anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis, arteriosclerosis, and tertiary lymphoid organ (TLO) formation.MethodsA total of 114 patients diagnosed with CrGN between 2010 and 2018 at two university-based hospitals has been retrospectively analyzed. Relationships between potential predictors and renal outcomes were analyzed using Cox proportional hazards model and linear regression analysis.ResultsThe mean age was 61.0 ± 15.3 years, and 49.1% were male. Among them, 92 (80.7%) and 11 (9.6%) patients were positive for ANCA and for anti-glomerular basement membrane antibody, respectively. During the median follow-up of 458.0 days, 55 patients (48.2%) had advanced to end-stage renal disease (ESRD). Cox proportional hazards analysis revealed that patients under the mixed and sclerotic classes had worse renal survival compared to those in the focal class (mixed: hazard ratio [HR], 3.74; 95% confidence interval [CI], 1.18 to 11.82; P = 0.025; sclerotic: HR, 4.84; 95% CI, 1.44 to 16.32; P = 0.011). Severe arteriosclerosis was also associated with poor renal survival (HR, 2.44; 95% CI, 1.04 to 5.77; P = 0.042). TLOs were observed in 41 patients (36.0%). Moreover, TLO formation was also a prognostic factor for ESRD (HR, 1.82; 95% CI, 1.03 to 3.21; P = 0.040). In the multivariate linear regression analysis, age and sclerotic class were independent predictors for the change in estimated glomerular filtration rate during 1 year after biopsy.ConclusionsSpecific histopathologic findings, histopathologic classification, severity of arteriosclerosis, and TLO formation provide helpful information in predicting renal outcomes associated with CrGN.

Introduction To investigate the correlation between serum anti-ABO immunoglobulin G (IgG) and IgG subclasses, anti-ABO IgG subclasses were measured by flow cytometry (FCM) in ABO-incompatible (ABOi) kidney transplant recipients. We also evaluated baseline anti-ABO C1q antibody. Method Baseline anti-ABO IgG titers were measured by both FCM and column agglutination technique methods in 18 ABOi kidney transplant recipients. The mean florescence intensity (MFI) ratios of baseline anti-ABO IgG subclasses and anti-ABO C1q antibody were obtained by FCM and followed-up after rituximab treatment, each plasmapheresis (PP) session, and kidney transplantation. Correlation between the values of IgG subclass and total IgG titer was analyzed. Results The baseline MFI ratios of total IgG, IgG1, IgG2, IgG3, and IgG4 were 202.46, 62.41, 30.01, 1.04, and 1.13, respectively. The MFI ratios of IgG1, IgG2, and total IgG measured at baseline and pre-PP were positively correlated with the baseline ABO titer was measured using the column agglutination technique. The numbers of PP sessions to reach the target titer were correlated with the baseline IgG and IgG1 levels. IgG1 and IgG2 as well as total IgG were removed effectively after serial PP. Anti-ABO C1q antibody was neither detected nor correlated with total IgG and any IgG subclasses. Conclusions Our findings suggest that IgG1 and IgG2 are the dominant IgG subclass in ABOi kidney transplant recipients. Baseline levels of IgG1 and IgG2 were correlated with baseline total IgG titer. However, anti-ABO C1q antibody was not detected in the present study.

Motor impairment is one of the common neurological conditions suffered by stroke patients, where this chronic immobility together with the absence of early limb mobilisation can lead to conditions such as joint contracture with spastic limbs. In this study, a soft robotic sock device was developed, which can provide compliant actuation to the ankle joint in the early stage of stroke recovery. The device is fitted with soft extension actuators and when the actuators are inflated, they extend and guide the foot into plantarflexion; upon deflation, the actuators will resume their initial conformations. Each actuator is linked to a pneumatic pump-valve control system that injects pressurised air into or release air from the system. In this study, the design and characterisation of the soft actuators will be presented, where the theoretical and experimental forces generated by the actuators were compared. The performance of the device was also evaluated on healthy subjects and the results had shown that the device was able to move the subjects' ankles into cycles of dorsiflexion-plantarflexion, in the absence of voluntary muscle effort. The findings suggested that the soft wearable robotic device was capable of assisting the subjects in performing repeated cycles of ankle flexion.

Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine. This study evaluated the association between GDF-15 and in-hospital mortality among patients with severe acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT). Among the multicenter prospective CRRT cohort between 2017 and 2019, 66 patients whose blood sample was available were analyzed. Patients were divided into three groups according to the GDF-15 concentrations. The median GDF-15 level was 7865.5 pg/mL (496.9 pg/mL in the healthy control patients). Baseline characteristics were not different among tertile groups except the severity scores and serum lactate level, which were higher in the third tertile. After adjusting for confounding factors, the patients with higher GDF-15 had significantly increased risk of mortality (second tertile: adjusted hazards ratio [aHR], 3.67; 95% confidence interval [CI], 1.05–12.76; p = 0.041; third tertile: aHR, 6.81; 95% CI, 1.98–23.44; p = 0.002). Furthermore, GDF-15 predicted in-hospital mortality (area under the curve, 0.710; 95% CI, 0.585–0.815) better than APACHE II and SOFA scores. Serum GDF-15 concentration was elevated in AKI patients requiring CRRT, higher in more severe patients. GDF-15 is a better independent predictor for in-hospital mortality of critically ill AKI patients than the traditional risk scoring system such as APACHE II and SOFA scores.

This letter presents a fully fabric-based bidirectional soft robotic glove designed to assist hand impaired patients in rehabilitation exercises and performing activities of daily living. The glove provides both active finger flexion and extension for hand assistance and rehabilitative training, through its embedded fabric-based actuators that are fabricated by heat press and ultrasonic welding of flexible thermoplastic polyurethane-coated fabrics. Compared to previous developed elastomeric-based actuators, the actuators are able to achieve smaller bend radius and generate sufficient force and torque to assist in both finger flexion and extension at lower air pressure. In this letter, experiments were conducted to characterize the performances of the glove in terms of its kinematic and grip strength assistances on five healthy participants. Additionally, we present a graphical-user interface that allows user to choose the desired rehabilitation exercises and control modes, which include button-controlled-assistive mode, cyclic movement training, intention-driven task-specific training, and bilateral rehabilitation training.

In elderly population, gait disorders are common where majority of these disorders are associated as symptoms of neurodegenerative diseases including Parkinson’s Disease (PD), Huntingtons Disease (HD), and Amyotrophic Lateral Sclerosis (ALS). In addition to affected mobility, the patients are also susceptible to greater risk of falls, hence increasing the demand for caretakers. With the trend of aging population, personal assistive device could be deployed to assist patients to regain independence and improve their quality of life. This paper proposes an end-to-end solution architecture for real-time standalone wearable gait assistive device to automate the rehabilitation activity. A key aspect of this study is to incorporate recurrent neural network (RNN) model that provides accurate pattern recognition and output actuation cue to the patients. Prototype and simulation data was used to show the feasibility of the proposed architecture and machine learning model. Preliminary results indicate favorable accuracy gait cycle detection for implementation. However, further optimizations are required to lower the computational costs and shorten the time lag between cycles to ensure low cost feasibility of the device.

Rationale: Anti-angiotensin II type 1 receptor antibodies (AT1R-Abs) have been demonstrated to increase the risk of antibody-mediated rejection. We report a case of AT1R-Ab mediated rejection which caused early critical cortical infarction. Patient concerns: A 52-year-old man with end-stage kidney disease underwent preemptive kidney transplantation (KT) from his wife. He had no immunologic risk except ABO incompatibility. Proper desensitization treatment were applied prior to KT. On postoperative day 1, he showed stable clinical course with adequate urine output, but there was no decrease in serum creatinine level and imaging studies showed hypoperfusion in the transplanted kidney. Diagnoses: Allograft biopsy revealed total cortical infarction with severe necrotizing vasculitis, but the medullary area was preserved. Serum AT1R-Ab concentration was elevated from 10.9 U/mL before KT to 19.1 U/mL on 7 days after KT. Interventions: He was treated with plasmapheresis, intravenous immunoglobulin, rituximab, high-dose methylprednisolone, and bortezomib. Outcomes: The treatment showed a partial response, and he was discharged with 7.3 mg/dL creatinine level. At 4 months, his creatinine plateaued at 5.5 mg/dL and AT1R-Ab decreased to 3.6 U/mL. Lessons: This case highlights the risk of early active antibody-mediated rejection by preformed AT1R-Ab, suggesting its ability to exhibit atypical histopathologic findings, such as total cortical infarction.

Various hand exoskeletons have been proposed for the purposes of providing assistance in activities of daily living and rehabilitation exercises. However, traditional exoskeletons are made of rigid components that impede the natural movement of joints and cause discomfort to the user. This paper evaluated a soft wearable exoskeleton using soft elastomeric actuators. The actuators could generate the desired actuation of the finger joints with a simple design. The actuators were characterised in terms of their radius of curvature and force output during actuation. Additionally, the device was evaluated on five healthy subjects in terms of its assisted finger joint range of motion. Results demonstrated that the subjects were able to perform the grasping actions with the assistance of the device and the range of motion of individual finger joints varied from subject to subject. This work evaluated the performance of a soft wearable exoskeleton and highlighted the importance of customisability of the device. It demonstrated the possibility of replacing traditional rigid exoskeletons with soft exoskeletons that are more wearable and customisable.