Comparison of Different Types of Oral Adsorbent Therapy in Patients with Chronic Kidney Disease: A Multicenter, Randomized, Phase IV Clinical Trial

Purpose: Oral adsorbents delay disease progression and improve uremic symptoms in patients with chronic kidney disease (CKD). DW-7202 is a newly developed oral adsorbent with high adsorptive selectivity for uremic toxins. We evaluated patient preference for and adherence to DW-7202 versus AST-120 therapy and compared treatment efficacy and safety in patients with pre-dialysis CKD. Materials and methods: A seven-center, randomized, open-label, two-way crossover, active-controlled, phase IV clinical trial was conducted. Patients with stable CKD were randomly assigned to receive DW-7202 (capsule type) or AST-120 (granule type) for 12 weeks. The groups then switched to the other adsorbent and took it for the next 12 weeks. Patient preference was the primary outcome. Secondary outcomes included changes in estimated glomerular filtration rate (eGFR) and serum creatinine, cystatin C, and indoxyl sulfate (IS) levels. Results: Significantly more patients preferred DW-7202 than AST-120 (p<0.001). Patient adherence improved after switching from AST-120 to DW-7202; there was no apparent change in adherence after switching from DW-7202 to AST-120. Changes in eGFR and serum creatinine, cystatin C, and IS levels were not significantly different according to adsorbent type. There was also no significant difference in the incidences of adverse events during treatment with DW-7202 and AST-120. Conclusion: DW-7202 can be considered as an alternative to AST-120 in patients who cannot tolerate or show poor adherence to granule type adsorbents. Further studies to evaluate factors affecting patient preferences and improved adherence are warranted (Clinical trial registration No. NCT02681952).ope

신장 재이식 환자의 다발성 내장 침범 카포시육종에서 Sirolimus 치료를 통한 부분 관해 및 이식신 보존 1예

The use of immunosuppressant's increases the risk of developing malignancies in renal allograft patients. One of the most important malignancies, Kaposi's sarcoma, can cause mortality and graft failure among renal allograft patients. We report the case of a 39-year-old male diagnosed with multiple visceral Kaposi's sarcoma 6 months after a second cadaveric renal allograft. The patient's renal function was markedly deteriorated at admission and required hemodialysis initially. Radiologic studies revealed Kaposi's sarcoma in multiple lymph nodes, liver, lung, and peritoneum. The excisional biopsy of an inguinal lymph node confirmed this diagnosis. After diagnosis, tacrolimus treatment was gradually decreased, and sirolimus treatment initiated. The patient did not receive any chemotherapy or radiotherapy. The Kaposi's sarcoma lesions decreased dramatically (both in size and number) 1 month after sirolimus treatment, and kidney graft function improved. This case thus shows successful sirolimus treatment of visceral Kaposi's sarcoma in a renal allograft patient.ope

Tissue-engineered vascular microphysiological platform to study immune modulation of xenograft rejection

Most of the vascular platforms currently being studied are lab-on-a-chip types that mimic capillary networks and are applied for vascular response analysis in vitro. However, these platforms have a limitation in clearly assessing the physiological phenomena of native blood vessels compared to in vivo evaluation. Here, we developed a simply fabricable tissue-engineered vascular microphysiological platform (TEVMP) with a three-dimensional (3D) vascular structure similar to an artery that can be applied for ex vivo and in vivo evaluation. Furthermore, we applied the TEVMP as ex vivo and in vivo screening systems to evaluate the effect of human CD200 (hCD200) overexpression in porcine endothelial cells (PECs) on vascular xenogeneic immune responses. These screening systems, in contrast to 2D in vitro and cellular xenotransplantation in vivo models, clearly demonstrated that hCD200 overexpression effectively suppressed vascular xenograft rejection. The TEVMP has a high potential as a platform to assess various vascular-related responses.ope

Strategies to Overcome Memory T Cells Mediatied Allograft Injury.

During the last few decades our knowledge of transplantation has been remarkably expanded to the point where transplants are a standard treatment modality. However, despite the fact that certain tolerogenic protocols seemed to be very successful in small animal models, researchers anticipated the same outcomes in humans, which has mostly not been true yet. Immunological memory is known to be one of the reasons for such discrepancies. Donor-specific memory T cells are thought to be a crucial barrier in transplant success due to their unique properties. Recently, efforts to overcome this issue have been made, and several protocols showed the inhibition of memory T cell functions both in vitro and in vivo. In this review, we discuss the role of memory T cells in transplant rejection and the rising strategies to overcome this barrier.ope

Modified Peritoneal Dialysis Catheter Insertion: Comparison with a Conventional Method

PURPOSE: The conventional trocar and cannula method in peritoneal dialysis (PD) catheter insertion has its limitation in clinical setting. The aim of this study was to compare a modified method for percutaneous PD catheter insertion with the conventional method, and demonstrate advantages of the modified method. MATERIALS AND METHODS: Patients at a single center who had percutaneous PD catheters inserted by nephrologists from January 2006 until September 2012, using either a modified method (group M) or the conventional trocar and cannula method (group C), were retrospectively analyzed, in terms of baseline characteristics, complications experienced up to 3 months after the procedure, and the suitability of the procedure for patients. RESULTS: Group M included 82 subjects, while group C included 66 cases. The overall early complication rate in group M (1.2%) was significantly lower than that in group C (19.7%) (p<0.001). The catheter revision rate during timeframe for early complications was significantly lower in group M (0%) than in group C (6.1%) (p=0.024). When comparing Procedure time (1 h 3 min±16 min vs. 1 h 36 min±19 min, p<0.01), immediate post-procedural pain (2.43±1.80 vs. 3.14±2.07, p<0.05), and post-procedure days until ambulation (3.95±1.13 days vs. 6.17±1.34 days, p<0.01), group M was significantly lower than group C. There was no significant difference in total hospitalization period (14.71±7.05 days vs. 13.86±3.7 days). CONCLUSION: Our modified PD catheter insertion method shows its advantages in early complication rate, early complications revision rate, and the patients' conveniences.ope

A multicenter, randomized, open-label, comparative, phase IV study to evaluate the efficacy and safety of combined treatment with mycophenolate mofetil and corticosteroids in advanced immunoglobulin A nephropathy

Background: It remains unclear whether immunosuppressive agents are effective in patients with immunoglobulin A nephropathy (IgAN). We investigated the efficacy of a mycophenolate mofetil (MMF) and corticosteroid combination therapy in patients with advanced IgAN. Methods: We conducted a multicenter, randomized, placebo-controlled, parallel-group study of 48 weeks administration of MMF and corticosteroids in biopsy-proven advanced IgAN patients with estimated glomerular filtration rate (eGFR) of 20-50 mL/min/1.73 m2 and urine protein-to-creatinine ratio (UPCR) of &gt;0.75 g/day. The primary outcome was complete (UPCR &lt; 0.3 g/day) or partial (&gt;50% reduction of UPCR compared to baseline) remission at 48 weeks. Results: Among the 48 randomized patients, the percentage that achieved complete or partial remission was greater in the combination therapy group than in the control group (4.2% vs. 0% and 29.1% vs. 5.0%, respectively). Compared with the combination therapy group, eGFR in the control group decreased significantly from week 36 onward, resulting in a final adjusted mean change of -4.39 ± 1.22 mL/min/1.73 m2 (p = 0.002). The adjusted mean changes after 48 weeks were 0.62 ± 1.30 and -5.11 ± 1.30 mL/min/1.73 m2 (p = 0.005) in the treatment and control groups, respectively. The UPCR was significantly different between the two groups; the adjusted mean difference was -0.47 ± 0.17 mg/mgCr and 0.07 ± 0.17 mg/mgCr in the treatment and control group, respectively (p = 0.04). Overall adverse events did not differ between the groups. Conclusion: In advanced IgAN patients with a high risk for disease progression, combined MMF and corticosteroid therapy appears to be beneficial in reducing proteinuria and preserving renal function.ope

Evaluation of accuracy and efficiency of Double Fourier Series (DFS) spectral dynamical core

학위논문(석사) -- 서울대학교대학원 : 자연과학대학 지구환경과학부, 2023. 8. 손석우.본 논문은 두 가지 이상화 실험 검증사례를 통해 이중 푸리에 급수(DFS) 분광 역학코어의 성능을 구면 조화 함수(SPH) 분광 역학코어와 비교 평가한다. 추가적으로, 계산 오류를 완화하기 위해 최근 개발되었지만 현재까지 2차원 천해방정식에만 적용된 DFS의 남북방향 확장 계수를 계산하는 새로운 접근법도 같이 검증한다. 첫번째 검증 사례인 3차원 변형류 상의 물질 수송 실험에서는 SPH와 DFS 시뮬레이션 간의 차이가 현저하지 않으며, 새로운 DFS 계산 방식은 결과값의 언더슈팅 문제에 있어서 조금이나마 우수한 결과를 보인다. 두번째 검증 사례인 경압파동 생성 실험에서는 DFS로 모의된 파동 패턴은 높은 해상도에서 SPH로 모의된 파동 패턴과 정량적으로 유사하지만 계산 비용이 상당히 낮다. 그러나 새로운 DFS 계산 방식은 원래의 DFS에 비해 두드러진 이점을 제공하지 않으며, 약간의 계산 비용 증가가 있다. 이 결과는 현재의 DFS 분광법이 고해상도 글로벌 모델링을 위한 실용적이고 대체 가능한 역학코어가 될 수 있음을 시사한다.The double Fourier series (DFS) spectral dynamical core is evaluated for the two idealized test cases in comparison with the spherical harmonics (SPH) spectral dynamical core. A new approach in calculating the meridional expansion coefficients of DFS, which was recently developed to alleviate a computational error but only applied to the 2D spherical shallow water equation, is also tested. In the 3D deformational tracer transport test, the difference is not conspicuous between SPH and DFS simulations, with a slight outperformance of the new DFS approach in terms of undershooting problem. In the baroclinic wave development test, the DFS-simulated wave pattern is quantitatively similar to the SPH-simulated one at high resolutions, but with a substantially lower computational cost. The new DFS approach does not offer a salient advantage compared to the original DFS while computation cost slightly increases. This result suggests that the current DFS spectral method can be a practical and alternative dynamical core for high-resolution global modeling.제 1 장 서 론 1 제 2 장 DFS 방법 소개 및 비교 5 제 3 장 실험 설계 9 제 1 절 실험1: 3D deformational tracer transport 9 제 2 절 실험2: Dry baroclinic wave development 10 제 4 장 실험 결과 12 제 1 절 실험1 12 제 2 절 실험2 13 제 3 절 모델 실행 시간 16 제 4 절 토의 18 제 5 장 요약 및 제언 21 참고문헌 24 Tables 28 Figures 32 Abstract 38석

Regulatory T cell expressed MyD88 is critical for prolongation of allograft survival

MyD88 signaling directly promotes T-cell survival and is required for optimal T-cell responses to pathogens. To examine the role of T-cell-intrinsic MyD88 signals in transplantation, we studied mice with targeted T-cell-specific MyD88 deletion. Contrary to expectations, we found that these mice were relatively resistant to prolongation of graft survival with anti-CD154 plus rapamycin in a class II-mismatched system. To specifically examine the role of MyD88 in Tregs, we created a Treg-specific MyD88-deficient mouse. Transplant studies in these animals replicated the findings observed with a global T-cell MyD88 knockout. Surprisingly, given the role of MyD88 in conventional T-cell survival, we found no defect in the survival of MyD88-deficient Tregs in vitro or in the transplant recipients and also observed intact cell homing and expression of Treg effector molecules. MyD88-deficient Tregs also fail to protect allogeneic bone marrow transplant recipients from chronic graft-versus-host disease, confirming the observations of defective regulation seen in a solid organ transplant system. Together, our data define MyD88 as having a divergent requirement for cell survival in non-Tregs and Tregs, and a yet-to-be defined survival-independent requirement for Treg function during the response to alloantigen.ope

Acute Kidney Injury: Definition, Incidence, Etiology, Outcome.

Acute kidney injury (AKI) is characterized as acute decline of renal function. AKI is frequently combined in hospitalized patients and worsen the outcome of the affected patients. Recently new criteria named RIFLE and AKIN were made to define AKI more uniformly. Recent studies with RIFLE/AKIN showed that even less severe forms of AKI are associated with reduced survival and worse outcome. In this review, we will discuss on the definition, Incidence, Etiology and outcome of AKI.ope

A Personalized and Learning Approach for Identifying Drugs with Adverse Events

Purpose: Adverse drug events (ADEs) are associated with high health and financial costs and have increased as more elderly patients treated with multiple medications emerge in an aging society. It has thus become challenging for physicians to identify drugs causing adverse events. This study proposes a novel approach that can improve clinical decision making with recommendations on ADE causative drugs based on patient information, drug information, and previous ADE cases. Materials and methods: We introduce a personalized and learning approach for detecting drugs with a specific adverse event, where recommendations tailored to each patient are generated using data mining techniques. Recommendations could be improved by learning the associations of patients and ADEs as more ADE cases are accumulated through iterations. After consulting the system-generated recommendations, a physician can alter prescriptions accordingly and report feedback, enabling the system to evolve with actual causal relationships. Results: A prototype system is developed using ADE cases reported over 1.5 years and recommendations obtained from decision tree analysis are validated by physicians. Two representative cases demonstrate that the personalized recommendations could contribute to more prompt and accurate responses to ADEs. Conclusion: The current system where the information of individual drugs exists but is not organized in such a way that facilitates the extraction of relevant information together can be complemented with the proposed approach to enhance the treatment of patients with ADEs. Our illustrative results show the promise of the proposed system and further studies are expected to validate its performance with quantitative measures.ope