Subnanosecond phase transition dynamics in laser-shocked iron.

Iron is one of the most studied chemical elements due to its sociotechnological and planetary importance; hence, understanding its structural transition dynamics is of vital interest. By combining a short pulse optical laser and an ultrashort free electron laser pulse, we have observed the subnanosecond structural dynamics of iron from high-quality x-ray diffraction data measured at 50-ps intervals up to 2500 ps. We unequivocally identify a three-wave structure during the initial compression and a two-wave structure during the decaying shock, involving all of the known structural types of iron (α-, γ-, and ε-phase). In the final stage, negative lattice pressures are generated by the propagation of rarefaction waves, leading to the formation of expanded phases and the recovery of γ-phase. Our observations demonstrate the unique capability of measuring the atomistic evolution during the entire lattice compression and release processes at unprecedented time and strain rate.

Adapting re-usable elastomeric respirators to utilise anaesthesia circuit filters using a 3D-printed adaptor - a potential alternative to address N95 shortages during the COVID-19 pandemic.

The COVID-19 pandemic has increased the demand for disposable N95 respirators. Re-usable elastomeric respirators may provide a suitable alternative. Proprietary elastomeric respirator filters may become depleted as demand increases. An alternative may be the virus/bacterial filters used in anaesthesia circuits, if they can be adequately fitted onto the elastomeric respirators. In addition, many re-usable elastomeric respirators do not filter exhaled breaths. If used for sterile procedures, this would also require modification. We designed a 3D-printed adaptor that permits elastomeric respirators to interface with anaesthesia circuit filters and created a simple modification to divert exhaled breaths through the filter. We conducted a feasibility study evaluating the performance of our modified elastomeric respirators. A convenience sample of eight volunteers was recruited. Quantitative fit testing, respiratory rate and end-tidal carbon dioxide were recorded during fit testing exercises and after 1 h of wear. All eight volunteers obtained excellent quantitative fit testing throughout the trial. The mean (SD) end-tidal carbon dioxide was 4.5 (0.5) kPa and 4.6 (0.4) kPa at baseline and after 1 h of wear (p = 0.148). The mean (SD) respiratory rate was 17 (4) breaths.min-1 and 17 (3) breaths.min-1 at baseline and after 1 h of wear (p = 0.435). Four out of eight subjects self-reported discomfort; two reported facial pressure, one reported exhalation resistance and one reported transient dizziness on exertion. Re-usable elastomeric respirators to utilise anaesthesia circuit filters through a 3D-printed adaptor may be a potential alternative to disposable N95 respirators during the COVID-19 pandemic.

Factors Associated With Waiting Time to Deceased Donor Kidney Transplantation in Transplant Candidates.

Although a nationwide activation system has been developed to increase deceased donor kidney transplantation (DDKT), there is still enormous discrepancy between transplant need and deceased donor supply in Korea, and therefore waiting time to DDKT is still long. We need to determine the current status of waiting time and the risk factors for long waiting time. We retrospectively analyzed the medical records of the patients on the wait list for DDKT at the Seoul National University Hospital from 2000 to 2017. Among 2,211 wait-listed patients, 606 (27.5%) received DDKT and mean waiting time to DDKT was 45 months. Among them, blood type A was most prevalent (35.6%) and type AB was the least (14.0%). Panel-reactive assay (PRA) was positive in 59 (11.0%) in the first transplant group and 25 (35.0%) in retransplant group. Waiting time in PRA-positive recipients was 63 and 66 months in the first transplant group and retransplant group, respectively. However, waiting time for patients with negative PRA was 42.8 months. Waiting time was shorter in blood type AB (39 months) than other types (46 months). Waiting time was the shortest in children and adolescents. Among patients who were still on the wait list, retransplantation candidates, especially with PRA higher than 50%, had longer waiting time than first transplant candidates. In conclusion, non-AB blood type, positive PRA, and adult age were significantly associated with long waiting time. Therefore, it is necessary to establish a management strategy such as tailored desensitization for highly sensitized patients on the wait list to reduce their waiting time.

VDJ Gene Usage of B Cell Receptors in Peripheral Blood of ABO-incompatible Kidney Transplantation Patients.

INTRODUCTION: B cell subtypes and immunoglobulin variable (V), diversity (D), joining (J) gene segment usage of B cell receptors in ABO-incompatible (ABOi) kidney transplantation (KT) in comparison to ABO-compatible KT have not been studied. The aims of this study were to analyze the VDJ gene segment usages of B cell receptors in peripheral blood of ABOi KT recipients. METHODS: Eighteen ABOi KT patients with accommodation (ABOiA), 10 ABO-compatible stable KT patients (ABOcS), and 10 ABOi KT patients with biopsy-proven acute antibody-mediated rejection (ABOiR) at day 10 after transplantation were selected. Complete transcriptomes of their peripheral blood samples were sequenced and analyzed through RNA sequencing. RESULTS: By family, immunoglobulin heavy chain variable 3 (IGHV3), immunoglobulin light kappa chain variable 1 (IGKV1), immunoglobulin light lambda chain variable 2 (IGLV2), and immunoglobulin light lambda chain joining 3 (IGLJ3) gene segments were most frequently used in all groups, and their usage was not statistically different among the three groups except for IGHV3 and IGKV1. IGKV1 was more frequently used in the ABOiA group than in the ABOcS group. According to individual gene segments, IGHV3-7, IGHV3-15, IGHV4-59, IGKV3-11, IGLV1-44, IGLV2-14, IGLV4-69, and IGLV7-46 were more frequently used in the ABOcS group than other groups, and IGKV3-7 was more frequently used in the ABOiR group than other groups. IGLV5-52 and IGLV7-43 were more frequently used in the ABOiA group than in ABOcS group. CONCLUSIONS: Our findings suggest that RNA sequencing transcriptomic analyses of peripheral blood can provide information on the VDJ gene usage of B cell receptors and the mechanisms of accommodation and immune reaction in ABOi KT.

Comparison of body surface area-based and weight-based dosing format for oral prednisolone administration in small and large-breed dogs.

This study compared the pharmacokinetics of Prednisolone (PDS) in small- and large breed dogs with a dosing format based on body surface area (BSA) or body weight (BW). The maximum concentration and area under the curve in large-breed dogs orally administered 2 mg/kg PDS were significantly greater than those in small-breed dogs given 2 mg/kg and in large-breed dogs given 40 mg/m2. The higher blood concentrations that result from BW-based dosing of oral PDS in large-breed dogs can be more than required for effect. Meanwhile, BSA dosing at 40 mg/m may be suboptimal. These findings confirm important differences between standard PDS dosing schemes in dogs while highlighting the need to further optimize PDS dosing in large-breed dogs.

Renal Allograft Function Is a Risk Factor of Left Ventricular Remodeling After Kidney Transplantation.

BACKGROUND: Cardiovascular disease is the leading cause of morbidity and mortality in kidney transplantation (KT) patients. The prevalence of left ventricular hypertrophy increases with the progression of renal insufficiency. METHODS: We investigated the association between the progression of renal insufficiency and left ventricular hypertrophy after KT. We reviewed KT patients at Seoul National University Hospital from January 1973 to December 2009. The creatinine elevation ratio (CER, the percentage change in the creatinine level from 1 month to 5 years after transplant) was calculated as follows: (creatinine level at 5 years minus creatinine level at 1 month)/creatinine level at 1 month × 100. RESULTS: The study population was classified into a high-CER group (CER ≥25%) and low-CER group (CER <25%). Mean left ventricular mass index (LVMI) values were 135.7 and 134.7 g/m2 before KT and 101.7 and 123.7 g/m2 at 5 years after KT in the low-CER and high-CER groups, respectively. The LVMI before or 1 year after KT was not different between the 2 groups, but the LVMI at 5 years post-transplant was higher in the high-CER group than in the low-CER group. The LVMI increased after its initial decrease in the high-CER group, whereas its reduction was maintained in the low-CER group during the 5 years after KT (P = .009, repeated-measures analysis of variance). CONCLUSIONS: These data suggest that deterioration of renal allograft function is associated with left ventricular remodeling after KT.

Pharmacokinetics and Acid Suppressant Efficacy of Esomeprazole after Intravenous, Oral, and Subcutaneous Administration to Healthy Beagle Dogs.

BACKGROUND: Esomeprazole is an S-enantiomer of omeprazole that has favorable pharmacokinetics and efficacious acid suppressant properties in humans. However, the pharmacokinetics and effects on intragastric pH of esomeprazole in dogs have not been reported. OBJECTIVE: To determine the pharmacokinetics of esomeprazole administered via various routes (PK study) and to investigate the effect of esomeprazole on intragastric pH with a Bravo pH monitoring system (PD study). ANIMALS: Seven adult male Beagle dogs and 5 adult male Beagle dogs were used for PK and PD study, respectively. METHODS: Both studies used an open, randomized, and crossover design. In the PK study, 7 dogs received intravenous (IV), subcutaneous (SC), and oral doses (PO) of esomeprazole (1 mg/kg). Each treatment period was separated by a washout period of at least 10 days. Esomeprazole plasma concentrations were measured by HPLC/MS/MS. In the efficacy study, intragastric pH was recorded without medication (baseline pH) and following IV, SC, and PO esomeprazole dosing regimens (1 mg/kg) in 5 dogs. RESULTS: The bioavailability of esomeprazole administered as PO enteric-coated granules and as SC injections was 71.4 and 106%, respectively. The half-life was approximately 1 hour. Mean ± SD percent time intragastric pH was ≥3 and ≥4 was 58.9 ± 21.1% and 40.9 ± 17.3% for IV group, 75.8 ± 16.4% and 62.7 ± 17.7% for SC group, 88.2 ± 8.9% and 82.5 ± 7.7% for PO group, and 12.5 ± 3.6% and 3.7 ± 1.8% for baseline. The mean percent time with intragastric pH was ≥3 or ≥4 was significantly increased regardless of the dosing route (P < .05). CONCLUSION: The PK parameters for PO and SC esomeprazole administration were favorable, and esomeprazole significantly increased intragastric pH after IV, PO, and SC administration. IV and SC administration of esomeprazole might be useful when PO administration is not possible. No significant adverse effects were observed.

Increasing Use of the Expanded Criteria for Living Kidney Donation and Good Outcomes of Living Kidney Donors in Korea.

BACKGROUND: Donor shortage for kidney transplantation may increase the number of expanded-criteria living donors (ECLDs). We investigated recent trends for ECLD use and the long-term outcomes of living kidney donors. METHODS: We retrospectively analyzed medical records of 1,144 living kidney donors who donated at the Seoul National University Hospital from 1993 to 2015. The expanded criteria for living donation allow the following: age ≥60 years, body mass index >30 kg/m2, history of hypertension, estimated glomerular filtration rate <80 mL/min, proteinuria or microscopic hematuria, and fasting glucose >100 mg/dL. RESULTS: The mean age of donors was 40.7 ± 10.8 years, and there were 600 women (52.4%). A total of 466 donors (40.7%) met the ECLD criteria, and the proportion of ECLDs increased over time. Only 5 donors died after donation over a median follow-up of 7 years. No donor developed end-stage renal disease (ESRD). A urine protein-creatinine ratio ≥0.3 g/gCr was found in 14 patients and was more common in the ECLDs than in the standard-criteria living donors. The follow-up loss rate of donors was 59.3% at 5 years. CONCLUSIONS: Both mortality and ESRD were very rare in carefully selected living kidney donors. However, living donors should be followed more carefully, because the follow-up loss rate was very high and ECLDs are increasingly used.

Pharmacokinetic study of meropenem in healthy beagle dogs receiving intermittent hemodialysis.

Meropenem, a second carbapenem antimicrobial agent with a broad spectrum of activity, is used to treat sepsis and resistant-bacterial infections in veterinary medicine. The objective of this study was to identify the pharmacokinetics of meropenem in dogs receiving intermittent hemodialysis (IHD) and to determine the proper dosing in renal failure patients receiving IHD. Five healthy beagle dogs were given a single i.v. dose of 24 mg/kg of meropenem and received IHD. The blood flow rate, dialysate flow, and ultrafiltration rate were maintained at 40 mL/min, 300 mL/min, and 40 mL/h, respectively. Blood samples were collected for 24 h from the jugular vein and from the extracorporeal arterial and venous line. Urine samples and dialysate were also collected. The concentrations of meropenem were assayed using HPLC/MS/MS determination. The peak plasma concentration was 116 ± 37 µg/mL at 15 min. The systemic clearance was 347 ± 117 mL/h/kg, and the steady-state volume of distribution was 223 ± 67 mL/kg. Dialysis clearance was 71.1 ± 34.3 mL/h/kg, and the extraction ratio by hemodialysis was 0.455 ± 0.150. The half-life (T1/2 ) in dogs with IHD decreased compared with those without IHD, and the reduction in T1/2 was greater in renal failure patients than in normal patients. Sixty-nine percent and 21% of the administered drug were recovered by urine and dialysate in the unchanged form, respectively. In conclusion, additional dosing of 24 mg/kg of meropenem after dialysis could be necessary according to the residual renal function of the patient based on the simulated data.

Health-Related Quality of Life of Kidney Transplantation Patients: Results from the KoreaN Cohort Study for Outcome in Patients With Kidney Transplantation (KNOW-KT) Study.

BACKGROUND: As patient and graft survival rates have been improving after kidney transplantation, health-related quality of life (HR-QOL) has become an important indicator of effective treatment. This study aimed to evaluate changes in HR-QOL after kidney transplantation. MATERIALS AND METHODS: The KoreaN cohort study for Outcome in patients With Kidney Transplantation (KNOW-KT) is a multicenter, observational, 9-year, cohort study. The HR-QOL of patients in the KNOW-KT study was assessed before transplantation and 2 years after transplantation using the Kidney Disease Quality of Life Short Form (KDQOL-SF) including chronic kidney disease targeted area and the Medical Outcome Study 36-item Short Form Health Survey (SF-36). Multivariate linear regression was used to identify significant factors associated with follow-up QOL scores. RESULTS: A total of 175 patients from 8 centers were analyzed. All QOL scores including the total QOL score, chronic kidney disease targeted score, and SF-36 at the 2-year follow-up were significantly increased compared to baseline values. Both physical and mental scale scores were improved after transplantation. CONCLUSION: The QOL scores for both the mental and physical scales were improved at 2 years after kidney transplantation. High glomerular filtration rate at 2 years, high baseline QOL score, and low body mass index were associated with good follow-up QOL scores. Kidney transplantation for an Asian population with end-stage renal disease can result in better QOL as well as better patient and graft survival.

The pharmacokinetics of the ß2-adrenoceptor agonist, tulobuterol, in Beagle dogs following transdermal and intravenous administration.

Tulobuterol is a ß2-adrenergic agonist that was the first bronchodilator approved as a transdermal patch for humans. Previous studies have examined the pharmacokinetics of tulobuterol in humans but not in the veterinary species. In this study, the pharmacokinetics of tulobuterol was examined in healthy Beagle dogs after transdermal and intravenous administration. The Cmax was 2.09 ng/mL at 16.0 h for a 0.2 mg/kg patch and 4.85 ng/mL at 13.6 h for a 0.4 mg/kg patch. The effective blood level in humans is 1-3 ng/mL, a concentration achieved using the 0.2 mg/kg patch in dogs. In conclusion, application of a 0.2 mg/kg tulobuterol patch to healthy dogs led to an apparently effective blood concentration for 24 h.

Charge-ordering cascade with spin-orbit Mott dimer states in metallic iridium ditelluride.

Spin-orbit coupling results in technologically-crucial phenomena underlying magnetic devices like magnetic memories and energy-efficient motors. In heavy element materials, the strength of spin-orbit coupling becomes large to affect the overall electronic nature and induces novel states such as topological insulators and spin-orbit-integrated Mott states. Here we report an unprecedented charge-ordering cascade in IrTe2 without the loss of metallicity, which involves localized spin-orbit Mott states with diamagnetic Ir(4+)-Ir(4+) dimers. The cascade in cooling, uncompensated in heating, consists of first order-type consecutive transitions from a pure Ir(3+) phase to Ir(3+)-Ir(4+) charge-ordered phases, which originate from Ir 5d to Te 5p charge transfer involving anionic polymeric bond breaking. Considering that the system exhibits superconductivity with suppression of the charge order by doping, analogously to cuprates, these results provide a new electronic paradigm of localized charge-ordered states interacting with itinerant electrons through large spin-orbit coupling.

Pilot study on interfractional and intrafractional movements using surface infrared markers and EPID for patients with rectal cancer treated in the prone position.

OBJECTIVE: To evaluate interfractional and intrafractional movement of patients with rectal cancer during radiotherapy with electronic portal imaging device (EPID) and surface infrared (IR) markers. METHODS: 20 patients undergoing radiotherapy for rectal cancer with body mass index ranging from 18.5 to 30 were enrolled. Patients were placed in the prone position on a couch with a leg pillow. Three IR markers were put on the surface of each patient and traced by two stereo cameras during radiotherapy on a twice-weekly basis. Interfractional isocentre movement was obtained with EPID images on a weekly basis. Movement of the IR markers was analysed in correlation with the isocentre movement obtained from the EPID images. RESULTS: The maximum right-to-left (R-L) movement of the laterally located markers in the horizontal isocentre plane was correlated with isocentre translocation with statistical significance (p = 0.018 and 0.015, respectively). Movement of the surface markers was cyclical. For centrally located markers, the 95% confidence intervals for the average amplitude in the R-L, cranial-to-caudal (C-C) and anterior-to-posterior (A-P) directions were 0.86, 2.25 and 3.48 mm, respectively. In 10 patients, intrafractional movement exceeding 5 mm in at least one direction was observed. Time-dependent systematic movement of surface markers during treatment, which consisted of continuous movement towards the cranial direction and a sail back motion in the A-P direction, was also observed. CONCLUSION: Intrafractional movement of surface markers has both cyclic components and time-dependent systematic components. Marker deviations exceeding 5 mm were mainly seen in the A-P direction. Pre- or post-treatment EPID images may not provide adequate information regarding intrafractional movement because of systematic movement in the A-P direction during radiotherapy. ADVANCES IN KNOWLEDGE: This work uncovered a sail back motion of patients in the A-P direction during radiotherapy. Pre- or post-treatment EPID images may not provide accurate positioning of patients in the A-P direction because of this time-dependent intrafractional motion.

Protective effect of peptide GV1001 against renal ischemia-reperfusion injury in mice.

BACKGROUND: Ischemia reperfusion injury (IRI) is a common complication after kidney transplantation. Peptide GV1001 is a peptide vaccine representing a 16-amino acid human telomerase reverse transcriptase sequence, which has been reported to possess potential antineoplastic and anti-inflammatory activity. This study aimed to investigate the potential effects of peptide GV1001 on renal IRI. METHODS: Peptide GV1001 was subcutaneously administered to C57BL6/J mice 30 minutes before and 12 hours after bilateral IRI. Sham operation and phosphate-buffered saline (PBS) injection were used as controls. Blood and renal tissues were harvested at 1 day after IRI. RESULTS: Peptide GV1001 treatment significantly attenuated renal functional deterioration after IRI (peptide GV1001 group vs PBS group; blood urea nitrogen, P < .05; creatinine, P < .05). Peptide GV1001 treatment also attenuated renal tissue injury (tubular injury score; the peptide GV1001 group vs PBS group; P < .001). Renal apoptosis was also lower in the peptide GV1001 group. Immunohistochemical studies showed that IRI increased perirenal infiltration of both neutrophils and macrophages, and that peptide GV1001 significantly attenuated this process. Expression of interleukin-6 and monocyte chemotactic protein-1 was significantly reduced by peptide GV1001 treatment. CONCLUSIONS: Peptide GV1001 ameliorates acute renal IRI by reducing inflammation and apoptosis; therefore, it is promising as a potential therapeutic agent for renal IRI. The mechanisms of protection should be explored in further studies.

Efficacy and safety of hepatitis A vaccination in kidney transplant recipients.

BACKGROUND: In recent years, symptomatic hepatitis A virus (HAV) infection has been reported with increasing frequency in Korea. Therefore, HAV vaccination should be considered in kidney transplant recipients (KTRs). The study investigated the efficacy and safety of HAV vaccination in KTRs under modern triple immunosuppressive agents. METHODS: We evaluated the seroprevalence of anti-HAV immunoglobulin-G (IgG) in KTRs who had visited the Seoul National University Hospital from March 2011 to August 2012. Seronegative patients were immunized with 2 doses of HAV vaccine at a 6-month interval. Seroconversion of anti-HAV IgG was determined 1 month after the second vaccine dose, and adverse effects were monitored after each vaccination. RESULTS: Among a total 416 KTRs who were screened, 338 (81.2%) patients were seropositive for anti-HAV IgG. However, among patients who were under 40 years of age, only 31.8% were seropositive. Fifty-two seronegative recipients (mean age 34.1 years, 71.2% male) had received 2 doses of vaccine, and only 14 of these patients (26.9%) showed seroconversion. Vaccine responders had lower serum creatinine (1.19 ± 0.24 vs. 1.45 ± 0.49 mg/dL, P = 0.013), higher plasma hemoglobin levels (14.4 ± 1.9 vs. 12.8 ± 1.8 g/dL, P = 0.006), and had lower tacrolimus use than cyclosporine use (57.1% vs. 84.2%, P = 0.040) compared with non-responders. Responders had a tendency of taking lower dose of prednisolone (3.5 ± 1.6 vs. 4.3 ± 1.2 mg/day, P = 0.076), and having fewer infection events (14.3 vs. 40.5%, P = 0.076). Multivariate analysis indicated that higher hemoglobin levels and lower serum creatinine levels were significant prognostic factors for seroconversion. Overall, the vaccine was well tolerated in all patients. CONCLUSION: HAV IgG screening is necessary for KTRs, especially young recipients. HAV vaccination was safe in KTRs; however, poor response to HAV vaccination makes it important to identify seronegative patients as early as possible and vaccinate them before end-stage renal disease occurs.

Initial report of the Korean Organ Transplant Registry: the first report of national kidney transplantation data.

PURPOSE: A national organ transplant registry is an indispensable organizational requirement for patient care, research, and planning. Even though the Korean Network for Organ Sharing (KONOS) has established a database for a waiting list, organ allocation, and incidence of organ transplantation since 2000, an integrated registry including post-transplantation data is needed for better understanding of organ transplantation. Recently, the Korean Society for Transplantation (KST) and the Korean Center for Disease Control (KCDC) designed a web-based organ transplant registry, named the Korean Organ Transplant Registry (KOTRY). As an initial project of KOTRY, we retrospectively analyzed kidney transplantations (KTs) performed in 2009 and 2010. METHODS: A total of 2292 KTs (91.9%) from 46 hospitals (80.7%) were collected and analyzed. Ninety-five elements related to KT were selected and analyzed. RESULTS: Proportions of male recipients and retransplantations were 58.4% and 7.1%, respectively. Even though glomerulonephritis was the most common cause of end-stage renal disease (ESRD) (28.4%), the number of diabetic nephropathy cases was increasing. The living donor (LD) to deceased donor (DD) ratio was 1.69:1. Because of a serious organ shortage in Korea, DD kidneys with a low initial estimated glomerular filtration rate (eGFR) of <45 mL/min/1.73 m(2) (21.2%) and expanded criteria donors (ECDs; 18.3%) are frequently used. Other noticeable findings are the increasing number of wife donors and ABO-incompatible (ABOi) transplants for O(+) recipients. CONCLUSIONS: The epidemiological profile of transplantation is different from country to country. The number of organ transplantations in East Asian countries is rapidly growing, however, there are few epidemiological data about this region in the literature. With the establishment of KOTRY, it was possible to present the first nationwide epidemiological data of Korean KTs.

Utility of QuantiFERON-TB assay for prediction of tuberculosis development in kidney transplant patients in an intermediate-tuberculosis-burden country: lack of evidence for enhanced prediction for short-term tuberculosis development.

INTRODUCTION: Although a latent tuberculosis (TB) infection is a risk factor for active TB, the diagnosis of latent TB infection is difficult in end-stage renal disease patients. PATIENTS AND METHODS: We retrospectively compared the results of the QuantiFERON-TB (QFT) test and the tuberculin skin test in patients on the waiting list for kidney transplantation (KT), and investigated whether the QFT test can predict TB development in KT recipients in an intermediate-TB-burden country. RESULTS: The incidence of post-KT TB was 283 cases/100,000 patient-years among 1274 KT recipients at the Seoul National University Hospital. The overall standardized incidence ratio of TB was 4.358 compared with the general population. A past history of TB infection, smoking history, myocardial infarction after KT, and pneumocystis infection were significant predictors of subsequent TB development (adjusted odds ratios were 3.618, 2.959, 9.993, and 5.708, respectively). Among the 129 recipients who had the QFT test, 42 patients (32.5%) had positive a QFT. At a median follow-up of 8.4 ± 6.8 months, 1 patient with positive QFT results developed TB after KT, and 1 of the 87 patients with negative QFT results developed TB after KT. In both of these 2 cases, active TB developed despite isoniazid prophylaxis. Among 272 patients on the waiting list for KT, the tuberculin skin test and QFT were positive in 22.8% and 35.3%, respectively. The degree of agreement between the 2 tests was poor (κ = 0.352). CONCLUSIONS: The QFT test did not predict subsequent short-term TB development. Furthermore, a long-term and larger-scale study is needed to confirm our results.

Impact of vitamin D, bisphosphonate, and combination therapy on bone mineral density in kidney transplant patients.

BACKGROUND: Osteoporosis can develop and become aggravated in kidney transplant patients; however, the best preventive options for post-transplantation osteoporosis remain controversial. METHODS: We retrospectively analyzed cohort of 182 renal transplant recipients of mean age 46.7 ± 12.1 years including 47.3% women. Seventy-three patients received neither vitamin D nor bisphosphonate after transplantation (group 1). The other patients were classified into the following 3 groups: calcium plus vitamin D (group 2; n = 40); bisphosphonate (group 3; n = 18); and both regimens (group 4; n = 51). Bone mineral density (BMD) was evaluated by dual-energy X-ray absorptiometry at baseline and at 1 year after transplantation. RESULTS: At 1 year after transplantation, T-scores of the femoral neck and entire femur were significantly decreased in group 1 (-0.23 ± 0.65 [P = .004] and -0.21 ± 0.74 [P = .018], respectively), whereas the lumbar spine was significantly increased in group 4 (0.27 ± 0.79; P = .020). Post hoc analysis demonstrated that the delta T-score was significantly lower in group 1 than in group 4 (P = .009, 0.035, and 0.031 for lumbar spine, femoral neck, and entire femur, respectively). In a multivariate analysis adjusted by age, sex, body mass index, dialysis duration, diabetes, calcineurin inhibitors, estimated glomerular filtration rate, and persistent hyperparathyroidism, both group 2 and group 4 showed protective effects on BMD reduction (odds ratio [OR], 0.165; 95% confidence interval [CI] 0.032-0.845 [P = .031]; and OR, 0.169; 95% CI, 0.045-0.626 [P = .008]; respectively). However, group 3 did not show a protective effect (OR, 0.777; 95% CI, 0.198-3.054; P = .718), because their incidence of persistent hyperparathyroidism after transplantation was significantly higher (50.0%) than the other groups (P < .001). The incidence of bone fractures did not differ among the groups. CONCLUSIONS: Combination therapy with vitamin D and bisphosphonate was the most effective regimen to improve BMD among kidney recipients.

Prevalence of abnormal in vitro closure time using the Platelet Function Analyzer-100 in chronic kidney disease patients and analysis of associated factors.

AIM: Platelet Function Analyzer- 100 evaluates platelet function by determining time to occlusion of an aperture in a membrane coated with collagen and epinephrine (CEPI) or collagen and ADP (CADP) during the flow of citrated whole blood. We sought to determine prevalence of abnormal in vitro closure time (CT) in chronic kidney disease (CKD) patients and to analyze associated factors. MATERIALS AND METHODS: CEPI-CT (normal, 82 - 182 sec in Korean), CADP-CT (normal, 62 - 109 sec), CBC, serum creatinine (Cr) and blood urea nitrogen (BUN) were measured in CKD patients, 30 with Stage I, 36 with Stage II, 30 with Stage III, 56 with Stage IV, 283 with Stage V (79 with pre-dialysis Stage V, 130 on chronic hemodialysis (CHD), and 74 on chronic peritoneal dialysis (CPD)). Estimated glomerular filtration rate (eGFR) was calculated with a MDRD equation. RESULTS: Abnormal CEPI-CT and CADP-CT occurred in < 15% of Stage I - III, 20% of Stage IV, and 41% and 54%, respectively, of Stage V patients. There were no differences in prevalence of abnormal CEPI-CT and CADP-CT among predialysis Stage V, CHD and CPD patients. CEPI-CT and CADP-CT were correlated with BUN, Cr and platelet counts in predialysis patients, and with platelet counts in dialysis patients, and CEPI-CT was correlated with BUN, Cr in CPD patients. Neither, however, was correlated with age, gender, hemoglobin or hematocrit. CONCLUSION: Prevalence of abnormal in vitro CT increases as stage worsens in CKD patients. In vitro CT is correlated with BUN, Cr and platelet counts in predialysis and total CKD patients.

Higher serum beta2-microglobulin levels are associated with better survival in chronic hemodialysis patients: a reverse epidemiology.

AIMS: beta2-Microglobulin (beta2-M) has been considered a surrogate marker of putative mid-molecular weight (MW) uremic toxins, compounds difficult to dialyze by low-flux dialysis membranes. This study was performed to evaluate the relationship between serum beta2-M and survival of chronic hemodialysis (CHD) patients and the association of beta2-M levels and factors associated with mortality. METHODS: Part I of this study is a retrospective cohort evaluation that determined the relationship between beta2-M and mortality, and Part II is a cross-sectional study that evaluated the relationship between beta2-M and factors associated with mortality. Laboratory parameters, including beta2-M, albumin, prealbumin, creatinine, blood urea nitrogen (BUN), high-sensitivity C-reactive protein (hs-CRP), lipid battery, KT/V, and normalized protein nitrogen appearance (nPNA), were reviewed in Part I and measured in Part II. Clinical and demographic data, including age, sex, duration of hemodialysis, presence of cardiovascular disease, and presence of diabetes mellitus, were also recorded. RESULTS: Part I: During the follow-up period of 5 years, there were 95 all-cause deaths among the 289 patients. Comparison of survivors and non-survivors indicated that serum beta2-M was higher in survivors (36.8 ± 12.3 vs. 32.6 ± 13.2 µg/ml, p = 0.009). Kaplan-Meier analysis indicated that all-cause mortality in the lower beta2-M group was significantly higher compared to the higher beta2-M group (p < 0.0001). Multivariate Cox regression analyses indicated elevated beta2-M levels were significantly associated with lower mortality rate (relative risk: 0.608; 95% CI: 0.37 to 0.99; p = 0.046). Part II: The mean serum beta2-M concentration was 37.1 ± 14.4 µg/ml. Univariate analysis indicated that beta2-M was positively correlated with nPNA, duration of HD, BMI, and the concentrations of creatinine, albumin, BUN, and hs-CRP, but was negatively correlated with HDL-C concentration. Multiple regression analysis indicated that levels of nPNA (p < 0.001), duration of hemodialysis (p < 0.001), creatinine (p < 0.001), albumin (p = 0.006), BUN (p = 0.011), and HDL-C (p = 0.038) were independently associated with serum beta2-M concentration. CONCLUSION: Our results showed that higher serum beta2-M levels are associated with better survival in CHD patients and that nutritional status might be an independent predictor of serum beta2-M concentration in these patients.