Comparative Study of Diabetes Knowledge, Attitudes, Family Support, Self-efficacy, and Self-management Behaviors Between Cancer Survivors With Diabetes and Diabetes Patients Without Cancer.

BACKGROUND: Studies have compared diabetes management quality indicators, focusing on physiological markers such as hemoglobin A1c, between cancer survivors with diabetes and general diabetes patients. However, research comparing differences in diabetes self-management behaviors and the factors influencing them between these groups is lacking. OBJECTIVES: This study aimed to compare self-management behaviors, guided by the information-motivation-behavior model, between cancer survivors with diabetes and general diabetes patients. In addition, we aimed to identify differences in factors such as diabetes knowledge, attitudes, family support, and self-efficacy that may influence diabetes self-management behaviors in both groups. METHODS: A total of 125 cancer survivors with diabetes and 126 general diabetes patients participated in this cross-sectional study. A structured questionnaire assessed demographics, diabetes knowledge, attitudes, self-efficacy, and self-management behaviors. RESULTS: Regarding diabetes education, 47.0% of cancer survivors and 61.6% of general diabetes patients received education. The cancer survivors had lower diabetes knowledge scores (10.30 ± 4.15, P < .001), a lower perceived value of strict blood glucose control (4.10 ± 0.56, P < .001), and less family support (15.50 ± 7.50, P = .019) than the patients without cancer (13.51 ± 3.84, 4.25 ± 0.65, and 17.57 ± 6.40, respectively). CONCLUSION: This study reveals significant differences in diabetes self-management between cancer survivors and general diabetes patients. Cancer survivors showed lower diabetes knowledge, glucose control perception, and family support. These findings highlight the need for tailored self-management programs for cancer survivors. IMPLICATIONS FOR PRACTICE: This study offers insights for developing tailored diabetes self-management programs and educational interventions for cancer survivors.

Prediction of diabetes mellitus after kidney transplantation using patient-specific induced pluripotent stem cells.

BACKGROUND: Multiple risk factors are involved in new-onset diabetes mellitus (DM) after organ transplantation; however, their ability to predict clinical prognosis remains unclear. Therefore, we investigated whether patient-specific induced pluripotent stem cells (iPSCs) could help predict DM development before performing kidney transplantation (KT). METHODS: We first performed whole transcriptome and functional enrichment analyses of KT patient-derived iPSCs. Our results revealed that insulin resistance, type 2 DM, and transforming growth factor beta signaling pathways are associated between the groups of DM and non-DM. We next determined whether the genetic background was associated with development of iPSCs into pancreatic progenitor (PP) cells. RESULTS: The levels of differentiation-related key markers of PP cells were significantly lower in the DM group than in the non-DM group. Moreover, the results of tacrolimus toxicity screening showed a significant decrease in the number of PP cells of the DM group compared with the non-DM group, suggesting that these cells are more susceptible to tacrolimus toxicity. CONCLUSION: Taken together, these results indicate that PP cells of the DM group showed low developmental potency accompanied by a significantly different genetic background compared with the non-DM group. Thus, genetic analysis can be used to predict the risk of DM before KT.

Generation of a human induced pluripotent stem cell line from a patient with dent disease.

Dent disease, an X-linked tubular disorder, is a rare condition that leads to low-molecular-weight proteinuria, hypercalciuria, kidney stones, and chronic kidney disease. Here, we successfully established a human induced pluripotent stem cells (hiPSC) line from peripheral blood mononuclear cells of 10-year-old male with Dent disease 1 caused by the mutation of Chloride Voltage-Gated Channel 5 gene. This hiPSCs displayed features similar to human embryonic stem cells, including pluripotency-associated markers expression, normal karyotype, and the ability to differentiate into cells representing all three germ layers. The implications of this research extend to the potential development of novel treatments for Dent disease.

Discovery of cellular and genetic signatures of immune tolerance in kidney transplant recipients through single cell RNA sequencing analysis.

The objective of this study was to uncover distinct cellular and genetic signatures of transplant operational tolerance (TOT) in kidney transplant recipients (KTRs) through single cell RNA sequencing (scRNA-seq) using peripheral blood mononuclear cells (PBMCs). PBMCs were isolated from 12 KTRs, including those with TOT (TOT, n = 4), stable allograft function on maintenance immunosuppression (STA, n = 4) and biopsy-proven allograft rejection (BPAR, n = 4). ScRNA-seq of PBMCs was analyzed using 20 cell surface marker antibody sequencing to annotate clusters and 399 immune response panel to identify gene expression. Differences in cellular distribution and gene expression were compared among the three groups. Heatmap hierarchical clustering showed that overall cellular distribution pattern was distinct in TOT in comparison with those in the other two groups, with the proportion of B cells being higher in TOT, attributed to immature B cell fraction (TOT vs. STA vs. BPAR: 4.61% vs. 1.27% vs. 2.53%, p = 0.01). Transcript analysis of B cells revealed that genes involved in allo-immune pathway were downregulated in TOT. In T cell subset analysis, the proportion of naïve T cells and regulatory T cells (Tregs) was increased. In transcript analysis, genes associated with inflammation were decreased, while expression levels of CCR6 in Tregs were increased in TOT. Proportions of NKT and NK cells were increased in TOT than in the other two groups. This study showed that TOT has distinct cellular and genetic signatures such as increases of immature B cells, naïve T cells and Tregs and high expression levels of CCR6 in Tregs.

CRISPR-Cas9-Mediated Correction of SLC12A3 Gene Mutation Rescues the Gitelman's Disease Phenotype in a Patient-Derived Kidney Organoid System.

The aim of this study is to explore the possibility of modeling Gitelman's disease (GIT) with human-induced pluripotent stem cell (hiPSC)-derived kidney organoids and to test whether gene correction using CRISPR/Cas9 can rescue the disease phenotype of GIT. To model GIT, we used the hiPSC line CMCi002 (CMC-GIT-001), generated using PBMCs from GIT patients with SLC12A3 gene mutation. Using the CRISPR-Cas9 system, we corrected CMC-GIT-001 mutations and hence generated CMC-GIT-001corr. Both hiPSCs were differentiated into kidney organoids, and we analyzed the GIT phenotype. The number of matured kidney organoids from the CMC-GIT-001corr group was significantly higher, 3.3-fold, than that of the CMC-GIT-001 group (12.2 ± 0.7/cm2 vs. 3.7 ± 0.2/cm2, p < 0.05). In qRT-PCR, performed using harvested kidney organoids, relative sodium chloride cotransporter (NCCT) mRNA levels (normalized to each iPSC) were increased in the CMC-GIT-001corr group compared with the CMC-GIT-001 group (4.1 ± 0.8 vs. 2.5 ± 0.2, p < 0.05). Consistently, immunoblot analysis revealed increased levels of NCCT protein, in addition to other tubular proteins markers, such as LTL and ECAD, in the CMC-GIT-001corr group compared to the CMC-GIT-001 group. Furthermore, we found that increased immunoreactivity of NCCT in the CMC-GIT-001corr group was colocalized with ECAD (a distal tubule marker) using confocal microscopy. Kidney organoids from GIT patient-derived iPSC recapitulated the Gitelman's disease phenotype, and correction of SLC12A3 mutation utilizing CRISPR-Cas9 technology provided therapeutic insight.

Impact of Low-Level Donor-Specific Anti-HLA Antibody on Posttransplant Clinical Outcomes in Kidney Transplant Recipients.

Background: The clinical significance of low-level donor-specific anti-HLA antibody (low-DSA) remains controversial. We investigated the impact of low-DSA on posttransplant clinical outcomes in kidney transplant (KT) recipients. Methods: We retrospectively reviewed 1,027 KT recipients, namely, 629 living donor KT (LDKT) recipients and 398 deceased donor KT (DDKT) recipients, in Seoul St. Mary's Hospital (Seoul, Korea) between 2010 and 2018. Low-DSA was defined as a positive anti-HLA-DSA result in the Luminex single antigen assay (LABScreen single antigen HLA class I - combi and class II - group 1 kits; One Lambda, Canoga Park, CA, USA) but a negative result in a crossmatch test. We compared the incidence of biopsy-proven allograft rejection (BPAR), changes in allograft function, allograft survival, patient survival, and posttransplant infections between subgroups according to pretransplant low-DSA. Results: The incidence of overall BPAR and T cell-mediated rejection did not differ between the subgroups. However, antibody-mediated rejection (ABMR) developed more frequently in patients with low-DSA than in those without low-DSA in the total cohort and the LDKT and DDKT subgroups. In multivariate analysis, low-DSA was identified as a risk factor for ABMR development. Its impact was more pronounced in DDKT (odds ratio [OR]: 9.60, 95% confidence interval [CI]: 1.79-51.56) than in LDKT (OR: 3.76, 95% CI: 0.99-14.26) recipients. There were no significant differences in other outcomes according to pretransplant low-DSA. Conclusions: Pretransplant low-DSA has a significant impact on the development of ABMR, and more so in DDKT recipients than in LDKT recipients, but not on long-term outcomes.

CRISPR/Cas9-mediated A4GALT suppression rescues Fabry disease phenotypes in a kidney organoid model.

The objective of this study was to investigate whether CRISPR/Cas9-mediated suppression of A4GALT could rescue phenotype of Fabry disease nephropathy (FDN) using human induced pluripotent stem cells (hiPSCs) derived kidney organoid system. We generated FDN patient-derived hiPSC (CMC-Fb-002) and FD-specific hiPSCs (GLA-KO) by knock-out (KO) of GLA in wild-type (WT) hiPSCs using CRISPR/Cas9. We then performed A4GALT KO in both CMC-Fb-002 and GLA-KO to make Fb-002-A4GALT-KO and GLA/A4GALT-KO, respectively. Using these hiPSCs, we generated kidney organoids and compared alpha-galactosidase-A enzyme (α-GalA) activity, globotriaosylceramide (Gb-3) deposition, and zebra body formation under electron microscopy (EM). We also compared mRNA expression levels using RNA-seq and qPCR. Generated hiPSCs showed typical pluripotency markers without chromosomal disruption. Expression levels of GLA in CMC-Fb-002 and GLA-KO and expression levels of A4GALT in Fb-002-A4GALT-KO and GLA/A4GALT-KO were successfully decreased compared to those in WT-hiPSCs, respectively. Generated kidney organoids using these hiPSCs expressed typical nephron markers. In CMC-Fb-002 and GLA-KO organoids, α-GalA activity was significantly decreased along with increased deposition of Gb-3 in comparison with WT organoids. Intralysosomal inclusion body was also detected under EM. However, these disease phenotypes were rescued by KO of A4GALT in both GLA/A4GALT-KO and Fb-002-A4GALT-KO kidney organoids. RNA-seq showed increased expression levels of genes related to FDN progression in both GLA-mutant organoids compared to those in WT. Such increases were rescued in GLA/A4GALT-KO or Fb-002-A4GALT-KO organoids. CRISPR/Cas9 mediated suppression of A4GALT could rescue FDN phenotype. Hence, it can be proposed as a therapeutic approach to treat FDN.

Anterior-First Approach for Latissimus Dorsi Myocutaneous Flap Breast Reconstruction: A Refined Elevation Method with Detailed Video Instructions.

Background: The latissimus dorsi myocutaneous (LDMC) flap is a preferred flap in breast reconstruction for its wide surface area and volume. Since the flap is situated in the midback area, a lateral decubitus approach is a conventional method. However, proper visualization and access to the thoracodorsal vascular pedicle or muscle insertion is difficult from the lateral approach, causing inefficiency and surgeon fatigue. We propose the 'anterior-first' approach in LDMC flap reconstruction, where the landmark structures are first approached from the supine-anterior position through the mastectomy incision. Methods: From January 2014 to December 2020, 48 patients who received immediate breast reconstruction with LDMC flap were included in the study. Patients received reconstruction with the conventional approach (n = 20), or anterior-first approach (n = 28). Demographic factors and the operative outcomes were retrospectively analyzed and compared between the two groups. Results: Compared to the conventional approach group, the anterior-first approach group showed improved efficiency in the duration of total reconstruction (228 versus 330 min, p < 0.001), and flap elevation (139 versus 200 min, p < 0.001). No difference in complication rate and time to drain removal was observed (p = 0.14 and >0.9, respectively). Conclusion: The anterior-first approach for breast reconstruction with LDMC flap provides surgeons with an enhanced surgical exposure and superior ergonomics, leading to a safer and more efficient flap elevation.

Combined impact of the inter and intra-patient variability of tacrolimus blood level on allograft outcomes in kidney transplantation.

Introduction: Tacrolimus (TAC) has been widely used as an immunosuppressant after kidney transplantation (KT); however, the combined effects of intra-patient variability (IPV) and inter-patient variability of TAC-trough level (C0) in blood remain controversial. This study aimed to determine the combined impact of TAC-IPV and TAC inter-patient variability on allograft outcomes of KT. Methods: In total, 1,080 immunologically low-risk patients who were not sensitized to donor human leukocyte antigen (HLA) were enrolled. TAC-IPV was calculated using the time-weighted coefficient variation (TWCV) of TAC-C0, and values > 30% were classified as high IPV. Concentration-to-dose ratio (CDR) was used for calculating TAC inter-patient variability, and CDR < 1.05 ng•mg/mL was classified as rapid metabolizers (RM). TWCV was calculated based on TAC-C0 up to 1 year after KT, and CDR was calculated based on TAC-C0 up to 3 months after KT. Patients were classified into four groups according to TWCV and CDR: low IPV/non-rapid metabolizer (NRM), high IPV/NRM, low IPV/RM, and high IPV/RM. Subgroup analysis was performed for pre-transplant panel reactive antibody (PRA)-positive and -negative patients (presence or absence of non-donor-specific HLA-antibodies). Allograft outcomes, including deathcensored graft loss (DCGL) and biopsy-proven allograft rejection (BPAR), were compared. Results: The incidences of DCGL, BPAR, and overall graft loss were the highest in the high-IPV/RM group. In addition, a high IPV/RM was identified as an independent risk factor for DCGL. The hazard ratio of high IPV/RM for DCGL and the incidence of active antibody-mediated rejection were considerably increased in the PRA-positive subgroup. Discussion: High IPV combined with RM (inter-patient variability) was closely related to adverse allograft outcomes, and hence, more attention must be given to pre-transplant PRA-positive patients.

Therapeutic effect of multiple functional minicircle vector encoding anti-CD25/IL-10/CXCR3 in allograft rejection model.

BACKGROUND/AIMS: We previously proposed minicircle vector technology as the potential platform for the development and production of new biologics. In this study, we have designed a novel target molecule for the treatment of allograft rejection and evaluated its feasibility as the therapeutic agent in this disease using the minicircle vector system. METHODS: We engineered vectors to carry cassette sequences for anti-CD25, interleukin-10 (IL-10), and C-X-C motif chemokine receptor 3 (CXCR3) fusion protein, and then isolated minicircle vectors from the parent vectors. We verified the substantial production of anti-CD25/IL-10/CXCR3 fusion protein from minicircles and their duration in HEK293T cells and mice models. We also evaluated whether minicircle-derived anti-CD25/IL-10/CXCR3 has therapeutic effects in a skin allograft in mice model. RESULTS: We confirmed the production of anti-CD25/IL-10/CXCR3 from minicircle by its significant availability in cells transfected with the minicircle and in its conditioned media. After a single injection of minicircle by hydrodynamic injection via mouse tail vein, luminescence or red fluorescence was maintained until 40 days in the liver tissue, suggesting the production of anti-CD25/IL-10/CXCR3 protein from minicircles via protein synthesis machinery in the liver. Mice treated with the minicircle encoding anti-CD25/IL-10/CXCR3 showed prolonged skin allograft survival times accompanied by improved immunologic regulation e.g., reduction of the lymphocyte population of Th1, Th2, and Th17 and an induction of regulatory T cells. CONCLUSION: These findings implied that self-generated anti-CD25/IL-10/CXCR3 protein drug by minicircle technology is functionally active and relevant for reducing allograft rejection. The minicircle vector system may be useful for developing new biological drugs, avoiding manufacturing or practical problems.

Development and psychometric testing of learning immersion scale in clinical simulation: A methodological study.

BACKGROUND: Immersion during clinical simulation has been suggested to be important for learning effects. However, no valid and reliable instruments have been available for measuring the learner's immersion during simulation experience. OBJECTIVES: To develop a Learning Immersion Scale in Simulation (LISS) and evaluate its psychometric properties. DESIGN: A methodological study design was employed to develop and validate the instrument. SETTINGS: Two universities in South Korea. PARTICIPANTS: A convenience sample of 204 nursing students. METHODS: A literature review and a focus group interview were conducted to determine the properties of learning immersion during simulation experience. Content validity was assessed by a panel of 10 experts. Nursing students who participated in high-fidelity patient simulation (n = 204) were asked to complete the preliminary LISS, after which Students Satisfaction and Self-Confidence in Learning Scale and Learning Flow Scale for Adults were administered for assessing the convergent and criterion validity. Data were analyzed using exploratory factor analyses, Pearson's correlation, and Cronbach's alpha. RESULTS: Exploratory factor analyses extracted a four-factor solution, explaining 65.2% of the total variance. The convergent and criterion validity and internal consistency and half reliability were satisfied. CONCLUSIONS: The LISS is a short multi-dimensional instrument with good psychometric validity and reliability that has potential utility for clinical simulation education and research.

Comparison of CT volumetry versus nuclear renography for predicting remaining kidney function after uninephrectomy in living kidney donors.

Computed tomography (CT) and nuclear renography are used to determine kidney procurement in living kidney donors (LKDs). The present study investigated which modality better predicts kidney function after donation. This study included 835 LKDs and they were divided into two subgroups based on whether the left-right dominance of kidney volume was concordant with kidney function (concordant group) or not (discordant group). The predictive value for post-donation kidney function between the two imaging modalities was compared at 1 month, 6 months, and > 1 year in total cohort, concordant, and discordant groups. Split kidney function (SKF) measured by both modalities showed significant correlation with each other at baseline. SKFs of remaining kidney measured using both modalities before donation showed significant correlation with eGFR (estimated glomerular filtration rate) after donation in the total cohort group and two subgroups, respectively. CT volumetry was superior to nuclear renography for predicting post-donation kidney function in the total cohort group and both subgroups. In the discordant subgroup, a higher tendency of kidney function recovery was observed when kidney procurement was determined based on CT volumetry. In conclusion, CT volumetry is preferred when determining procurement strategy especially when discordance is found between the two imaging modalities.

Effect of dual inhibition of DPP4 and SGLT2 on tacrolimus-induced diabetes mellitus and nephrotoxicity in a rat model.

Sodium/glucose co-transporter-2 inhibitor (SGLT2i) or dipeptidyl peptidase IV inhibitor (DPP4i) is a newer anti-diabetic drug in type II diabetes mellitus (DM), but their use in tacrolimus (TAC)-induced DM is still undetermined. We performed this study to evaluate the effect of these two drugs in TAC-induced DM and nephrotoxicity in ex vivo and in vivo. In the experimental Sprague Dawley rat model of TAC-induced DM and nephrotoxicity, dual inhibition of DPP4 and SGLT2 significantly decreased blood glucose level, HbA1C and increased plasma insulin levels and pancreatic islet size compared with each drug. In the kidney, dual inhibition improved renal function decreased interstitial fibrosis and profibrotic cytokines compared with DPP4i and SGLT2i alone. Increased oxidative stress by TAC was remarkably decreased with DPP4i or SGLT2i in serum, pancreatic and renal tissues and this decrease was much more significant in the combination group. In in vitro study, TAC decreased the cell viability of human kidney-2(HK-2) cells and insulin-secreting beta-cell-derived line(INS-1) cells. SGLT2i protected TAC-induced cell death in HK-2 cells, but not in INS-1 cells. The addition of DPP4i to SGLT2i compensated for a lack of protective effect of SGLT2i on INS-1 cells. This finding provides the rationale for the combined treatment of SGLG2i and DPP4i in TAC-induced DM and nephrotoxicity.

Alleviation of renal ischemia/reperfusion injury by exosomes from induced pluripotent stem cell-derived mesenchymal stem cells.

BACKGROUND/AIMS: Renal ischemia followed by reperfusion (I/R) is a leading cause of acute kidney injury (AKI), which is closely associated with high morbidity and mortality. Studies have shown that induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) exert powerful therapeutic effects in renal ischemia. However, the efficacy of iMSC-derived exosomes (iExo) on I/R injuries remains largely unknown. METHODS: Human iPSCs were differentiated into iMSCs using a modified one-step method. Ultrafiltration, combined with purification, was used to isolate iExo from iMSCs. iExo was administered following I/R injury in a mouse model. The effect of iExo on I/R injury was assessed through changes in renal function, histology, and expression of oxidative stress, inflammation, and apoptosis markers. Further, we evaluated its association with the extracellular signal-regulated kinase (ERK) 1/2 signaling pathway. RESULTS: Mice subjected to I/R injury exhibited typical AKI patterns; serum creatinine level, tubular necrosis, apoptosis, inflammatory cytokine production, and oxidative stress were markedly increased compared to sham mice. However, treatment with iExo attenuated these changes, significantly improving renal function and tissue damage, similar to the renoprotective effects of iMSCs on I/R injury. Significant induction of activated ERK 1/2 signaling molecules was observed in mice treated with iExo compared to those in the I/R injury group. CONCLUSION: The present study demonstrates that iExo administration ameliorated renal damage following I/R, suggesting that iMSC-derived exosomes may provide a novel therapeutic approach for AKI treatment.

Newly diagnosed metastatic pulmonary calcification in a kidney transplantation recipient: a case report.

Metastatic pulmonary calcification (MPC) is defined as calcium deposition in lung tissues. It is commonly seen in end-stage renal disease patients. However, MPC occurring in kidney transplant recipients (KTRs) is rare. We report a case of MPC in a 55-year-old female patient after successful kidney transplantation (KT). One year after KT, bisphosphonate and vitamin D were prescribed for osteoporosis. Then, 4.5 years after KT, we incidentally found multiple nodular lesions on chest X-ray (CXR) without any symptoms. Chest computed tomography showed multiple high-density nodules. A bone scan confirmed MPC in the right middle lobe and right lower lobe. A retrospective review of pretransplant blood chemistry revealed the following: serum calcium level, 11.2 mg/dL; phosphorus level, 3.2 mg/dL; intact parathyroid hormone level, lower than 2.5 pg/mL; and 24-hour urine calcium level, within normal limits (WNL). After KT, all of these parameters remained WNL. Therefore, hidden adynamic bone disease might have been aggravated by bisphosphonate and vitamin D supplementation, causing MPC. Both were discontinued. She was monitored by routine CXR, and MPC did not progress. Since MPC is commonly asymptomatic and difficult to diagnose in KTRs, caution is required when administering such medications. Patient should be followed up with routine CXR.

Alterations in the Mineral Bone Metabolism of Living Kidney Donors After Uni-Nephrectomy: Prospective Observational Study.

We investigated the dynamic change of mineral bone metabolism and explored factors associated with the alteration of mineral bone metabolism in the living kidney donors (LKDs) after uni-nephrectomy. One-hundred forty-four prospective LKDs who underwent kidney donation between May 2016 and September 2018 were enrolled. Laboratory evaluation regarding mineral bone metabolism including intact parathyroid hormone (iPTH), renal fractional excretion of phosphate (FEPi), and technetium-99m diethylenetriaminepentaacetate (99mTc-DTPA) scan was performed predonation and 6 months after donation. We divided donors into two groups, the low ΔFEPi and high ΔFEPi groups, according to the change of FEPi after donation, and investigated significant risk factors associated with high ΔFEPi. At 6 months after uni-nephrectomy, estimated glomerular filtration rate (eGFR) significantly declined by 30.95 ml/min/1.73 m2 (p < 0.001), but the measured GFR (mGFR) of the remaining kidney by 99mTc-DTPA scan showed significant increase. Serum phosphorus decreased (p < 0.001), whereas FEPi (13.34-20.23%, p < 0.001) and serum iPTH (38.70-52.20 pg/ml, p < 0.001) showed significant increase. In the high ΔFEPi group, the proportion of preexisting hypertension (HTN) was higher, the baseline FEPi was lower, and the percent decline in eGFR was greater. Moreover, all of these factors were independently associated with high ΔFEPi upon multivariable logistic regression analysis. LKDs showed a significant change in mineral bone metabolism after uni-nephrectomy, especially when the donors had preexisting HTN, lower baseline FEPi, and showed greater loss of kidney function. Hence, strict monitoring of the mineral bone metabolism parameters and bone health may be required for these donors.

Modeling of endothelial cell dysfunction using human induced pluripotent stem cells derived from patients with end-stage renal disease.

BACKGROUND: Endothelial cell (EC) dysfunction is a frequent feature in patients with end-stage renal disease (ESRD). The aim of this study was to generate human induced pluripotent stem cells, differentiate ECs (hiPSC-ECs) from patients with ESRD, and appraise the usefulness of hiPSC-ECs as a model to investigate EC dysfunction. METHODS: We generated hiPSCs using peripheral blood mononuclear cells (PBMCs) isolated from three patients with ESRD and three healthy controls (HCs). Next, we differentiated hiPSC-ECs using the generated hiPSCs and assessed the expression of endothelial markers by immunofluorescence. The differentiation efficacy, EC dysfunction, and molecular signatures of EC-related genes based on microarray analysis were compared between the ESRD and HC groups. RESULTS: In both groups, hiPSCs and hiPSC-ECs were successfully obtained based on induced pluripotent stem cell or EC marker expression in immunofluorescence and flow cytometry. However, the efficiency of differentiation of ECs from hiPSCs was lower in the ESRD-hiPSCs than in the HC-hiPSCs. In addition, unlike HC-hiPSC-ECs, ESRD-hiPSC-ECs failed to form interconnecting branching point networks in an in vitro tube formation assay. During microarray analysis, transcripts associated with oxidative stress and inflammation were upregulated and transcripts associated with vascular development and basement membrane extracellular matrix components were downregulated in ESRD-hiPSC-ECs relative to in HC-hiPSC-ECs. CONCLUSION: ESRD-hiPSC-ECs showed a greater level of EC dysfunction than HC-hiPSC-ECs did based on functional assay results and molecular profiles. hiPSC-ECs may be used as a disease model to investigate the pathophysiology of EC dysfunction in ESRD.

Intrapatient Variability in Tacrolimus Trough Levels Over 2 Years Affects Long-Term Allograft Outcomes of Kidney Transplantation.

This study aimed to determine the impact of tacrolimus (TAC) trough level (C0) intrapatient variability (IPV) over a period of 2 years after kidney transplantation (KT) on allograft outcomes. In total, 1,143 patients with low immunologic risk were enrolled. The time-weighted coefficient variability (TWCV) of TAC-C0 was calculated, and patients were divided into tertile groups (T1: < 24.6%, T2: 24.6%-33.7%, T3: ≥ 33.7%) according to TAC-C0-TWCV up to post-transplant 1st year. They were classified into the low/low, low/high, high/low, and high/high groups based on a TAC-C0-TWCV value of 33.7% during post-transplant 0-1st and 1st-2nd years. The allograft outcomes among the three tertile and four TAC-C0-TWCV groups were compared. The T3 group had the highest rate of death-censored allograft loss (DCGL), and T3 was considered an independent risk factor for DCGL. The low/low group had the lowest and the high/high group had the highest risk for DCGL. Moreover, patients with a mean TAC-C0 of ≥5 ng/ml in the high/high group were at the highest risk for DCGL. Thus, TAC-IPV can significantly affect allograft outcomes even with a high mean TAC-C0. Furthermore, to improve allograft outcomes, a low TAC-IPV should be maintained even after the first year of KT.

Outcomes of Remote Patient Monitoring for Automated Peritoneal Dialysis: A Randomized Controlled Trial.

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.