Flank donor nephrectomy: efficacy in the donor and recipient

Since August 1983, 115 patients have undergone live donor nephrectomy via an extraperitoneal flank approach with rib resection. Over-all hospital stay was short and morbidity was negligible. Early graft function was excellent as determined by urinary output in the first 20 hours postoperatively (mean 6,442 cc) and low nadir serum creatinine (mean 1.57 mg. per dl.). Acute tubular necrosis or urinary fistula developed in 3 kidneys (2.6 per cent). In the entire series, only 1 graft (0.8 per cent) was lost to technical complications. We conclude that an extraperitoneal flank approach to live donor nephrectomy is safe for the donor, and provides a structurally and functionally sound allograft for the recipient.     

体液免疫在不同纲(罗非鱼/大鼠)肝细胞移植排斥反应中的作用

目的探讨罗非鱼到大鼠肝细胞移植的体液免疫排斥反应机制。方法SD大鼠随机分为移植组和对照组。对照组脾内注射生理盐水,实验组脾内移植2×10~7个罗非鱼肝细胞。术后以苏木素-伊红(HE)染色法观察移植物组织学变化,免疫组织化学SABC法检测移植物周围大鼠IgM、IgG。结果移植后2h罗非鱼肝细胞形态完整,4h部分肝细胞边界不清,核固缩、溶解,8 h后很难见到正常肝细胞。移植后1h移植物周围可见IgM,18h移植物周围可见IgG。结论罗非鱼肝细胞移植到大鼠脾脏内可短期存活,体液免疫诱发的超急性排斥反应是导致其早期死亡的原因之一。     

猪到食蟹猴异种小肠移植后受体凝血功能变化的研究

目的研究猪到食蟹猴异种小肠移植后,不同时间点受体凝血功能的变化,并探讨其与超急性异种排斥反应（HAXR）的关系。方法建立猪到食蟹猴异位节段小肠移植模型,分别在移植前及移植小肠再灌注后15,30,60,120rain各时间点行常规凝血指标检查和血栓弹力图（TEG）检查,分析小肠移植术后受体凝血功能的变化,判断移植肠存活情况。结果共行猪到食蟹猴异种节段小肠移植5例,血管吻合成功率为100％,移植小肠中位存活时间为165rain（33-245min）。移植小肠再灌注后30min,抗凝血酶Ⅲ由术前（100±19）％降至（54±16）％,凝血酶原时间由术前（11±2）S升至（20±5）s,部分活化的凝血酶时间由术前（21±3）S升至（88±29）S,国际标准化比值由术前1．0±0．2升至1．7±0．3。再灌注后60min,D-二聚体由术前（0．09±0．07）mg／L升至（0．70±0．49）mg/L。再灌注后120min,受体纤维蛋白原由术前（1．81±0．24）g/L降至（0．76±0．17）g／L,血小板计数由术前（340±81）×10^9逐渐降低至（155±7）×10^9。移植小肠再灌注后60rain,TEG指标与术前相比,LY30由（4±2）％升至（31±7）％,最大振幅由（63±5）mm降至（25±16）mm。再灌注后120min,受体R值由（6．9±1．3）血n升至（16．8±2．7）min,K值由（2±1）min升至（15±5）min。TEG曲线提示,移植前受体凝血功能正常,移植小肠再灌注15,30min后,受体凝血功能呈现高凝状态,合并纤溶亢进;移植小肠再灌注后60,120min,受体凝血功能表现为消耗性低凝状态。所有受体在移植后均出现典型的超急性异种排斥反应（HAXR）病理表现,主要为移植小肠黏膜充血、水肿、散在出血点以及间质出血表现。结论受体凝血功能随HAXR发生而出现逐渐恶化的趋势,凝血功能检测可以在一定程度上反映HAXR的发生情况。     

细胞免疫在不同纲(罗非鱼/大鼠)肝细胞移植排斥反应中的作用

目的 探讨罗非鱼到大鼠肝细胞移植的细胞免疫排斥反应机制.方法 SD 大鼠随机分为移植组和对照组,实验组脾内移植2伊107 个罗非鱼肝细胞,对照组脾内注射生理盐水.术后以HE 染色法观察移植物组织学变化,SABC 免疫组化法检测移植物周围大鼠CD4、CD8 阳性细胞.结果 肝移植术后2 h 罗非鱼肝细胞形态完整,4 h出现部分肝细胞边界不清,核固缩、溶解,8 h 后很难见到正常肝细胞.移植后4 h 移植物周围可见CD4 和CD8 阳性细胞聚集.结论 在罗非鱼肝细胞移植到大鼠脾内诱发的排斥反应中,细胞免疫可能具有重要作用.     

Laparoscopic live donor nephrectomy: the recipient

BACKGROUND: Laparoscopic live donor nephrectomy offers advantages to the donor in terms of decreased pain and shorter recuperation. Heretofore no detailed analysis of the recipient of laparoscopically procured kidneys has been performed. The purpose of this study was to determine whether laparoscopic donor nephrectomy had any deleterious effect on the recipient. METHODS: A retrospective review was conducted of all live donor renal transplantations performed from January 1995 through April 1998. The control group received kidneys procured via a standard flank approach (Open). Rejection was diagnosed histologically. Creatinine clearance was calculated using the Cockroft-Gault formula. RESULTS: A total of 110 patients received kidneys from laparoscopic (Lap) and 48 from open donors. One-year recipient (100% vs. 97.0%) and graft (93.5% vs. 91.1%) survival rates were similar for the Open and Lap groups, respectively. A similar incidence of vascular thrombosis (3.4% vs. 2.1%, P=NS) and ureteral complications (9.1% vs. 6.3%, P=NS) were seen in the Lap and Open groups, respectively. The incidence of acute rejection for the first month was 30.1% for the Lap group and 31.9% for the Open group (P=NS). The rate of decline of serum creatinine level in the early posttransplantation period was initially greater in the Open group, but by postoperative day 4 no significant difference existed. No difference was observed in allograft function long-term. The median length of hospital stay was 7.0 days for both groups. CONCLUSIONS: Laparoscopic live donor nephrectomy does not adversely effect recipient outcome. The previously demonstrated benefits to the donor, and the increased willingness of individuals to undergo live kidney donation, coupled with the acceptable outcomes experienced by recipients of laparoscopically procured kidneys justifies the continued development and adoption of this operation.     

Early weaning completely eliminates porcine cytomegalovirus from a newly established pig donor facility for xenotransplantation

For clinical xenotransplantation, transplants must be free of porcine cytomegalovirus (PCMV). Piglets become infected primarily in the perinatal period by the mother sow. While individual donor animals can be protected from infection by isolation husbandry, success is not guaranteed and this strategy poses the risk of undetected infections and raises animal welfare questions. Here, we present the establishment of a completely PCMV‐negative pig herd for breeding donor animals for xenotransplantation. Eleven pregnant DanAvl Basic hybrid sows were purchased from a designated pathogen‐free (DPF), PCMV‐positive colony and transferred to a new pig facility at the Centre for Innovative Medical Models (CiMM) 4 weeks prior to farrowing. At the age of 24 hours, piglets were early‐weaned and transferred to a commercially available Rescue Deck system dedicated to motherless rearing of piglets. Sows were removed from the facility. The PCMV status of F1‐generation animals was determined at regular intervals over a period of 14 months by a sensitive real‐time PCR‐based detection method testing blood, nasal swabs and cultured peripheral blood mononuclear cells (PBMCs). F1 sows were used as recipients of genetically modified embryos to generate a xenotransplant donor herd. Offspring were tested for PCMV accordingly. All offspring have remained PCMV negative over the whole observation period of 14 months. A completely PCMV‐negative pig herd for xenotransplantation has thus been successfully established.     

The use of donor and recipient screening for toxoplasma in the era of universal trimethoprim sulfamethoxazole prophylaxis

BACKGROUND: Toxoplasmosis is a serious complication of solid organ transplantation. The highest risk of infection and disease occurs in heart recipients with primary infection transmitted by a seropositive donor to a seronegative recipient (donor-recipient mismatch). Toxoplasmosis has been reported to occur in noncardiac transplant recipients; however, no large studies examining the frequency of such events or the need for serologic screening exist. METHODS: A retrospective cohort study of 1,006 solid organ transplant recipients transplanted in our center between 1984 and 1997 was performed to examine the incidence of Toxoplasma seroconversion, reactivation, and clinical toxoplasmosis and to evaluate the impact of trimethoprim sulfamethoxazole (TMP/SMX) prophylaxis on these outcomes. RESULTS: Pretransplant Toxoplasma seroprevalence was 13.4% in donors and 17.8% in recipients. The incidence of Toxoplasma donor-recipient mismatch was 9.5% during the 14-year study period, and only 39.1% of mismatched recipients received TMP/SMX prophylaxis. Only four patients seroconverted, of whom two had received prophylaxis. There were no cases of clinical disease; either primary or reactivation. CONCLUSIONS: We therefore conclude that in transplant centers with low Toxoplasma seroprevalence, routine screening for Toxoplasma in solid organ donors and recipients is not necessary, particularly in the era of routine TMP/SMX prophylaxis.     

Complement and renal transplantation: from donor to recipient

Long-term kidney graft survival is affected by different variables including donor condition, ischemia-reperfusion injury, and graft rejection during the transplantation process. The complement system is an important mediator of renal ischemia-reperfusion injury and in rejecting allografts. However, donor complement C3 seems to be crucial in renal transplantation-related injury as renal injury is attenuated in C3 deficient kidney grafts. Interestingly, before ischemia-reperfusion induced C3 expression, C3 is already induced in donors suffering from brain death. Therefore, strategies targeting complement activation in the brain-dead donor may increase graft viability and transplant outcome.     

A review of pig liver xenotransplantation: Current problems and recent progress

Pig liver xenotransplantation appears to be more perplexing when compared to heart or kidney xenotransplantation, even though great progress has been achieved. The relevant molecular mechanisms involved in xenogeneic rejection, including coagulopathy, and particularly thrombocytopenia, are complex, and need to be systematically investigated. The deletion of expression of Gal antigens in the liver graft highlights the injurious impact of nonGal antigens, which continue to induce humoral rejection. Innate immunity, particularly mediated by macrophages and natural killer cells, interplays with inflammation and coagulation disorders. Kupffer cells and liver sinusoidal endothelial cells (LSECs) together mediate leukocyte, erythrocyte, and platelet sequestration and phagocytosis, which can be exacerbated by increased cytokine production, cell desialylation, and interspecies incompatibilities. The coagulation cascade is activated by release of tissue factor which can be dependent or independent of the xenoreactive immune response. Depletion of endothelial anticoagulants and anti‐platelet capacity amplify coagulation activation, and interspecies incompatibilities of coagulation‐regulatory proteins facilitate dysregulation. LSECs involved in platelet phagocytosis and transcytosis, coupled with hepatocyte‐mediated degradation, are responsible for thrombocytopenia. Adaptive immunity could also be problematic in long‐term liver graft survival. Currently, relevant evidence and study results of various genetic modifications to the pig donor need to be fully determined, with the aim of identifying the ideal transgene combination for pig liver xenotransplantation. We believe that clinical trials of pig liver xenotransplantation should initially be considered as a bridge to allotransplantation.     

Hypertension in renal transplantation: donor and recipient risk factors

AIMS: To determine the respective roles of donor and recipient factors in the subsequent development of hypertension after renal transplantation. PATIENTS AND METHODS: All the patients transplanted between January 1990 and December 1999 who still had a functioning graft 1 year post-transplant (n = 321) were retrospectively studied. Blood pressure was assessed at 1 year post-transplant. Hypertension was defined as a systolic BP > or equal 140 mmHg or diastolic BP > or equal 90 mmHg, or use of antihypertensive medication. Relevant donor and recipient characteristics were recorded. RESULTS: Two-hundred-and-sixty-three patients (82%) were hypertensive. In multivariate analysis, pretransplant hypertension (RR, 1.74, 95% CI, 1.07 to 2.87), anticalcineurin use (RR, 2.59, 95% CI, 1.13 to 5.92), urinary protein excretion (RR, 1.84, 95% CI, 1.06 to 3.18), BMI (RR, 1.08, 95% CI, 1.01 to 1.16), donor age (RR, 1.28,95% CI, 1.05 to 1.59, for each 10-year increase in donor age) and donor aortorenal atheroma (OR, 2.34; 95% CI, 1.24 to 4.46) were associated with hypertension. Among patients under calcineurin inhibitors, those receiving cyclosporine were more prone to have hypertension than those receiving tacrolimus (88.7% vs 78%; p = 0.04). CONCLUSION: Both recipient and donor factors contribute to hypertension in RTR.     

受体血清“封闭”供肝与眼镜蛇毒因子抑制异种肝移植超急排斥反应的协同作用

目的 探讨受体血清(recipient serum,RS)“封闭”供肝与眼镜蛇毒因子(CVF)抑制肝移植超急性排斥反应(HAR)的协同作用.方法 采用改良“双套管法”制作豚鼠→SD大鼠原位肝移植HAR模型.取豚鼠和SD大鼠各24只,分别作为供体和受体.供受体随机配对.移植前采集受体大鼠近交系其他个体血清,灭活补体备用.实验随机分为4组(n=6),受体血清(RS)实验组移植前用0.1％ RS的林格氏液(Ringer)“封闭”供肝,CVF实验组受体大鼠在术前24h经尾静脉注射CVF 50 μg/kg,另设RS+CVF联合实验组和Ringer液对照组.采用改良“双套管法”行豚鼠→SD大鼠原位肝移植;观察供肝植入后形态学改变、受体存活时间、移植肝病理损害程度和受体肝功能.结果 各实验组大鼠异种供肝植入后均未见明显花斑样改变.各实验组大鼠移植后存活时间较对照组[(45.2±13.9)min]均明显延长(P＜0.05),其中RS+CVF组大鼠存活时间[(161.5±30.9) min]长于RS组[(88.1±19.7) min](P＜0.01)或CVF组[(125.2±25.5)min] (P＜0.05).各实验组大鼠血清丙氨酸转氨酶(ALT)均明显低于对照组[(126.1±23.3)U/L] (P＜0.05),RS+ CVF组ALT[(63.2±13.9)U/L]明显低于CVF组[(79.9±18.1)U/L](P＜0.05)或RS组[(106.1±19.3)U/L](P＜0.01).各实验组移植肝血栓、出血、水肿等病理损害(积分)均较对照组明显减轻(P＜0.05),其中RS+CVF组大鼠移植肝病理损害最轻(P＜0.05).结论 受体血清“封闭”供肝与CVF对肝移植HAR均具有一定的抑制作用,两者具有协同作用.     

Transplant recipient renal function is donor renal mass- and recipient gender-dependent.

The effect of both donor renal mass and gender on renal function, in both gender recipients, was examined. Qualifying consecutive living-donor renal transplants (n = 730) were stratified into 4 donor-recipient groups: female-female (n = 177), male-female (n = 151), female-male (n = 240), male-male (n = 162). Groups were equivalent in age, race, body mass index (BMI), match, ischemia time, operative time, and estimated glomerular filtration rate (eGFR). Female recipients had lower serum creatinine (Cr(s)). Male recipients had higher Cr(s) wherever they received a female allograft. Male recipients of male kidneys had a higher eGFR than all other groups for 3 years. Renal function of the recipient correlated with the renal mass of the donor within each group. Male and female kidneys functioned equivalently in the female-recipient environment. Large nephron-mass male donor kidneys function more poorly in female recipients. The male kidney loses 15-20 ml/min eGFR in the female host. The diminished graft function may be related to androgen deprivation. Female and male donor kidneys function equivalently in the male recipient if adjusted for renal mass transplanted. Female kidneys improve eGFR by 7-10 ml/min by being transplanted into a male environment. Donor renal mass and gender affect recipient graft function Expectations of ultimate recipient renal function should take into account both the gender and mass disparity of the donor-recipient pair.