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.

Coupled magnetic cycloids in multiferroic TbMnO3 and Eu3/4Y1/4MnO3.

Based on the detailed Mn L(2,3)-edge x-ray resonant scattering results, we report a new complexity in the magnetic order of multiferroic orthomangnites, which has been considered as the simple A-type cycloid order inducing ferroelectricity. The Dzyaloshinskii-Moriya interaction involved in the orthorhombic distortion brings on F-type canting from the A type, and the ordering type becomes the off-phase synchronized bc cycloid in TbMnO(3) or the tilted antiphase ab cycloid in Eu(3/4)Y(1/4)MnO(3). The F-type canting is responsible for the magnetic field-driven multiferroicity to weak ferromagnetism transition.

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.

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.

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.

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.

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.

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.

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.

Arch type pathologic suprapatellar plica.

The authors encountered a case of arch type pathologic suprapatellar plica that was excised using an arthroscopic technique. It is reported with a review of the literature.

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.

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.

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.

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.

Spin-lattice order in frustrated ZnCr2O4.

Using synchrotron x-ray and neutron diffraction, we disentangle spin-lattice order in highly frustrated ZnCr2O4 where magnetic chromium ions occupy the vertices of regular tetrahedra. Upon cooling below 12.5 K the quandary of antialigning spins surrounding the triangular faces of tetrahedra is resolved by establishing weak interactions on each triangle through an intricate lattice distortion. However, the resulting spin order is not simply a Néel state on strong bonds, but rather a complex coplanar spin structure, indicating that antisymmetric and/or further neighbor exchange interactions also play a role as ZnCr2O4 resolves conflicting magnetic interactions.

Non-resonant and resonant x-ray scattering studies on multiferroic TbMn2O5.

Comprehensive x-ray scattering studies, including resonant scattering at Mn L, Tb L, and M edges, were performed on single crystals of TbMn2O5 for crystallographic data to elucidate the nature of its commensurate and incommensurate phases. The scattering results provide direct evidence of symmetry lowering to the ferroelectric phase driven by magnetically induced lattice modulations and show the presence of multiple magnetic orders. The competing orders under spin-frustrated geometry are believed to cause discommensuration and result in the commensurate-to-incommensurate phase transition around 24 K. It is proposed that the low temperature incommensurate phase consists of commensurate domains separated by antiphase domain walls which change both signs of spontaneous polarizations and x-ray scattering amplitudes for forbidden reflections.

Orbital and bonding anisotropy in a half-filled GaFeO3 magnetoelectric ferrimagnet.

We investigated the orbital anisotropy of GaFeO3 using the Fe L2,3-edge x-ray magnetic circular dichroism and the polarization dependent O K-edge x-ray absorption spectroscopy. We found that the system shows a considerably large orbital momentum and anisotropic Fe-O bonding, which are unexpected in a half-filled d5 system such as GaFeO3. The orbital and bonding anisotropies, which turn out to be induced by the lattice distortions with exotic off-centering site movements, contribute the large magnetocrystalline energy and magnetoelasticity. These results provide critical clues on the microscopic understanding of the magnetoelectricity.

Direct observation of large electronic domains with memory effect in doped manganites.

We use a spatially resolved, direct spectroscopic probe for electronic structure with an additional sensitivity to chemical compositions to investigate high-quality single crystal samples of La(1/4)Pr(3/8)Ca(3/8)MnO3, establishing the formation of distinct insulating domains embedded in the metallic host at low temperatures. These domains are found to be at least an order of magnitude larger in size compared to previous estimates and exhibit memory effects on temperature cycling in the absence of any perceptible chemical inhomogeneity, suggesting long-range strains as the probable origin.