Strategic Planning and Essential Steps for Establishing a Uterine Transplant and Rehabilitation Program: From Idea to Reality.

UTx is performed to address absolute uterine infertility in the presence of uterine agenesis, a nonfunctional uterus, or after a prior hysterectomy. After the initial success of UTx resulting in a livebirth (2014) in Sweden, there are over 70 reported UTx surgeries resulting in more than 40 livebirths worldwide. Currently, UTx has been performed in over 10 countries. As UTx is transitioning from an "experimental procedure" to a clinical option, an increasing number of centers may contemplate a UTx program. This article discusses essential steps for establishment of a successful UTx program. These principles may be implemented in cis- and transgender UTx candidates.

National Trends in Cholecystectomy and Endoscopic Retrograde Cholangiopancreatography During Index Hospitalization for Mild Gallstone Pancreatitis.

BACKGROUND: Guidelines call for cholecystectomy during the index hospitalization for patients with gallstone pancreatitis. Therefore, the study sought to determine the trends for cholecystectomy and Endoscopic Retrograde Cholangiopancreatography (ERCP) for mild gallstone pancreatitis. METHODS: A retrospective analysis of the 2010-2018 Nationwide Readmission Database (NRD) was performed to identify patients with mild gallstone pancreatitis. The primary aim was to identify the trends in the use of cholecystectomy in these patients, and the secondary aim was to assess if ERCP alone was protective against readmission. RESULTS: A total of 510,470 patients with mild gallstone pancreatitis were identified. There has been an increasing trend in ERCP use (25% in 2018 vs. 22% in 2010; p-0.001) and a decline in cholecystectomy (37% in 2018 vs. 46% in 2010; p-0.001) prior to discharge. Multivariate analysis revealed higher 30-day readmission for patients who underwent ERCP without cholecystectomy (odds ratio1.3; 95% confidence interval, 1.1-3.5) during the index admission. CONCLUSIONS: There has been a decline in the use of cholecystectomy during index hospitalization for mild gallstone pancreatitis. In addition, ERCP was not protective against 30-day readmission from mild gallstone pancreatitis.

Economic evaluation of suture versus clip anastomosis in arteriovenous fistula creation.

OBJECTIVE: Techniques such as the use of nonpenetrating vascular clips for arteriovenous fistula (AVF) anastomotic creation have been developed in an effort to reduce fistula-related complications. However, the outcomes data for the use of clips have remained equivocal, and the cost evaluations to support their use have been largely theoretical. Therefore, the present study aimed to determine both the clinical and the cost outcomes of AVFs created with nonpenetrating vascular clips compared with the continuous suture technique during a 10-year period at a single institution. METHODS: All patients undergoing AVF creation in the upper extremity from 2009 through 2018 were retrospectively analyzed. The patient demographics and AVF outcomes were collected and compared stratified by the surgical technique used. A cost analysis was performed of a subgroup of patients from 2013 to 2018. RESULTS: During the 10-year study period, 916 AVFs were created (79% using the continuous suture technique and 21% using nonpenetrating vascular clips). Patient demographics and comorbid conditions did not differ between the two groups, and no differences were present in maturation, primary patency, assisted primary patency, or complication rates between the two groups at 1 year. The suture group had a shorter time to maturation (4.3 months vs 5.5 months; P < .01) and improved secondary patency compared with the clip group (77.13% vs 69.59%; P = .03) The cost analysis of the procedures revealed a significant difference in direct costs (suture, $1389.26 vs clip, $1716.51; P < .01) and contribution margin (suture, $1770.19 vs clip, $1128.36; P < .01) for the two groups. CONCLUSIONS: Both suture and clip techniques in AVF creation demonstrated equivalent rates of maturation, primary patency, assisted primary patency, and complications at 1 year with higher expense associated with the use of clips. Thus, in an effort to reduce the economic burden of healthcare in the United States, the findings from the present study support the preferential use of the standard polypropylene suture technique when creating upper extremity AVFs.

Comparative incidence and outcomes of COVID-19 in kidney or kidney-pancreas transplant recipients versus kidney or kidney-pancreas waitlisted patients: A single-center study.

BACKGROUND: COVID-19 epidemiologic studies comparing immunosuppressed and immunocompetent patients may provide insight into the impact of immunosuppressants on outcomes. METHODS: In this retrospective cohort study, we assembled kidney or kidney-pancreas transplant recipients who underwent transplant from January 1, 2010, to June 30, 2020, and kidney or kidney-pancreas waitlisted patients who were ever on the waitlist from January 1, 2019, to June 30, 2020. We identified laboratory-confirmed COVID-19 until January 31, 2021, and tracked its outcomes by leveraging informatics infrastructure developed for an outcomes research network. RESULTS: COVID-19 was identified in 62 of 887 kidney or kidney-pancreas transplant recipients and 20 of 434 kidney or kidney-pancreas waitlisted patients (7.0% vs. 4.6%, p = .092). Of these patients with COVID-19, hospitalization occurred in 48 of 62 transplant recipients and 8 of 20 waitlisted patients (77% vs. 40%, p = .002); intensive care unit admission occurred in 18 of 62 transplant recipients and 2 of 20 waitlisted patients (29% vs. 10%, p = .085); and 7 transplant recipients were mechanically ventilated and died, whereas no waitlisted patients were mechanically ventilated or died (11% vs. 0%, p = .116). CONCLUSIONS: Our study provides single-center data and an informatics approach that can be used to inform the design of multicenter studies.

Prostate cancer in renal transplant recipients.

As patients with end-stage renal disease are receiving renal allografts at older ages, the number of male renal transplant recipients (RTRs) being diagnosed with prostate cancer (CaP) is increasing. Historically, the literature regarding the management of CaP in RTR's is limited to case reports and small case series. To date, there are no standardized guidelines for screening or management of CaP in these complex patients. To better understand the unique characteristics of CaP in the renal transplant population, we performed a literature review of PubMed, without date limitations, using a combination of search terms including prostate cancer, end stage renal disease, renal transplantation, prostate cancer screening, prostate specific antigen kinetics, immunosuppression, prostatectomy, and radiation therapy. Of special note, teams facilitating the care of these complex patients must carefully and meticulously consider the altered anatomy for surgical and radiotherapeutic planning. Active surveillance, though gaining popularity in the general low risk prostate cancer population, needs further study in this group, as does the management of advance disease. This review provides a comprehensive and contemporary understanding of the incidence, screening measures, risk stratification, and treatment options for CaP in RTRs.

Outcomes after combined liver-kidney transplant vs. kidney transplant followed by liver transplant.

INTRODUCTION: The decision for isolated kidney transplant (KT) vs. combined liver-kidney transplant (CLKT) in patients with end-stage renal disease (ESRD) with compensated cirrhosis remains controversial. We sought to determine outcomes of patients requiring listing for a liver transplant (LT) following either a cadaveric or living donor KT and compare these outcomes to similar patients receiving a CLKT. METHODS: Our dataset included the United Network for Organ Sharing (UNOS)/Standard Transplant and Analysis and Research (STAR) kidney files from 1987 to 2012 after being joined with the liver files from 2002 to 2012. Outcomes of patients who received a CLKT with an international normalized ratio (INR) ≤1 and total bilirubin ≤1 were compared to patients who received a primary KT and subsequently required listing for LT between zero and five yr or after five yr. RESULTS: For the three groups, 244 patients had a CLKT, 216 were wait-listed for LT between zero and five yr after KT (0-5 WL), and 320 were wait-listed five yr after KT (+5 WL). From the time of KT, the 0-5 WL group had significantly worse survival than the CLKT group and the +5 WL group. The +5 WL had the best survival of all groups. For the 0-5 WL group, 45% underwent LT and 40% died while waiting compared to the +5 WL group with 53% having LT and 26% died while waiting. At the time of LT, the 0-5 WL group had a higher model for end-stage liver disease (MELD) score, higher incidence of being in the ICU at the time of transplant, and higher incidence of requiring life support. From the time of LT, the CLKT trended toward better survival (p = 0.0549) than both the 0-5 WL and +5 WL groups, which had equivalent survival. CONCLUSION: The 0-5 WL group is a higher risk group with poorer survival due to a higher incidence of dying on the waitlist. Better identification of patients with a high risk for hepatic decompensation following KT and agreement for regional exception for LT in the event of decompensation may improve utilization of organs and better survival for those patients.

Increased transfusion-free survival following auxiliary pig liver xenotransplantation.

BACKGROUND: Pig to baboon liver xenotransplantation typically results in severe thrombocytopenia and coagulation disturbances, culminating in death from hemorrhage within 9 days, in spite of continuous transfusions. We studied the contribution of anticoagulant production and clotting pathway deficiencies to fatal bleeding in baboon recipients of porcine livers. METHODS: By transplanting liver xenografts from α1,3-galactosyltransferase gene-knockout (GalT-KO) miniature swine donors into baboons as auxiliary organs, leaving the native liver in place, we provided the full spectrum of primate clotting factors and allowed in vivo mixing of porcine and primate coagulation systems. RESULTS: Recipients of auxiliary liver xenografts develop severe thrombocytopenia, comparable to recipients of conventional orthotopic liver xenografts and consistent with hepatic xenograft sequestration. However, baboons with both pig and native livers do not exhibit clinical signs of bleeding and maintain stable blood counts without transfusion for up to 8 consecutive days post-transplantation. Instead, recipients of auxiliary liver xenografts undergo graft failure or die of sepsis, associated with thrombotic microangiopathy in the xenograft, but not the native liver. CONCLUSION: Our data indicate that massive hemorrhage in the setting of liver xenotransplantation might be avoided by supplementation with primate clotting components. However, coagulation competent hepatic xenograft recipients may be predisposed to graft loss related to small vessel thrombosis and ischemic necrosis.

Increased levels of anti-non-Gal IgG following pig-to-baboon bone marrow transplantation correlate with failure of engraftment.

BACKGROUND: The development of genetically modified pigs, which lack the expression of alpha 1-3 galactosyl transferase, (GalT-KO pigs) has facilitated the xenogeneic transplantation of porcine organs and tissues into primates by avoiding hyperacute rejection due to pre-existing antibodies against the Gal epitope. However, antibodies against other antigens (anti-non-Gal antibodies), are found at varying levels in the pre-transplant sera of most primates. We have previously found that baboons with high levels of pre-transplant anti-non-Gal IgG, conditioned with a non-myeloablative conditioning regimen, failed to engraft following pig-to-baboon bone marrow transplantation (Xenotransplantation, 17, 2010 and 300). Two baboons with low levels of pre-transplant anti-non-Gal IgG, conditioned with the same regimen, showed porcine bone marrow progenitors at 28 days following transplantation, suggesting engraftment. These baboons also showed evidence of donor-specific hyporesponsiveness. This observation led us to investigate the hypothesis that selecting for baboon recipients with low pre-transplant anti-non-Gal IgG levels might improve engraftment levels following GalT-KO pig-to-baboon bone marrow transplantation. METHODS: Five baboons, with low pre-transplant anti-non-Gal IgG levels, received transplantation of bone marrow cells (1-5 × 10(9) /kg of recipient weight) from GalT-KO pigs. They received a non-myeloablative conditioning regimen consisting of low-dose total body irradiation (TBI) (150 cGy), thymic irradiation (700 cGy), anti-thymocyte globulin (ATG), and tacrolimus. In addition, two baboons received Rituximab and Bortezomib (Velcade) treatment as well as extra-corporeal immunoadsorption using GalT-KO pig livers. Bone marrow engraftment was assessed by porcine-specific PCR on colony forming units (CFU) of day 28 bone marrow aspirates. Anti-non-Gal antibody levels were assessed by serum binding toward GalT-KO PBMC using flow cytometry (FACS). Peripheral macro-chimerism was measured by FACS using pig and baboon-specific antibodies and baboon anti-pig cellular responses were assessed by mixed lymphocyte reactions (MLR). RESULTS: As previously reported, two of five baboons demonstrated detectable bone marrow engraftment at 4 weeks after transplantation. Engraftment was associated with lack of an increase in anti-non-Gal IgG levels as well as cellular hyporesponsiveness toward pig. Three subsequent baboons with similarly low levels of pre-existing anti-non-Gal IgG showed no engraftment and an increase in anti-non-Gal IgG antibody levels following transplantation. Peripheral macrochimerism was only seen for a few days following transplantation regardless of antibody development. CONCLUSIONS: Selecting for baboon recipients with low levels of pre-transplant anti-non-Gal IgG did not ensure bone marrow engraftment. Failure to engraft was associated with an increase in anti-non-Gal IgG levels following transplantation. These results suggest that anti-non-Gal-IgG is likely involved in early bone marrow rejection and that successful strategies for combating anti-non-Gal IgG development may allow better engraftment. Since engraftment was only low and transient regardless of antibody development, innate immune, or species compatibility mechanisms will likely also need to be addressed to achieve long term engraftment.

Urinary reconstruction after kidney transplantation: pyeloureterostomy or ureteroneocystostomy.

PURPOSE: Ureteroneocystostomy (UCN) is the most widely used urinary reconstruction technique during kidney transplantation. Disadvantages of this technique include a high incidence of hematuria and reflux, plus the potential for obstruction resulting from distal ureteral fibrosis. Pyeloureterostomy (PU) avoids these complications but increases the technical complexity. METHODS: Between January 1990 and December 2005, 1066 adults patients underwent kidney transplantations; 768 patients (72.1%) had urinary reconstruction by PU and 298 (27.9%) underwent UNC. RESULTS: Patients in the PU group underwent simultaneous ipsilateral native nephrectomy. The operative time was longer in the PU group compared with the UNC group: 210 ± 36 min versus 182 ± 24 min (P < 0.001). Overall surgical complications in the PU group were comparable to those in the UNC group (9.5% versus 12.3%). The urinary complication rate was also comparable in both groups: 3.2% (25 of 768) in the PU group and 5% (15 of 298) in the UNC group. However, urinary obstruction comprised 60% of urinary complications in the UNC group, compared with 32% in the PU group (P < 0.01). We treated most urinary complications non-operatively. However, 24% of patients (six of 25) in the PU group needed operative intervention or revision for ureteral reconstruction, compared with 46.6% (seven of 15) in the UNC group (P < 0.01). CONCLUSIONS: Pyeloureterostomy is a safe and effective method for urinary tract reconstruction in renal transplantation. Pyeloureterostomy should be part of every transplant surgeon's armamentarium.

Up to 9-day survival and control of thrombocytopenia following alpha1,3-galactosyl transferase knockout swine liver xenotransplantation in baboons.

BACKGROUND: With standard miniature swine donors, survivals of only 3 days have been achieved in primate liver-transplant recipients. The recent production of alpha1,3-galactosyl transferase knockout (GalT-KO) miniature swine has made it possible to evaluate xenotransplantation of pig organs in clinically relevant pig-to-non-human primate models in the absence of the effects of natural anti-Gal antibodies. We are reporting our results using GalT-KO liver grafts. METHODS: We performed GalT-KO liver transplants in baboons using an immunosuppressive regimen previously used by our group in xeno heart and kidney transplantation. Post-operative liver function was assessed by laboratory function tests, coagulation parameters and histology. RESULTS: In two hepatectomized recipients of GalT-KO grafts, post-transplant liver function returned rapidly to normal. Over the first few days, the synthetic products of the donor swine graft appeared to replace those of the baboon. The first recipient survived for 6 days and showed no histopathological evidence of rejection at the time of death from uncontrolled bleeding, probably caused by transfusion-refractory thrombocytopenia. Amicar treatment of the second and third recipients led to maintenance of platelet counts of over 40 000 per µl throughout their 9- and 8-day survivals, which represents the longest reported survival of pig-to-primate liver transplants to date. Both of the last two animals nevertheless succumbed to bleeding and enterococcal infection, without evidence of rejection. CONCLUSIONS: These observations suggest that thrombocytopenia after liver xenotransplantation may be overcome by Amicar therapy. The coagulopathy and sepsis that nevertheless occurred suggest that additional causes of coagulation disturbance must be addressed, along with better prevention of infection, to achieve long-term survival.

Excorporeal normothermic machine perfusion resuscitates pig DCD livers with extended warm ischemia.

BACKGROUND: The shortage in donor livers has led to increased use of allografts derived from donation after cardiac death (DCD). The compromised viability in these livers leads to inferior post-transplantation allograft function and survival compared with donation after brain death (DBD) donor grafts. In this study, we reconditioned DCD livers using an optimized normothermic machine perfusion system. METHODS: Livers from 12 Yorkshire pigs (20-30 kg) were subjected to either 0 min (WI-0 group, n = 6) or 60 min (WI-60 group, n = 6) of warm ischemia and 2 h of cold storage in UW solution, followed by 4 h of oxygenated sanguineous normothermic machine perfusion. Liver viability and metabolic function were analyzed hourly. RESULTS: Warm ischemic livers showed elevated transaminase levels and reduced ATP concentration. After the start of machine perfusion, transaminase levels stabilized and there was recovery of tissue ATP, coinciding with an increase in bile production. These parameters reached comparable levels to the control group after 1 h of machine perfusion. Histology and gross morphology confirmed recovery of the ischemic allografts. CONCLUSION: Our data demonstrate that metabolic and functional parameters of livers with extended warm ischemic time (60 min) can be significantly improved using normothermic machine perfusion. We hereby compound the existing body of evidence that machine perfusion is a viable solution for reconditioning marginal organs.

Protein S deficiency in a living liver donor.

Protein S deficiency is a thrombophilia associated with increased risk of thromboembolic episodes in affected patients. Traditionally, protein S deficiency in a potential donor was considered an absolute contraindication to living donor liver transplantation, both due to the increased risk incurred by the thrombophilic donor as well as the risk of transmitting the thrombophilia to the liver recipient, as protein S is predominantly produced by the liver. We present the first successful case of living donor liver transplantation using a donor with asymptomatic protein S deficiency. Interestingly, whereas the donor continued to have protein S levels approximately 50% of normal, the recipient maintained normal levels of protein S post-transplant, potentially due to compensation by extra-hepatic protein S production. We discuss the prior literature of protein S deficiency acquired via liver transplantation, and we evaluate potential criteria by which the safety of transplants utilizing this pool of donors may be enhanced.

Association between Preoperative Steroids and Outcomes in Patients Undergoing Pancreaticoduodenectomy using the National Surgical Quality Improvement Program.

BACKGROUND: A national study analyzing the association between preoperative steroid use and outcomes after pancreatic resections is lacking. The purpose of this study is to evaluate the association between preoperative steroids and outcomes after pancreaticoduodenectomy using a national database. MATERIALS AND METHODS: A retrospective analysis of patients undergoing pancreaticoduodenectomy was performed using the National Surgical Quality Improvement Program (NSQIP) database (2014-2019). In addition, we utilized propensity score matching to compare patients on preoperative steroids to those who were not. Outcomes measured included 30-day complications and mortality, need for readmission, a prolonged hospital length of stay, delayed gastric emptying, and pancreatic fistula. RESULTS: After propensity score matching, there were 438 patients in the steroid group and 876 patients in the no steroid group. There was no difference in pancreatic fistula (23.8% vs. 21.7%; p-0.3), delayed gastric emptying (21.1% vs.20.1%; p-0.06), major complications (31.8% vs. 30.1%; p-0.1), and mortality (3.5% vs. 3.2%; p-0.6) between the two groups. CONCLUSION: Glucocorticoids did not reduce the incidence of overall complications, postoperative fistula, and delayed gastric emptying following pancreaticoduodenectomy.

Successful treatment of refractory hypertension with bilateral nephrectomy in a patient with chronic kidney disease stage 3.

We present a case of life-threatening refractory hypertension (rHTN) in a patient with stage 3b chronic kidney disease that was unresponsive to open surgical renal denervation (RDN) but responded to bilateral nephrectomy (BLN). Both RDN and BLN reduce the increased sympathetic activation in rHTN. However, RDN has yet to show reductions in blood pressure adequate for the average patient with rHTN, and BLN has thus far been reserved for patients with preexisting end-stage kidney disease (ESKD). Our case suggests that there are patients with rHTN that warrant consideration of BLN prior to developing ESKD.

Heat Stroke as a Cause of Liver Failure and Evaluation of Liver Transplant.

Heat stroke is a multiple organ dysfunction syndrome of poorly understood pathogenesis. Exertional heat stroke with acute liver failure is a rarely reported condition. Liver transplant has been recommended as treatment in cases of severe liver dysfunction; however, there are only 5 described cases of long-term survival after this procedure in patients with heat stroke. Here, we present 2 cases of young athletes who developed heat stroke. Both patients developed acute liver failure and were listed for liver transplant. Liver function tests of one patient improved, and he was discharged on postoperative day 13. The other patient showed no signs of improvement and liver biopsy showed massive necrosis. The patient underwent combined kidney-liver transplant and was discharged on postoperative day 17. After a follow-up of longer than 6 years, both patients are doing well with normal liver function and no neurologic sequelae. We also reviewed all published cases of hepatic failure associated with heat stroke and found 9 published cases of liver transplant for heat stroke in the English literature. Conservative management appears to be justified in heat stroke-associated liver failure, even in the presence of accepted criteria for emergency liver transplant. If the liver does not show signs of recovery and hepatic decompensation progresses, liver transplant should be performed.

Graft repair of arteriovenous fistula aneurysms is associated with decreased long-term patency.

INTRODUCTION: Arteriovenous fistula (AVF) aneurysms are a chronic complication which can be disfiguring, painful, and can rupture. Here, we compare the outcomes between three different methods of AVF aneurysm repair. METHODS: One-way ANOVA, Chi-square, and Fisher Exact analyses were used to compare demographics. Multivariate logistic regression compared outcomes. Kaplan-Meier estimate illustrated long-term fistula patency. RESULTS: There were no differences between demographics in the aneurysmorrhaphy, end-to-end anastomosis, and synthetic graft groups. The odds of patients who received graft repair losing primary patency within one year compared to the aneurysmorrhaphy group was 3.5 (p = 0.025). Graft repair patients were 6.7 times more likely to develop an infection compared to aneurysmorrhaphy (p = 0.014). Synthetic grafts also exhibited accelerated rates of complete access loss compared to autogenous methods (p = 0.034). CONCLUSIONS: Graft repair of AVF aneurysms results in higher rates of infection and decreased primary and ultimate patency compared to autogenous repair techniques. Therefore, synthetic grafts should be avoided whenever possible.

Can Donor-Derived Cell-Free DNA Detect Graft-Versus-Host Disease in Solid Organ Transplantation: A Case Report.

Graft-versus-host disease (GVHD) is a rare complication after solid organ transplant. We present a case of GVHD after simultaneous pancreas kidney transplant. The patient was diagnosed with a cutaneous biopsy after developing the classic symptoms of maculopapular rash, diarrhea, and pancytopenia. However, this patient had unexplained elevations in donor-derived cell-free DNA (dd-cfDNA) for months before the onset of GVHD symptoms. We hypothesize that GVHD may be associated with elevated dd-cfDNA as a result of massive donor lymphocyte proliferation and turnover. Further investigation is warranted because earlier diagnosis and treatment could improve outcomes in an otherwise lethal disease.

End-to-end anastomosis as a superior repair type to prevent recurrence of arteriovenous fistula aneurysms and improve patency outcomes.

BACKGROUND: Arteriovenous fistulae (AVF) complicated by aneurysms are repaired through several mechanisms. Little is known about risk factors for aneurysm recurrence or the efficacy of subsequent repair of recurring aneurysms. METHODS: About 291 patients underwent AVF aneurysm repair between 2009 and 2019 at a large urban medical center. Patients who underwent staged repair, had a primary graft with pseudoaneurysm, were status-post kidney transplant, or using other dialysis access at the time of repair were excluded. One hundred sixty-two patients were included in the study, of which 52 developed a secondary aneurysm. Chi-square and t-test analyses were used to compare demographics. Multivariate logistic regression was used to examine independent risk factors for aneurysm recurrence. Of the 52 patients with recurrent aneurysms, 41 were repaired again. Patency was examined for each group 1 year postoperatively. RESULTS: Patients without secondary aneurysms were more likely to have a Charlson Comorbidity Index score ⩾5 (p = 0.045). Males were 2.8 times more likely to develop a secondary aneurysm compared to females (p = 0.023). Patients who underwent elective compared to emergent or urgent surgery for primary aneurysms were significantly less likely to recur (OR = 0.222; p = 0.016). Primary aneurysms repaired by end-to-end anastomosis, compared to aneurysmorrhaphy or graft, were significantly less likely to recur (OR = 0.239; p = 0.041). Among patients with secondary aneurysms, those repaired via end-to-end anastomosis had a significantly higher primary patency rate 1 year postoperatively (p = 0.024). Secondary aneurysm repairs exhibited 1-year primary and secondary patency rates of 51.2% and 82.9%, respectively. CONCLUSIONS: End-to-end anastomosis reduces risk of recurrence and demonstrates superior patency rates when repairing recurrent aneurysms. It remains unclear why some patients are prone to aneurysm recurrence, however continued attempts to repair existing vascular access are proven to be successful.

HLA-mismatched renal transplantation without maintenance immunosuppression.

Five patients with end-stage renal disease received combined bone marrow and kidney transplants from HLA single-haplotype mismatched living related donors, with the use of a nonmyeloablative preparative regimen. Transient chimerism and reversible capillary leak syndrome developed in all recipients. Irreversible humoral rejection occurred in one patient. In the other four recipients, it was possible to discontinue all immunosuppressive therapy 9 to 14 months after the transplantation, and renal function has remained stable for 2.0 to 5.3 years since transplantation. The T cells from these four recipients, tested in vitro, showed donor-specific unresponsiveness and in specimens from allograft biopsies, obtained after withdrawal of immunosuppressive therapy, there were high levels of P3 (FOXP3) messenger RNA (mRNA) but not granzyme B mRNA.