The Stockholm experience with ABO-incompatible kidney transplantations without splenectomy

BACKGROUND: ABO-incompatible kidney transplantations have previously only been performed after several pre-operative sessions of plasmapheresis followed by splenectomy, and with the conventional triple-drug immunosuppressive protocol being reinforced with anti-lymphocyte globulin and B-cell-specific drugs. We have designed a protocol without splenectomy, based on antigen-specific immunoadsorption, rituximab and a conventional triple-drug immunosuppressive protocol. METHODS: The protocol called for a 1-month pre-transplantation conditioning period, starting with one dosage of rituximab and followed by full-dose tacrolimus, mycophenolate mofetil and prednisolone. Antigen-specific immunoadsorption was performed on pre-transplantation days -6, -5, -2 and -1. After the last session, 0.5 g/kg of intravenous immunoglobulin (IVIG) was administered. Postoperatively, three more apheresis sessions were given every third day. RESULTS: Twenty-one patients have received transplants with this protocol. The ABO-antibodies (Abs) were readily removed by the antigen-specific immunoadsorption and were kept at a low level post-transplantation by further adsorptions. There were no side effects, and all but one patient have normal renal transplant function. CONCLUSIONS: We conclude that after one infusion each of rituximab and IVIG, and antigen-specific immunoadsorption, blood-group incompatible renal transplantations can be performed with standard immunosuppression and without splenectomy, and with excellent short- and long-term results.     

Successful ABO-incompatible kidney transplantations without splenectomy using antigen-specific immunoadsorption and rituximab

BACKGROUND: Historically, ABO-incompatible kidney transplantations have only been undertaken after splenectomy and unspecific plasmapheresis and with quadruple drug immunosuppression plus B-cell specific drugs. We have evaluated a protocol for ABO-incompatible kidney transplantation without splenectomy using antigen-specific immunoadsorption, rituximab, and a conventional triple-drug immunosuppressive regimen. METHODS: The protocol called for a 10-day pretransplant conditioning period starting with one dosage of rituximab and followed by full dose tacrolimus, mycophenolate mofetil, and prednisolone. Antigen-specific immunoadsorption was performed on pretransplant days -6, -5, -4, and -1. After the last session, 0.5 g/kg of intravenous immunoglobulin was administered. Postoperatively, three more apheresis sessions were given every third day. Furthermore, if there was a significant increase in the antibody titers, extra sessions were considered. RESULTS: Four patients have received transplants with this protocol. The donor-recipient blood groups were A2/O, B/O, B/A, and A1/O. The ABO-antibodies were readily removed by the antigen-specific immunoadsorption and were kept at a low level posttransplantation by further adsorptions. There were no side effects, and all patients have normal renal-transplant function. CONCLUSIONS: We conclude that after one infusion each of rituximab and intravenous immunoglobulin and antigen-specific immunoadsorption, blood-group-incompatible renal transplantations can be performed with standard immunosuppression and without splenectomy.     

Bleeding complications in pediatric ABO-incompatible kidney transplantation

Background

ABO-incompatible renal transplantation (ABOi-RTx) following preconditioning with immunoadsorption (IA) and rituximab is a promising approach to facilitate living-related RTx. However, clinical experience is limited in pediatric patients.

Methods

Three patients underwent living-related ABOi-RTx in our center. Preoperative IA was performed six, ten and 11 times in patient one, two and three, respectively, to achieve isoagglutinin titers of ≤1:8 on the day of transplantation; rituximab was administered once. The immunosuppressive regimen further comprised tacrolimus, mycophenolate, methylprednisolone and basiliximab; immunoglobulin G (IgG) was infused on the day of ABOi-RTx.

Results

All three patients achieved normal renal function within 2–6 days post-RTx. Major postoperative bleeding occurred in two patients, with one requiring repeated blood transfusions and the other a surgical revision 4 h after RTx, despite local citrate anticoagulation use during the preoperative IA procedures in the latter patient. A pyelonephritis-associated increase of the isoagglutinin IgG/IgM titers to 1:64/1:128 led to a biopsy-proven acute humoral rejection in the third patient, which was treated successfully with plasma exchange and methylprednisolone pulses. The estimated glomerular filtration rate at 18, 8 and 23 months post-RTx was 96, 52 and 74 ml/min/1.73 m², respectively.

Conclusions

ABOi-RTx can successfully be performed in pediatric patients after preconditioning with quadruple immunosuppression, rituximab and IA. Caution is required regarding bleeding complications, which are most likely due to the unspecific binding of coagulation factors during repeated IA.     

ABO-incompatible pediatric kidney transplantation in a single-center trial

We have performed ten pediatric kidney transplantations from living-related ABO-incompatible donors. All patients underwent preoperative plasmapheresis with or without immunoadsorption to reduce isoagglutinin. Primary immunosuppression consisted of methyl-prednisolone, cyclosporin or tacrolimus, azathioprine, anti-lymphocyte globulin, and/or deoxyspergualin. At transplantation splenectomy was simultaneously performed in all patients. Median follow-up is 65 months (range 4-95 months). The patient and graft survival rates are 100% to date. Post-transplantation isoagglutinin titers did not increase more than 1:32, except for 1 patient, without uncontrollable vascular rejection episodes. Despite the heavy immunosuppressive regimen, cytomegalovirus infection occurred in only three patients, who were successfully treated with ganciclovir and cytomegalovirus high-titer gamma globulin. Our small series clearly shows that the preoperative reduction of isoagglutinin, splenectomy, and strict immunosuppressive therapy lead to successful long-term results in children.     

Second cadaveric kidney transplantations in the pediatric population

Objective

To evaluate the functional outcomes and complications among a series of second in comparison to first kidney transplantations in pediatric patients.

Materials and methods

We reviewed 163 consecutive kidney transplants in pediatric recipients performed from 1978 to present: 120 cases (69.3%) were first transplants (group A) and 43 (24.8%), second transplant (group B). We analyzed the incidences of delayed graft function (DGF), medical and surgical complications, as well as medium- and long-term graft survivals.

Results

We observed DGF among 51 group A patients (43%) versus 32.5% of group B. Ten patients suffered vascular complications in group A (8.3%) versus one in group B (2.3%) (P < .05). The 15-year graft survivals were 54.2% for group A and 45% for group B. The 15-year patient survivals were 84.9% in group A versus 93.6% in group B.

Conclusions

Second kidney transplantations for children are a satisfactory option that achieves good functional results as well as acceptable graft and patient survivals.     

Implementation of a Protocol for ABO-incompatible kidney transplantation--a three-center experience with 60 consecutive transplantations

BACKGROUND: A new protocol for ABO-incompatible kidney transplantation has recently been introduced. We report here on the joint experience of the implementation in Stockholm and Uppsala, Sweden and Freiburg, Germany. METHODS: The new protocol utilizes antigen-specific immunoadsorption to remove existing ABO-antibodies, rituximab, and intravenous immunoglobulin to prevent the rebound of antibodies, and conventional tacrolimus, mycophenolate-mofetil, and prednisolone immunosuppression. Sixty consecutive ABO-incompatible kidney transplantations were included in the study. The outcome is compared with the results of 274 ABO-compatible live donor transplantations performed during the same period. RESULTS: Two of the ABO-incompatible grafts have been lost (non-compliance and death with functioning graft). All the remaining 58 grafts had good renal function at a follow-up of up to 61 months. We did not observe any late rebound of antibodies and there were no humoral rejections. Graft survival was 97% for the ABO-incompatible compared with 95% for the ABO-compatible. Patient survival was 98% in both groups. There was a significant variation in preoperative A/B-antibody titer between the centers, with a median 1:8 in Uppsala, median 1:32 in Stockholm and median 1:128 in Freiburg. More preoperative antibody adsorptions were therefore needed in Freiburg than in Stockholm and Uppsala. CONCLUSIONS: The new protocol was easily implemented and there were no graft losses that could be related to ABO-incompatibility. A significant inter-institutional variation in the measurement of anti-AB-antibodies was found, having a substantial impact on the number of immunoadsorptions and consequently on the total cost for the procedure. A standardized fluorescence-activated cell sorting technique for antibody quantification is much needed.     

Comparison of paired exchange kidney transplantations with living related kidney transplantations

Objective

Paired-exchange kidney transplantation (PETx) gains an importance because it is difficult to find suitable organs. The aim of this study was to compare biochemical and clinical parameters of PETx with those of living-related kidney transplantation (LRTx).

Method

The 57 PETx included 18 female and 39 male recipients among 1081 LRTx in 360 females and 721 males (N = 1138) whose operations were performed between November 21, 2008, and March 1, 2011. These two groups were compared for graft and patient survival, rejections, serum creatinine levels, glomerular filtration rates (GFRs), and other biochemical parameters.

Results

The PETx patients were older than the LRTx patients (45.4 ± 13.2 years versus 40.9 ± 13.5 years; P = .014). HLA mismatch was higher in the PETx group (4.7 ± 0.7 versus 3.56 ± 1.6; P = .000). First- and second-year serum creatinine and GFR values were similar between the two groups. Acute rejection episodes (PETx: 13/57; LRTx: 226/1081, P = .925), patient loss (0/57 versus 34/1081; P = .174) and graft loss (1/57 versus 55/1081; P = .257) were similar between the two groups.

Conclusion

Our study showed similar biochemical and clinical findings of PETx versus LRTx over 2 years posttransplantation.     

From ABO-incompatible human kidney transplantation to xenotransplantation

The development (in 1981) of a protocol for successful renal allotransplantation across ABO barriers is outlined. From this experience, the concept of "adaptation", subsequently termed "accommodation", was defined. It was then hypothesized that a similar approach might allow pig-to-human organ xenotransplantation. This hypothesis was explored in the pig-to-baboon renal transplantation model, with graft survival for a maximum of 23 days. Rejection episodes were temporarily reversed, providing encouragement that discordant xenotransplantation would one day prove successful. Finally, the preparation of the thymokidney, developed as a means of inducing xenotolerance, is briefly reviewed.     

儿童ABO血型不合与相合肝移植疗效比较的Meta分析

目的  应用Meta分析对儿童ABO血型不合肝移植（ILT）与儿童ABO血型相合肝移植（CLT）的疗效进行比较。方法  检索PubMed、Embase、Cochrane library、中国知网、万方、维普等国内外数据库,检索时间截至2017年5月。根据制定的纳入标准和排除标准筛选符合要求的文献,提取数据。采用Review Manager 5.3软件,应用随机效应模型或固定效应模型进行Meta分析。结果  共纳入11篇英文文献,均为回顾性队列研究。Meta分析结果表明ILT组受者术后1年存活率明显低于CLT组[比值比（OR）=0.64,95%可信区间（CI）0.49~0.83,P=0.0007）];ILT组术后排斥反应发生率明显高于CLT组（OR=1.96,95% CI 1.03~3.72,P=0.04）;两组的术后3、10年受者存活率,术后1、3、10年移植物存活率,术后胆道并发症发生率差异无统计学意义（均为P > 0.05）。结论  与CLT比较,ILT受者1年存活率较低而排斥反应发生率较高,但两组受者和移植物长期存活率及胆道并发症发生率相似。表明ILT是在紧急情况下挽救患者生命或长时间无法等到血型相合的肝源时较为理想的选择。     

Results of 300 kidney transplantations

Kidney transplantation is a widely used method for the treatment o fend-stage renal disease. Between September 3, 1993 and December 2002 a total of 300 kidney transplantations were performed at the Department of Surgery at the Medical University of Pécs. In 24 patients simultaneous kidney and pancreas transplantation was performed. The mean age of the 189 male and 111 female patients was 42 years. The HLA B, Dr tissue antigen mismatches was 1.63. The average cold ischemic time was 1199 minutes whereas the average anastomotic time was 43 minutes. Early surgical complications happened to 16 patients. In spite of the immunosuppressive treatment 26 acute steroid resistant rejection have occurred, 9 of which were irreversible. In our opinion the meticulous surgical technique is as important as the postoperative care is. The early and late complications of 300 renal transplants are reviewed by the authors.     

Multicentre trial of ABO-incompatible kidney transplantation

A multicentre study of ABO incompatible kidney transplantation using Biosynsorb was started in Japan in November 1989. A total of 51 cases were registered comprising 23 cases of A incompatibility, 26 cases of B incompatibility and two cases of AB incompatibility. The removal of antibodies (IgG and IgM) was carried out using Biosynsorb in 16 cases, plasmapheresis in four cases and use of both combined in 31 cases. The treatment using Biosynsorb was repeated 3.4 times on average. Serum titres of anti-A (IgG and IgM) antibodies decreased to 4.9 ± 5.0 and 2.7 ± 1.7 and for anti-B titres decreased to 2.8 ± 3.5 and 2.4 ± 3.2. Rejection was found in 33 cases: hyperacute one, accelerated acute five, and acute 27. In two cases rejection was developed concomitantly with a steep elevation in antibody titres. Three patients died, two with functioning grafts. Eight grafts were lost. Patient and graft survivals at 2 years were 94.1% and 84.3%, respectively. From these results it is concluded that: 1. Biosynsorb and plasmapheresis are effective in removing anti-A and anti-B antibodies; 2. graft and patient survivals are similar to those in ABO compatible cases; 3. anti-A and anti-B titres less than 16 are recommended at the time of transplantation; 4. anti-A and anti-B titres higher than 128 may be considered as a risk factor for rejection in the early stages after transplantation.     

Outcomes of renal transplantations with multiple vessels

Aim

We reviewed our renal transplantation experience with multiple renal arteries and veins.

Method

We divided the patients who underwent renal transplantation between 2004 and 2009 into two groups according to the vascular structure: multiple (group 1) versus single (group 2). Vascular anastomoses were primarily completed in an end-to-side manner to the external iliac artery and vein. The number of involved vessels was 51 among the 23 patients in group 1. We evaluated the function of the transplanted kidney using scintigraphic studies and serum creatinine levels.

Results

The male:female ratios were 15:8 and 73:30, mean ages 31.9 (range = 12-64) and 33.4 (range = 17-64) years, and the living related:cadaveric donor ratios 18:5 and 75:28 for groups 1 and 2, respectively. There was one case of acute rejection in group 1, and seven cases in group 2. The number of kidneys with delayed function was 11 in group 2 and one in group 1. Two perirenal abscesses, two urinary fistulae, one lymphocele, two hematomas around the kidney, and four renal artery stenoses were seen in group 2. The complication rates were 21.79% in group 1 and 35.92% in group 2. (χ² = 1.70, P > .05). The mean creatinine levels at 1 month after the transplantation were 1.21 ± 0.38 mg/dL and 1.12 ± 0.31 mg/dL in groups 1 and 2, respectively (P = .215).

Conclusion

The incidences of postoperative complications were not different for renal grafts involving multiple versus single vessels.     

Outcomes of laparoscopic resection of Meckel's diverticulum are equivalent to open laparotomy

Purpose

Meckel's diverticulum (MD) is a common congenital anomaly caused by failure of involution of the omphalomesenteric duct. Enthusiasm for minimally invasive surgery (MIS) in children has burgeoned as technologies have advanced, but the outcomes of laparoscopic resection in comparison to open laparotomy for MD remain poorly defined. We queried a large national database to compare current practice patterns and clinical outcomes between surgical approaches for MD in the pediatric population.

2000例次肾移植的临床研究

目的 对我院１９７２年～１９９９年５月间１７３９例尿毒症行肾移植手术患者（２００例次）进行临床研究。方法 总结１９８５年以后人／肾１、３、５年的存活率;肾移植主要并发症及其处理原则;影响患者再次移植存活率的因素。ＨＬＡ－抗原／基因配型及ＰＲＡ检测。结果 ⑴自１９８５年临床使用环孢霉素Ａ（ＣｓＡ）后其１年人肾存活率为８７．３３％,３年人肾存活率为８０．１７％,５年人肾存活率为６７．０４％。⑵５０岁以     

Outcomes of kidney transplantations in children weighing 15 kilograms or less: a retrospective cohort study

Kidney transplantation (KT) is often delayed in small children because of fear of postoperative complications. We report early‐ and long‐term outcomes in children transplanted at ≤15 kg in the two largest Belgian pediatric transplant centers. Outcomes before (period 1) and since the introduction of basiliximab and mycophenolate‐mofetil in 2000 (period 2) were compared. Seventy‐two KTs were realized between 1978 and 2016: 38 in period 1 and 34 in period 2. Organs came from deceased donors in 48 (67%) cases. Surgical complications occurred in 25 KTs (35%) with no significant difference between the two periods. At least one acute rejection (AR) occurred in 24 (33%) KTs with significantly less patients experiencing AR during period 2: 53% and 12% in period 1 and, period 2 respectively (P < 0.001). Graft survival free of AR improved significantly in period 2 compared with period 1: 97% vs. 50% at 1 year; 87% vs. 50% at 10 years post‐KT (P = 0.003). Graft survival tended to increase over time (period 1: 74% and 63% at 1 and 5 years; period 2: 94% and 86% at 1 and 5 years; P = 0.07), as well as patient survival. Kidney transplantation in children ≤15 kg remains a challenging procedure with 35% of surgical complications. However, outcomes improved and are nowadays excellent in terms of prevention of AR, patient and graft survival.     

Outcomes of breast-conservation therapy for invasive lobular carcinoma are equivalent to those for invasive ductal carcinoma

BACKGROUND: Breast-conservation therapy (BCT), including wide local excision and postoperative irradiation, is considered standard treatment for early-stage invasive ductal carcinoma (IDC). The use of BCT in patients with invasive lobular carcinoma (ILC) has been questioned because of concerns regarding ipsilateral breast recurrence and risk of bilateral breast cancer. We evaluated our institutional experience with BCT and compared treatment outcomes for ILC with those for IDC. METHODS: A review of our BCT database revealed 84 patients with ILC and 1,126 with IDC with stage I or II disease treated with BCT and radiation between 1976 and 1999. We evaluated local-regional recurrence, disease-specific survival, and contralateral breast cancer rates in both groups. RESULTS: The 5- and 10-year local-regional recurrence rates for the ILC group were 1% and 7%, respectively, and 4% and 9%, respectively, for the IDC group (P = .70). There were no significant differences in the 5- and 10-year disease-specific survival rates between the groups. Contralateral breast cancer occurred in 11.3% of patients with IDC and 11.9% of patients with ILC. CONCLUSIONS: BCT achieves similar local-regional control and survival outcomes in selected patients with ILC or IDC. Breast-conservation therapy is an appropriate treatment strategy for patients with early-stage invasive lobular carcinoma.