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Hericium erinaceus, also known as lion’s mane mushroom, is an edible and medicinal mushroom that belongs to the family Hericiaceae. We previously reported hericene A as an anti-diabetic constituent of H. erinaceus and the effect of cultivation substrates on its content was investigated. As the continuation, the contents of five major compounds such as hericenes A-D, which exerted α-glucosidase inhibitory activity, together with ergosterol were investigated depending on cultivation stages. H. erinaceus was cultured for 25 days (5 stages) to induce fruiting bodies, and the contents of the compounds at each stage were quantified. All the five compounds were detected in fruiting body by HPLC analysis. Among the hericene derivatives in the mushroom, the content of hericene A was the highest, followed by hericene C and the content of hericenes B and D was relative low. All four hericene derivatives present in the highest content at stage 4 whereas the content of ergosterol was highest at stage 5. The highest α-glucosidase inhibitory activity of H. erinaceus was measured at stage 4, which correlates with the contents of hericene derivatives. Conclusively, H. erinaceus with better efficacy and high content of active constituents can be secured by the optimization of cultivation conditions.
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Purpose@#The immunomodulatory effects of thalidomide (TM) and dexamethasone (DX) on immune cells and their co-stimulatory, co-inhibitory molecules in vitro and in vivo have been previously reported. The current study investigated the effects of TM and the combinatorial treatment with DX on immune cells using a murine cardiac allograft transplantation model. @*Materials and Methods@#Intraabdominal transplant of cardiac allografts from BALB/c (H-2d ) donors to C57BL/6 (H-2b ) recipients was performed. After transplantation, mice were injected daily with TM or DX or a combination of both TM and DX (TM/DX) by intraperitoneal route until the time of graft loss. CD4+ T cell subsets and CD11c+ cells in the peripheral blood mononuclear cells and spleen were examined and quantified with flow cytometry. Serum IL-6 levels were measured by enzyme-linked immunosorbent assay on day 7. @*Results@#The mean graft survivals were 6.86 days in the untreated group, and 10.0 days in the TM/DX group (p<0.001). The TM/DX treatment affected the CD4+ T cell subsets without suppressing the total CD4+ T cell population. The CD4 + FOXP3+ /CD4+ CD44hi T cell ratio increased. Increase in cell counts and median fluorescence intensity on CD11c+ CD85k+ with TM/DX were observed. The inhibition of pro-inflammatory cytokine interleukin-6 was also observed. @*Conclusion@#These outcomes suggest the immunomodulating effect of the TM/DX combinatorial treatment. In conclusion, TM/ DX combination may be a promising immunomodulatory approach for preventing allograft rejection and improving graft survival by inducing tolerance in transplantation.
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Cordycepin is a characteristic bioactive compound of Cordyceps militaris with various beneficial effects. Cordyceps grows on both grains and insects, and the content of cordycepin varies depending on the cultivation conditions. In this study, the effect of culture conditions on the cordycepin content was analyzed and the extraction conditions were optimized. Analysis of cordycepin content in Pupae-Cordyceps found that it was highly affected by temperature in culture conditions. In the case of mycelium, it grows well at 20 and 25 oC, but not at 30 oC. However, the content of cordycepin was highest at 30oC and less at 20 oC. The fruiting body also showed a similar tendency: growth was 20 oC > 25 oC > 30 oC, but the cordycepin content was 30 oC > 25 oC > 20 oC. The content of cordycepin decreased after the fruiting bodies were produced. Next, extraction conditions such as solvent and time were optimized for maximum cordycepin content using response surface methodology(RSM). There was a large difference in the content of cordycepin according to the content of ethanol and the extraction temperature. Through RSM, it was confirmed that the optimum condition for extraction of cordycepin was 48.9 oC using 49.0% ethanol, and 160.9 mg/g extract could be obtained under this condition. In conclusion, this study suggested the optimized conditions for the cultivation and extraction of Pupae-Cordyceps for maximizing the content of cordycepin, and this may be applied to the discovery of materials using cordycepin.
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Cordycepin is a characteristic bioactive compound of Cordyceps militaris with various beneficial effects. Cordyceps grows on both grains and insects, and the content of cordycepin varies depending on the cultivation conditions. In this study, the effect of culture conditions on the cordycepin content was analyzed and the extraction conditions were optimized. Analysis of cordycepin content in Pupae-Cordyceps found that it was highly affected by temperature in culture conditions. In the case of mycelium, it grows well at 20 and 25 oC, but not at 30 oC. However, the content of cordycepin was highest at 30oC and less at 20 oC. The fruiting body also showed a similar tendency: growth was 20 oC > 25 oC > 30 oC, but the cordycepin content was 30 oC > 25 oC > 20 oC. The content of cordycepin decreased after the fruiting bodies were produced. Next, extraction conditions such as solvent and time were optimized for maximum cordycepin content using response surface methodology(RSM). There was a large difference in the content of cordycepin according to the content of ethanol and the extraction temperature. Through RSM, it was confirmed that the optimum condition for extraction of cordycepin was 48.9 oC using 49.0% ethanol, and 160.9 mg/g extract could be obtained under this condition. In conclusion, this study suggested the optimized conditions for the cultivation and extraction of Pupae-Cordyceps for maximizing the content of cordycepin, and this may be applied to the discovery of materials using cordycepin.
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Purpose@#In organ transplantation, the need for immune modulation rather than immune suppression has been emphasized. In this study, we investigated whether combinatorial treatments of with thalidomide (TM) and dexamethasone (DX) might be new approaches to induce systemic immunomodulation on T cells and other immune cells that regulate the expression of co-inhibitory molecules. @*Materials and Methods@#Naïve splenic T cells from C57BL/6 mice were sort-purified and cultured in vitro for CD4+ T cell proliferation and regulatory T cell (Treg) conversion in the presence of TM or/and DX. Expression of cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed death-1 (PD-1) in proliferated and converted T cells was quantified by flow cytometry. We also quantified in vivo expression of CTLA-4 and PD-1 on splenic CD4+ T cells and other immune cells isolated from TM- or/and DX-treated mice. Mixed lymphocytes reactions (MLR) were performed to evaluate the capacity of immune cells in carrying out immune responses. @*Results@#CTLA-4 expressions in effector T cells in vivo and in Tregs in vivo/vitro significantly increased upon TM/DX combinatorial treatment. Corresponding to increased CTLA-4 expression in T cells, the expression of ligand molecules for CTLA-4 significantly increased in splenic dendritic cells in TM/DX-treated groups. In addition, MLR results demonstrated that splenocytes isolated from TM/DX-treated mice significantly suppressed the proliferation of T cells isolated from other strains. @*Conclusion@#Based on these results, we suggest that TM/DX combinatorial treatments might be efficient immunomodulatory methods for regulating T cell immunity.
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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).
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Tregs have a role in immunological tolerance and immune homeostasis by suppressing immune reactions, and its therapeutic potential is critical in autoimmune diseases and cancers. There have been multiple studies conducted on Tregs because of their roles in immune suppression and therapeutic potential. In tumor immunity, Tregs can promote the development and progression of tumors by preventing effective anti-tumor immune responses in tumor-bearing hosts. High infiltration of Tregs into tumor tissue results in poor survival in various types of cancer patients. Identifying factors specifically expressed in Tregs that affect the maintenance of stability and function of Tregs is important for understanding cancer pathogenesis and identifying therapeutic targets. Thus, manipulation of Tregs is a promising anticancer strategy, but finding markers for Treg-specific depletion and controlling these cells require fine-tuning and further research. Here, we discuss the role of Tregs in cancer and the development of Treg-targeted therapies to promote cancer immunotherapy.
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Tregs have a role in immunological tolerance and immune homeostasis by suppressing immune reactions, and its therapeutic potential is critical in autoimmune diseases and cancers. There have been multiple studies conducted on Tregs because of their roles in immune suppression and therapeutic potential. In tumor immunity, Tregs can promote the development and progression of tumors by preventing effective anti-tumor immune responses in tumor-bearing hosts. High infiltration of Tregs into tumor tissue results in poor survival in various types of cancer patients. Identifying factors specifically expressed in Tregs that affect the maintenance of stability and function of Tregs is important for understanding cancer pathogenesis and identifying therapeutic targets. Thus, manipulation of Tregs is a promising anticancer strategy, but finding markers for Treg-specific depletion and controlling these cells require fine-tuning and further research. Here, we discuss the role of Tregs in cancer and the development of Treg-targeted therapies to promote cancer immunotherapy.
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Tregs have a role in immunological tolerance and immune homeostasis by suppressing immune reactions, and its therapeutic potential is critical in autoimmune diseases and cancers. There have been multiple studies conducted on Tregs because of their roles in immune suppression and therapeutic potential. In tumor immunity, Tregs can promote the development and progression of tumors by preventing effective anti-tumor immune responses in tumor-bearing hosts. High infiltration of Tregs into tumor tissue results in poor survival in various types of cancer patients. Identifying factors specifically expressed in Tregs that affect the maintenance of stability and function of Tregs is important for understanding cancer pathogenesis and identifying therapeutic targets. Thus, manipulation of Tregs is a promising anticancer strategy, but finding markers for Treg-specific depletion and controlling these cells require fine-tuning and further research. Here, we discuss the role of Tregs in cancer and the development of Treg-targeted therapies to promote cancer immunotherapy.
Subject(s)
Humans , Autoimmune Diseases , Homeostasis , Immunotherapy , T-Lymphocytes, Regulatory , Tumor MicroenvironmentABSTRACT
During virus infection, T cells must be adapted to activation and lineage differentiation states via metabolic reprogramming. Whereas effector CD8⁺ T cells preferentially use glycolysis for their rapid proliferation, memory CD8⁺ T cells utilize oxidative phosphorylation for their homeostatic maintenance. Particularly, enhanced AMP-activated protein kinase (AMPK) activity promotes the memory T cell response through different pathways. However, the level of AMPK activation required for optimal memory T cell differentiation remains unclear. A new metformin derivative, IM156, formerly known as HL156A, has been reported to ameliorate various types of fibrosis and inhibit in vitro and in vivo tumors by inducing AMPK activation more potently than metformin. Here, we evaluated the in vivo effects of IM156 on antigen-specific CD8⁺ T cells during their effector and memory differentiation after acute lymphocytic choriomeningitis virus infection. Unexpectedly, our results showed that in vivo treatment of IM156 exacerbated the memory differentiation of virus-specific CD8⁺ T cells, resulting in an increase in short-lived effector cells but decrease in memory precursor effector cells. Thus, IM156 treatment impaired the function of virus-specific memory CD8⁺ T cells, indicating that excessive AMPK activation weakens memory T cell differentiation, thereby suppressing recall immune responses. This study suggests that metabolic reprogramming of antigen-specific CD8⁺ T cells by regulating the AMPK pathway should be carefully performed and managed to improve the efficacy of T cell vaccine.
Subject(s)
AMP-Activated Protein Kinases , Cell Differentiation , Fibrosis , Glycolysis , Immunologic Memory , In Vitro Techniques , Lymphocytic choriomeningitis virus , Lymphocytic Choriomeningitis , Memory , Metformin , Oxidative Phosphorylation , T-LymphocytesABSTRACT
BACKGROUND/AIMS: The true incidence of aristolochic acid nephropathy (AAN) is thought to be underestimated because numerous ingredients known or suspected to contain aristolochic acid (AA) are used in traditional medicine in Korea. METHODS: We collected data on cases of AAN since 1996 via a database in Korea. We evaluated the year of AAN development, route to obtaining AA-containing herbal medicine, gender, reason for taking AA-containing herbal medicine, clinical manifestations, histological findings, phytochemical analysis, and prognosis of patients with AAN. RESULTS: Data on 16 cases of AAN were collected. Thirteen cases developed AAN before and three cases after the prohibition of AA-containing herbal medicine by the Korea Food and Drug Administration. Patients were prescribed AA-containing herbal medicine from oriental clinics or had purchased it from traditional markets. AAN was distributed in all age groups. Young females were most commonly exposed to AA-containing herbal medicine for slimming purposes and postpartum health promotion, while older adults took AA-containing compounds for the treatment of chronic diseases. The most common symptoms presented at hospitalization were nausea and vomiting, and acute kidney injury was accompanied by Fanconi syndrome in almost half of the patients. Phytochemical analysis of AA in herbal medicine was available in six cases. Progression to end stage renal disease (ESRD) was observed in seven patients (43.8%), and five patients (31.3%) had progressed to ESRD within 6 months of diagnosis. CONCLUSIONS: Our report shows that patients were still exposed to AA-containing herbal medicine and that there is a possibility of underdiagnosis of AAN in Korea. A stronger national supervision system of herbal ingredients and remedies in oriental medicine is needed to prevent AAN.
Subject(s)
Adult , Female , Humans , Acute Kidney Injury , Chronic Disease , Diagnosis , Fanconi Syndrome , Health Promotion , Herbal Medicine , Hospitalization , Incidence , Kidney Failure, Chronic , Korea , Medicine, East Asian Traditional , Medicine, Traditional , Nausea , Organization and Administration , Postpartum Period , Prognosis , United States Food and Drug Administration , VomitingABSTRACT
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.
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Aged , Humans , Aging , Clinical Decision-Making , Complement System Proteins , Data Mining , Decision Trees , Drug-Related Side Effects and Adverse Reactions , Learning , PrescriptionsABSTRACT
BACKGROUND: Although the beneficial effects of statin treatment in dyslipidemia and atherosclerosis have been well studied, there is limited information regarding the renal effects of statins in diabetic nephropathy. We aimed to investigate whether, and which, statins affected renal function in Asian patients with diabetes. METHODS: We enrolled 484 patients with diabetes who received statin treatment for more than 12 months. We included patients treated with moderate-intensity dose statin treatment (atorvastatin 10 to 20 mg/day or rosuvastatin 5 to 10 mg/day). The primary outcome was a change in estimated glomerular filtration rate (eGFR) during the 12-month statin treatment, and rapid renal decline was defined as a >3% reduction in eGFR in a 1-year period. RESULTS: In both statin treatment groups, patients showed improved serum lipid levels and significantly reduced eGFRs (from 80.3 to 78.8 mL/min/1.73 m² for atorvastatin [P=0.012], from 79.1 to 76.1 mL/min/1.73 m² for rosuvastatin [P=0.001]). A more rapid eGFR decline was observed in the rosuvastatin group than in the atorvastatin group (48.7% vs. 38.6%, P=0.029). Multiple logistic regression analyses demonstrated more rapid renal function loss in the rosuvastatin group than in the atorvastatin group after adjustment for other confounding factors (odds ratio, 1.60; 95% confidence interval, 1.06 to 2.42). CONCLUSION: These results suggest that a moderate-intensity dose of atorvastatin has fewer detrimental effects on renal function than that of rosuvastatin.
Subject(s)
Humans , Asian People , Atherosclerosis , Atorvastatin , Diabetes Mellitus , Diabetic Nephropathies , Dyslipidemias , Glomerular Filtration Rate , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Logistic Models , Renal Insufficiency, Chronic , Rosuvastatin CalciumABSTRACT
BACKGROUND: The optimal immunosuppressive strategy for renal transplant recipients at high immunological risk requires clarification. We compared the 3 year outcomes of a sirolimus group (tacrolimus plus sirolimus) to those of a control group (tacrolimus plus mycophenolate mofetil). METHODS: This observational study was an extension of a prospective pilot study. We assessed acute rejection, glomerular filtration rate, adverse events, graft, and patient survival. RESULTS: Overall, 43% of the sirolimus group versus 78% of the control group were still on the initial immunosuppressive regimen at 3 years (P=0.005), and most discontinuations in each group were due to adverse events. No differences were observed between two groups with respect to acute rejection. The mean glomerular filtration rate at 36 months was greater in the sirolimus group than in the control group, but this was not statistically significant (64.0±6.8 mL/min/1.73 m² vs. 61.8±17.1 mL/min/1.73 m², P=0.576). Graft and patient survival were similar in both groups. Importantly, mean tacrolimus through levels were significantly lower in the sirolimus group than in the control group at each time point. No neoplasm was reported in the sirolimus group. In the control group, three cases of neoplasms developed during the study period. CONCLUSIONS: The sirolimus group had a greater number of discontinuations, particularly related to adverse events. Nevertheless, optimal concentration of sirolimus allowed reduced calcineurin inhibitor exposure in high immunologic risk patients, without increasing the risk of acute rejection and graft failure.
Subject(s)
Humans , Calcineurin , Glomerular Filtration Rate , Immunosuppression Therapy , Kidney Transplantation , Kidney , Observational Study , Pilot Projects , Prospective Studies , Sirolimus , Tacrolimus , Transplant Recipients , TransplantsABSTRACT
Objective: To evaluate various types of samples from the different marine environments as sources of actinomycetes from the Yalujiang coastal wetland, North China, and to screen their antimicrobial properties. Further, the identified actinomycetes were characterized based on morphological, biochemical, and physiological characteristics. Methods: Eight different production media were used to isolate actinomycetes from different stations of marine soil sediments in Yalujiang coastal wetland and the genotypic positions were established by 16S rDNA. Results: A total of 172 actinomycetal isolates were obtained from 13 samples using five media. The most effective culture media in the isolation of actinobacteria were Gause's Synthetic agar and Starch-casein agar. Among 172 isolates, 46 isolates (26.74%) showed antibacterial activity, 70.93% belonged to the genus Streptomyces, others were Micromonospora spp. and Rhodococcus spp. Out of the 46 isolates, two cultures were further supported by morphological characterization analysis. Conclusions: This is the first report about actinomycetes isolated from Yalujiang coastal wetland and it seems that the promising isolates from the unusual/unexplored wetland may prove to be an important step in the development of microbial natural product research.
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Objective:To evaluate various types of samples from the different marine environments as sources of actinomycetes from the Yalujiang coastal wetland, North China, and to screen their antimicrobial properties. Further, the identified actinomycetes were characterized based on morphological, biochemical, and physiological characteristics. Methods:Eight different production media were used to isolate actinomycets from different stations of marine soil sediments in Yalujiang coastal wetland and the genotypic positions were established by 16S rDNA. Results:A total of 172 actinomycetal isolates were obtained from 13 samples using five media. The most effective culture media in the isolation of actinobacteria were Gause’s Synthetic agar and Starch-casein agar. Among 172 isolates, 46 isolates (26.74%) showed antibacterial activity, 70.93%belonged to the genus Streptomyces, others were Micromonospora spp. and Rhodococcus spp. Out of the 46 isolates, two cultures were further supported by morphological characterization analysis. Conclusions: This is the first report about actinomycetes isolated from Yalujiang coastal wetland and it seems that the promising isolates from the unusual/unexplored wetland may prove to be an important step in the development of microbial natural product research.
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PURPOSE: Continuous renal replacement therapy (CRRT) has been established for critically ill acute kidney injury (AKI) patients. In addition, some centers consist of a specialized CRRT team (SCT) with physicians and nurses. To our best knowledge, however, ona a few studies have yet been carried out on the superiority of SCT management. MATERIALS AND METHODS: A total of 551 patients, who received CRRT between January 2008 and March 2009, were divided into two groups based on the controller of CRRT. The impact of the CRRT management on 28-day mortality was compared between two groups by Kaplan-Meier curve and Cox analysis. RESULTS: During the study period, the number of filters used, down-time per day, and intensive care unit length of day were significantly higher in non-SCT group than in SCT group (6.2 hrs vs. 5.0 hrs, p=0.042; 5.0 hrs vs. 3.8 hrs, p<0.001; 27.5 days vs. 21.1 days, p=0.027, respectively), while net ultrafiltration rate was significantly lower in non-SCT group than SCT group (28.0 mL/kg/hr vs. 29.5 mL/kg/hr, p=0.043, respectively). In addition, 28-day mortality rate was significantly lower in SCT group than with non-SCT group (p=0.031). Moreover, Cox regression analysis showed that 28-day mortality rate was significantly lower in SCT control group, even after adjusting for age, gender, severity scores, biomarkers, risk, injury, failure, loss, and end-stage renal disease, and contributing factors (hazard ratio 0.91, p=0.046). CONCLUSION: A well-trained CRRT team could be beneficial for mortality improvement of AKI patients requiring CRRT.
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Acute Kidney Injury/mortality , Biomarkers , Critical Illness/mortality , Intensive Care Units , Kaplan-Meier Estimate , Kidney Failure, Chronic/therapy , Patient Care Team , Proportional Hazards Models , Renal Replacement Therapy/methods , Retrospective Studies , Time Factors , Treatment OutcomeABSTRACT
The optimal immunosuppressive strategy for renal transplant recipients at high immunologic risk remains a topic of investigation. This prospective single arm pilot study was undertaken to evaluate the safety and efficacy of a combined tacrolimus and sirolimus regimen in recipients at immunological high risk and to compare outcomes with a contemporaneous control group received tacrolimus and mycophenolate mofetil. Patients that received a renal allograft between 2010 and 2011 at high risk (defined as panel reactive antibodies > 50%, 4 or more human leukocyte antigen mismatches, or retransplantation) were enrolled. All patients received basiliximab induction and corticosteroids. A total of 28 recipients treated with tacrolimus and sirolimus were enrolled in this study and 69 recipients were retrospectively reviewed as a control group. The sirolimus group showed a higher, but not statistically significant, incidence of biopsy proven acute rejection and a lower glomerular filtration rate than the control group. Furthermore, sirolimus group was associated with significant increases in BKV infection (P = 0.031), dyslipidemia (P = 0.004), and lymphocele (P = 0.020). The study was terminated prematurely due to a high incidence of adverse events. A de novo tacrolimus/sirolimus combination regimen may not be an ideal choice for recipients at high immunological risk.
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Drug Therapy, Combination/methods , Graft Rejection/diagnosis , Immunocompromised Host , Immunosuppressive Agents/administration & dosage , Kidney Transplantation/adverse effects , Longitudinal Studies , Sirolimus/administration & dosage , Survival Rate , Tacrolimus/administration & dosage , Treatment OutcomeABSTRACT
PURPOSE: Recently, bortezomib has been used to treat antibody-mediated rejection (AMR) refractory to conventional treatment such as plasmapheresis, intravenous immunoglobulin, and rituximab. The authors aimed to describe their experiences when bortezomib was used to treat refractory AMR. MATERIALS AND METHODS: Eleven refractory AMR episodes treated with bortezomib were included in this study. The patients received one or two cycles of bortezomib (1.3 mg/m2) on days 1, 4, 8, and 11. RESULTS: Bortezomib effectively reduced antibodies against various targets, including human leukocyte antigen (HLA) class I and II, ABO blood group antigen, and angiotensin II type 1 receptor. Antibodies were depleted or reduced significantly in eight AMR episodes. Overall, there was a significant improvement in the mean estimated glomerular filtration rate (eGFR) at 3 months after therapy (36.91+/-22.15 mL/min/1.73 m2) versus eGFR at time of AMR diagnosis (17.00+/-9.25 mL/min/1.73 m2; p=0.007). All six early-onset AMR episodes (within 6 months post-transplantation) showed full recovery of allograft function. Additionally, three of the five late-onset AMR episodes (>6 months post-transplantation) showed improved allograft function. CONCLUSION: Anti-humoral treatment based on bortezomib might be an effective strategy against refractory AMR caused by various types of antibodies. Notably, this treatment could be more effective in early-onset AMR than in late-onset AMR.