Effect of Statin Therapy on Cardiovascular Outcome in Stroke Patients with Low Baseline Low-Density Lipoprotein Cholesterol.

OBJECTIVES: To investigate whether post-stroke statin therapy reduces subsequent major vascular events in statin-naïve patients with pretreatment low-density lipoprotein cholesterol (LDL-C) below the recommended target (≤70 mg/dL for atherosclerotic stroke and ≤100 mg/dL for non-atherosclerotic stroke) at stroke onset. METHODS: Patients from an ongoing stroke registry who had an ischemic stroke between 2011 and 2020 were screened. Statin naïve patients with baseline LDL-C below the target were assessed. The effect of post-stroke statin therapy on major vascular events (composite of recurrent stroke, myocardial infarction, and death) was investigated using weighted Cox regression analyses using stabilized inverse probability treatment weighting. RESULTS: The baseline LDL-C level of the 1,858 patients (mean age 67.9 ± 15.3 years, 61.4% men, 13.2% atherosclerotic stroke) included in the study was 75.7 ± 17.0 mg/dL. Statins were prescribed to 1,256 (67.7%) patients (low-to-moderate intensity, 23.5%; high intensity, 44.1%). Post-stroke statin therapy was associated with a lower risk of major vascular events during 1-year follow-up (weighted hazard ratio 0.55, 95% confidence interval 0.42-0.71). In a subgroup of patients who were at very high risk of atherosclerotic cardiovascular disease with LDL-C <55 mg/dL or patients who were not at very high risk of atherosclerotic cardiovascular disease with LDL-C <70 mg/dL, post-stroke statin therapy was also associated with a reduction in major vascular events (weighted hazard ratio 0.45, 95% confidence interval 0.29-0.70). The intensity of the most beneficial statin varied by subtype of stroke. INTERPRETATION: Statin therapy may improve vascular outcomes after ischemic stroke, even in cases of LDL-C below the target without pre-stroke lipid-lowering therapy. ANN NEUROL 2024;95:876-885.

Deciphering the importance of culture pH on CD22 CAR T-cells characteristics.

BACKGROUND: Chimeric antigen receptor (CAR) T-cells have demonstrated significant efficacy in targeting hematological malignancies, and their use continues to expand. Despite substantial efforts spent on the optimization of protocols for CAR T-cell manufacturing, critical parameters of cell culture such as pH or oxygenation are rarely actively monitored during cGMP CAR T-cell generation. A comprehensive understanding of the role that these factors play in manufacturing may help in optimizing patient-specific CAR T-cell therapy with maximum benefits and minimal toxicity. METHODS: This retrospective study examined cell culture supernatants from the manufacture of CAR T-cells for 20 patients with B-cell malignancies enrolled in a phase 1/2 clinical trial of anti-CD22 CAR T-cells. MetaFLEX was used to measure supernatant pH, oxygenation, and metabolites, and a Bio-Plex assay was used to assess protein levels. Correlations were assessed between the pH of cell culture media throughout manufacturing and cell proliferation as well as clinical outcomes. Next-generation sequencing was conducted to examine gene expression profiles of the final CAR T-cell products. RESULTS: A pH level at the lower range of normal at the beginning of the manufacturing process significantly correlated with measures of T-cell expansion and metabolism. Stable or rising pH during the manufacturing process was associated with clinical response, whereas a drop in pH was associated with non-response. CONCLUSIONS: pH has potential to serve as an informative factor in predicting CAR T-cell quality and clinical outcomes. Thus, its active monitoring during manufacturing may ensure a more effective CAR T-cell product.

Assessment and comparison of viability assays for cellular products.

BACKGROUND AIMS: Accurate assessment of cell viability is crucial in cellular product manufacturing, yet selecting the appropriate viability assay presents challenges due to various factors. This study compares and evaluates different viability assays on fresh and cryopreserved cellular products, including peripheral blood stem cell (PBSC) and peripheral blood mononuclear cell (PBMC) apheresis products, purified PBMCs and cultured chimeric antigen receptor and T-cell receptor-engineered T-cell products. METHODS: Viability assays, including manual Trypan Blue exclusion, flow cytometry-based assays using 7-aminoactinomycin D (7-AAD) or propidium iodide (PI) direct staining or cell surface marker staining in conjunction with 7-AAD, Cellometer (Nexcelom Bioscience LLC, Lawrence, MA, USA) Acridine Orange/PI staining and Vi-CELL BLU Cell Viability Analyzer (Beckman Coulter, Inc, Brea, CA, USA), were evaluated. A viability standard was established using live and dead cell mixtures to assess the accuracy of these assays. Furthermore, precision assessment was conducted to determine the reproducibility of the viability assays. Additionally, the viability of individual cell populations from cryopreserved PBSC and PBMC apheresis products was examined. RESULTS: All methods provided accurate viability measurements and generated consistent and reproducible viability data. The assessed viability assays were demonstrated to be reliable alternatives when evaluating the viability of fresh cellular products. However, cryopreserved products exhibited variability among the tested assays. Additionally, analyzing the viability of each subset of the cryopreserved PBSC and PBMC apheresis products revealed that T cells and granulocytes were more susceptible to the freeze-thaw process, showing decreased viability. CONCLUSIONS: The study demonstrates the importance of careful assay selection, validation and standardization, particularly for assessing the viability of cryopreserved products. Given the complexity of cellular products, choosing a fit-for-purpose viability assay is essential.

Association of coronary artery calcium with adverse cardiovascular outcomes and death in patients with chronic kidney disease: results from the KNOW-CKD.

BACKGROUND: In East Asian countries, patients with chronic kidney disease (CKD) have lower cardiovascular risk profiles and experience fewer cardiovascular events (CVEs) than those in Western countries. Thus the clinical predictive performance of well-known risk factors warrants further testing in this population. METHODS: The KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD) is a multicenter, prospective observational study. We included 1579 participants with CKD G1-G5 without kidney replacement therapy between 2011 and 2016. The main predictor was the coronary artery calcium score (CACS). The primary outcome was a composite of nonfatal CVEs or all-cause mortality. Secondary outcomes included 3-point major adverse cardiovascular events (MACEs; the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke), all CVEs and all-cause mortality. RESULTS: During a median follow-up of 5.1 years, a total of 123 primary outcome events occurred (incidence rate 1.6/100 person-years). In the multivariable Cox model, a 1-standard deviation log increase in the CACS was associated with a 1.67-fold [95% confidence interval (CI), 1.37-2.04] higher risk of the primary outcome. Compared with a CACS of 0, the hazard ratio associated with a CACS >400 was 4.89 (95% CI 2.68-8.93) for the primary outcome. This association was consistent for secondary outcomes. Moreover, inclusion of the CACS led to modest improvements in prediction indices of the primary outcome compared with well-known conventional risk factors. CONCLUSIONS: In Korean patients with CKD, the CACS was independently associated with adverse cardiovascular outcomes and all-cause death. The CACS also showed modest improvements in prediction performance over conventional cardiovascular risk factors.

Practice of dialysis access interventional nephrology procedures in the Asia-Pacific region: Getting lay of the land.

AIM: This cross-sectional survey aimed to determine the prevalence of Interventional Nephrology (IN) practice amongst nephrologists in the Asia-Pacific Region (APR), specifically related to dialysis access (DA). METHODS: The Association of VA and intervenTionAl Renal physicians (AVATAR) Foundation from India conducted a multinational online survey amongst nephrologists from the Asia-Pacific to determine the practice of IN in the planning, creation, and management of dialysis access. The treatment modalities, manpower and equipment availability, monthly cost of treatment, specifics of dialysis access interventions, and challenges in the training and practice of IN by nephrologists were included in the survey. RESULTS: Twenty-one countries from the APR participated in the survey. Nephrologists from 18 (85.7%) countries reported performing at least one of the basic dialysis access-related IN procedures, primarily the placement of non-tunnelled central catheters (n-TCC; 71.5%). Only 10 countries (47.6%) reported having an average of <4% of nephrologists performing any of the advanced IN access procedures, the most common being the placement of a peritoneal dialysis (PD) catheter (20%). Lack of formal training (57.14%), time (42.8%), incentive (38%), institutional support (38%), medico-legal protection (28.6%), and prohibitive cost (23.8%) were the main challenges to practice IN. The primary obstacles to implementing the IN training were a lack of funding and skilled personnel. CONCLUSION: The practice of dialysis access-related IN in APR is inadequate, mostly due to a lack of training, backup support, and economic constraints, whereas training in access-related IN is constrained by a lack of a skilled workforce and finances.

STEM Image Analysis Based on Deep Learning: Identification of Vacancy Defects and Polymorphs of MoS2.

Scanning transmission electron microscopy (STEM) is an indispensable tool for atomic-resolution structural analysis for a wide range of materials. The conventional analysis of STEM images is an extensive hands-on process, which limits efficient handling of high-throughput data. Here, we apply a fully convolutional network (FCN) for identification of important structural features of two-dimensional crystals. ResUNet, a type of FCN, is utilized in identifying sulfur vacancies and polymorph types of MoS2 from atomic resolution STEM images. Efficient models are achieved based on training with simulated images in the presence of different levels of noise, aberrations, and carbon contamination. The accuracy of the FCN models toward extensive experimental STEM images is comparable to that of careful hands-on analysis. Our work provides a guideline on best practices to train a deep learning model for STEM image analysis and demonstrates FCN's application for efficient processing of a large volume of STEM data.

Cavity-dumped mode-locked Alexandrite laser oscillator with 100 mJ pulses stabilized by using a double trigger system.

We report a mode-locked Alexandrite single pulse laser with cavity dumping. Mode locking was achieved by using an AOM and an EOM was used for Q-switching and cavity dumping. The instability of the single pulse laser energy output was reduced down to a tenth of that of the conventional single trigger system by introducing a novel double trigger system. The single pulse laser energy and pulse width were 100 mJ and 475 ps in multiple mode and 12.5 mJ and 275 ps in single mode, obtained without a laser amplifier.

Size-Related Differences in Computed Tomography Markers of Hematoma Expansion in Acute Intracerebral Hemorrhage.

BACKGROUND: Noncontrast computed tomography (NCCT) markers for hematoma expansion (HE) in intracerebral hemorrhage (ICH) are difficult to be found in small ICHs, of which can also expand. We aimed to investigate whether there were size-related differences in the prevalence of NCCT markers and their association with HE. METHODS: This retrospective analysis of prospectively collected stroke registry included 267 consecutive patients with ICH who underwent baseline NCCT within 12 h of onset. Qualitative NCCT markers, including heterogeneous density and irregular shape, were assessed. Hematoma density, defined as mean Hounsfield unit of hematoma, and hematoma volume were measured by semiautomated planimetry. Hematoma volume was categorized as small (≤ 10 ml) and large (> 10 ml). Associations of NCCT markers with HE were analyzed using multivariable logistic regression analyses. The model performances of NCCT markers and hematoma density were compared using receiver operating characteristic curves. RESULTS: Hematoma expansion occurred in 29.9% of small ICHs and 35.5% of large ICHs. Qualitative NCCT markers were less frequently observed in small ICHs. Heterogeneous density, irregular shape, and hematoma density were associated with HE in small ICH (adjusted odds ratios [95% confidence interval] 3.94 [1.50-10.81], 4.23 [1.73-10.81], and 0.72 [0.60-0.84], respectively), and hematoma density was also related to HE in large ICH (0.84 [0.73-0.97). The model performance was significantly improved in small ICHs when hematoma density was added to the baseline model (DeLong's test, p = 0.02). CONCLUSIONS: The prevalence of NCCT markers and their association with HE differed according to hematoma volume. Quantitative hematoma density was associated with HE, regardless of hematoma size.

Comparison of the Efficacy and Safety of Tacrolimus and Low-Dose Corticosteroid with High-Dose Corticosteroid for Minimal Change Nephrotic Syndrome in Adults.

BACKGROUND: Tacrolimus is used as a steroid-sparing immunosuppressant in adults with minimal change nephrotic syndrome. However, combined treatment with tacrolimus and low-dose steroid has not been compared with high-dose steroid for induction of clinical remission in a large-scale randomized study. METHODS: In this 24-week open-label noninferiority study, we randomized 144 adults with minimal change nephrotic syndrome to receive 0.05 mg/kg twice-daily tacrolimus plus once-daily 0.5 mg/kg prednisolone, or once-daily 1 mg/kg prednisolone alone, for up to 8 weeks or until achieving complete remission. Two weeks after complete remission, we tapered the steroid to a maintenance dose of 5-7.5 mg/d in both groups until 24 weeks after study drug initiation. The primary end point was complete remission within 8 weeks (urine protein: creatinine ratio <0.2 g/g). Secondary end points included time until remission and relapse rates (proteinuria and urine protein: creatinine ratio >3.0 g/g) after complete remission to within 24 weeks of study drug initiation. RESULTS: Complete remission within 8 weeks occurred in 53 of 67 patients (79.1%) receiving tacrolimus and low-dose steroid and 53 of 69 patients (76.8%) receiving high-dose steroid; this difference demonstrated noninferiority, with an upper confidence limit below the predefined threshold (20%) in both intent-to-treat (11.6%) and per-protocol (17.0%) analyses. Groups did not significantly differ in time until remission. Significantly fewer patients relapsed on maintenance tacrolimus (3-8 ng/ml) plus tapered steroid versus tapered steroid alone (5.7% versus 22.6%, respectively; P=0.01). There were no clinically relevant safety differences. CONCLUSIONS: Combined tacrolimus and low-dose steroid was noninferior to high-dose steroid for complete remission induction in adults with minimal change nephrotic syndrome. Relapse rates were significantly lower with maintenance tacrolimus and steroid compared with steroid alone. No clinically-relevant differences in safety findings were observed.

Serum uric acid is associated with coronary artery calcification in early chronic kidney disease: a cross-sectional study.

BACKGROUND: Although uric acid (UA) is regarded as a risk factor for cardiovascular disease, whether UA is an independent risk factor contributing to coronary artery calcification in chronic kidney disease (CKD) is not well known. We evaluated whether UA level is associated with coronary artery calcium (CAC) score in a predialysis CKD cohort. METHODS: A total of 1,350 subjects who underwent coronary computed tomography as part of the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease were analysed. We conducted a logistic regression analysis to evaluate the association between UA and the presence of CAC. RESULTS: CAC was detected in 705 (52.2 %) patients, and the level of UA was significantly higher in CAC > 0 patients. UA showed a positive relationship with CAC > 0 in age- and sex-adjusted logistic regression analysis (Odds ratio (OR) 1.11, 95 % confidence interval (CI) 1.04-1.19, P = 0.003). However, UA showed no association with CAC > 0 in multivariate analysis. Further analysis showed that UA showed a positive association with CAC > 0 only in estimated glomerual filtration rate (eGFR) > 60 ml/min/1.73 m2 (OR 1.23, 95 % CI 1.02-1.49, P = 0.036) but not in eGFR 30-59 ml/min/1.73 m2 (OR 0.92, 95 % CI 0.78-1.08, P = 0.309) or < 30 ml/min/1.73 m2 (OR 0.92, 95 % CI 0.79-1.08, P = 0.426). CONCLUSIONS: UA level was significantly associated with CAC in early CKD, but not in advanced CKD.

Identification of Molecules from Coffee Silverskin That Suppresses Myostatin Activity and Improves Muscle Mass and Strength in Mice.

Coffee has been shown to attenuate sarcopenia, the age-associated muscle atrophy. Myostatin (MSTN), a member of the TGF-ß growth/differentiation factor superfamily, is a potent negative regulator of skeletal muscle mass, and MSTN-inhibition increases muscle mass or prevents muscle atrophy. This study, thus, investigated the presence of MSTN-inhibitory capacity in coffee extracts. The ethanol-extract of coffee silverskin (CSE) but not other extracts demonstrated anti-MSTN activity in a pGL3-(CAGA)12-luciferase reporter gene assay. CSE also blocked Smad3 phosphorylation induced by MSTN but not by GDF11 or Activin A in Western blot analysis, demonstrating its capacity to block the binding of MSTN to its receptor. Oral administration of CSE significantly increased forelimb muscle mass and grip strength in mice. Using solvent partitioning, solid-phase chromatography, and reverse-phase HPLC, two peaks having MSTN-inhibitory capacity were purified from CSE. The two peaks were identified as ßN-arachinoyl-5-hydroxytryptamide (C20-5HT) and ßN-behenoyl-5-hydroxytryptamide (C22-5HT) using mass spectrometry and NMR analysis. In summary, the results show that CSE has the MSTN-inhibitory capacity, and C20-5HT and C22-5HT are active components of CSE-suppressing MSTN activity, suggesting the potential of CSE, C20-5HT, and C22-5HT being developed as agents to combat muscle atrophy and metabolic syndrome.

Discovery of indane propanamides as potent and selective TRPV1 antagonists.

A series of indane-type acetamide and propanamide analogues were investigated as TRPV1 antagonists. The analysis of structure-activity relationship indicated that indane A-region analogues exhibited better antagonism than did the corresponding 2,3-dihydrobenzofuran and 1,3-benzodioxole surrogates. Among them, antagonist 36 exhibited potent and selective antagonism toward capsaicin for hTRPV1 and mTRPV1. Further, in vivo studies indicated that antagonist 36 showed excellent analgesic activity in both phases of the formalin mouse pain model and inhibited the pain behavior completely at a dose of 1 mg/kg in the 2nd phase.

Acute kidney injury with extreme hyperuricemia after antithymocyte globulin treatment in a kidney transplant recipient with underlying aplastic anemia: a case report.

BACKGROUND: The occurrences of hyperuricemia and acute kidney injury after antithymocyte globulin treatment are unusual in kidney transplant recipients. Here, we report a unique case of acute kidney injury with extreme hyperuricemia after antithymocyte globulin treatment in a kidney transplant recipient with underlying aplastic anemia. CASE PRESENTATION: A 40-year-old woman with aplastic anemia who received a kidney transplant 5 years 6 months before presented to our emergency department with complaints of oliguria, generalized edema, and general weakness 6 days after receiving antithymocyte globulin treatment for acute T-cell-mediated rejection. Urinalysis revealed 100 uric acid crystal particles. The blood chemistry test results showed rapid increases in serum creatinine (from 2.86 mg/dL to 5.58 mg/dL) and uric acid levels (from 10.2 mg/dL to 32.7 mg/dL), which suggested acute uric acid nephropathy. Tumor lysis syndrome was suspected to be the cause of the acute uric acid nephropathy; hence, the patient was reevaluated for aplastic anemia. Human leukocyte antigen-DR15 was positive, and flow cytometry revealed a low percentage of glycophosphatidyl inositol-deficient granulocytes (2.9%), which suggested paroxysmal nocturnal hemoglobinuria clones. These findings indicate that the previously diagnosed aplastic anemia had either originally been hypocellular myelodysplastic syndrome (MDS) or later transformed into hypocellular MDS, which is a type of bone marrow failure syndrome. CONCLUSIONS: Clinicians should consider unexpected tumor lysis syndrome to be the cause of complications after antithymocyte globulin treatment in kidney transplant recipients with underlying bone marrow failure syndrome.

Discrepant glomerular filtration rate trends from creatinine and cystatin C in patients with chronic kidney disease: results from the KNOW-CKD cohort.

BACKGROUND: Serum creatinine (Cr) and cystatin C (CysC) can both be used to estimate glomerular filtration rate (eGFRCr and eGFRCysC). However, certain conditions may cause discrepancies between eGFR trends from Cr and CysC, and these remain undetermined in patients with chronic kidney disease (CKD). METHODS: A total of 1069 patients from the Korean CKD cohort (KNOW-CKD), which enrolls pre-dialytic CKD patients, whose Cr and CysC had been followed for more than 4 years were included in the sample. We performed trajectory analysis using latent class mixed modeling and identified members of the discrepancy group when patient trends between eGFRCr and eGFRCysC differed. Multivariate logistic analyses with Firth's penalized likelihood regression models were performed to identify conditions related to the discrepancy. RESULTS: Trajectory patterns of eGFRCr were classified into three groups: two groups with stable eGFRCr (stable with high eGFRCr and stable with low eGFRCr) and one group with decreasing eGFRCr. Trajectory analysis of eGFRCysC also showed similar patterns, comprising two groups with stable eGFRCysC and one group with decreasing eGFRCysC. Patients in the discrepancy group (decreasing eGFRCr but stable & low eGFRCysC; n = 55) were younger and had greater proteinuria values than the agreement group (stable & low eGFRCr and eGFRCysC; n = 706), differences that remained consistent irrespective of the measurement period (4 or 5 years). CONCLUSIONS: In the present study, we identify conditions related to discrepant trends of eGFRCr and eGFRCysC. Clinicians should remain aware of such potential discrepancies when tracing both Cr and CysC.

Genetic Control of Lyme Arthritis by Borrelia burgdorferi Arthritis-Associated Locus 1 Is Dependent on Localized Differential Production of IFN-ß and Requires Upregulation of Myostatin.

Previously, using a forward genetic approach, we identified differential expression of type I IFN as a positional candidate for an expression quantitative trait locus underlying Borrelia burgdorferi arthritis-associated locus 1 (Bbaa1). In this study, we show that mAb blockade revealed a unique role for IFN-ß in Lyme arthritis development in B6.C3-Bbaa1 mice. Genetic control of IFN-ß expression was also identified in bone marrow-derived macrophages stimulated with B. burgdorferi, and it was responsible for feed-forward amplification of IFN-stimulated genes. Reciprocal radiation chimeras between B6.C3-Bbaa1 and C57BL/6 mice revealed that arthritis is initiated by radiation-sensitive cells, but orchestrated by radiation-resistant components of joint tissue. Advanced congenic lines were developed to reduce the physical size of the Bbaa1 interval, and confirmed the contribution of type I IFN genes to Lyme arthritis. RNA sequencing of resident CD45- joint cells from advanced interval-specific recombinant congenic lines identified myostatin as uniquely upregulated in association with Bbaa1 arthritis development, and myostatin expression was linked to IFN-ß production. Inhibition of myostatin in vivo suppressed Lyme arthritis in the reduced interval Bbaa1 congenic mice, formally implicating myostatin as a novel downstream mediator of the joint-specific inflammatory response to B. burgdorferi.

Arterial Stiffness as a Risk Factor for Subclinical Coronary Artery Calcification in Predialysis Chronic Kidney Disease: From the KNOW-CKD Study.

BACKGROUND/AIMS: Both arterial stiffness and coronary artery calcification (CAC) are important predictors of cardiovascular disease in the general population and in chronic kidney disease (CKD) patients. Recent studies on arterial stiffness and CAC in subjects with preserved renal function have verified the association between the two. However, the relationship is not well evaluated in CKD patients. METHODS: This cross-sectional study analyzed 1,385 predialysis CKD patients from the KNOW-CKD cohort. Participants were divided into four groups according to brachial-ankle pulse wave velocity (baPWV) quartile. Coronary artery calcium scores (CACS) were assessed using cardiac computed tomography and CAC was defined as a CACS >100. RESULTS: CAC prevalence was higher in the higher baPWV groups (6.4, 9.8, 23.7, and 43.8% for the 1st to 4th quartiles of baPWV, respectively, p < 0.001). In Tobit regression analyses that were fully adjusted for traditional and renal cardiovascular risk factors, the CACS ratio comparing the highest and lowest baPWV quartiles was 3.03 (95% CI, 1.59-6.87). Similarly, the OR for CAC in the highest baPWV quartile compared to the lowest quartile was 1.98 (95% CI, 1.09-3.60) in a fully adjusted multivariate logistic model. Results were consistent across analyses with different cutoffs for CAC or with different clinically relevant subgroups. CONCLUSION: Increased arterial stiffness measured by high baPWV was associated with CAC in a predialysis CKD cohort. Longitudinal studies are needed to determine the effect of arterial stiffness on the development or progression of CAC in CKD.

Body Mass Index, waist circumference, and health-related quality of life in adults with chronic kidney disease.

PURPOSE: Obesity is linked to poor health-related quality of life (HRQOL) in the general population, but its role in chronic kidney disease (CKD) is uncertain. METHODS: We conducted a cross-sectional study that investigated 1880 participants from the KoreaN cohort study for Outcome in patients With CKD (KNOW-CKD) who underwent complete baseline laboratory tests, health questionnaires, and HRQOL. HRQOL was assessed by physical component summary (PCS) and mental component summary (MCS) of the SF-36 questionnaire. We used multivariable linear regression models to examine the relationship between Body Mass Index (BMI) and sex-specific waist circumference (WC) with HRQOL. RESULTS: Adults with higher BMI and greater WC showed lower PCS. After adjusting for age, sex, socioeconomic state, comorbidities, and laboratory findings, we found that WC, but not BMI, was associated with PCS. Greater WC quintiles were associated with lower PCS [WC-4th quintile (ß, - 2.63, 95% CI - 5.19 to - 0.06) and WC-5th quintile (ß, - 3.71, 95% CI - 6.28 to - 1.15)]. The association between WC and PCS was more pronounced in older adults, woman, patients with diabetes, cardiovascular disease, or lower eGFR. The relationship between BMI and WC with MCS was not significant. CONCLUSIONS: In adults with CKD, WC is a better indicator of poor physical HRQOL than BMI. The association between WC and physical HRQOL is modified by age, sex, eGFR, and comorbidities such as diabetes and cardiovascular disease.

Bioimpedance spectroscopy-guided fluid management in peritoneal dialysis patients with residual kidney function: A randomized controlled trial.

AIM: Bioimpedance spectroscopy (BIS) allows volume status to be assessed objectively. This study evaluated the effect of BIS-guided fluid management on residual kidney function (RKF), volume status, and cardiovascular events in peritoneal dialysis (PD) patients. METHODS: A multicenter, prospective, randomized, controlled trial was conducted over 12 months in 2013-2017. Non-anuric PD patients (urine volume ≥ 500 mL/day) were randomized to clinical method-guided management (n = 98) or BIS-guided management (n = 103). The volume in the BIS group was controlled with BIS, with the aim of achieving the target overhydration (OH) goal of -2.0 to +2.0 L. The volume in the control group was controlled by clinical assessment alone. The groups were compared in terms of change in RKF and volume status at 12 months relative to baseline and in terms of cardiovascular event rates during a median follow-up period of 36 months. RESULTS: Compared with the controls, the BIS group did not show a significant improvement in change in OH, after adjustments were made for covariates (P = 0.191). The two groups did not differ in terms of delta OH, renal creatinine and urea clearance, and 24 h urine volume. The control and BIS groups also did not differ significantly in terms of change in peritoneal ultrafiltration volume, blood pressure, body weight and echocardiographic variables or in cardiovascular event rates (10.2% vs 11.3%; P = 0.953). CONCLUSION: Bioimpedance spectroscopy-guided fluid management did not show an additional benefit to achieve euvolemia, and did not affect the decline in RKF in non-anuric PD patients.

Impact of acute kidney injury in expanded criteria deceased donors on post-transplant clinical outcomes: multicenter cohort study.

BACKGROUND: The problem of organ shortage is an important issue in kidney transplantation, but the effect of kidney donation on AKI is unclear. The aim of this study was to investigate the impact of acute kidney injury (AKI) on post-transplant clinical outcomes for deceased donor kidney transplantation (DDKT) using standard criteria donors (SCDs) versus expanded criteria donors (ECDs). METHODS: Five-hundred nine KT recipients receiving kidneys from 386 deceased donors (DDs) were included from three transplant centers. Recipients were classified into the SCD-KT or ECD-KT group according to corresponding DDs and both groups were divided into the AKI-KT or non-AKI-KT subgroups according to AKI in donor. We compared the clinical outcomes among those four groups and investigated the interaction between AKI in donors and ECD on allograft outcome. RESULTS: The incidence of delayed allograft function was higher when the donors had AKI within SCD-KT and ECD-KT groups. In allograft biopsies within 3 months, chronic change was more significant in the AKI-ECD-KT subgroup than in the non-AKI-ECD-KT subgroup, but it did not differ between AKI-SCD-KT and non-AKI-SCD-KT group. AKI-ECD-KT showed higher risk for death-censored allograft failure than the other three groups and a significant interaction was observed between AKI in donors and ECD on the allograft outcome. CONCLUSIONS: The presence of AKI in ECDs significantly impacted the long-term allograft outcomes of kidney transplant recipients, but it did not in SCDs.

The Adiponectin Receptor Agonist AdipoRon Ameliorates Diabetic Nephropathy in a Model of Type 2 Diabetes.

Adiponectin exerts renoprotective effects against diabetic nephropathy (DN) by activating the AMP-activated protein kinase (AMPK)/peroxisome proliferative-activated receptor-α (PPARα) pathway through adiponectin receptors (AdipoRs). AdipoRon is an orally active synthetic adiponectin receptor agonist. We investigated the expression of AdipoRs and the associated intracellular pathways in 27 patients with type 2 diabetes and examined the effects of AdipoRon on DN development in male C57BLKS/J db/db mice, glomerular endothelial cells (GECs), and podocytes. The extent of glomerulosclerosis and tubulointerstitial fibrosis correlated with renal function deterioration in human kidneys. Expression of AdipoR1, AdipoR2, and Ca2+/calmodulin-dependent protein kinase kinase-ß (CaMKKß) and numbers of phosphorylated liver kinase B1 (LKB1)- and AMPK-positive cells significantly decreased in the glomeruli of early stage human DN. AdipoRon treatment restored diabetes-induced renal alterations in db/db mice. AdipoRon exerted renoprotective effects by directly activating intrarenal AdipoR1 and AdipoR2, which increased CaMKKß, phosphorylated Ser431LKB1, phosphorylated Thr172AMPK, and PPARα expression independently of the systemic effects of adiponectin. AdipoRon-induced improvement in diabetes-induced oxidative stress and inhibition of apoptosis in the kidneys ameliorated relevant intracellular pathways associated with lipid accumulation and endothelial dysfunction. In high-glucose-treated human GECs and murine podocytes, AdipoRon increased intracellular Ca2+ levels that activated a CaMKKß/phosphorylated Ser431LKB1/phosphorylated Thr172AMPK/PPARα pathway and downstream signaling, thus decreasing high-glucose-induced oxidative stress and apoptosis and improving endothelial dysfunction. AdipoRon further produced cardioprotective effects through the same pathway demonstrated in the kidney. Our results show that AdipoRon ameliorates GEC and podocyte injury by activating the intracellular Ca2+/LKB1-AMPK/PPARα pathway, suggesting its efficacy for treating type 2 diabetes-associated DN.