Association of serum sodium levels with fractures and mortality in patients undergoing maintenance hemodialysis.

BACKGROUND: Hyponatremia is implicated in pathological bone resorption and has been identified as a risk factor for bone fracture in the general population. However, there are limited data on the association between serum sodium levels and fracture risk in patients undergoing hemodialysis (HD). METHODS: We analyzed a historical cohort of 2220 maintenance HD patients to examine the association between serum sodium levels and the risk of fracture and mortality. We also examined the association between serum sodium levels and osteoporosis, based on metacarpal bone mineral density, in a subcohort of 455 patients with available data. In addition, we examined the association between serum sodium levels and bone turnover markers in a separate cross-sectional cohort of 654 maintenance HD patients. RESULTS: During a median follow-up of 5.4 years, 712 patients died, 113 experienced clinical fractures, and 64 experienced asymptomatic vertebral fractures. Lower serum sodium levels were associated with an increased risk of mortality (HR 1.06 per 1 mEq/L decrease; 95% CI 1.03-1.09) but not with the risk of clinical fracture (HR 1.04 per 1 mEq/L decrease; 95% CI 0.97-1.11). A similar lack of association was observed for asymptomatic vertebral fracture and any fracture. Serum sodium levels were also not associated with osteoporosis in a subcohort with available data (n = 455) or with bone alkaline phosphatase or tartrate-resistant acid phosphatase-5b in a separate cross-sectional cohort. CONCLUSION: Serum sodium levels were associated with mortality but not with fracture risk, osteoporosis, or bone turnover markers in maintenance HD patients.

Water intake, baseline biopsy, and graft function after living donor kidney transplantation.

Increased water intake is recommended for kidney transplant recipients; however, its efficacy remains controversial. We hypothesized that pre-existing histological findings of the allograft might modulate the impact of water intake. We retrospectively analyzed 167 adults with living-donor kidney transplants (April 2011-May 2020; median observation period, 77 months) whose baseline biopsy data were available. We compared the chronic-change group (n = 38) with the control group (n = 129) to assess the impact of self-reported daily water intake on the estimated glomerular filtration rate (eGFR). The range distribution of water intake was as follows: - 1000 ml (n = 4), 1000-1500 ml (n = 23), 1500-2000 ml (n = 64), 2000-2500 ml (n = 57), 2500-3000 ml (n = 16), and 3000 - ml (n = 3). Donor age was significantly higher in the chronic-change group. In the control group, the ΔeGFR/year increase was correlated with water intake. However, the increase in the water intake of the chronic-change group significantly decreased ΔeGFR/year (1000-1500 ml: + 1.95 ml/min/1.73 m2 and > 2000 ml: - 1.92 ml/min/1.73 m2, p = 0.014). This study suggested a potential influence of increased water intake on recipients with marginal grafts in living donor kidney transplantation.

Acetate attenuates kidney fibrosis in an oxidative stress-dependent manner.

Short-chain fatty acids (SCFAs) are the end products of the fermentation of dietary fibers by the intestinal microbiota and reported to exert positive effects on host physiology. Acetate is the most abundant SCFA in humans and is shown to improve acute kidney injury in a mouse model of ischemia-reperfusion injury. However, how SCFAs protect the kidney and whether SCFAs have a renoprotective effect in chronic kidney disease (CKD) models remain to be elucidated. We investigated whether acetate and other SCFAs could attenuate the kidney damage. In in vitro experiments, cell viability of acetate-treated human kidney 2 (HK-2) cells was significantly higher than that of vehicle-treated in an oxidative stress model, and acetate reduced cellular reactive oxygen species (ROS) production. In mitochondrial analysis, the MitoSOX-positive cell proportion decreased, and transcription of dynamin-1-like protein gene, a fission gene, was decreased by acetate treatment. In in vivo experiments in mice, acetate treatment significantly ameliorated fibrosis induced by unilateral ureteral obstruction, and the oxidative stress marker phosphorylated histone H2AX (γH2AX) was also reduced. Further, acetate treatment ameliorated dysmorphic mitochondria in the proximal tubules, and ROS and mitochondrial analyses suggested that acetate improved mitochondrial damage. Our findings indicate a renoprotective effect of acetate in CKD.

The Resistive Index by Doppler Ultrasonography as a Predictor of the Long-Term Outcomes After Kidney Transplantation.

BACKGROUND: Doppler ultrasonography (US) is a noninvasive examination for assessing graft function after kidney transplantation. Although Doppler US is routinely performed, only a few reports have investigated whether a high resistive index (RI) detected by Doppler US affects graft function and survival. We hypothesized that there is a relationship between a high RI and inferior outcomes after kidney transplantation. METHODS: We included 164 living kidney transplant patients treated between April 2011 and July 2019. We divided the patients into 2 groups according to RI (cut-off, 0.7) 1 year after transplantation. RESULTS: The recipient was significantly older in the high RI (≥0.7) group. Moreover, there were significant differences in the prevalence of pretransplant diabetes mellitus and the value of pretransplant hemoglobin A1c. Regarding long-term outcome, there was no significant difference in overall graft survival (5 years, 92.6% vs 91.8%; 10 years, 85.0% vs 67.9%; P = .64). On the other hand, the mortality was significantly worse in the high RI group (5 years, 99.1% vs 93.9%; 10 years, 96.4% vs 70.0%, P = .013). CONCLUSIONS: A high RI might predict mortality after kidney transplantation.

Appointment Nonadherence and Graft Outcomes in Living Donor Kidney Transplantation.

BACKGROUND: Medication nonadherence is associated with worse graft outcomes but is hard to recognize in clinical settings due to its self-reporting nature. We hypothesized that appointment nonadherence might be associated with worse graft outcomes in living donor kidney transplantation. METHODS: We included 167 adult living-donor kidney transplants whose grafts survived >2 years from April 2011 to May 2020. Thirty-two cases of appointment nonadherence were identified and compared with the controls (n = 135). RESULTS: Younger age, male sex, higher body weight, and parent donor were significantly observed in the appointment nonadherence group. The appointment nonadherence group was significantly associated with worse graft survival (5 years: 82.3% vs 98.9%, P < .001, 10 years: 67.2% vs 89.6%, P < .001), de novo donor-specific antibody production, acute rejection, as well as the decline of graft function. Furthermore, appointment nonadherence had a 4-fold higher risk of graft loss after an adjustment with recipient age, sex, body weight, and donor type (adjusted hazard ratio: 3.93, 95% CI: 1.15-13.42, P = .029). CONCLUSIONS: Appointment nonadherence might be an alternative predictor for worse graft outcomes after living donor kidney transplantation.

Evaluation of Malarial Var2CSA-Displaying Baculovirus Vector in Transduction Efficiency in Human Cancer Cells.

Baculovirus vectors (BVs) are able to use for gene transduction in mammalian cells and are recognized as growing viral vectors for cancer gene therapy applications. The transduction efficiency of BVs varies among cancer cell types. To improve the transduction efficiency of BVs in human cancer cells, BV displaying malarial variant surface antigen 2-chondroitin sulfate A (var2CSA) molecules was developed in this study. Var2CSA plays a critical role in the sequestration of Plasmodium falciparum-infected erythrocytes in the placenta. Moreover, var2CSA binds to cancer cells via placenta-like chondroitin sulfate A (CSA), but not to non-cancer cells. Var2CSA BV showed significantly higher gene transduction than control BV in HepG2 and Huh7 cells, human hepatic cancer cells as well as AsPC-1 cells, human pancreatic cancer cells. The transduction efficiency of var2CSA BV was significantly inhibited by the anti-gp64 antibody, free heparin, and CSA. The results of this study suggest that var2CSA BV would be an improved vector for cancer gene therapies, especially in the treatment of hepatic and pancreatic cancers.

Two-year outcomes of low-exposure extended-release tacrolimus and mycophenolate mofetil regimen in de novo kidney transplantation: A multi-center randomized controlled trial.

BACKGROUND: Once-daily extended-release tacrolimus (TACER) is commonly administered following kidney transplantation (KTx); however, its optimal dosage remains unknown. METHODS: In this multi-center, randomized controlled trial, 62 living donor KTx recipients were assigned to either standard-exposure (SE; n = 32) or low-exposure (LE; n = 30) TACER (Graceptor®, Astellas Pharm Inc.) groups. All patients received basiliximab and mycophenolate mofetil (MMF). The primary outcomes were acute rejection, graft/patient survival, and the secondary outcomes were incidence of cytomegalovirus infection, and de novo donor-specific antibodies (dnDSA) production. RESULTS: The tacrolimus trough level and estimated area under the blood concentration-time curve (eAUC) were significantly higher in SE than in LE (SE vs. LE; 1 year: 5.0 ± 0.9 ng/ml and 206.9 ± 26.8 ng h/ml vs. 3.4 ± 1.0 ng/ml and 153.9 ± 26.4 ng h/ml; 2 years: 4.8 ± 1.0 ng/ml and 204.9 ± 30.1 ng h/ml vs. 3.8 ± 0.9 ng/ml and 164.4 ± 27.0 ng h/ml). In contrast, the dosage and eAUC of MMF did not differ between groups. Two-year graft and patient survival rates were 100% in both groups, and acute rejection rates were 0% and 10% in the SE and LE, respectively (p = 0.11). The mean estimated glomerular filtration rates did not differ between the groups. Cytomegalovirus infection was slightly lower in the LE (SE: 12.5% and LE: 6.7%, p = 0.37). In the LE, four cases of dnDSA were noted within 2 years of transplantation; no case was observed in the SE (p = 0.034). CONCLUSIONS: Although the LE TACER regimen showed similar rates of acute rejection, as well as graft and patient survival compared with SE after KTx, LE was significantly more associated with dnDSA. Further investigation of its long-term effect on graft survival is warranted. (University Hospital Medical Information Network Clinical Trials Registry ID: UMIN000033089).

Long-term impact of baseline serum uric acid levels on living kidney donors: a retrospective study.

BACKGROUND: Preoperative characteristics of living kidney donors are commonly considered during donor selection and postoperative follow-up. However, the impact of preoperative uric acid (UA) levels is poorly documented. The aim of this study was to evaluate the association between preoperative serum UA levels and post-donation long-term events and renal function. METHODS: This was a single-center retrospective analysis of 183 living kidney donors. The donors were divided into high (≥5.5 mg/dl) and low (< 5.5 mg/dl) UA groups. We analyzed the relationship between preoperative UA levels and postoperative estimated glomerular filtration rate (eGFR), as well as adverse events (cardiovascular events and additional prescriptions for hypertension, gout, dyslipidemia, and diabetes mellitus), over 5 years after donation. RESULTS: In total, 44 donors experienced 52 adverse events over 5 years. The incidence of adverse events within 5 years was significantly higher in the high UA group than in the low UA group (50% vs. 24%, p = 0.003); this was true even after the exclusion of hyperuricemia-related events (p = 0.047). UA emerged as an independent risk factor for adverse events (p = 0.012). Donors with higher UA levels had lower eGFRs after donation, whereas body mass index, hemoglobin A1c, blood pressure, and low-density lipoprotein cholesterol did not have any impact on the eGFR. CONCLUSIONS: The findings suggest that preoperative UA levels should be considered during donor selection and postoperative follow-up.

Evaluation of Combinatory Effects of Plasmodium Circumsporozoite Protein and Complement Regulatory Protein Expression of Recombinant Baculovirus Vectors.

Baculovirus vectors (BVs) are safely able to transduce foreign genes and express them in mammalian cells. However, the transduction activity of BVs is strongly reduced by the attack of serum complement, which is one of the major obstacles in the use of BVs for in vivo gene transfer. One strategy to overcome this problem is the display of complement regulatory proteins (CRPs) on BV virions. We previously developed CD46-decay accelerating factor (DAF)-CD59 triple fusion type BV showing potent complement resistance. We also developed BVs expressing Plasmodium circumsporozoite protein (CSP) to enhance transduction efficacy in hepatic cells. In this study, we investigated the combination of CSP and CRPs in a BV system to evaluate transduction efficacy along with complement resistance. To accomplish the combination of CSP and CRPs, we generated insect Sf9 cells stably expressing CRPs, to which CSP type BV was infected. The BVs collected from these infected cells were confirmed to possess both CSP and CRPs in virions. We demonstrated that CSP-CD46-DAF-CD59 type BV, containing both CSP and CD46-DAF-CD59, showed a significant increase in transduction efficacy in human hepatoma HepG2 cells under intact serum exposure compared with control type BV or CSP type BV, retaining both advantages of CSP and CD46-DAF-CD59. Collectively, these results demonstrated that the utilization of stably expressing Sf9 cells to introduce the protein products of interest, e.g., CRPs into BVs, would be useful strategy to generate BVs with novel functions such as resistance against serum complement attack.

Changes in Fibroblast Growth Factor 23 and Soluble Klotho Levels After Hemodialysis Initiation.

RATIONALE & OBJECTIVE: Patients with chronic kidney failure have markedly elevated fibroblast growth factor 23 (FGF-23) levels and decreased soluble Klotho levels. However, no studies have examined the effects of hemodialysis initiation on the levels of these hormones and other parameters of mineral metabolism. STUDY DESIGN: Prospective single-arm study. SETTING & PARTICIPANTS: 20 individuals with incident kidney failure initiating hemodialysis. EXPOSURE: Initiation of hemodialysis. Dose adjustments of phosphate binders and vitamin D receptor activators and use of calcimimetics, erythropoiesis-stimulating agents, and intravenous iron were prohibited. OUTCOMES: Changes in serum levels of FGF-23, soluble Klotho, and other biochemical parameters of mineral metabolism, measured before and after each hemodialysis session, for a total of 4 sessions over 5 days. ANALYTICAL APPROACH: Repeated-measures analysis of variance. RESULTS: At baseline, participants had 18-fold higher median FGF-23 levels and 1.6-fold lower mean soluble Klotho levels compared with age- and sex-matched healthy individuals. Initiation of hemodialysis led to progressive reductions in serum phosphorus, intact parathyroid hormone, and FGF-23 levels, with dialysis-related fluctuations. No reductions were observed in levels of α1-microglobulin, which has molecular weight comparable to FGF-23. The magnitude of the FGF-23 level reductions was strongly associated with concomitant changes in serum phosphorus levels but not with the changes in intact parathyroid hormone levels. Soluble Klotho levels did not change after the initiation of hemodialysis. LIMITATIONS: Single-arm design, small sample size, short follow-up period. CONCLUSIONS: Initiation of hemodialysis in patients with chronic kidney failure led to progressive reductions in FGF-23 levels in association with reductions in serum phosphorus levels. These results suggest that phosphorus is a strong inducer of FGF-23 production and that regulation of FGF-23 production is a rapid process.

HbA1c and Aortic Calcification Index as Noninvasive Predictors of Pre-Existing Histopathological Damages in Living Donor Kidney Transplantation.

We previously reported that allografts from living donors may have pre-existing histopathological damages, defined as the combination of interstitial fibrosis (ci), tubular atrophy (ct), and arteriolar hyalinosis (ah) scores of ≧1, according to the Banff classification. We examined preoperative characteristics to identify whether the degree of these damages was related to metabolic syndrome-related factors of donors. We conducted a single-center cross-sectional analysis including 183 living kidney donors. Donors were divided into two groups: chronic change (ci + ct ≧ 1 ∩ ah ≧ 1, n = 27) and control (n = 156). Preoperative characteristics, including age, sex, blood pressure, hemoglobin A1c (HbA1c), aortic calcification index (ACI), and psoas muscle index (PMI), were analyzed. Comparing the groups, the baseline estimated glomerular filtration rate was not significantly different; however, we observed a significant difference for ACI (p = 0.009). HbA1c (p = 0.016) and ACI (p = 0.006) were independent risk factors to predict pre-existing histopathological damages, whereas PMI was not. HbA1c correlated with ct scores (p = 0.035), and ACI correlated with ci (p = 0.005), ct (p = 0.021), and ah (p = 0.017). HbA1c and ACI may serve as preoperative markers for identifying pre-existing damages on the kidneys of living donors.

Optimizing Intraoperative Blood Pressure to Improve Outcomes in Living Donor Renal Transplantation.

BACKGROUND: Adequate renal perfusion at the time of unclamping is important because it has been known to affect outcomes in renal transplantation. Nevertheless, the ideal intraoperative systolic arterial pressure (SAP) has not been well defined. METHODS: We performed a retrospective analysis of 106 living donor renal transplants performed at our center from June 2010 to May 2019. We divided the cohort into 2 groups according to our center's goal SAP of ≥150 mm Hg: 57 patients had SAP ≥150 mm Hg and 49 patients had SAP <150 mm Hg. We analyzed pretransplant characteristics, intraoperative measurements, and postoperative laboratory values to validate our center's target SAP at the time of reperfusion. This study strictly complied with the Helsinki Congress and the Istanbul Declaration regarding donor sources. RESULTS: Patients with SAP ≥150 mm Hg had been on dialysis for a significantly shorter duration before transplant compared with those who had SAP <150 mm Hg. In the SAP ≥150 mm Hg group, urinary sodium excretion normalized earlier, and they had a significantly smaller stroke volume variation, higher cardiac output and cardiac index, earlier initial urination, and higher intraoperative urine output. There were no differences in intraoperative volume repletion, central venous pressure, or postoperative estimated glomerular filtration rate. CONCLUSION: Achieving SAP ≥150 mm Hg at the time of reperfusion may be associated with early stabilization of graft function. Nevertheless, our data suggested that recipients with a prolonged dialysis history are less likely to achieve SAP ≥150 mm Hg at the time of unclamping in living donor renal transplantation.

Is the Living Donor Kidney Profile Index Valuable in Japanese Patients?

INTRODUCTION: The Living Kidney Donor Profile Index (LKDPI) was recently proposed in the United States to evaluate living donor quality. Japan has a largely different renal transplant circumstance, such as a high ABO incompatibility rate. The aim of this study was to validate the LKDPI among the Japanese population and adjust the score. METHODS: We performed a retrospective analysis of 133 living donors in renal transplant in our institution. We analyzed the clinical characteristics and outcomes, and created a modified LKDPI score considering the favorable ABO incompatible kidney transplant outcomes in Japan. RESULTS: Median (interquartile range [IQR]) donor age was 59 (51 to 65) and median (IQR) body mass index was 22.9 kg/m2 (20.9 to 25.2). ABO incompatibility rate was 28.5%. Median (IQR) donor estimated glomerular filtration rate (eGFR) (Chronic Kidney Disease Epidemiology Collaboration equation) was 108.7 mL/min/1.73 m2 (99.9 to 115.5). The 1-year graft survival rate was 98.5%, and the 3-year graft survival rate was 97%. The incidence of antibody mediated rejection was 5.2%. The median (IQR) LKDPI score was 30.2 (11.8 to 46.8). This was significantly higher than the previously reported score in the United States, which was 12.8 (-0.8 to 27.2). The modified LKDPI (mLKDPI) score was 23.2 (4.1 to 35.1). LKDPI and mLKDPI did not show a diagnostic value in graft survival; however, LKDPI and mLKDPI showed significant diagnostic value in eGFR at 1 year (area under the curve [AUC]=0.627, P = .017; and AUC=0.673, P = .01). CONCLUSION: Our outcomes had better survival even though with higher ABO incompatibility rate. According to original LKDPI, our donor pool is higher than the general US population. In this study, lower LKDPI tended to be associated with good allograft function, and mLKDPI has better diagnostic value than LKDPI. To compare internationally, an adjusted model for Japan might be necessary based on the outcomes of a large population.

Impact of Very Low-Dose Trimethoprim-Sulfamethoxazole on Serum Creatinine after Renal Transplantation: A Retrospective Study.

BACKGROUND: It is well known that high-dose trimethoprim, through its effect of inhibiting creatinine secretion, increases serum creatinine levels without changes in real glomerular filtration rate. However, there has been no report regarding the effect of very low-dose trimethoprim on serum creatinine levels after renal transplantation. METHODS: We retrospectively investigated 76 renal transplantation recipient outpatients who completed their course of initial prophylaxis at our institution. Twelve patients who experienced events that might affect their serum creatinine levels were excluded. Fifty-one patients who required readministration of trimethoprim-sulfamethoxazole to prevent a possible outbreak of pneumocystis jirovecii pneumonia and 13 patients who did not receive readministration (control) were analyzed. Dosage was 80 mg/400 mg (per tablet), administered as 3 tablets per week for 30.6 ± 13.5 days. This study strictly complied with the Helsinki Congress and the Istanbul. Declaration regarding donor source. RESULTS: All patients completed readministration without adverse events. Serum creatinine increased significantly in the readministration group (1.40 ± 0.64 mg/dL to 1.48 ± 0.70 mg/dL, P < .01) while not in the control group. The higher the initial serum creatinine level, the greater the increase of Δ serum creatinine (R = 0.59, P < .001). Sex, baseline urine protein level, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use, donor type, and time after renal transplantation did not affect Δ serum creatinine. Serum creatinine returned to baseline levels after cessation. CONCLUSIONS: Very low-dose trimethoprim-sulfamethoxazole prophylaxis significantly raised serum creatinine reversibly by 6% after renal transplantation.

Factors related to suboptimal recovery of renal function after living donor nephrectomy: a retrospective study.

BACKGROUND: The renal function of the remaining kidney in living donors recovers up to 60~70% of pre-donation estimated-glomerular filtration rate (eGFR) by compensatory hypertrophy. However, the degree of this hypertrophy varies from donor to donor and the factors related to it are scarcely known. METHODS: We analyzed 103 living renal transplantations in our institution and divided them into two groups: compensatory hypertrophy group [optimal group, 1-year eGFR ≥60% of pre-donation, n = 63] and suboptimal compensatory hypertrophy group (suboptimal group, 1-year eGFR < 60% of pre-donation, n = 40). We retrospectively analyzed the factors related to suboptimal compensatory hypertrophy. RESULTS: Baseline eGFRs were the same in the two groups (optimal versus suboptimal: 82.0 ± 13.1 ml/min/1.73m2 versus 83.5 ± 14.8 ml/min/1.73m2, p = 0.588). Donor age (optimal versus suboptimal: 56.0 ± 10.4 years old versus 60.7 ± 8.7 years old, p = 0.018) and uric acid (optimal versus suboptimal: 4.8 ± 1.2 mg/dl versus 5.5 ± 1.3 mg/dl, p = 0.007) were significantly higher in the suboptimal group. The rate of pathological chronicity finding on 1-h biopsy (ah≧1 ∩ ct + ci≧1) was much higher in the suboptimal group (optimal versus suboptimal: 6.4% versus 25.0%, p = 0.007). After the multivariate analysis, the pathological chronicity finding [odds ratio (OR): 4.8, 95% confidence interval (CI): 1.3-17.8, p = 0.021] and uric acid (per 1.0 mg/dl, OR: 1.5, 95% CI: 1.1-2.2, p = 0.022) were found to be independent risk factors for suboptimal compensatory hypertrophy. CONCLUSION: Chronicity findings on baseline biopsy and higher uric acid were associated with insufficient recovery of the post-donated renal function.

Protection of Baculovirus Vectors Expressing Complement Regulatory Proteins against Serum Complement Attack.

Baculovirus vectors (BVs) enable safe and efficient gene delivery to mammalian cells and are useful in a wide range of applications, including gene therapy and in vivo analysis of gene functions. We previously developed BVs expressing malaria sporozoite surface proteins for targeting liver cells or hepatocytes. However, BVs are known to be very vulnerable to complement attack and efforts to overcome their inactivation based on complement are important. In this study, BVs expressing complement regulatory proteins (CRPs) on the surfaces of virions were developed to inhibit complement reactions. Decay accelerating factor (DAF; CD55)-type BVs exhibited significantly higher complement resistance than control BVs without any CRPs in HepG2 cells transduction, although the transduction efficacy of DAF-type BV was low. In contrast, CD46-DAF-CD59 fusion type BVs showed significantly higher transduction efficacy and complement resistance than both control and DAF-type BVs. DAF-type and CD46-DAF-CD59 type BVs repressed formation of the membrane attack complex, a terminal product of complement reaction cascades, induced by BVs. These results suggest that the CD46-DAF-CD59 fusion construct confers complement protection ability superior to that of the DAF construct in gene delivery under complement active serum.

Malaria sporozoite protein expression enhances baculovirus-mediated gene transfer to hepatocytes.

BACKGROUND: Baculovirus vector (BV) is able to transduce foreign genes into mammalian cells efficiently and safely by incorporating a mammalian promoter. In the present study, we tailored the surface proteins expressed by malaria sporozoites to enhance hepatocyte transduction. Sporozoites infect hepatocytes within minutes of initial entry into the blood circulation. Infectivity and hepatocyte-specific selectivity are mediated by the interplay between hepatocytes and sporozoite surface proteins. The circumsporozoite protein (CSP) and the thrombospondin-related anonymous protein (TRAP) bind to the heparan sulfate proteoglycan on the hepatocyte surface and contribute to sporozoite infection and hepatocyte selectivity. METHODS: BVs displaying an ectodomain consisting of three different CSP variants (full-length, N-terminal and C-terminal) or TRAP on the virus envelope were constructed, and the resulting in vitro hepatocyte transduction efficiency was evaluated. RESULTS: We demonstrated improved hepatocyte transduction efficiency in BVs expressing CSP or TRAP ectodomains compared to BVs without malaria surface proteins. In addition, gene transduction efficiencies for BVs displaying CSP or TRAP are higher than those expressing the preS1 antigen of the hepatitis B virus. CONCLUSIONS: BVs expressing CSP or TRAP in the ectodomain could represent a promising hepatocyte-specific gene delivery methodology. Copyright © 2016 John Wiley & Sons, Ltd.

Use of long-term catheters in Japan: implant procedures, maintenance methods, and future aspects.

The Japanese society for dialysis therapy (JSDT) launched the second edition of 'Guidelines for Vascular Access Construction and Repair for Chronic Hemodialysis' concerning the vascular access in 2011. The indication of long-term catheters is strictly limited in these guidelines because of possible high risks of infections including sepsis and obstruction of catheters with thrombus. In Japan, the long-term catheters would be needed more frequently to prepare the very rapid demographic change within a decade, under the condition that the material and structure of these catheters will be more resistant against the complications.