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Meng-Kun Tsai

Publications and source records attributed to Meng-Kun Tsai.

15 recordsLinked to original sources
PubMed2006

Initial experience with ABO-incompatible live donor renal transplantation.

The serious shortage of cadaveric organs has prompted the development of ABO-incompatible live donor renal transplantation. We report our experience of the initial two live donor ABO incompatible renal transplants at our hospital. The first patient was a 55-year-old type A female who received a kidney from her AB type husband. The second patient was a 27-year-old type O male who received renal transplantation from his type A father. Preconditioning immunosuppressive therapy in the two patients with tacrolimus, mycophenolate mofetil and methylprednisolone was started 7 days before transplantation. During the period of preconditioning, double filtration plasmapheresis (DFPP) was employed to remove anti-A and -B antibodies. Laparoscopic splenectomy and renal transplantation were performed after the anti-donor ABO antibodies were reduced to a titer of 1:4. Rituximab, a humanized monoclonal anti-CD20 antibody, was administered to the second patient due to a rebound in the anti-A antibody titer during the preconditioning period. Under a tacrolimus-based immunosuppressive regimen, both patients recovered very well without any evidence of rejection. Serum creatinine levels were 1.0 and 1.4 mg/dL at 6 and 3 months after transplantation, respectively. These cases illustrate that with new immunosuppressive agents, DFPP and splenectomy, ABO-incompatible renal transplantation can be successfully conducted in end-stage renal disease patients whose only available live donors are blood group incompatible.

ABO Blood-Group System↗
PubMed2005

Multiple negative feedbacks on CD152 expression in allograft tolerance.

BACKGROUND: CD152 has been implicated in tolerance induction. This study investigated how CD80 and CD86 regulated CD152 expression in a low-responding cardiac transplant model with CD152-mediated long-term graft acceptance. METHODS: A low-responding cardiac transplant model from BALB/c to B10.A was used. Donor-specific stimulation and multiple antibody blockade of the CD80/CD86:CD28/CD152 co-stimulatory pathway was applied to the splenic T cells from B10.A recipients with 100-day grafts (B10.A-100). Proliferation assays, quantitative (Q) real-time polymerase chain reaction (PCR), flow cytometric analyses, and fluorescence microscopy were conducted to examine the roles of CD80 and CD86 in CD152 expression. RESULTS: B10.A-100 splenic T cells were hyporesponsive to donor-specific stimulation, and anti-CD80, anti-CD86, or anti-CD152 treatment significantly enhanced the proliferation response of the B10.A-100 splenic T cells. Proliferation assays and Q-PCR revealed that CD152 inhibited T-cell proliferation and, at the same time, decreased CD152 expression by secluding CD80 and CD86 from CD28 engagement. Flow cytometric analyses and fluorescence microscopy showed that CD28 engagement facilitated intracellular accumulation of CD152. Besides, CD152 engagement by CD80 decreased CD152 mRNA transcription, and CD152 engagement by CD86 inhibited surface expression of CD152. CONCLUSIONS: CD80 and CD86 controlled CD152-mediated allograft tolerance by multiple negative feedbacks on CD152 mRNA and surface expression.

Animals↗
PubMed2005

Expanding the donor pool: use of renal transplants from non-heart-beating donors supported with extracorporeal membrane oxygenation.

In response to organ shortage, we used the renal grafts from non-heart-beating donors (NHBDs). Extracorporeal membrane oxygenation (ECMO) was used to maintain NHBDs before organ procurement. We compared the results of renal transplantation from different donors, including heart-beating donors (HBDs), living-related donors (LDs), and NHBDs supported with ECMO. From February 1998 to June 2003, we recruited 219 patients receiving renal transplantation at National Taiwan University Hospital. Among them, 31 received kidneys from NHBDs supported with ECMO, 120 from HBDs, and 68 from LDs. Multiple organ transplant recipients were not included in this study. We compared the graft survival, serum creatinine levels, and estimated glomerular filtration rates of the three groups. The rate of delayed graft function was higher in NHBD recipients (41.9%) than in HBD recipients (27.0%) and LD recipients (10.9%) (p = 0.003). In the NHBD group, the recipients of grafts with delayed function had significantly longer ECMO runs (63.1 +/- 3.0 min) than those without delayed function (53.7 +/- 2.5 min) (p = 0.024). Estimated glomerular filtration rate (p = 0.472) and mean serum creatinine level (p = 0.286) were not significantly different between the three groups using a longitudinal approach. The 5-yr graft survival rates for NHBD (88.4%, 95% CI: 0.680-0.962), HBD (83.2%, 95% CI: 0.728-0.899), and LD transplant recipients (89.3%, 95% CI: 0.619-0.974) were not significantly different (p = 0.239). The 5-yr patient survival rates for NHBD, HBD, and LD transplant recipients were 100, 93.0 (95% CI: 0.859-0.966) and 100% respectively. The long-term allograft survival and function of kidneys from NHBDs supported by ECMO, HBD, and LD did not differ significantly. Long ECMO running time tended to delay graft function.

Adult↗
PubMed2005

Effects of calcineurin inhibitors on sirolimus pharmacokinetics during staggered administration in renal transplant recipients.

STUDY OBJECTIVE: To compare the effects of different calcineurin inhibitors on sirolimus pharmacokinetics during long-term, staggered administration in kidney transplant recipients. Design. Randomized, open-label, parallel-group trial. SETTING: A medical center and one of its teaching hospitals in Taiwan. PATIENTS: Twenty-two de novo kidney transplant recipients. INTERVENTION: Patients received cyclosporine microemulsion or tacrolimus capsules twice/day in combination with once-daily sirolimus solution and corticosteroids. Sirolimus was administered 6 hours after the morning dose of cyclosporine or tacrolimus. After receiving a 6-mg loading dose of sirolimus, participants received sirolimus 2 mg/day for at least 7 days. Neither the cyclosporine nor the tacrolimus dosage was adjusted for at least 3 days before and during blood sampling for pharmacokinetic profiling. MEASUREMENTS AND MAIN RESULTS: One patient dropped out because of trimethoprim-sulfamethoxazole-related hepatotoxicity. We observed no differences between the two patient groups in terms of their demographic data, renal and liver function, or dosage of sirolimus during the study. During multiple-dose administration, the area under the whole-blood concentration-time curve and the peak and trough concentrations of sirolimus in the cyclosporine group were, respectively, 1.46 (95% confidence interval [CI] 1.21-1.71), 1.42 (95% CI 1.08-1.76), and 1.42 (95% CI 1.09-1.76) times higher than those of the tacrolimus group, even though sirolimus was administered 6 hours after the other agents. CONCLUSION: Sirolimus pharmacokinetics may change significantly when calcineurin inhibitors are switched, even with staggered administration, which may not completely prevent a drug interaction between cyclosporine and sirolimus solution.

Adult↗
PubMed2005

Effects of conversion from sirolimus oral solution to tablets in stable Taiwanese renal transplant recipients.

BACKGROUND AND PURPOSE: Sirolimus (SRL) has a considerable inter- and intra- individual variability in clearance. Steady-state trough concentration (C(0)) is a reliable index of SRL exposure. This study assessed the effect of conversion of SRL oral solution to tablet form on C(0) in stable renal transplant recipients. METHODS: Twenty two stable renal transplant recipients who had received calcineurin inhibitor (CNI)/SRL solution/ steroid for more than 3 months before conversion from SRL solution to tablets were included. C(0) values of SRL were compared for the periods of use of each dosage form. The relation between liver function and SRL levels was also assessed. RESULTS: With a dose of 0.03 mg/kg/day, SRL solution and tablets achieved a similar dose-adjusted C(0) (mean +/- SEM, 2.9 +/- 0.3 ng/mL/mg) upon conversion. Similar results were found when multiple SRL C(0) values from different dosage form periods were compared. Four patients with persistent liver enzyme elevation had significantly higher dose-adjusted SRL C(0) values with both the solution (mean +/- SEM, 4.5 +/- 0.7 vs 2.3 +/- 0.1 ng/mL/mg; p < 0.01) and the tablet formulation (4.0 +/- 0.5 vs 2.6 +/- 0.2 ng/mL/mg; p < 0.05). CONCLUSIONS: Conversion from SRL solution to SRL tablets did not significantly affect the dose-adjusted SRL C(0). The dose-adjusted C(0) of SRL in patients with persistent liver enzyme elevation was significantly higher than in those with normal liver function.

Administration, Oral↗
PubMed2005

Prognostic significance of six-month estimated glomerular filtration rate in cadaveric renal transplantation.

BACKGROUND AND PURPOSE: We hypothesized a linear relative-risk model for graft survival of cadaveric renal transplantation, with a 6-month estimated glomerular filtration rate (GFR) employed as the linear parameter quantifying functioning renal mass and the detrimental effects of early chronic allograft nephropathy. METHODS: A retrospective study was conducted in a 15-year series of cadaveric renal transplantations (n = 227) with cyclosporin-based immunosuppression in a single transplant center. The Cockcroft-Gault formula was used for estimation of GFR, with a correction factor of 0.85 used for women. Stepwise Cox's regression analyses were applied to examine the prognostic significance of the 6-month estimated GFR. RESULTS: The Kaplan-Meier 5- and 10-year graft survival rates for this study were 80.67% and 59.43%, respectively. From univariate analysis, recipient gender, acute rejection and 6-month estimated GFR were significantly associated with graft survival (p < 0.05). Acute rejection became less significant (p = 0.0033) than 6-month estimated GFR (p = 0.0001) when 6-month estimated GFR was introduced in the stepwise regression procedures. CONCLUSION: We demonstrated that 6-month estimated GFR is a significant prognostic indicator in cadaveric renal transplantation and is an essential parameter in the regression modeling of long-term graft survival.

Adolescent↗
PubMed2004

The role of B7 ligands (CD80 and CD86) in CD152-mediated allograft tolerance: a crosscheck hypothesis.

BACKGROUND: The regulatory mechanism by which the B7 ligands (CD80 and CD86) direct the CD28/CD152 costimulatory pathways is unclear. This study investigated the role of CD80 and CD86 in a CD152-mediated allograft tolerance model. METHODS: A low-responding cardiac transplant model (BALB/c-->B10.A) with possible long-term acceptance was used. Immunocytochemical and flow cytometric analyses of the graft-infiltrating cells were conducted to characterize this transplant model. The influence of anti-CD80 and anti-CD86 treatments on the proliferation and interleukin (IL)-2 productions of the tolerated splenocytes (SC) was analyzed. The role of CD80 and CD86 in the induction and maintenance of the graft acceptance in this transplant model were also tested. RESULTS: B10.A mice could accept the BALA/c cardiac allografts (11/22), and an anti-CD152 antibody blocked the graft acceptance (10/10). Immunocytochemical and flow cytometric analyses showed that CD152+ cells were predominant among the CD4+ cells infiltrating the 100-day grafts of the B10.A recipients (B10.A-100). Either anti-CD80 or anti-CD86 treatment significantly enhanced polyclonal proliferation and IL-2 production of the B10.A-100 SC. Blockade of either CD80 or CD86 prohibited the tolerance transmitted by adoptive transfer, and anti-CD80 or anti-CD86 plus skin grafting undermined the established allograft tolerance. CONCLUSIONS: Both CD80 and CD86 were essential for the induction and maintenance of the CD152-mediated allograft tolerance.

Adoptive Transfer↗
PubMed2004

Hand-assisted versus total laparoscopic live donor nephrectomy.

BACKGROUND AND PURPOSE: The optimal minimally invasive procedure to procure live donor kidneys for renal transplantation has not been established. This study compared the donor outcome of hand-assisted laparoscopic live donor nephrectomy (H-LLDN) with total laparoscopic live donor nephrectomy (T-LLDN). METHODS: The outcomes of 12 donors undergoing H-LLDN were compared to that of a subsequent series of 12 donors undergoing T-LLDN. Body mass index, operation time, warm ischemia time, hospital stay, surgical complications, and short-term graft function were compared between the 2 groups. RESULTS: LLDN was successfully performed in all 24 donors. Both approaches resulted in excellent early graft function. The mean operation time in T-LLDN (215 minutes) was slightly shorter than that in H-LLDN (258 minutes), suggesting that the skills developed as surgeons learned the H-LLDN procedure had transferred to their performance of T-LLDN. The mean warm ischemia time of the T-LLDN group (4.5 minutes) was longer than that of the H-LLDN group (3.8 minutes), although this difference was not significant. One minor tear of the lumbar vein occurred in the H-LLDN group and the resultant bleeding necessitated blood transfusion. One mechanical failure occurred when the renal vein was divided by endoscopic gastrointestinal anastomosis in the T-LLDN group. The length of hospital stay, resumption of diet, and the use of narcotic analgesics were not different between the 2 groups. CONCLUSIONS: Both H-LLDN and T-LLDN are safe and effective approaches for the procurement of live donor kidneys. The benefits of the H-LLDN technique include direct manual control of the operative field and increased safety margin. The development of a hospital LLDN program by starting with a hand-assisted approach may reduce the potential bleeding complications and facilitate the safe transition to the cosmetically preferable total laparoscopic approach.

Adult↗
PubMed2003

Effect of sirolimus in combination with low-dose cyclosporine and steroids on acute renal allograft rejection.

BACKGROUND AND PURPOSE: Sirolimus is a novel immunosuppressive drug with much less nephrotoxicity than cyclosporine. The efficacy and toxicity of the combination of sirolimus and low-dose cyclosporine therapy were compared with data from records of a previous cyclosporine-based regimen used in patients with renal allograft transplantation. PATIENTS AND METHODS: A prospective study was conducted to assess the clinical effects of a sirolimus (6 mg loading dose over 48 hours plus 2 mg/day maintenance)/cyclosporine (8 mg/kg/day) combination regimen. Three male and 9 female renal transplant recipients were enrolled in the study. The primary endpoint was the incidence of acute rejection. The efficacy and adverse effects of the combined therapy were compared with those recorded in medical records of 24 renal transplant recipients who had received a cyclosporine-based regimen (10 mg/kg/day). RESULTS: The 12-month acute rejection rate of the study group was 16.67% (2/12), and that of the cyclosporine-based group 29.16% (7/24). One patient in the study group died of complications sustained during a radical operation for recurrent bladder carcinoma during the sixth post-transplant month. The 12-month graft and patient survival rates of the study group were both 91.8%. In the 12 months post-transplant, the mean serum creatinine levels of the study group were significantly lower than those of the historic group at months 1, 3, and 4. The average cyclosporine trough levels of the study group were significantly lower than those of the historic group at months 1, 2, and 12. The average daily doses of prednisolone in the study group were also lower than those of the historic group at months 2, 3, 4, and 12. CONCLUSIONS: The sirolimus/cyclosporine combination regimen reduced the incidence of acute renal allograft rejection, did not affect renal function, and reduced the dosage of cyclosporine and steroids compared with the cyclosporine regimen.

Acute Disease↗
PubMed2003

Successful living-related renal transplantation in a 2-year-old girl weighing less than 10 kilograms.

The success of renal transplantation for infants weighing less than 10 kg is very limited because of graft thrombosis. We report a successful living-related renal transplant in a 2-year-old girl weighing 9.5 kg. Chronic renal failure was diagnosed 1 month before the transplantation. Laparoscopic donor nephrectomy was performed to retrieve the left kidney of her father, a 36-year-old man weighing 70 kg, and the recipient operation was conducted via a right retroperitoneal approach. The right native kidney of the recipient was removed to accommodate the graft kidney during the transplant surgery. The graft renal artery, renal vein, and ureter were anastomosed to the recipient abdominal aorta, inferior vena cava, and bladder, respectively. The abdominal fascial defect was closed with absorbable mesh grafting, and the skin was closed primarily. With intensive fluid therapy and monitoring after reperfusion of the graft kidney, the patient recovered uneventfully and was discharged with an FK506-based immunosuppressive regimen 2 weeks after the operation. Renal function was good, and serum creatinine was 0.5 mg/dL 6 months after the operation.

Body Weight↗
PubMed2003

Sirolimus add-on rescue therapy can benefit patients with chronic renal allograft dysfunction.

BACKGROUND AND PURPOSE: Nephrotoxicity caused by calcineurin inhibitors (CNIs) contributes to chronic renal allograft dysfunction (CRAD). This retrospective cohort study evaluated the immunosuppressive and nephrotoxic effects of sirolimus add-on therapy with minimization of CNI in patients with CRAD. METHODS: Twenty patients with CRAD were recruited to receive sirolimus add-on rescue (SRL-AR) therapy. The SRL-AR therapy added 6 mg of sirolimus for loading and 2 mg/day for maintenance to CNI-based maintenance immunosuppressive regimens and reduced the dose of CNI, either cyclosporine or tacrolimus, by half at the initiation of sirolimus loading. The primary endpoint of the study was estimated glomerular filtration rate (GFR) determined using the Cockcroft-Gault formula. The efficacy of this SRL-AR therapy was evaluated by comparison to a historic group of 30 patients with CRAD who received a tacrolimus-based rescue therapy. RESULTS: Of the 20 patients receiving sirolimus therapy, 2 had graft failure during the 12-month follow-up. The post-rescue GFR values of the patients receiving sirolimus therapy showed greater improvement than those of the historic group during follow-up except for month 8, with the differences in GFR changes reaching significance at months 1 to 5 (p < 0.05). Multiple regression analysis identified graft age and GFR upon rescue in addition to the SRL-AR therapy as significant factors associated with post-rescue GFR changes. CONCLUSIONS: This study demonstrated that SRL-AR therapy combined with reduced CNI doses could effectively improve short-term renal function of patients with CRAD. The long-term outcome of rescuing CRAD is likely to depend on factors including graft age and GFR upon rescue.

Adolescent↗
PubMed2002

Handport-assisted laparoscopic living-donor nephrectomy; initial experience in Taiwan.

The feasibility of handport-assisted laparoscopic living-donor nephrectomy in Taiwan was assessed by comparison with conventional open nephrectomy. Six serial patients undergoing laparoscopic living-donor nephrectomy (LLDN) were compared with six patients undergoing open donor nephrectomy. Body-mass index (BMI), operating time, hospital stay, and short-term graft function were assessed in both groups of patients. Handport-assisted LLDN was successfully attempted in all six patients. Mean ischemic time was 4.5 min in the laparoscopic group. There was no major complication in either group. Short-term graft function was good in all patients, except for one case of chronic rejection with mild azotemia in the open group. The length of stay was significantly longer in the open group, but the operation time of the laparoscopic group was much longer than that of the open group. There was no difference in the resumption of diet and in the use of narcotic analgesics in addition to patient-controlled analgesia. LLDN is a technically demanding approach. With handport assistance, the surgeons could shorten their learning curve. While initial graft function rates are equal to those of the open method, cosmesis and hospital stay are improved by the laparoscopic approach. Longer follow-up and larger patient numbers are needed to confirm these initial results in Taiwan.

Adult↗
PubMed2002

Reduction of human-to-pig cellular response by alteration of porcine MHC with human HLA DPW0401 exogenes.

BACKGROUND: In pig-to-human discordant xenotransplantation, the xenograft can be rejected by a formidable human xenogenic T-cell response, even if the graft has gone through hyperacute rejection or delayed xenograft rejection (acute vascular rejection). We therefore examined, in this study, whether the human-to-pig cellular response could be attenuated through the generation of a transgenic pig for human HLA II. METHODS: With the technique of microinjection, we produced the HLA DPw0401 transgenic pig. The expression of the HLA DPw0401 gene on peripheral blood mononuclear cells (PBMCs) of the transgenic pig was examined by reverse transcriptase-polymerase chain reaction and flow cytometry. The antigenicity of the transgenic HLA DPw0401 molecule was tested by the HLA DPw0401-primed lymphocyte test reagent. The cellular response was analyzed by xenogenic mixed lymphocyte culture. RESULTS: The mRNA and protein of HLA DPw0401 were expressed in the PBMCs of the transgenic pig. The PBMCs of the HLA transgenic pig induced a stronger cellular reaction to HLA DPw0401-primed lymphocyte test reagents than the nontransgenic littermate pig (n=7, P<0.01). In direct xenogenic mixed lymphocyte culture with responders from HLA DPw0401(+) humans, the PBMCs from the HLA DPw0401 transgenic pig, as compared with those from the normal pig, induced a lower degree of xenogenic cellular response to human PBMCs (n=4, P=0.08). CONCLUSIONS: Our preliminary data demonstrated the possibility that the human HLA DPw0401 phenotype can be transferred onto porcine cells through the generation of HLA transgenic pigs and make the PBMCs of humans more tolerant to porcine cells.

Animals↗
PubMed2002

Efficacy of low-dose mycophenolate mofetil therapy for Taiwanese renal transplantation patients receiving primary cyclosporine immunosuppression.

BACKGROUND AND PURPOSE: Mycophenolate mofetil (MMF) in combination with cyclosporine or tacrolimus prevents acute rejection and chronic allograft failure in renal transplantation in Western countries. We began to add low-dose MMF to primary cyclosporine immunosuppressive therapy in renal transplantation at the Department of Surgery of National Taiwan University Hospital in 1998. This study compared low-dose MMF to conventional therapy in Taiwanese renal transplant recipients. METHODS: This retrospective cohort study determined the efficacy of low-dose MMF therapy (1 g/day in divided doses). A total of 275 cases with allograft kidney transplants were grouped according to whether they received transplants before or after the adoption of MMF therapy (Period I: 1987-1993; Period II: 1994-1997; Period III: 1998-September 2000). The prognostic significance of MMF therapy and graft and patient survival rate in each time period were assessed. RESULTS: The 18-month graft survival rate was 84.9% in Period I, 86.3% in Period II, and 91.9% in Period III. The 5-year graft survival rates in Periods I and II were 69.3% and 76.6%, respectively. Acute rejection was significantly detrimental to graft survival (p = 0.048), while MMF therapy was significantly advantageous to graft survival (p = 0.015); treatment when MMF was available was also significantly associated with better graft survival (p = 0.043). There was a negative correlation between acute rejection and graft survival (p = 0.035); MMF therapy produced a protective effect on graft survival independent of acute rejection (p = 0.010). CONCLUSION: Low-dose MMF therapy significantly improved graft survival after renal transplantation in Taiwanese kidney allograft recipients.

Acute Disease↗