| Objective:1. Shorten the warm ischemia time will benefits the graft survival. Complex multiorgan procurement including perfusion, dissection and preservation simultaneously has lots of advantages, it can minimize the ischemia time, reduce the tissue injury related to ischemia-reperfusion, improve the clinical outcome and overcome the limitation of donor source to meet the needs in multiple tissue and organ transplantation.2. To discuss the optimal way of organ harvesting (kidney, liver) including operation device, dissection methods and perfusion solution choosing. Basing on these three parts, we want to develop a set of suitable technique to achieve best cost-effectiveness.3. Using the randomized, open-label, comparative study to evaluate the efficacy and safety of steroids tapering in tacrolimus/cyclosporine based triple immunosuppression regimen in renal transplant recipients.MethodsSection â… The impact of perfusion, dissection and preservation on the outcome of renal transplantation (Animal model)Animal experiment: Ten dogs including male and female were divided into group A and group B (5 in each group) without heparin usage before operation. In Group A, we used the operation device came from self-producer of our center to do perfusion, dissection and preservation of multiple organ simultaneously. After opening incision, cannulas were placed into abdominal aorta for in situ low temperature perfusion. No organ was dissociated before perfusion. Conventional methods were performed inGroup B. Operation duration, warm and cold ischemia time were recorded in both groups. The objective is to evaluate the difference between two groups on warm ischemia, cold ischemia, organ usage and quality of organ preservation.Section â…¡The effect of perfusion, dissection and preservation of donor organ on the clinicaloutcome of renal transplantation (Clinical study)Clinical study: Group A adopted complex multiorgan procurement while Group B used conventional technique to remove, perfuse and preserve the kidney which had been used for ten years in our center. The objective was to compare the difference of warm ischemia, utilization rate of tissue and organs and total cost in these two groups..After using in situ perfusion and dissection, Group A got 52 kidneys and 15 livers. There were three steps in organ procurement: â‘ Establish in situ low temperature perfusion. â‘¡Remove liver â‘¢ Remove kidney.Group B used the conventional procedure: Remove kidney firstly, then gives perfusion. The total number of the kidney obtained was 12.Section â…¢Is the choice of immunosuppression agents will take effect on the clinicaloutcome of renal transplantation?This study is a randomized, open-label comparative trial. Sixty patients were randomized into two groups as the ratio of 2:1. Group A (n=40) received triple therapy and the protocol was tacrolimus +Aza+steroids; group B(n=20) administered cyclosporine+Aza+steroids. After that, the dosage of Aza and steroids were gradually reduced according to the following protocol. Patients were followed at Week 1, 2, 4, 8 and 12 postoperation. At each visit, clinical and laboratory assessment were carried out. Patients would take the tapering regimen if the serum creatinine is stable (<2.0mg/dl) and no rejection episode during the study period. On the contrary, if thecreatine was more than 2.0mg/dl or there was an acute rejection, the original immunosuppression regimen would go on basing on the experience.Study medication Tacrolimus (FK506) group:FK506 was administered after 48 hours posttransplantation at a dosage of 0.1-0.2mg/kg/d. In the first on 30 days, the through concentration was adjusted to 10-20ng/ml, then decreased to 5-15ng/ml. FK506 was given every 12 hours per day and should be concerned the influence of the food. Cvclosporine (CsA) group:CsA was administered after 48 hours posttranplantation. The dosage was 6-llmg/kg/d and divided into twice a day. In the first 30 days the through concentration was adjusted to 200-400mg/ml, then tapered to 150-300mg/ml . Azathioprine(Aza)Initial dose was 0.1-0.2g/d and reduced to 0.05-0.lg/d after one month.Steroids reduction/withdrawl in FK506 groupDay 0: Methylprednisolone(MP) lg ivdripDay 1 :MP 0.5g ivdripDay 2:MP0.5g ivdripDay 3: Prednisone lmg/kg/d PO.qdFrom day 4, prednisone was reduced 5mg everyday until 15mg/d PO, then reduced2.5mg every 2-4 weeks till O.lmg/kg.doIf the serum creatinine<2.0mg/dl and no rejection episode, steroids could bedecreased again or even discontinued.Steroids reduction/withdrawl in CsA group Day 0: MP lg ivdrip Day l:MP0.5g ivdripDay 2:MP0.5g ivdripDay 3: Prednisone lmg/kg/d PO.qdFrom day 4, prednisone was reduced 5mg everyday until 20mg/d PO.By Day 30 reduced 5mg prednisone tol5mg PO.qd. If the serum creatinine<2.0mg/dland no rejection episode, in the first three months steroids could be reduced again?Target through concentration of FK506 Day 0-30: 10-15ng/ml Day 31-365: 5-15ng/mlTarget through concentration of CsA Day 0-30: 200-400mg/ml, Day31-365:150-300mg/mlResult 1: It was different about the organ dissection time in two different groups. Group A used the self-producer device to perform the perfusion, dissection and preservation of multiorgan simultaneously. The mean value of warm ischemia time is 4 minutes; cold ischemia time is 1.5 hours. Group B firstly excised the kidneys, and then gave perfusion and preservation. The mean value of warm ischemia time is 8 minutes, which was longer than Group A, while cold ischemia time is same 1.5 hours. There were significant difference on organ utilization and quality of preservation. For Group A, ten kidneys were all perfused completely, perfusion pressures 120mmHg. After perfusion, the kidneys were pale colored without piebald and petechiae. In Group B, only 5 kidneys got complete perfusion; the perfusion pressure in 3 kidneys was more than 120mmHg; the other 2 kidneys occurred petechiae. Since the coagulation was fast in the dog, these two kidneys could not be used in transplantation.Result 2: The mean time from non-heart beating to get ready for operation was2.5min in Group A., and the period of establishment of low temperature perfusion from opening incision was 1.5min, mean time of warm ischemia of liver and kidney were 4min. Urine excretion could be seen in 1-8 minutes after blood vessel was opened in all of the forty renal transplant recipients. Nobody needed dialysis after operation. Group B took a mean time of 2.5min to get ready for operation, the duration of operation was 5.5 min and warm ischemia time is 8 min. 10 patients (50%) had urine excretion in 1-8 min after opening blood vessels. Urine excretion delayed to 20 min in 2 patients and the 2 patients needs dialysis therapy once or twice because of oligauria.Result 3: FK506+Aza+Pred CSA+Aza+PredPatient and graft survival 100% (40/40) 100% (20/20)Acute rejection 10% (4/40) 40% (8/20)ATN 5.00% (2/40) 5.00% (1/20)PTLD 0% 0%Mean serun crestinine at 3 months 95 + 12 125 + 23 (fj.mol/L)Hypertension 10.0%(4/40) 15.0%(3/20)Hyperlipemia 10%(4/40) 25.0%(5/20)New onset of insulin- dependent diabetes 0 0Gastrointestinal complication 5.0% (2/40) 5.0% (1/20)Infection rate 10.0% (4/40) 10.0%(2/20)Cushing syndrome 0 40% (8/20)Osteoporosis and/or avascular necrosis of 0 0 the femoral headMental disturbance, hirsutism 0 80.0% (16/20)Neurotoxicity 5.0% (2/40) 10%(2/20)Nephrotoxicity No NoQuality of life Good Good...
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