Living donor kidney transplantation in crossmatch-positive patients enabled by peritransplant immunoadsorption and anti-CD20 therapy

Living donor kidney transplantation in crossmatch-positive patients is a challenge that requires specific measures. Ten patients with positive crossmatch results (n = 9) or negative crossmatch results but strong donor-specific antibodies (DSA; n = 1) were desensitized using immunoadsorption (IA) and anti-CD20 antibody induction. IA was continued after transplantation and accompanied by HLA antibody monitoring and protocol biopsies. After a median of 10 IA treatments, all patients were desensitized successfully and transplanted. Median levels of mean fluorescence intensity (MFI) of Luminex-DSA before desensitization were 6203 and decreased after desensitization and immediately before transplantation to 891. Patients received a median of seven post-transplant IA treatments. At last visit, after a median follow-up of 19 months, 9 of 10 patients had a functioning allograft and a median Luminex-DSA of 149 MFI; serum creatinine was 1.6 mg/dl, and protein to creatinine ratio 0.1. Reversible acute antibody-mediated rejection was diagnosed in three patients. One allograft was lost after the second post-transplant year in a patient with catastrophic antiphospholipid syndrome. We describe a treatment algorithm for desensitization of living donor kidney transplant recipients that allows the rapid elimination of DSA with a low rate of side effects and results in good graft outcome.     

Pancreas transplantation

Pancreas transplantation is now standard of care for selected patients with diabetes and end-stage renal failure or life-threatening diabetic complications. The morbidity and mortality of pancreas transplantation is higher than other transplant types, and for this reason selection criteria for both donors and recipients are more stringent. Meticulous organ retrieval technique and back-table preparation, and a standard implantation technique using enteric drainage are central to good outcomes. Modern immunosuppression has reduced acute rejection rates and lowered the need for long-term corticosteroids. Results have improved over time and recipients of a simultaneous kidney-pancreas transplant can now expect 5-year transplant survival of over 75%. The addition of a pancreas to a kidney transplant for suitable recipients has clear benefits in both length and quality of life, and there is increasing evidence that pancreatic transplantation can reduce or halt the progression of diabetic nephropathy, neuropathy, retinopathy and cardiovascular disease. In patients with normal renal function, pancreatic islet transplantation offers an alternative with reduced peri-procedural morbidity and mortality, at the expense of lower rates of long-term insulin independence.     

Pancreas transplantation

Pancreas transplantation is now standard of care for selected patients with diabetes and end-stage renal failure or life-threatening diabetic complications. The morbidity and mortality of pancreas transplantation is higher than other transplant types, and for this reason selection criteria for both donors and recipients are more stringent. Meticulous organ retrieval technique and back-table preparation, and a standard implantation technique using enteric drainage are central to good outcomes. Modern immunosuppression has reduced acute rejection rates and lowered the need for long-term corticosteroids. Results have improved over time and recipients of a simultaneous kidney–pancreas transplant can now expect 5-year transplant survival of around 75%. The addition of a pancreas to a kidney transplant for suitable recipients has clear benefits in both length and quality of life, and there is increasing evidence that pancreatic transplantation can reduce or halt the progression of diabetic nephropathy, neuropathy, retinopathy and cardiovascular disease. In patients with normal renal function, pancreatic islet transplantation offers an alternative with reduced peri-procedural morbidity and mortality, at the expense of lower rates of long-term insulin independence.     

Pancreas transplantation

Pancreas transplantation is now the standard of care for selected patients with diabetes and end-stage renal failure or life-threatening diabetic complications. The morbidity and mortality of pancreas transplantation is higher than other transplant types, and for this reason selection criteria for both donors and recipients are more stringent. Meticulous organ retrieval technique and back-table preparation, and a standard implantation technique using enteric drainage are central to good outcomes. Modern immunosuppression has reduced acute rejection rates and lowered the need for long-term corticosteroids. Results have improved over time and recipients of a simultaneous kidney–pancreas transplant can now expect 5-year transplant survival of around 75%. The addition of a pancreas to a kidney transplant for suitable recipients has clear benefits in both length and quality of life, and there is increasing evidence that pancreatic transplantation can reduce or halt the progression of diabetic nephropathy, neuropathy, retinopathy and cardiovascular disease. In patients with normal renal function, pancreatic islet transplantation offers an alternative with reduced peri-procedural morbidity and mortality, at the expense of lower rates of long-term insulin independence.     

Pancreas transplantation

Pancreas transplantation is now the standard of care for selected patients with diabetes and end-stage renal failure, with clear benefits in duration and quality of life. The indication for transplantation in patients with other severe diabetic complications are less clearly defined and the benefits less certain. The criteria for donor selection are more rigorous than for kidney and liver transplantation; selection of suitable organs and surgical retrieval technique are critical to success as the transplanted pancreas is vulnerable to preservation injury and post-transplant pancreatitis. Modern immunosuppressive strategies have reduced rejection rates and lowered the need for steroids; this has enabled surgical developments, particularly the enteric drainage of exocrine secretions, which have further reduced postoperative complications. As well as data relating to greater life expectancy, there is increasing evidence of stabilisation or long-term improvement in retinal, cardiovascular and neurological complications of diabetes. In patients with normal renal function, pancreatic islet transplantation may provide similar benefits without the morbidity of whole organ transplantation; this may be offered to patients suffering from life-threatening episodes of hypoglycaemic unawareness.     

胰肾联合移植的排斥反应

目的　探讨胰肾联合移植术后的排斥反应。方法　对我院施行的 3例胰肾联合移植的病人 ,采用FK5 0 6 MMF Perid Zenapax四联免疫治疗方案 ,通过床边彩超及Cr、BUN、血糖等来监测移植物的排斥反应。对排斥反应采用激素冲击疗法 ,对激素不敏感者采用OKT3治疗。结果　3例患者中有 2例出现排斥反应 ,其发生率达 6 6 % ;在出现排斥反应时 ,首先表现为低热、全身不适 ,尿量减少 ,血Cr、BUN升高 ,彩超示移植物血流阻抗升高 ,之后才是血糖升高。结论　胰肾联合移植中 ,排斥反应与多种因素有关 ,移植肾对移植胰具有保护作用 ,肾脏可以作为监测胰腺排异的窗口 ,彩超检查可以作为筛选移植物排异反应的手段。     

Pancreas transplantation alone in children: a case report

Abstract: Pancreas transplantation (PT) is a relatively uncommon therapy for non‐uremic type 1 diabetes, as the severity of diabetes must warrant the risk of immunosuppression. In pediatric diabetic patients, who are less likely to display uremia because of the duration of diabetes, there is very little experience with pancreas transplantation alone (PTA). This report describes a 13‐yr‐old male PTA recipient. This patient was initially diagnosed with type 1 diabetes mellitus at the age of four yr. Following a multidisciplinary evaluation, PTA was found to be indicated based on a history of severe labile diabetes and hypoglycemic unawareness resulting in frequent episodes of hypoglycemia and hospital admissions. Because of the failure of medical management of the patient’s diabetes, a whole organ bladder and systemic drained PTA was performed. Immunosuppression included thymoglobulin, tacrolimus, mycophenolate mofetil, and steroids. Early outcome was uneventful and patient was discharged 12 d after surgery normoglycemic and insulin‐free. An episode of acute rejection (Maryland grade II) 20‐d post‐transplant was successfully treated with corticosteroids. A second and more severe episode of rejection (Maryland grade IV) occurred 13 months post‐transplant, requiring treatment with thymoglobulin and conversion from steroid to sirolimus. On tacrolimus, sirolimus, and mycophenolic acid, he remains euglycemic and insulin‐free 38 months after PTA. His quality‐of‐life is judged to be superior to his insulin dependent state prior to transplantation. According to the medical literature, this is the youngest patient ever to undergo PTA.     

Pancreas transplantation after bariatric surgery

Obese transplant candidates are at increased risk for perioperative and postoperative complications. In many transplant programs, morbid obesity is considered to be an exclusion criterion for transplantation. The only potential option that would grant these patients access to transplant is weight loss. Non-operative weight loss strategies such as behavioral modifications, exercise, diet, or medication have only very limited success in achieving long-term weight loss. In contrast, bariatric surgery was shown to achieve not only more excessive weight loss, but more importantly, this weight loss can be sustained for longer periods of time. Therefore, bariatric surgery presents an attractive option for weight loss for morbidly obese transplant candidates. We report our experience with four patients who underwent bariatric surgery prior to successful pancreas transplantation. Even though gastric bypass and laparoscopic adjustable gastric band present as equivalent alternatives for weight reduction, we believe that in the population of morbidly obese diabetic patients who are possible candidates for pancreas transplantation, laparoscopic adjustable gastric band placement is the more suitable procedure.     

Renal transplantation in sensitized recipients with positive luminex and negative CDC (complement‐dependent cytotoxicity) crossmatches

Recently, Luminex‐crossmatch (LumXm) was introduced. The aim of this study was to evaluate clinical outcomes in sensitized recipients with a positive Luminex‐crossmatch (LumXm (+)) and a negative complement‐dependent cytotoxicity crossmatch (CDCXm (?)) after renal transplantation. Fifty‐five renal transplant recipients with a CDCXm (?) and PRA class I or II ≥20% were enrolled in this study between February 2008 and December 2010 at Severance Hospital. Eighteen patients displayed LumXm (+) defined as LumXm positive class I or II and 37 patients displayed LumXm (?). Mean duration of follow‐up was 18.9 ± 8.3 months. During this period, no patient death or graft loss occurred. The incidence of biopsy‐proven or clinically presumed rejection was higher in the LumXm (+) group (n = 12, 66.7%) than in the LumXm (?) group (n = 6, 18.2%) (P = 0.001). All biopsy‐proven acute rejections (n = 12) were diagnosed as acute cellular rejection. No significant difference in mean serum creatinine level or eGFR was observed between the groups at 18 months post‐transplantation. The short‐term outcome of renal transplantation in sensitized patients with a LumXm (+) and a CDCXm (?) may be considered to be acceptable. However, patients with a LumXm (+) have a substantially higher immunological risk for the development of acute cellular rejection.     

Laparoscopic Biopsies in Pancreas Transplantation

As there is no precise laboratory test or imaging study for detection of pancreas allograft rejection, there is increasing interest in obtaining pancreas tissue for diagnosis. Pancreas allograft biopsies are most commonly performed percutaneously, transcystoscopically, or endoscopically, yet pancreas transplant surgeons often lack the skills to perform these types of biopsies. We have performed 160 laparoscopic pancreas biopsies in 95 patients. There were 146 simultaneous kidney–pancreas biopsies and 14 pancreas‐only biopsies due to pancreas alone, kidney loss, or extraperitoneal kidney. Biopsies were performed for graft dysfunction (89) or per protocol (71). In 13 cases, an additional laparoscopic procedure was performed at the same operation. The pancreas diagnostic tissue yield was 91.2%; however, the pancreas could not be visualized in eight cases (5%) and in 6 cases the tissue sample was nondiagnostic (3.8%). The kidney tissue yield was 98.6%. There were four patients with intraoperative complications requiring laparotomy (2.5%) with two additional postoperative complications. Half of all these complications were kidney related. There were no episodes of pancreatic enzyme leak and there were no graft losses related to the procedure. We conclude that laparoscopic kidney and pancreas allograft biopsies can be safely performed with very high tissue yields.     

Pancreas transplantation considering the spectrum of body mass indices

Afaneh C, Rich B, Aull MJ, Hartono C, Kapur S, Leeser DB. Pancreas transplantation considering the spectrum of body mass indices.
Clin Transplant 2011: 25: E520–E529. © 2011 John Wiley & Sons A/S. Abstract: Background: In kidney, liver, heart, and lung transplantation, extremes of body mass index (BMI) have been reported to influence post‐operative outcomes and even survival. Given the limited data in pancreas transplantation, we sought to elucidate the influence of BMI on outcomes. Methods: We reviewed 139 consecutive pancreas transplants performed at our institution and divided them into four categories based on BMI: underweight (≤18.5 kg/m²), normal (18.6–24.9 kg/m²), overweight (25–29.9 kg/m²), and obese (≥30 kg/m²). Parameters analyzed included post‐operative complications, early graft loss, one‐yr acute rejection rate (AR), non‐surgical infections, and survival. Results: Demographic data were similar between the groups. Compared with normal, only obese patients trended toward more post‐operative complications (p = 0.06). Underweight and obese patients had significantly more post‐operative infectious complications than normal (p = 0.0005 and p = 0.03, respectively). Obese patients had more complications requiring percutaneous drainage compared with normal (p = 0.03). Overweight and obese patients had significantly more complications requiring re‐laparotomy (p = 0.03 and p = 0.048, respectively). Early graft loss, AR, non‐surgical infections, and patient and graft survival rates were not different between normal and underweight, overweight, or obese patients (p > 0.05). Conclusions: Extremes of BMI were associated with increased morbidity. Donors and recipients should be carefully selected to maximize potential for successful outcomes.     

A case of acute humoral rejection in liver transplantation: successful treatment with plasmapheresis and mycophenolate mofetil

We present a case of a 23-year-old female who underwent orthotopic liver transplantation (OLTx) for biliary atresia, 22 years after a failed Kasai operation. Unusually, her postoperative course was complicated by severe acute humoral rejection. In this case report, we discuss her management as well as the role of plasmapheresis in treating allograft dysfunction secondary to acute humoral rejection in liver transplant patients.     

Acute Pancreas Allograft Rejection Is Associated With Increased Risk of Graft Failure in Pancreas Transplantation

The effect of acute allograft rejection (AR) on long‐term pancreas allograft function is unclear. We retrospectively studied 227 consecutive pancreas transplants performed at our institution between January 1, 998 and December 31, 2009 including: 56 simultaneous pancreas and kidney (SPK), 69 pancreas transplantation alone (PTA); and 102 pancreas after kidney (PAK) transplants. With a median follow‐up of 6.1 (IQR 3–9) years, 57 patients developed 79 episodes of AR, and 19 experienced more than one episode. The cumulative incidence for AR was 14.7%, 19.7%, 26.6% and 29.1% at 1, 2, 5 and 10 years. PTA transplant (hazards ratio [HR] = 2.28, p = 0.001) and donor age (per 10 years) (HR = 1.34, p = 0.006) were associated with higher risk for AR. The first AR episode after 3 months post PT was associated with increased risk for complete loss (CL) (HR 3.79, p < 0.001), and the first AR episode occurring during 3‐ to 12‐month and 12‐ to 24‐month periods after PT were associated with significantly increased risk for at least partial loss (PL) (HR 2.84, p = 0.014; and HR 6.25, p < 0.001, respectively). We conclude that AR is associated with increased risk for CL and at least PL. The time that the first AR is observed may influence subsequent graft failure.     

Antibody-Mediated Rejection of a Pancreas Allograft

The role of antibody-mediated rejection (AMR) in pancreas transplantation is poorly understood. Here, we report on a patient who developed AMR of his pancreas allograft after receiving a simultaneous pancreas-kidney transplant. Pre-operative enhanced cytotoxicity and flow cytometry T-cell crossmatches were negative; B-cell crossmatches were not performed as per institutional protocol. The patient's post-operative course was significant for elevated serum amylase levels and development of hyperglycemia approximately 1 month after transplantation. A pancreatic biopsy at this time showed no cellular infiltrate but strong immunofluorescent staining for C4d in the interacinar capillaries. Analysis of the patient's serum identified donor-specific HLA-DR alloantibodies. He received intravenous immunoglobulin (IVIg), rituximab and plasmapheresis, and his pancreatic function normalized. We conclude that clinically significant AMR can develop in a pancreas allograft and recommend that pancreatic biopsies be assessed for C4d deposition if the patient has risk factors for AMR and/or the pathologic evidence for cell-mediated rejection is underwhelming.     

Successful living donor renal transplantation despite ABO incompatibility and a positive crossmatch

Potential live kidney donors have been rejected when the prospective recipients are blood type or crossmatch incompatible. By utilizing plasmapheresis combined with intravenous immune globulin (PP/IVIg) prior to surgery, donor-specific antibodies against blood group or human leukocyte antigens (HLA) have been removed, thereby allowing successful renal transplantation. A 26-yr-old male with a panel reactive antibody level of 100% and repeated positive crossmatches against deceased donor kidney offers, including zero HLA mismatched donors, successfully underwent ABO-incompatible kidney transplantation from his HLA-identical but nevertheless crossmatch-incompatible sister. The initial anti-A blood group isoagglutinin titers were 128, 256, and 1024 at room temperature, 37 degrees C, and 37 degrees C anti-IgG enhanced, respectively. With an individualized PP/IVIg regimen based on donor-specific antibody titer, however, the relevant antibodies were adequately reduced and hyperacute rejection avoided. Subsequent antibody-mediated rejection, likely directed against a minor histocompatibility antigen, was diagnosed on postoperative day 7 and successfully treated. Neither ABO, or crossmatch incompatibility, or both in combination prohibit kidney transplantation.     

Overcoming a Positive Crossmatch in Living-Donor Kidney Transplantation

Many patients who have an otherwise acceptable living-kidney donor do not undergo transplantation because of the presence of antibodies against the donor cells resulting in a positive crossmatch. In the current study, 14 patients with a positive cytotoxic crossmatch (titer 相似文献   

Flow cytometry crossmatching as a predictor of acute rejection in sensitized recipients of cadaveric renal transplants

Flow cytometry crossmatching (FCXM) was developed as a more sensitive assay than the standard complement-dependent cytotoxicity crossmatch (CDCXM) for the detection of anti-donor antibodies, that mediate hyperacute rejection and graft loss in the early post-transplant period in renal transplant recipients. The role of FCXM in predicting long-term clinical outcome in renal allograft recipients is unclear. This study examines the role of FCXM in predicting long-term clinical outcome in highly sensitized recipients of cadaveric renal transplants. All patients (n = 100) with peak panel reactive antibody (PRA) levels > 30%, who received cadaveric renal transplants between 1/1/'90 and 12/31/'95 at our institution, were divided into FCXM + and FCXM - groups. The incidence of acute rejection was determined for each group during the first yr after transplant. Graft survival rates at 1, 2, and 3 yr, and creatinine levels were also compared between groups. FCXM + patients experienced a higher incidence of acute rejection during the first yr after transplant (69 vs. 45%), and a higher percentage of FCXM + patients had more than one episode of acute rejection during the first yr after transplant (34 vs. 8%) when compared to FCXM - patients. There was no statistically significant difference in 1-, 2-, or 3-yr graft survival between FCXM + and FCXM - patients (76 vs. 83, 62 vs. 80, 62 vs. 72%, respectively). These results suggest that sensitized FCXM + cadaveric renal transplant recipients have a higher incidence of acute rejection episodes in the first yr after transplant. Given the association of multiple rejection episodes with poor long-term allograft survival, FCXM may be a useful predictor of long-term clinical outcome in this sub-group of renal transplant recipients.     

Outcomes of simultaneous kidney-pancreas transplantation in African-American recipients: a case-control study

INTRODUCTION: Previous studies have suggested that African-American (AA) ethnicity is a risk factor for rejection and graft loss after kidney transplantation. However, little data is available regarding outcomes after simultaneous kidney pancreas transplantation (SKPT) in AA recipients. The objective of this study was to compare the outcomes of SKPT in AA patients to matched Caucasian patients as controls. METHODS: From January 1996 to September 1999, we performed 79 SKPTs, including 10 in AA recipients. Ten Caucasian controls were selected and matched for age, gender, weight, timing and technique of transplantation, and immunosuppressive regimen. Clinical outcomes were collected and compared between the two groups. RESULTS: The two groups were well matched for donor and recipient demographic, immunologic and transplant characteristics, including 2 patients in each group with type 2 diabetes. All patients received tacrolimus (TAC), mycophenolate mofetil (MMF) and steroids, and about half in each group received antibody induction therapy. Patient survival was 100% in both groups with a mean follow-up of 18 months (range 6 47). Kidney and pancreas graft survival rates were both 80% in the AA and 100% in the Caucasian groups, respectively (p = 0.14). All but one kidney (in the AA group) and all pancreas grafts experienced immediate function. There were two immunologic kidney and two immunologic pancreas graft losses in the AA group. No grafts were lost due to technical problems. The mean length of initial hospital stay was 16 d in the AA group compared to 10 d in the Caucasian group (p = 0.07). The AA group had a slight increase in the number of readmissions (mean 2.2 AA vs. 1.6 Caucasian, p = 0.08). The incidence of biopsy-proven pancreas acute rejection was significantly higher in the AA group (50%) compared to the Caucasian group (10%) (p = 0.05). The incidence of either kidney or pancreas acute rejection was also higher in the AA group (60% AA vs. 20% Caucasian, p = 0.06). TAC levels were comparable at specific times after transplantation, al-though there was a trend toward higher doses of TAC in the AA group to achieve therapeutic levels. The incidences of relaparotomy (30% AA vs. 20% Caucasian) and major infection (40% AA vs. 60% Caucasian) were similar between groups. Renal and pancreas allograft functions were comparable between groups at specific times after transplantation. CONCLUSIONS: These results suggest that SKPT in AA recipients may be associated with a higher incidence of rejection and immunologic graft loss compared to matched Caucasian controls.