Search

Abstract Signal peptides and secretory carrier proteins are commonly used to secrete heterologous recombinant protein in Gram-negative bacteria. The Escherichia coli osmotically-inducible protein Y (OsmY) is a carrier protein that secretes a target protein extracellularly, and we have previously applied it in the Bacterial Extracellular Protein Secretion System (BENNY) to accelerate directed evolution. In this study, we reported the first application of random and combinatorial mutagenesis on a carrier protein to enhance total secretory target protein production. After one round of random mutagenesis followed by combining the mutations found, OsmY(M3) (L6P, V43A, S154R, V191E) was identified as the best carrier protein. OsmY(M3) produced 3.1 ± 0.3 fold and 2.9 ± 0.8 fold more secretory Tfu0937 β-glucosidase than its wildtype counterpart in E. coli strains BL21(DE3) and C41(DE3), respectively. OsmY(M3) also produced more secretory Tfu0937 at different cultivation temperatures (37 °C, 30 °C and 25 °C) compared to the wildtype. Subcellular fractionation of the expressed protein confirmed the essential role of OsmY in protein secretion. Up to 80.8 ± 12.2% of total soluble protein was secreted after 15 h of cultivation. When fused to a red fluorescent protein or a lipase from Bacillus subtillis, OsmY(M3) also produced more secretory protein compared to the wildtype. In this study, OsmY(M3) variant improved the extracellular production of three proteins originating from diverse organisms and with diverse properties, clearly demonstrating its wide-ranging applications. The use of random and combinatorial mutagenesis on the carrier protein demonstrated in this work can also be further extended to evolve other signal peptides or carrier proteins for secretory protein production in E. coli.

Kelulut honey was dehydrated at 40, 55, and 70°C up to 84 h in a dehydrator. The changes of its properties and qualities in terms of moisture content, water activity, hygroscopicity, moisture adsorption isotherm, colour intensity, total phenolic content (TPC), viscosity, glass transition temperature (Tg), surface stickiness, hydroxymethylfurfural (HMF) content, and diastase activity were evaluated. The dehydration process for 18 h between temperatures of 55 and 70°C can safely produce Kelulut honey product with less than 8% moisture content and water activity below 0.6. Similar quality of Kelulut honey dehydrated at lower temperature between 40 and 55°C requires up to 36 h of dehydration. These recommended dehydration conditions were able to increase TPC of honey from 7.86% from its original value for the shorter duration of 18 h and lower dehydration temperature of 40°C and up to 70.9% for the longer duration of 36 h and higher temperature of 70°C. Dehydrated honey was darker, more viscous, and stickier. The increase of HMF content in dehydrated honey at 40 and 55°C up to 36 h was not significant which are at 0 and 5.81 mg/kg honey, respectively, and at 70°C, it was about 80 mg/kg honey. The honey was found to have very low diastase activity ranging from 0 to 0.75 DN, thereby causing its changes to be insignificant during dehydration.

Background: This study aimed to identify adverse events following the first three doses of COVID-19 vaccines in hemodialysis (HD) patients. Risk factors associated with postvaccination adverse events were explored., Methods: Postvaccination adverse events in 438 HD patients who received 3 doses of COVID-19 vaccines were prospectively assessed. The adverse events among three doses were compared using generalized linear mixed models. Factors associated with adverse events were assessed with multivariate analyses., Results: The vast majority of participants received Oxford/AstraZeneca ChAdOx1 as their first two doses and Moderna mRNA-1273 as their third dose. Overall, 79%, 50% and 84% of the participants experienced at least one adverse event after their first, second, and third doses, respectively. These adverse events were mostly minor, short-lived and less than 5% reported daily activities being affected. Compared with the first dose, the second dose caused a lower rate of adverse events. Compared with the first dose, the third dose elicited a higher rate of injection site reactions and a lower rate of systemic reactions. Multivariate analyses showed that every 10-year increase of age (odds ratio 0.67, 95% confidence intervals 0.57-0.79) was associated with decreased risk of adverse events, while female sex (2.82, 1.90-4.18) and arteriovenous fistula (1.73, 1.05-2.84) were associated with increased risk of adverse events. Compared with Oxford/AstraZeneca ChAdOx1, Moderna mRNA-1273 was associated with an increased risk of injection site reactions., Conclusions: COVID-19 vaccination was well tolerated in HD patients. Age, sex, dialysis vascular access and vaccine types were associated with postvaccination adverse events.

Background: Cryptococcosis is one of the most frequent fungal eye infections in patients with immunosuppression. Currently, treatment approaches for non-meningeal, non-pulmonary cryptococcosis are based on those used for cryptococcal meningitis or pneumonia., Case Presentation: We present a rare case of non-meningeal, non-pulmonary cryptococcosis with clinical manifestations limited to one eye of a cadaveric kidney transplant recipient with chronic-active antibody-mediated rejection. Typical manifestations, diagnosis, and treatments, including antifungal therapies, adjunctive therapies, and immunosuppression reduction, are discussed. After timely diagnosis and treatment, her visual acuity recovered to baseline without recurrence or sequelae of cryptococcosis., Conclusions: Clinicians should be aware of rare presentations of fungal infections, especially when a kidney transplant recipient with rejection has been treated with intensive immunosuppressants. Early diagnosis with individualized therapies may have a favorable prognosis., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Previous studies on clinical decision support systems (CDSSs) for the management of renal anemia in patients with end-stage kidney disease undergoing hemodialysis have previously focused solely on the effects of the CDSS. However, the role of physician compliance in the efficacy of the CDSS remains ill-defined., Objective: We aimed to investigate whether physician compliance was an intermediate variable between the CDSS and the management outcomes of renal anemia., Methods: We extracted the electronic health records of patients with end-stage kidney disease on hemodialysis at the Far Eastern Memorial Hospital Hemodialysis Center (FEMHHC) from 2016 to 2020. FEMHHC implemented a rule-based CDSS for the management of renal anemia in 2019. We compared the clinical outcomes of renal anemia between the pre- and post-CDSS periods using random intercept models. Hemoglobin levels of 10 to 12 g/dL were defined as the on-target range. Physician compliance was defined as the concordance of adjustments of the erythropoietin-stimulating agent (ESA) between the CDSS recommendations and the actual physician prescriptions., Results: We included 717 eligible patients on hemodialysis (mean age 62.9, SD 11.6 years; male n=430, 59.9%) with a total of 36,091 hemoglobin measurements (average hemoglobin and on-target rate were 11.1, SD 1.4, g/dL and 59.9%, respectively). The on-target rate decreased from 61.3% (pre-CDSS) to 56.2% (post-CDSS) owing to a high hemoglobin percentage of >12 g/dL (pre: 21.5%; post: 29%). The failure rate (hemoglobin <10 g/dL) decreased from 17.2% (pre-CDSS) to 14.8% (post-CDSS). The average weekly ESA use of 5848 (SD 4211) units per week did not differ between phases. The overall concordance between CDSS recommendations and physician prescriptions was 62.3%. The CDSS concordance increased from 56.2% to 78.6%. In the adjusted random intercept model, the post-CDSS phase showed increased hemoglobin by 0.17 (95% CI 0.14-0.21) g/dL, weekly ESA by 264 (95% CI 158-371) units per week, and 3.4-fold (95% CI 3.1-3.6) increased concordance rate. However, the on-target rate (29%; odds ratio 0.71, 95% CI 0.66-0.75) and failure rate (16%; odds ratio 0.84, 95% CI 0.76-0.92) were reduced. After additional adjustments for concordance in the full models, increased hemoglobin and decreased on-target rate tended toward attenuation (from 0.17 to 0.13 g/dL and 0.71 to 0.73 g/dL, respectively). Increased ESA and decreased failure rate were completely mediated by physician compliance (from 264 to 50 units and 0.84 to 0.97, respectively)., Conclusions: Our results confirmed that physician compliance was a complete intermediate factor accounting for the efficacy of the CDSS. The CDSS reduced failure rates of anemia management through physician compliance. Our study highlights the importance of optimizing physician compliance in the design and implementation of CDSSs to improve patient outcomes., (©Ju-Yeh Yang, Kai-Hsiang Shu, Yu-Sen Peng, Shih-Ping Hsu, Yen-Ling Chiu, Mei-Fen Pai, Hon-Yen Wu, Wan-Chuan Tsai, Kuei-Ting Tung, Raymond N Kuo. Originally published in JMIR Formative Research (https://formative.jmir.org), 03.05.2023.)

Introduction: Although high-dose erythropoiesis-stimulating agent (ESA) has been shown to increase mortality risk and adverse cardiovascular events in hemodialysis patients, the safety of extremely low-dose ESA is unclear., Methods: We retrospectively analyzed the association between ESA dose and mortality in the monthly dosing range of 0-43,000 U of equivalent epoetin alfa in 304 Taiwan hemodialysis patients by using Cox proportional hazard model and cubic spline model., Results: Compared with mean monthly ESA dose of 15,000-25,000 U (mean ± standard deviation 20,609 ± 2,662 U), monthly ESA dose of less than 15,000 U (mean ± standard deviation 7,413 ± 4,510 U) is associated with increased mortality. Monthly ESA dose of 25,001-43,000 U (mean ± standard deviation 31,160 ± 4,304 U) is not associated with higher mortality risk than monthly ESA dose of 15,000-25,000 U. The results were consistent in Cox proportional hazard models and cubic spline models. Subgroup analyses showed no significant heterogeneities among prespecified subgroups., Conclusions: Extremely low dose of ESA in hemodialysis patients may be associated with increased mortality risk. Future studies are warranted to prove this association., (© 2023 S. Karger AG, Basel.)

Purpose: A non-invasive way of assessing post-transplant renal graft function has been needed. This study aimed to assess the micro-structural and micro-functional status of graft kidneys by using intravoxel incoherent motion- (IVIM-) diffusion-weighted imaging (DWI) to investigate delayed graft function (DGF) immediately after transplantation., Method: A prospective study was conducted on 37 patients, 14 with early graft function (EGF) and 23 with DGF (9 with complication, 14 without) who underwent IVIM-DWI, most often within 1-7 days after kidney transplantation. A total of 37 cases were collected and all the participants have been well-informed and signed their consents. In addition, the study conducted in this paper was approved by the Ethics Committee of Clinical Research, Taichung Veterans General Hospital (IRB number: CE14065). Using biexponential analysis of slow diffusion coefficient ( D slow ), fast diffusion coefficient ( D fast ), and perfusion fraction was performed. The apparent diffusion coefficient (ADC) was calculated by use of a monoexponential model. All parameters were measured from three different regions-of-interest (ROI), covering the entire renal parenchyma, cortex, and medulla., Results: D slow , perfusion fraction, and ADC were significantly higher in patients with EGF than DGF (all p values values <0.001). Especially, ADC measured from ROI covering the entire kidney parenchyma had the best cut-off value (1.93 μ m 2 /msec) with the highest area under the receiver operating characteristic curve (AUC 0.943) in differentiating EGF from DGF. For analysis of pair-wise differences, only the perfusion fraction values, measured from the ROI covering the renal cortex, were significantly higher in 14 DGF patients with no complications than in the 9 DGF patients with complications, with the best cut-off value of 12.3% and the AUC of 0.844., Conclusion: Noninvasive IVIM-DWI reliably differentiates DGF from EGF after kidney transplantation, and it may aid in identifying posttransplant complications and indications for renal biopsy., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Yung-Chieh Chang et al.)

Background and Objectives: The immunogenicity of vaccines is known to be attenuated in patients with end-stage kidney disease due to uremia. Patients on dialysis were excluded from coronavirus disease 2019 (COVID-19) vaccine trials; thus, the effectiveness of vaccines for this population is unclear. The aim of this study was to explore whether Asian dialysis patients can effectively produce an immune response after being vaccinated with the first dose of the ChAdOx1 nCoV-19 vaccine., Design Setting, Participants, and Measurements: In this prospective cohort study, we included Asian hemodialysis patients who received the ChAdOx1 nCoV-19 vaccine. At 3 weeks after the first dose of vaccination, we assessed the humoral immune response by measuring anti-SARS-CoV-2 S antibody titers. The primary outcome was the seropositive rate following vaccination, defined as an antibody titer greater than or equal to 0.8 U/ml. Factors associated with seropositivity were explored in multivariate logistic regression analyses., Results: In total, 434 participants were included. The mean age was 64 years, the mean dialysis vintage was 6 years, and 61% of the participants were men. At a mean time of 22 days from vaccination, 56% of the participants were seropositive. The vast majority (88%) had low antibody titers (< 15 U/ml). The multivariate logistic regression analyses showed that older age (every increase of 10 years, odds ratio [OR] 0.80, 95% CI 0.65-0.98, p = 0.03) was negatively associated with seropositivity and that higher Kt/V (every increase of 0.1, OR 1.14, 95% CI 1.01-1.28, p = 0.03) and higher serum albumin level (every increase of 0.1 g/dl, OR 1.09, 95% CI 1.02-1.18, p = 0.02) were positively associated with seropositivity., Conclusions: In Asian hemodialysis patients, the seropositive rate was low, and most had low antibody titers after the first dose of the ChAdOx1 nCoV-19 vaccine. Younger age, better dialysis adequacy, and higher albumin levels were associated with seropositivity., (© 2022 International Society for Hemodialysis.)

Objective: We analyzed the efficacy and safety of an everolimus with reduced-exposure calcineurin inhibitor (EVR+rCNI) versus mycophenolic acid with standard-exposure CNI (MPA+sCNI) regimen in Asian patients from the TRANSFORM study., Methods: In this 24-month, open-label study, de novo kidney transplant recipients (KTxRs) were randomized (1:1) to receive EVR+rCNI or MPA+sCNI, along with induction therapy and corticosteroids., Results: Of the 2037 patients randomized in the TRANSFORM study, 293 were Asian (EVR+rCNI, N = 136; MPA+sCNI, N = 157). At month 24, EVR+rCNI was noninferior to MPA+sCNI for the binary endpoint of estimated glomerular filtration rate (eGFR) < 50 ml/min/1.73 m 2 or treated biopsy-proven acute rejection (27.0% vs. 29.2%, P = .011 for a noninferiority margin of 10%). Graft loss and death were reported for one patient each in both arms. Mean eGFR was higher in EVR+rCNI versus MPA+sCNI (72.2 vs. 66.3 ml/min/1.73 m 2 , P = .0414) even after adjusting for donor type and donor age (64.3 vs. 59.3 ml/min/1.73 m 2 , P = .0582). Overall incidence of adverse events was comparable. BK virus (4.4% vs. 12.1%) and cytomegalovirus (4.4% vs. 13.4%) infections were significantly lower in the EVR+rCNI arm., Conclusion: This subgroup analysis in Asian de novo KTxRs demonstrated that the EVR+rCNI versus MPA+sCNI regimen provides comparable antirejection efficacy, better renal function, and reduced viral infections (NCT01950819)., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Galactose-deficient IgA 1 (Gd-IgA 1 ) and alternative complement pathway activation are considered to be involved in the pathogenesis of IgA nephropathy (IgAN). Nevertheless, the relationships between alternative pathway activation and disease activity or Gd-IgA 1 level remains unclear., Methods: Ninety-eight biopsy-diagnosed IgAN, twenty-five primary focal segmental sclerosis (FSGS) patients and forty-two healthy individuals were recruited in this study. Among them, fifty IgAN patients received immunosuppression. Follow-up blood samples at 1 and 3~6 months after immunosuppression were collected. Plasma levels of complement C5a, factor Ba and Gd-IgA 1 were measured and analyzed. Immunostaining for complement was performed in twenty-five IgAN and FSGS patients., Results: At baseline, IgAN patients had higher levels of plasma C5a, factor Ba and Gd-IgA 1 than control subjects. Gd-IgA 1 levels positively correlated with plasma C5a and factor Ba. In addition, levels of factor Ba and Gd-IgA 1 were positively associated with proteinuria and negatively associated with renal function. Immunostaining revealed positive staining for factor Bb and C3c in glomeruli in IgAN patients, but not in FSGS patients. At baseline, patients receiving immunosuppression had more severe proteinuria and higher factor Ba. After 6 months, eGFR declined and proteinuria persisted in patients without immunosuppression. In contrast, patients who received immunosuppression exhibited decreased plasma levels of C5a, factor Ba, and Gd-IgA 1 as early as 1 month after treatment. Proteinuria decreased and renal function also remained stable 6 months after immunosuppression., Conclusions: Our results indicate a close relationship between alternative complement pathway activation, Gd-IgA 1 concentration and clinical severity of IgAN. Level of complement factor B may be a potential marker for disease activity and therapeutic target in IgAN patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chiu, Lin, Shu, Fang, Chang, Chou, Wu, Chiang, Lin, Chen and Wu.)

Background: Di(2-ethylhexyl) phthalate (DEHP) is one of the most widely used phthalates and is associated with breast cancer. Ths association between DEHP and other types of cancer is not clear. DEHP may increase matrix metalloproteinase-9 that is critical for the development of urothelial cancer (UC). We examined the association between urinary phthalate metabolites and UC. CKD patients were selected as a control group because CKD patients are more at risk of UC than the general population., Methods: In this cross-sectional study, we measured seven urinary phthalate metabolites that are abundant and can be measured using HPLC-MS/MS in Taiwan CKD patients between Jul 2013 and Dec 2015. MiBP (a urinary metabolite of Dibutyl phthalates[DBP]) and MEHHP (a urinary metabolite of DEHP) were described because they are the most abundant phthalate metabolites. The association of phthalate (log-transformed) and UC were analyzed using logistic regression with adjustments for age, gender, renal function, use of traditional Chinese medicine, toxins (dye, organic solvent), and non-steroidal anti-inflammatory drugs., Results: We measured the urinary MEHHP and MiBP of 496 patients (224 UC and 272 CKD patients). The urinary MEHHP was associated with UC but MiBP was not. Medical history including the use of non-steroid anti-inflammatory drugs, exposure to environmental toxins (dye, paint, and organic solvent), and the use of traditional Chinese medicine was independently associated with UC. The adjusted odds ratio of MEHHP was 1.42 (95% confidence interval: 1.21-1.68)., Conclusion: Phthalate urinary metabolite(MEHHP) may be associated with UC in CKD patients and the association is independent of well-known risk factors of UC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Ltd.)

Urothelial carcinoma (UC) is the ninth most prevalent malignancy worldwide. Noninvasive and efficient biomarkers with high accuracy are imperative for the surveillance and diagnosis of UC. CKD patients were enrolled as a control group in this study for the discovery of highly specific urinary protein markers of UC. An iTRAQ-labeled quantitative proteomic approach was used to discover novel potential markers. These markers were further validated with 501 samples by ELISA assay, and their diagnostic accuracies were compared to those of other reported UC markers. BRDT, CYBP, GARS, and HDGF were identified as novel urinary UC biomarkers with a high discrimination ability in a population comprising CKD and healthy subjects. The diagnostic values of the four novel UC markers were better than that of a panel of well-known or FDA-approved urinary protein markers CYFR21.1, Midkine, and NUMA1. Three of our discovered markers (BRDT, HDGF, GARS) and one well-known marker (CYFR21.1) were finally selected and combined as a marker panel having AUC values of 0.962 (95% CI, 0.94-0.98) and 0.860 (95% CI, 0.83-0.89) for the discrimination between UC and normal groups and UC and control (healthy + CKD) groups, respectively.

Background: Type 2 diabetes is an important challenge given the worldwide epidemic and is the most important cause of end-stage renal disease (ESRD) in developed countries. It is known that patients with ESRD and advanced renal failure suffer from immunosenescence and premature T cell aging, but whether such changes develop in patients with less severe chronic kidney disease (CKD) is unclear., Method: 523 adult patients with type 2 diabetes were recruited for this study. Demographic data and clinical information were obtained from medical chart review. Immunosenescence, or aging of the immune system was assessed by staining freshly-obtained peripheral blood with immunophenotyping panels and analyzing cells using multicolor flow cytometry., Result: Consistent with previously observed in the general population, both T and monocyte immunosenescence in diabetic patients positively correlate with age. When compared to diabetic patients with preserved renal function (estimated glomerular filtration rate > 60 ml/min), patients with impaired renal function exhibit a significant decrease of total CD3 + and CD4 + T cells, but not CD8 + T cell and monocyte numbers. Immunosenescence was observed in patients with CKD stage 3 and in patients with more severe renal failure, especially of CD8 + T cells. However, immunosenescence was not associated with level of proteinuria level or glucose control. In age, sex and glucose level-adjusted regression models, stage 3 CKD patients exhibited significantly elevated percentages of CD28 - , CD127 - , and CD57 + cells among CD8 + T cells when compared to patients with preserved renal function. In contrast, no change was detected in monocyte subpopulations as renal function declined. In addition, higher body mass index (BMI) is associated with enhanced immunosenescence irrespective of CKD status., Conclusion: The extent of immunosenescence is not significantly associated with proteinuria or glucose control in type 2 diabetic patients. T cells, especially the CD8 + subsets, exhibit aggravated characteristics of immunosenescence during renal function decline as early as stage 3 CKD. In addition, inflammation increases since stage 3 CKD and higher BMI drives the accumulation of CD8 + CD57 + T cells. Our study indicates that therapeutic approaches such as weight loss may be used to prevent the emergence of immunosenescence in diabetes before stage 3 CKD., Competing Interests: Competing interestsNon-declared. The authors declare that the research was conducted in the absence of any commercial or financial relationships that serves as a potential conflict of interest. The results presented in this paper have not been published previously in whole or part, except in abstract format., (© The Author(s) 2020.)

Plasma leucine-Rich α-2-glycoprotein 1 (LRG1) is an innovative biomarker for inflammation and angiogenesis. Many adverse pathophysiological changes including inflammation, atherosclerosis, and premature mortality is associated with End-stage renal disease (ESRD). However, whether levels of plasma LRG1 correlate with the co-morbidities of ESRD patients is unknown. Plasma LRG1 and high-sensitivity C-reactive protein (hsCRP) were analyzed by ELISA in 169 hemodialysis patients from the Immunity in ESRD (iESRD) study. Patient demographics and comorbidities at the time of enrollment were recorded. Peripheral blood monocyte and T cell subsets were assessed by multicolor flow cytometry. In the univariate analysis, a higher level of LRG1 was associated with the presence of cardiovascular disease (CVD) and peripheral arterial occlusive disease (PAOD). In multivariate logistic regression models, higher LRG1 tertile was significantly associated with PAOD (odds ratio = 3.49) and CVD (odds ratio = 1.65), but not with coronary artery disease, history of myocardial infarction, or stroke after adjusting for gender, diabetes, hemoglobin, albumin, calcium-phosphate product, and level of hsCRP. In addition, the level of LRG1 had a positive correlation with IL-6, hsCRP, and also more advanced T cell differentiation. The association suggests that LRG1 participates in the progression of atherosclerosis by inducing inflammation. Therefore, the role of LRG1 in coexisting inflammatory response should be further investigated in the pathogenesis of cardiovascular morbidity and mortality in patients with ESRD.

TRK-100STP, a sustained-release preparation of the orally active prostacyclin analogue beraprost sodium, targets renal hypoxia. This study aimed to show the superiority of TRK-100STP over placebos in patients with chronic kidney disease (with either primary glomerular disease or nephrosclerosis) to determine the recommended dose. CASSIOPEIR (Chronic Renal Failure Asian Study with Oral PGI 2 Derivative for Evaluating Improvement of Renal Function) was a randomized, double-blind, placebo-controlled study conducted at 160 sites in seven Asia-Pacific countries and regions. Eligible patients (n = 892) were randomized to TRK-100STP 120, 240 μg, or placebo for a treatment period of up to 4 years. The primary efficacy endpoint was time to first occurrence of a renal composite: doubling of serum creatinine or occurrence of end-stage renal disease. No significant differences were observed in composite endpoints between TRK-100STP and placebo (P = 0.5674). Hazard ratios (95% CI) in the TRK-100STP 120 and 240 μg vs. placebo groups were 0.98 (0.78, 1.22) and 0.91 (0.72, 1.14), respectively. The overall incidence of adverse events and adverse drug reactions was comparable between treatment arms., (© 2019 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Background: Chronic active antibody-mediated rejection is a major etiology of graft loss in renal transplant recipients. However, there is no consensus on the optimal treatment strategies., Methods: Computerized records from Taichung Veterans General Hospital were collected to identify renal transplant biopsies performed in the past 7 years with a diagnosis of chronic active antibody-mediated rejection. The patients were divided into two groups according to treatment strategy: Group 1 received aggressive treatment (double filtration plasmapheresis and one of the followings: rituximab, intravenous immunoglobulin, antithymogycte globulin, bortezomib, or methylprednisolone pulse therapy); and group 2 received supportive treatment., Results: From February 2009 to December 2017, a total of 82 patients with biopsy-proven chronic antibody mediated rejection were identified. Kaplan-Meier analysis of death-censored graft survival showed a worse survival in group 2 (P = 0.015 by log-rank test). Adverse event-free survival was lower in group 1, whereas patient survival was not significantly different. Proteinuria and supportive treatment were independent risk factors for graft loss in multivariate analysis., Conclusions: Aggressive treatment was associated with better graft outcome. However, higher incidence of adverse events merit personalized treatment, especially for those with higher risk of infection. Appropriate prophylactic antibiotics are recommended for patients undergoing aggressive treatment.

In order to study the effect of nanosilver on soil nitrification microorganisms and nitrogen transformation, soil culture experiments were carried out. Yellow brown soil and paddy soil were first spiked with different doses of nanosilver (10, 50, 100 mg·kg -1 ) and silver ions (1, 5, 10 mg·kg -1 ). Then, the number of nitrifying bacteria, activity of soil invertase, amoA gene abundance, NH 4 + -N content, NO 3 - -N content, and soil potential ammonia oxidation rate were determined. The results showed that the number of nitrite bacteria and nitrate bacteria decreased significantly when the soils were treated with nanosilver and silver ions. Soil invertases were inhibited, and the effect on urease was greater than that on catalase. The amoA gene abundances of soil ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA) decreased, and the effect on the gene abundance of AOB was greater than that of AOA. When (NH 4 ) 2 SO 4 was added to the soil, nanosilver and silver ion pollutants caused NH 4 + -N to accumulate, and the contents of NO 3 - -N were reduced, the rate of ammonia oxidation decreased, and the transformation of ammonium nitrogen to nitrate nitrogen was inhibited. This research suggests that nanosilver and silver ions can have toxic effects on soil nitrification microorganisms and ammonium nitrogen conversion, and the degree of influence was found to be related to the soil physical and chemical properties.

Urothelial cancer (UC) is a common kidney cancer in Taiwan and patients with chronic kidney disease (CKD) are more at risk for UC than the general population. The diagnostic value of urine analysis and urine cytology is limited, especially in CKD patients. The aim of the study is to develop a nomogram to predict the risk of UC in CKD patients. We enrolled 169 UC patients and 1383 CKD patients from 9 hospitals in Taiwan between 2012 and 2015. CA125, HE4, clinical characteristics, and medical history were analyzed using multivariable logistic regression for its association with UC. A nomogram was developed to predict the risk of UC and was validated using Bootstrap. CA125 was associated with UC in CKD patients (OR: 5.91, 95% CI: 3.24-10.77) but HE4 was not (OR: 1.29, 95% CI: 0.67-2.35). A nomogram based on patients' age, estimated glomerular filtration rate, CA125 (log transformed), smoking, exposure of environmental toxin, use of nonsteroid anti-inflammatory drugs, and use of traditional Chinese medicine was conducted. The AUC of the nomogram was 0.90 (95% CI: 0.86-0.92, p < 0.01). Serum CA125 may identify UC patients from CKD patients but has limited diagnostic value due to low sensitivity. The diagnostic value of serum CA125 level can be improved by the combination with clinical characteristics including age, renal function, and medical history.

Background: Patients with end-stage renal disease (ESRD) exhibit a premature aging phenotype of the immune system. Nevertheless, the etiology and impact of these changes in ESRD patients remain unknown., Results: Compared to healthy individuals, ESRD patients exhibit accelerated immunosenescence in both T cell and monocyte compartments, characterized by a dramatic reduction in naïve CD4+ and CD8+ T cell numbers but increase in CD8+ T EMRA cell and proinflammatory monocyte numbers. Notably, within ESRD patients, aging-related immune changes positively correlated not only with increasing age but also with longer dialysis vintage. In multivariable-adjusted logistic regression models, the combination of high terminally differentiated CD8+ T cell level and high intermediate monocyte level, as a composite predictive immunophenotype, was independently associated with prevalent coronary artery disease as well as cardiovascular disease, after adjustment for age, sex, systemic inflammation and presence of diabetes. Levels of terminally differentiated CD8+ T cells also positively correlated with the level of uremic toxin p -cresyl sulfate., Conclusions: Aging-associated adaptive and innate immune changes are aggravated in ESRD and are associated with cardiovascular diseases. For the first time, our study demonstrates the potential link between immunosenescence in ESRD and duration of exposure to the uremic milieu., Competing Interests: The study is approved by both FEMH and NTUH’s institutional ethical committees (FEMH 103084-E and NTUYL 201511092 RINA) and informed consent was acquired from all participants.All authors consent to the publication of this final version of manuscript.Non-declared. The authors declare that the research was conducted in the absence of any commercial or financial relationships that serves as a potential competing interest. The results presented in this paper have not been published previously in whole or part, except in abstract format.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Chronic antibody-mediated rejection is the most common cause of late graft loss in renal transplant recipients. Visfatin is a pre-B cell colony-enhancing factor secreted by activated lymphocytes. We hypothesize that visfatin may play a role in the augmentation of B cell colonies and facilitate antibody-mediated rejection. Renal transplant recipients were randomly selected for the study. Fasting blood samples were obtained for the assay of visfatin. The participants were prospectively followed up for 3 years. A total of 146 patients were recruited for the study and were divided into 3 groups according to tertile of serum visfatin level. At the end of follow-up, 6 patients had graft loss, including 1 graft loss in tertile 1, 3 in tertile 2, and 2 in tertile 3 (P = .60). Fourteen patients experienced at least 1 episode of acute rejection, while 21 patients were diagnosed as having chronic rejection. The distribution of acute rejection was 10.2% in tertile 1, 10.2% in tertile 2, and 8.3% in tertile 3 (P = .94); chronic rejection occurred in 10.2%, 16.3%, and 16.7%, respectively (P = .59). We conclude that serum visfatin level was not correlated with either graft failure or patient mortality in a 3-year observation period., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Accumulating evidence indicates that persistent human cytomegalovirus (HCMV) infection is associated with several health-related adverse outcomes including atherosclerosis and premature mortality in individuals with normal renal function. Patients with end-stage renal disease (ESRD) exhibit impaired immune function and thus may face higher risk of HCMV-related adverse outcomes. Whether the level of anti-HCMV immune response may be associated with the prognosis of hemodialysis patients is unknown., Results: Among 412 of the immunity in ESRD study (iESRD study) participants, 408 were HCMV seropositive and were analyzed. Compared to 57 healthy individuals, ESRD patients had higher levels of anti-HCMV IgG. In a multivariate-adjusted logistic regression model, the log level of anti-HCMV IgG was independently associated with prevalent coronary artery disease (OR = 1.93, 95% CI = 1.2~ 3.2, p  = 0.01) after adjusting for age, sex, hemoglobin, diabetes, calcium phosphate product and high sensitivity C-reactive protein. Levels of anti-HCMV IgG also positively correlated with both the percentage and absolute number of terminally differentiated CD8+ and CD4+ CD45RA+ CCR7- T EMRA cells, indicating that immunosenescence may participate in the development of coronary artery disease., Conclusion: This is the first study showing that the magnitude of anti-HCMV humoral immune response positively correlates with T cell immunosenescence and coronary artery disease in ESRD patients. The impact of persistent HCMV infection should be further investigated in this special patient population., Competing Interests: The study is approved by both FEMH and NTUH’s institutional ethical committees (FEMH 103084-E and NTUYL 201511092 RINA) and informed consent was acquired from all participants.All authors consent to the publication of this final version of manuscript.Non-declared. The authors declare that the research was conducted in the absence of any commercial or financial relationships that serves as a potential conflict of interest. The results presented in this paper have not been published previously in whole or part, except in abstract format.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: Despite the development of biomarkers and noninvasive imaging tools, biopsy remains the only method for correctly diagnosing patients with unexplained hematuria, proteinuria and renal failure. Renal biopsy has been performed for several decades in Taiwan; however, a national data registry is still lacking until 2013., Methods: The Renal Biopsy Registry Committee was established within the Taiwan Society of Nephrology in January 2013. A biopsy registry format, including basic demographic data, baseline clinical features, laboratory data, and clinical and pathological diagnosis was developed. Approval from the local institutional review board was obtained in each participating medical center., Results: From January 2014 to September 2016, 1445 renal biopsies were identified from 17 medical centers. 53.8% cases were reported in men. After excluding renal transplantation, renal biopsies were commonly performed in patients with primary glomerulonephritis (48.1%), secondary glomerulonephritis (36.2%), followed by tubulointerstitial diseases (12.3%) and vascular nephropathy (3.4%). Among primary glomerulonephritis, IgA nephropathy (26.0%), focal segmental glomerulosclerosis (21.6%), and membranous nephropathy (20.6%) were most frequently diagnosed. Diabetic nephropathy (22.4%) and lupus nephritis (21.8%) were the most common among secondary glomerulonephritis. Patients with minimal change disease and membranous nephropathy had heavier proteinuria than those with focal segmental glomerulosclerosis and IgA nephropathy (P < 0.001). Patients with minimal change disease had higher serum IgM and IgE levels. The most common cause of nephrotic syndrome in primary glomerular disease was membranous nephropathy (28.8%), followed by minimal change disease (28.2%). IgA nephropathy was the leading cause of chronic nephritic syndrome, acute nephritic syndrome, and persistent hematuria. The incidence of primary glomerulonephritis was approximately 2.19 in 100,000/year., Conclusions: This is the first report of the National Renal Biopsy Registry in Taiwan. IgA nephropathy is the most common primary glomerulonephritis, while membranous nephropathy is the most common cause of nephrotic syndrome. Primary glomerulonephritis distribution in Taiwan is slightly different from that in other Asian countries.

Hyponatremia is the most common electrolyte disorder and also a predictor of mild cognition impairment. However, the association between hyponatremia and dementia in long follow up periods is rarely investigated. A retrospective cohort study was performed using the claims data of all insured residents who were covered by Taiwan's universal health insurance from 2000 to 2011. A total of 4900 hyponatremia patients and 19545 matched comparisons were recruited for the analysis. The incidences of hyponatremia and dementia were diagnosed with clinical protocol and defined using the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM). Cox proportional hazard regression and Kaplan-Meier curves were used for the analyses. Independent of adjusting factors, hyponatremia patients had 2.36-fold higher chances of suffering dementia, including Alzheimer's disease (AD) and non-AD dementia, than the comparisons. Severe hyponatremia patients had higher risks of suffering dementia than the non-severe hyponatremia patients (adjusted hazard ratio: 4.29 (95% CI: 3.47-5.31) versus 2.08 (95% CI: 1.83-2.37)). A dose response relationship was observed between hyponatremia and dementia. Those hyponatremia patients with baseline or incident stroke had significantly higher chances of suffering dementia compared with those patients without hyponatremia and stroke. Stroke is a significant modifier of the relationship between hyponatremia and dementia. Cerebrovascular disease after incident hyponatremia must be prevented to reduce the incidence of dementia.

Aim: This was a nationwide study by National Health Insurance Research Database to investigate the risk of urinary tract cancers (UTCs) for renin-angiotensin-aldosterone system inhibitors including spironolactone., Methods: A total of 32 167 UTC patients with hypertension were enrolled in the National Health Insurance program between 2005 and 2011., Results: Among different subclasses of renin-angiotensin-aldosterone system inhibitors, the adjusted odds ratio (OR) for UTC risk was 1.00 [95% confidence interval (CI) = 0.96-1.04] in angiotensin-converting enzyme inhibitors, 1.22 (95% CI = 1.18-1.26) in patients who received angiotensin II receptor blockers, 0.91 (95% CI = 0.87-0.96) in spironolactone. Spironolactone is associated with a significantly lower risk of prostate cancer (adjusted OR = 0.88, 95% CI = 0.82-0.94) in the male patients. A similar trend was observed in the female patients for the risk of bladder cancer (adjusted OR = 0.81, 95% CI = 0.72-0.92)., Conclusion: Our findings show that a lower risk of UTCs significantly associated with spironolactone in patients.

Background: Data for the risk of any solid cancer in patients with polycystic kidney disease are scarce. Therefore, we did a nationwide cohort study in Taiwan to establish the risk of cancer in patients with polycystic kidney disease without either chronic kidney disease or end-stage renal disease., Methods: From inpatient claims of the Taiwan National Health Insurance Research Database, we included patients aged 20 years and older and diagnosed with polycystic kidney disease between January, 1998 and December, 2010, in the polycystic kidney disease cohort. Patients with a history of cancer, a history of chronic kidney disease or of end-stage renal disease (recorded from the Registry of Catastrophic Illness Patient Database) were excluded. For each patient with polycystic kidney disease, one patient aged older than 20 years with no history of polycystic kidney disease or cancer was randomly selected from the National Health Insurance Research Database, matched 1:1 on the basis of the propensity score calculated by logistic regression, and was included in the control non-polycystic kidney disease cohort. The follow-up period for each patient was estimated from the index date to the date of diagnosis of cancer, or the patient was censored due to withdrawal from the insurance programme (eg, death, immigration, or imprisonment) or on Dec 31, 2011. The primary outcome of interest was a diagnosis of cancer during a 14-year follow-up period. The risk of cancer was represented as a hazard ratio (HR) calculated in Cox proportional hazard regression models., Findings: 4346 patients with polycystic kidney disease and 4346 without were enrolled in the study. The median follow-up period in the polycystic kidney disease cohort was 3·72 years (IQR 1·25-7·31) and in the non-polycystic kidney disease cohort was 4·96 years (2·29-8·38). The overall incidence of cancer was higher in the polycystic kidney disease cohort than in the control cohort (20·1 [95% CI 18·3-21·9] per 1000 person-years vs 10·9 [10·1-11·8] per 1000 person-years; crude hazard ratio (HR) 1·77 [95% CI 1·52-2·07]; HR adjusted for age, sex, frequency of medical visits, and comorbidities was 1·83 [1·57-2·15]). The specific risks (adjusted subhazard ratios) were significantly higher in the polycystic kidney disease cohort than that in the non-polycystic kidney disease cohort for liver cancer (1·49 [95% CI 1·04-2·13]; p=0·030), colon cancer (1·63 [1·15-2·30]; p=0·006), and kidney cancer (2·45 [1·29-4·65]; p=0·006)., Interpretation: To our knowledge, this is the first report of the association of polycystic kidney disease without end-stage renal disease with the risk of liver, colon, and kidney cancer. Health-care professionals should be aware of this risk, when treating patients with polycystic kidney disease., Funding: Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence, Academia Sinica Taiwan Biobank, Stroke Biosignature Project, NRPB Stroke Clinical Trial Consortium, Tseng-Lien Lin Foundation, Taiwan Brain Disease Foundation, Katsuzo and Kiyo Aoshima Memorial Funds, China Medical University Hospital, and Taiwan Ministry of Education., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Urinary biomarkers augment the diagnosis of acute kidney injury (AKI), with AKI after cardiovascular surgeries being a prototype of prognosis scenario. Glutathione S-transferases (GST) were evaluated as biomarkers of AKI. Urine samples were collected in 141 cardiovascular surgical patients and analyzed for urinary alpha-(α-) and pi-(π-) GSTs. The outcomes of advanced AKI (KDIGO stage 2, 3) and all-cause in-patient mortality, as composite outcome, were recorded. Areas under the receiver operator characteristic (ROC) curves and multivariate generalized additive model (GAM) were applied to predict outcomes. Thirty-eight (26.9%) patients had AKI, while 12 (8.5%) were with advanced AKI. Urinary π-GST differentiated patients with/without advanced AKI or composite outcome after surgery (p < 0.05 by generalized estimating equation). Urinary π-GST predicted advanced AKI at 3 hrs post-surgery (p = 0.033) and composite outcome (p = 0.009), while the corresponding ROC curve had AUC of 0.784 and 0.783. Using GAM, the cutoff value of 14.7 μg/L for π-GST showed the best performance to predict composite outcome. The addition of π-GST to the SOFA score improved risk stratification (total net reclassification index = 0.47). Thus, urinary π-GST levels predict advanced AKI or hospital mortality after cardiovascular surgery and improve in SOFA outcome assessment specific to AKI.

Background: Tacrolimus is the most commonly prescribed immunosuppressive drug after kidney transplantation (KTx). The trough level of tacrolimus (T0) is currently used for routine monitoring after KTx. The purpose of this study was to examine the association between the variability of T0 and acute rejection., Methods: All kidney transplant recipients (KTR) with tacrolimus-based regimen and episode of biopsy-proven acute rejection (BPAR) between January 2012 and October 2014 were enrolled in the acute rejection (AR) group. KTR with tacrolimus-based regimen and without episode of AR were enrolled in the control group. All of the results of T0 within 6 months before episode of acute rejection were used for the calculation of within-patient variability of T0. The percent coefficient of variation, which is calculated as (standard deviation of mean/mean) × 100%, was used to represent the concentration variability of tacrolimus., Results: In all, 25 KTR with AR and another 136 KTR without BPAR were enrolled in the study. The mean age of all 161 patients was 50.1 ± 10.4 years, and the mean duration after KTx was 4.3 ± 4.7 years. The average daily dose of tacrolimus was 5.7 ± 2.6 mg, and T0 was 5.4 ± 1.8 ng/mL. Age, sex, duration after KTx, daily dose of tacrolimus, and T0 were similar in both groups. Compared with the control group, the percent coefficient of variation of T0 was significantly higher in patients with BPAR 12.1% ± 7.9% vs 39% ± 15.6%, P<.001., Conclusions: The study results suggest that, in KTR, higher variability of tacrolimus trough level is associated with higher risk of acute rejection., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The aims of this study were to identify the incidence of renal failure requiring dialysis and to investigate the long-term outcome after renal failure in liver transplantation (LT) patients., Methods: The primary database used was the Taiwan National Health Insurance Research Database. Subjects with LT from 1997 to 2009 were included. Patients were grouped into the dialysis cohort if they once received hemodialysis owing to any pattern of renal failure during peri-transplantation periods or after LT. Otherwise, they were categorized into the nondialysis cohort. We conducted a retrospective observational study on the correlation of renal failure requiring dialysis and its effect on LT recipients., Results: The analysis included data of 1,771 LT recipients with a mean follow-up time of 3.8 ± 2.9 years. The mean age was 43.2 ± 19.3 years, and 69.4% were male. Overall patient survival was 86.2% at 1 year, 82.2% at 3 years, and 80.5% at 5 years. Renal failure requiring dialysis had developed in the 323 patients (18.2%). Among them, 26 individuals (1.5%) had progressed to end-stage renal disease without renal recovery after perioperative hemodialysis. Individuals who developed renal failure requiring dialysis had a higher mortality compared with LT recipients never requiring dialysis (hazard ratio, 8.75; 95% confidence interval, 7.0-10.9)., Conclusions: Renal failure requiring dialysis development after LT is common and carries high mortality in Chinese liver allograft recipients. Recognizing risk factors permits the timely institution of proper treatment, which is the key to reducing untoward outcomes., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to evaluate the prognosis of kidney transplant recipients with pretransplantation malignancy and the incidence of recurrent malignancy in kidney transplant recipients using claims data from Taiwan's universal health insurance program., Method: A total of 4350 transplant recipients were retrospectively analyzed. The rates of pretransplantation or recurrent malignancy, which was defined by their inclusion in the catastrophic illness patient registry using the International Classification of Diseases, 9th Revision, were evaluated. Cox proportional hazard regression and Kaplan-Meier curves were used for the analyses., Results: In total, there were 4350 kidney transplant recipients, 52.1% of patients were male, the mean age at transplantation was 45.8 years old, and the percentages of diabetes mellitus, hypertension, hepatitis B viral infection, and hepatitis C viral infection were 14%, 63.2%, 4.2%, and 2.4%, respectively. There were 95 patients (2.2%) with pretransplantation malignancy. The top 3 pretransplantation malignancies, in decreasing order, were urinary tract, kidney, and breast cancers. After kidney transplantation, 10 recipients had recurrent cancer. The overall cancer recurrence rate was 10.5%. These 10 cancers included urothelial carcinoma (n = 5), renal cell carcinoma (n = 3), breast cancer (n = 1), and thyroid cancer (n = 1). Eleven recipients had a secondary cancer. Patients without pretransplantation and post-transplantation malignancy had the best survival. Patients with pretransplantation malignancy had a greater occurrence of cancers and increased mortality regardless of whether or not they had recurrence of cancer., Conclusion: Our results suggest the higher risk of cancer, recurrent or secondary, and mortality after kidney transplantation. Adequate waiting time before transplantation and preventive strategies are strongly suggested in kidney transplant recipients with cancer history., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Data regarding the risk of various liver diseases among different hepatitis viruses in kidney transplantation have not yet been identified.We selected individuals with kidney transplantation (ICD-9-CM V420 or 996.81) from 2000-2009 from the catastrophic illness registry of National Health Insurance Research Database (NHIRD)as the study cohort. The two end-points in the study included overall death, and post-transplant occurrence of hepatic disease. After adjustment for other risk factors, the risk of mortality was increased in patients with HBV infection (N = 352) and with HCV infection (N = 275) compared to those with neither HBV nor HCV infection (N = 3485). In addition,renal transplant recipients with HBV alone,HCV alone, and both with HBV and HCVinfectionrespectively had an approximately 10-fold hazard ratio (HR) = 9.84, 95% confidence interval (CI): 4.61-21.0, 4-fold increased risk (HR = 4.40, 95% CI: 1.85-10.5)and 5-fold increased risk (HR = 4.63, 95% CI: 1.06-20.2)of hepatocellular carcinoma (HCC)compared to those with neither HBV nor HCV infection. Our findings showed a significant risk of de novo liver disease in recipients with hepatitis virus infection. Based on our findings, we reinforce the importance and impact of hepatitis virus in renal transplantation.

Renal biopsy remains the golden standard diagnosis of renal function deterioration. The safety in native kidney biopsy is well defined. However, it is a different story in allograft kidney biopsy. We conduct this retrospective study to clarify the safety of allograft kidney biopsy with indication.All variables were grouped by the year of biopsy and they were compared by Mann-Whitney U test (for continuous variables) or Chi-square test (for categorical variables). We collected possible factors associated with complications, including age, gender, body weight, renal function, cause of uremia, status of coagulation, hepatitis, size of needle, and immunosuppressants.We recruited all renal transplant recipients undergoing allograft biopsy between January of 2009 and December of 2014. This is the largest database for allograft kidney biopsy with indication. Of all the 269 biopsies, there was no difference in occurrence among the total 14 complications (5.2%) over these 6 years. There were only 3 cases of hematomas (1.11%), 6 gross hematuria (2.23%), 1 hydronephrosis (0.37%), and 2 hemoglobin decline (0.74%). The outcome of this cohort is the best compared to all other studies, and it is even better than the allograft protocol kidney biopsy. Among all possible factors, patients with pathological report containing "medullary tissue only" were susceptible to complications (P < 0.001, 1.8 of relative risk).In modern era, this study demonstrates the safety of allograft kidney biopsy with indication. Identifying the renal capsule before biopsy to avoid puncture into medulla is the most important element to prevent complications.

RANTES (Regulated on activation, normal T-cell expressed and secreted), recruits circulating leukocytes and augments inflammatory responses in many clinical conditions. Inflammatory responses in ischemia-reperfusion injury (IRI) significantly affect the unfavorable outcomes of acute kidney injury (AKI), and that infiltrating immune cells are important mediators of AKI. However, the significance of RANTES in AKI and whether hypoxia-induced LncRNAs are involved in the regulatory process of AKI are not known. Here we show that, in the kidney IRI mice model, significant RANTES expression was observed in renal tubular cells of wild type mice. RANTES deficient (RANTES(-/-)) mice showed better renal function by reducing the acute tubular necrosis, serum creatinine levels, infiltration of inflammatory cells and cytokine expressions compared to wild type. In vitro, we found that RANTES expression was regulated by NF-κB. Further, renal tubular cells showed deregulated LncRNA expression under hypoxia. Among HIF-1α dependent LncRNAs, PRINS (Psoriasis susceptibility-related RNA Gene Induced by Stress) was significantly up regulated in hypoxic conditions and had specific interaction with RANTES as confirmed through reporter assay. These observations show first evidence for RANTES produced by renal tubular cells act as a key chemokine in AKI and HIF-1α regulated LncRNA-PRINS might be involved in RANTES production.

Rheumatoid arthritis (RA) is associated with atherosclerosis. However, the relationship between RA and peripheral arterial occlusive disease (PAOD) remains unclear. We used a national health insurance database to identify a cohort of 30,812 patients diagnosed with RA between 2000 and 2011. Each RA patient was frequency-matched according to age and sex with a patient without RA from a control cohort. A multivariate Cox proportional hazards model was used to analyse the adjusted risk of PAOD. The incidence of PAOD was 1.73-fold higher (95% confidence interval [CI] = 1.57-1.91) in the RA cohort than in the non-RA cohort. The adjusted risk of PAOD was the highest in the patients with RA aged ≤ 49 years (hazard ratio [HR] = 3.39, 95% CI = 2.66-4.32). Patients with RA and various comorbidities showed a significantly higher risk of PAOD (HR = 9.62, 95% CI = 4.86-19.1) compared with control patients without comorbidity. The risk of PAOD increased during the first year of follow-up. In conclusion, patients with RA have an independently higher risk of PAOD compared with the general population. Patients with RA and various comorbidities and those at a young age and early stage of the disease have an increased risk of PAOD.

Homozygous familial hypercholesterolemia (HoFH) is a very rare condition (1 case per 1 million people) with a dismal outcome due to inevitable coronary artery disease that occurs when left untreated. Lipoprotein apheresis (LA), previously known as low-density lipoprotein (LDL) apheresis, is very effective in reducing LDL-cholesterol (LDL-C) if HoFH is refractory to aggressive drug therapy and diet control. In this study, we report a case with HoFH, who presented with xanthomata over the 4 limbs when she was 3 years old. When she was 11 years old, she began treatment with semi-selective LA with double filtration plasmapheresis (DFPP) once per week because HoFH was refractory to high-dose statin and diet control. LDL-C was reduced from 8.2 ± 0.9 to 2.69 ± 0.75 mmol/l (reduction rate = 67.3 ± 6.1%). The xanthomata over the 4 limbs were nearly completely resolved after 2 years of DFPP. Two years later, after the initiation of DFPP, we performed coronary angiography and echocardiography for regular checkup in the absence of chest pain, and the result was negative. To date (11 years after initiation of DFPP), she has not complained of any chest pain, shown intolerance to exercise, or exhibited ST-T change on electrocardiography. At the age of 20, multidetector computed tomography showed no significant stenosis over the coronary arteries. At the most recent follow-up visit, she was found to have good heart function and no xanthomata. LA is effective in the treatment of HoFH when drug therapy and diet control fail. With this treatment, pre-existing xanthomata can regress and coronary artery disease can be prevented., (© 2016 S. Karger AG, Basel.)

Systemic lupus erythematosus (SLE) is associated with atherosclerosis, but the relationship between SLE and peripheral arterial occlusive disease (PAOD) remains unclear. We sought to investigate this relationship by comparing cardiovascular complications in patients with and without SLE.Data on patients from 2000 to 2011 were collected from the National Health Insurance Research Database of Taiwan. The SLE cohort was frequency-matched according to age, sex, and history of diabetes mellitus (DM) with patients without SLE (control cohort). We evaluated the risk of cardiovascular complications, including hypertension, DM, stroke, chronic obstructive pulmonary disease, heart failure, coronary artery disease, and hyperlipidemia.The study included 10,144 patients with SLE and 10,144 control patients. The incidence of PAOD was 9.39-fold higher (95% confidence interval [CI] = 7.70-11.15) in the SLE cohort than in the non-SLE cohort. Moreover, SLE was an independent risk factor for PAOD. The adjusted risk of PAOD was highest in patients with SLE who were aged ≤34 years (hazard ratio = 47.6, 95% CI = 26.8-84.4). The risk of PAOD was highest during the first year of follow-up and decreased over time.Patients with SLE exhibit a higher incidence and an independently higher risk of PAOD compared with the general population. The PAOD risk is markedly elevated in patients with SLE who are young and in whom the disease is at an early stage.

Decoy receptor 3 (DcR3) expression in kidneys has been shown to predict progression of chronic kidney disease. We prospectively investigated a cohort comprising 96 renal transplant recipients (RTRs) undergoing graft kidney biopsies. Computer-assisted quantitative immunohistochemical staining value of DcR3 in renal tubular epithelial cells (RTECs) was used to determine the predictive role of DcR3 in kidney disease progression. The primary end point was doubling of serum creatinine and/or graft failure. A multivariate Cox proportional hazards model was used to assess the risk of DcR3 expression in rejected kidney grafts toward the renal end point. In total, RTRs with kidney allograft rejection were evaluated and the median follow-up was 30.9 months. The greater expression of DcR3 immunoreactivity in RTECs was correlated with a higher rate of the histopathological concordance of acute T cell-mediated rejection. Compared with 65 non-progressors, 31 progressors had higher DcR3 expression (HDE) regardless of the traditional risk factors. Cox regression analysis showed HDE was significantly associated with the risk of renal end point with a hazard ratio of 3.19 (95% confidence interval, 1.40 to 7.27; P = 0.006) after adjusting for other variables. In repetitive biopsies, HDE in tissue showed rapid kidney disease progression due to persistent inflammation.

Angiomyolipoma (AML) is a benign mesenchymal tumor composed of blood vessels, smooth muscle, and mature adipose tissue. AMLs in the kidney allografts are rare. We report a case of AML that was incidentally found 1 year after transplantation. Abdominal computed tomography showed a 4-cm renal tumor with contrast enhancement and an early washout pattern, resembling a renal cell carcinoma. Tumor biopsy proved a lipid-poor AML. Tumor diameter decreased to 2.4 cm after 6 months of treatment with sirolimus. Sirolimus not only reduces tumor size, but also benefits a transplant patient who needs immunosuppression., (© 2015 Steunstichting ESOT.)

Background/Purpose Retention of excess iron from transfused blood in organs in patients with renal anemia may lead to various systemic complications. Iron chelating agents such as deferasirox (DFX) decrease such iron overload. This study assessed the efficacy, safety, and tolerability of DFX in hemodialysis (HD) patients with iron overload. Methods We retrospectively (February 2008 to June 2012) reviewed data for eight HD patients with end-stage renal disease who were prescribed DFX (15 mg/kg/day) for transfusion-induced iron overload. Baseline and post-treatment levels of hematocrit, ferritin, erythropoietin (EPO), transferrin saturation (TSAT), total and unsaturated iron-binding capacity (TIBC and UIBC, respectively), and blood transfusion volumes were measured. Treatment efficacy was evaluated by observing changes in ferritin and TSAT during the study period; monthly EPO doses and blood transfusions were also recorded. Safety was evaluated in the form of adverse events. Results DFX administration caused statistically significant reductions in TSAT (68.2-49.2%; P = 0.036) and ferritin (3133.1-1215.6 ng/ml; P = 0.017). Significant post-treatment increases in UIBC (63.3-196.6 µg/dl; P = 0.018) and TIBC (210.0-422.4 µg/dl; P = 0.012) were also observed. While there were no significant differences in hematocrit values or EPO requirements after treatment, significant reductions in average monthly transfusion volumes (P = 0.026) were recorded. DFX was generally well tolerated; common adverse effects included nausea, vomiting, diarrhea, and abdominal pain. Conclusion DFX significantly improved iron metabolism in HD patients with iron overload and had an acceptable frequency of adverse effects.