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Background Kidney transplantation has established itself as the most appropriate mode of renal replacement therapy for the majority with end-stage kidney disease. Although at present this is applicable for children as well as adults, a few decades back kidney transplantation was not considered a first-line option in children. This was due to inferior outcomes following transplantation in this age group compared to that of adults. These poor results were attributed to challenges in paediatric transplantation such as the shortage of suitable donors, technical difficulties in performing a sound vascular anastomosis and the adverse effects of immunosuppressive medication on growth and development. However, current patient and graft-centred outcomes after paediatric transplantation equal or surpass that of adults. The advances in evaluation and management of specific surgical concerns in children who undergo transplantation, such as pre-transplant native nephrectomy, correction of congenital anomalies of the urinary tract, placement of an adult-sized kidney in a small child and minimizing the risk of allograft thrombosis, have contributed immensely for these remarkable outcomes. Conclusions In this review, we aim to discuss surgical factors that can be considered unique for children undergoing kidney transplantation. We believe that an updated knowledge on these issues will be invaluable for transplant clinicians, who are dealing with paediatric kidney transplantation.

Kidney transplantation is the best health option for patients with end-stage kidney disease. Ideally, a kidney transplant would last for the lifetime of each recipient. However, depending on the age of the recipient and details of the kidney transplant, there may be a need for a second, third, fourth, or even more kidney transplants. In this overview, the outcome of multiple kidney transplants for an individual is presented. Key issues include surgical approach and immunologic concerns. Included in the surgical approach is an analysis of transplant nephrectomy, with indications, timing, and immunologic impact. Allograft thrombosis, whether related to donor or recipient factors merits investigation to prevent it from happening again. Other posttransplant events such as rejection, viral illness (polyomavirus hominis type I), recurrent disease (focal segmental glomerulosclerosis), and posttransplant lymphoproliferative disease may lead to the need for retransplantation. The pediatric recipient is especially likely to need a subsequent kidney transplant. Finally, noncompliance/nonadherence can affect both adults and children. Innovative approaches may reduce the need for retransplantation in the future.

Background We describe the safety and efficacy of performing pediatric kidney transplantation with a modified extraperitoneal approach that includes mobilization of the native liver and kidney. Methods We retrospectively identified pediatric renal transplants performed using this technique between 2015 and 2019. Data on patient demographics, surgical technique, and intraoperative details were collected. Outcomes were measured by morbidity and re-operation at 90 days, as well as serum creatinine, allograft survival, and overall survival at 1 year. Results Twenty-one patients with a median age of 5 (IQR 3–9) years, weighing 17.5 (IQR 14.5–24) kg were included. Median donor age was 24 (IQR 19–31) years. No intraoperative complications occurred. One child required a right native nephrectomy to allow sufficient space. Postoperatively, all patients had immediate graft function without urine leak or allograft thrombosis. 90-day morbidity and re-operation rates were zero. Both 1-year allograft and overall survival were 100% (on follow-up of all 21 patients through 1 year post-transplant), with a median serum creatinine of 0.58 (IQR 0.47–0.70) mg/dl at 1 year post-transplant. Conclusions Pediatric kidney transplantation of adult renal allografts using an extraperitoneal approach with native liver and kidney mobilization has promising allograft and patient survival outcomes that eliminates peritoneal violation and may diminish the need for native nephrectomy.

Introduction Transplant units are exploring strategies to increase the availability of donor kidneys. The use of en-bloc kidney transplantation (EBKT) from paediatric donors represents one potential solution. We present our long-term experience with paediatric EBKT among adult recipients. Methods Twenty-three paediatric to adult EBKTs were performed by the Irish National Kidney Transplant Service between 1990 and 2016. The primary outcome variable was long-term en-bloc allograft survival rate. Secondary outcome variables were incidence of allograft thrombosis, incidence of delayed graft function, overall patient survival and serum creatinine at most recent follow-up. Outcomes were compared to single kidney transplant recipients from the same time period. Results Mean donor age was 1.8 ± 0.97 years (range: 7 months to 3 years). Recipient age was 46 ± 12 years. Mean follow-up was 133 ± 64 months (range: 36–264). Overall graft survival was 100%, 91% and 80% after 1, 5 and 10 years respectively, compared to 92%, 79% and 61% in single kidney transplant recipients ( p = 0.04). There were 5 cases of allograft failure, 3 due to death from unrelated causes. Median time to graft failure was 108 months (range: 36–172). Mean serum creatinine was 72.6 ± 21.6 μmol/l after the follow-up period. There were no cases of graft thrombosis or delayed graft function. Overall survival was 96.4%, 88.0%, 76.23% and 50.5% at 1, 5, 10 and 20 years respectively. Conclusion En-bloc paediatric kidney transplantation is associated with excellent long-term allograft and patient survival and is a feasible strategy for increasing the transplant donor pool in carefully selected recipients.

Background Cryopreserved arterial allografts are vascular substitutes used for arterial reconstructions in a septic field. Their use remains however limited by the shortage of donors. One of the possibilities to address this lack of grafts is to multiply the sources of retrieval. The objective of this preliminary study was the evaluation of the early clinical results and the microbiological safety of arterial grafts retrieved after death. Methods In addition to the standard conditions of arterial sampling, the criteria of inclusion for postmortem retrieval comprised the refrigeration of the body of the donor within 4 hr following the death, a 24-hr time limit from the death, and the availability of an adapted place for retrieval (surgical unit or death chamber respecting the required aseptic conditions). We only retrieved the femoral axes (FAs) and the aortoiliac bifurcation. The conditions of retrieval, transportation, preparation, and conservation were identical to those of cryopreserved arterial allografts harvested during standard multiple organs retrieval. We evaluated the bacteriological risk of contamination and the patency of the grafts in the short and medium term. Results In 2015 and 2016, 6 donors were included. Eleven FAs and 2 aortic bifurcations were harvested. The bacteriological samples done on arrival in bank and after thawing were negative in the 6 donors, but one of the 6 donors presented a bacterial contamination of other removed tissues, and the arterial grafts obtained from this donor were destroyed as a precaution (3 grafts). The quality of the grafts evaluated by the surgeon during harvesting was good in all the cases. The indications of allografts were arterial reconstruction in a septic field (n = 8) and aorto-hepatic bypass during hepatic transplantation (n = 1). One graft was unhopefully thawed without being used. At the end of the follow-up, 8 out of 9 grafts were patent. Two ruptures occurred in a context of locally persistent sepsis (crural abscess due to Salmonella typhi and persistent groin wound disunion with a polymicrobial flora). One allograft thrombosis was observed (aorto-hepatic bypass for transplantation). These complications were unrelated to the mode of graft harvesting. No aneurysmal evolution was observed. Conclusions The preliminary results of this protocol are encouraging because the immediate quality of the grafts was good with a risk of microbiological contamination identical with that of the usual harvesting mode. This mode of harvesting looks promising to reduce the shortage in arterial allografts and could be extended to harvest thoracic aortic allografts. However, results at a larger scale are necessary to confirm these data.

Context: The use of aspirin in chronic kidney disease (CKD) patients has been shown to reduce myocardial infarction but may increase major bleeding. However, its effects in kidney transplant recipients are unclear. Evidence Acquisitions: A literature search was performed using MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews from inception through September 2016. We included studies that reported odd ratios, relative risks or hazard ratios comparing outcomes of aspirin use in kidney transplant recipients. Pooled risk ratios (RR) and 95% confidence interval (CI) were assessed using a random-effect, generic inverse variance method. Results: We included 9 studies; enrolling 19 759 kidney transplant recipients that compared aspirin with no treatment. Compared to no treatment, aspirin reduced the risk of allograft failure (4 studies; RR: 0.57, 95% CI: 0.33 to 0.99), allograft thrombosis (2 studies; RR: 0.11, 95% CI: 0.02 to 0.53), and major adverse cardiac events (MACEs) or mortality (2 studies; RR: 0.72, 95% CI: 0.59 to 0.88), but not allograft rejection (3 studies; RR: 0.86, 95% CI: 0.45 to 1.65) or delayed graft function (DGF) (2 studies; RR: 1.00, 95% CI: 0.58 to 1.72) in kidney transplant recipients. The data on risk of major or minor bleeding were limited. Conclusions: Our meta-analysis demonstrates that administration of aspirin in kidney transplant recipients is associated with reduced risks of allograft failure, allograft thrombosis, and MACEs or mortality, but not allograft rejection or DGF. Future studies are needed to assess the risk of bleeding, and ultimately weigh the overall risks and benefits of aspirin use in specific kidney transplant patient populations.

Pancreas transplant achieves consistent long-term euglycemia in type 1 diabetes. Allograft thrombosis (AT) causes the majority of early graft failure. We compared outcomes of four anticoagulation regimens administered to 95 simultaneous kidney-pancreas or isolated pancreas transplanted between 1/1/2015 and 11/20/2018. Early postoperative anticoagulation regimens included the following: none, subcutaneous heparin/aspirin, with or without dextran, and heparin infusion. The regimens were empirically selected based on each surgeon's assessment of hemostasis of the operative field and personal preference. A sonographic-based global scoring system of AT is presented. The 47-month recipients and graft survival were 95% and 86%, respectively. Recipients with or without AT had similar survival. Five and four grafts were lost due to death and AT, respectively. Outcomes of prophylaxis regimens correlated with intensity of anticoagulation. Compared with no anticoagulation, an increase in hemorrhagic complications occurred exclusively with iv heparin. The higher arterial AT score found in regimens lacking antiplatelet therapy highlights the importance of early antiaggregants therapy. Abnormal fibrinolysis was associated with an increase in AT score. Platelet dysfunction, warm ischemia time, and enteric drainage were predictive of AT and, along with other known risk factors, were incorporated into an algorithm that matches intensity of early postoperative anticoagulation to the thrombotic risk.

To evaluate the effect of antiphospholipid antibodies (aPL) on renal allograft outcome after kidney transplantation.A systematic search of EMBASE and PubMed databases from inception to July 2018 was run according to PRISMA guidelines; Peto's odds ratio (OR) for rare events was used for the meta-analysis.Our inclusion/exclusion criteria were met by 22 cohort studies having different outcomes: allograft thrombosis (n = 9) and thromboprophylaxis (n = 3), allograft loss from any cause (n = 9), allograft malfunction (n = 3), duration (n = 2), glomerular filtration rate at 1 year (n = 3) and allograft rejection (n = 5). The pooled prevalence of allograft thrombosis and of thrombotic microangiopathy was greater in aPL+ve than negative recipients (10.4% vs 1.7%, p 0.0001 and 10.2% vs 0%, p = 0.005, respectively). The pooled prevalence of allograft thrombosis was 75% in patients not taking anticoagulation whereas none of the anticoagulated recipients developed thrombosis (p 0.0001). The pooled prevalence of allograft loss was greater in aPL+ve recipients (28% vs 18% respectively, p 0.0001); the pooled prevalence of aPL was greater in allograft loss recipients compared to those who did not lose it (51% vs 33%, p 0.0001). The pooled prevalence of allograft malfunction and rejection was similar in aPL-ve and aPL+ve recipients (32.2% vs 40.3% and 14.9% vs 14.4%, respectively) but graft duration was shorter in aPL+ve than aPL-ve recipients (p = 0.001) and glomerular filtration rate at 1 year was lower in aPL + ve than aPL-ve recipients (p 0.0001).APL relate strongly to allograft thrombosis, loss and duration but not to allograft malfunction and rejection. Oral antivitamin K anticoagulants effectively prevent allograft thrombosis in aPL recipients. The debate on the role of aPL in renal transplant is limited by the expression of data as percentage of recipients positive for aPL rather than aPL titres in many studies.

Pancreatic allograft thrombosis (PAT) remains the leading cause of nonimmunologic graft failure. Here, we propose a new computed tomography (CT) grading system of PAT to identify risk factors for allograft loss and outline a management algorithm by retrospective review of consecutive pancreatic transplantations between 2009 and 2014. Triple‐phase CT scans were graded independently by 2 radiologists as grade 0, no thrombosis; grade 1, peripheral thrombosis; grade 2, intermediate non‐occlusive thrombosis; and grade 3, central occlusive thrombosis. Twenty‐four (23.3%) of 103 recipients were diagnosed with PAT (including grade 1). Three (2.9%) grafts were lost due to portal vein thrombosis. On multivariate analysis, pancreas after simultaneous pancreas–kidney transplantation/solitary pancreatic transplantation, acute rejection, and CT findings of peripancreatic edema and/or inflammatory change were significant risk factors for PAT. Retrospective review of CT scans revealed more grade 1 and 2 thromboses than were initially reported. There was no significant difference in graft or patient survival, postoperative stay, or morbidity of recipients with grade 1 or 2 thrombosis who were or were not anticoagulated. Our data suggest that therapeutic anticoagulation is not necessary for grade 1 and 2 arterial and grade 1 venous thrombosis. The proposed grading system can assist clinicians in decision‐making and provide standardized reporting for future studies., The Cambridge Pancreatic Allograft Thrombosis grading system may be used to standardize reports of thrombosis, identify patients who would benefit from therapeutic anticoagulation, provide prognostic information, and allow better comparison of reports from different centers for improved understanding and management of this common condition.

Simultaneous pancreas-kidney (SPK) transplantation remains the most effective treatment for providing consistent and long-term euglycemia in patients having type 1 diabetes with renal failure. Thrombosis of the pancreatic vasculature continues to contribute significantly to early graft failure and loss. We compared the rate of thrombosis to graft loss and systematically reviewed risk factors impacting early thrombosis of the pancreas allograft following SPK transplantation. We searched the MEDLINE, EMBASE, The Cochrane Library, and PREMEDLINE databases for studies reporting thrombosis following pancreas transplantation. Identified publications were screened for inclusion and synthesized into a data extraction sheet. Sixty-three studies satisfied eligibility criteria: 39 cohort studies, 22 conference abstracts, and 2 meta-analyses. Newcastle-Ottawa Scale appraisal of included studies demonstrated cohort studies of low bias risk; 1127 thrombi were identified in 15 936 deceased donor, whole pancreas transplants, conferring a 7.07% overall thrombosis rate. Thrombosis resulted in pancreatic allograft loss in 83.3% of reported cases. This review has established significant associations between donor and recipient characteristics, procurement and preservation methodology, transplantation technique, postoperative management, and increased risk of early thrombosis in the pancreas allograft. Further studies examining the type of organ preservation fluid, prophylactic heparin protocol, and exocrine drainage method and early thrombosis should also be performed.

Renal allograft thrombosis involving either the renal artery or the veins is a well known entity in clinical practice. This complication of the renal transplant surgery is more common in the early part of the post transplant period and it is usually associated with acute antibody mediated rejection. This more commonly occurs in the paediatric renal transplant and also seems to have some relation to the duration of peritoneal dialysis pretransplant. However, the occurrence of graft thrombosis in isolation without clinical or histological graft rejection is not rare. We encountered a patient in whom the renal allograft thrombosis occurred after 6 weeks of commercial renal transplantation without any histological evidence of rejection.

INTRODUCTION Early allograft thrombosis is a devastating complication that often leads to graft loss after living donor kidney transplantation. In addition to the psychological effects on donor and recipient, it could make future kidney matches challenging due to sensitization. PATIENTS AND METHODS The Scientific Registry of Transplant Recipients (SRTR) was queried for adult patients undergoing living donor renal transplantation from 2001 to 2010. Sensitization was defined as a panel reactive antibody of ≥50%. Early allograft thrombosis included events within 30 d of transplantation. RESULTS In multivariable logistic regression, recipient female gender (odds ratio [OR] 2.24, p < 0.001) and right kidneys (OR 1.46, p < 0.001) were associated with increased risk of thrombosis, while increasing recipient age per 10 yr (OR 0.62, p < 0.001) and recipient Asian race/ethnicity (OR 0.34, p = 0.02) were protective. In a time-varying Cox model examining factors affecting the likelihood of retransplantation, the chance of retransplantation was 37% lower (p = 0.01) once patients became sensitized. The median time to sensitization after transplantation was 288 d. CONCLUSIONS Even with relatively brief exposure to foreign antigen, sensitization occurs and delays retransplantation for recipients of living donor kidneys with early allograft thrombosis.

Background: Microvascular thrombosis is an uncommon pathologic finding in cadaveric kidneys. It is associated with disseminated intravascular coagulation most frequently associated with head injuries and massive blood transfusions. The high rate of non-function published in the literature portends an ominous significance for transplanted organs, which have been discarded by many transplant centers. Methods: In this report, we document the effectiveness of ex vivo thrombolytic therapy with activase®, a plasminogen activator, injected intra-arterially in 12 kidneys with extensive histologic intraglomerular microvascular thrombosis prior to transplantation. All cold stored cadaveric kidneys were flushed for 50 min with 50 mg of activase® diluted in University of Wisconsin solution. Pre-flush and post-flush wedge biopsies were performed on the allografts. Results: All biopsies showed complete resolution of the intraglomerular microthrombi following activase® flush. One kidney clotted in the third week. Three patients developed delayed graft function (25%) of which one experienced allograft thrombosis following one month after transplantation. All remaining grafts are still functioning at a mean follow up of 55.1 months (range: 23–71) with a mean serum creatinine of 1.8 mg/dL (range: 0.8–2.5). Conclusions: Back table flush with activase® rapidly lyses severe intraglomerular microthrombi making them successfully transplantable. Pre-treatment with activase seems to be an effective therapeutic intervention for kidneys with massive intraglomerular thrombosis.

Thrombosis remains an important complication after kidney transplantation. Outcomes for graft and deep vein thrombosis are not favorable. The majority of early kidney transplant failure in adults is due to allograft thrombosis. Risk stratification, early diagnosis, and appropriate intervention are critical to the management of thrombotic complications of transplant. In patients with end-stage renal disease, the prevalence of acquired risk factors for thrombosis is significantly high. Because of hereditary and acquired risk factors, renal transplant recipients manifest features of a chronic prothrombotic state. Identification of hereditary thrombotic risk factors before transplantation may be a useful tool for selecting appropriate candidates for thrombosis prophylaxis immediately after transplantation. Short-term anticoagulation may be appropriate for all patients after kidney transplantation.

complication rates were 28.0% (95% CI 15.4 to 42.7%) for anticoagulants, compared to 12.13% (95% CI 0.8 to 33.93%) for aspirin þ anticoagulant, 0.31% (95% CI 0.0001 to 1.32%) for aspirin, and 6.1% (95% CI 2.2 to 11.7%) for the control group. CONCLUSIONS: Aspirin is more effective in reducing allograft thrombosis, after kidney transplantation, whether alone or in association with an anticoagulant, when compared to no drug prophylaxis, and without higher hemorrhagic complication rates. Anticoagulants, when used alone, do not show a beneficial effect on thrombosis rates, additionally yielding higher bleeding rates.

Renal transplantation improves survival and quality of life for patients with end-stage renal disease (ESRD). Improvements in immunosuppressive therapy have reduced early allograft loss due to acute rejection to very low levels. Early allograft loss, due to acute thrombotic complications, remains a constant and proportionally increasing complication of renal transplantation. Identifying risk factor(s) for thrombosis amenable to preventive strategies has been elusive. Epidemiological studies have attempted to define risk in terms of modifiable (drugs, dialysis modality, surgical procedure) and non-modifiable (age, diabetes mellitus, vascular anomalies) factors, or identify changes in coagulation or fibrinolysis promoting a more thrombotic state. Most recently the evolution of thrombophilia research has established the potential for inherited hypercoagulability to predispose to acute allograft thrombosis. Inheritance of the factor V Leiden (FVL), prothrombin G20210A mutation, or the presence of antiphospholipid antibodies (APA) may increase the risk of renal allograft thrombosis approximately 3-fold in selected patients. Patients with ESRD due to systemic lupus erythematosus (SLE) appear at particularly high risk of thrombosis, especially if they have either APA or detectable beta(2)-glycoprotein-1. Data for other hypercoagulable states such as hyperhomocystinemia or the C677T polymorphism of the methylenetetrahydrofolate reductase gene are deficient. Patients with APA, FVL, or prothrombin G20210A mutation also appear to have greater graft loss due to vascular rejection, possibly reflecting immunological injury upon the vascular wall exacerbated or induced by the prothrombotic state. While substantial in vitro data suggest cyclosporine is prothrombotic, an independent clinical association with allograft thrombosis is unproven. Interventions to reduce thrombotic risk including heparin, warfarin, and aspirin have been evaluated in both selected high-risk groups (heparin and warfarin) and unselected populations (heparin and aspirin). In unselected patients at low clinical risk, aspirin (75-150 mg/day) with or without a short period of unfractionated heparin (5000U twice a day for 5 days) appears to reduce the risk of renal allograft thrombosis significantly with a low risk of bleeding, especially when compared with low molecular weight heparins which risk accumulation in renal failure. In high-risk groups (identified thrombophilic risk factor, previous thrombosis, or SLE) longer period of heparin, with or without aspirin and maintenance with warfarin, should be considered. Re-transplantation following graft loss due to vascular thrombosis can be undertaken with a low risk of recurrence. Further prospective studies evaluating both putative risk factors and intervention strategies are required to determine whether routine clinical screening for thrombophilic factors is justified.

Introduction Although multiple studies of demographic variables have been associated with allograft thrombosis, these results are not routinely reproducible. Are ESRD patients with hypercoagulable states (HCS) (antithrombin III deficiency, protein S or C deficiency, activated protein C resistance, and anticardiolipin antibodies) at predictably greater risk for allograft thrombosis? Methods Between 1996 and 1999, all renal transplant candidates were screened for hypercoagulability risk factors [HRF] (multiple arteriovenous access thromboses, prior deep vein thrombosis, prior allograft thrombosis, collagen vascular disease, multiple miscarriages, diabetes, autoimmune disease, and Fabry's disease). HRF(+) candidates were then tested for HCS status. We administered preemptive posttransplant i.v. Heparin in HCS(+) patients and observed the impact of this intervention upon the incidence of allograft thrombosis. We compared demographic data and incidence of allograft thrombosis in an historic control (346 patients transplanted between June 31, 1992, and March 5, 1996) not tested for HCS and a study cohort (502 patients transplanted between March 6, 1996, and June 31, 1999) prospectively screened for HRF. HRF(+) patients who were HCS(+) in the study cohort received i.v. heparin immediately after transplant and p.o. warfarin as outpatients. Results Demographic characteristics previously implicated in allograft thrombosis were equivalently distributed in both cohorts with the exceptions that more living-donor transplants (33.1% vs. 15.3%) were performed in study cohort, CIT>24 hr occurred in more control patients (37.3% vs. 22.1%) and more study patients (16.7% vs. 0%) received tacrolimus. Hypercoagulable states were found upon reevaluating five of seven controls (71.4%), who lost prior allografts to thrombosis. Hypercoagulable states were prospectively detected in 10 study patients with hypercoagulability risk factors. Most (9 of 10) study patients receiving anticoagulation have achieved long-term allograft function. Study group allograft thrombosis incidence was reduced (1.59% vs. 4.05%). Hypercoagulable states were demonstrated in most episodes of allograft thrombosis. Control patients who lost prior allografts to thrombosis were anticoagulated after retransplantation and 100% achieved long-term allograft function. Conclusions Long-term allograft function has been achieved in 90% of study patients when prophylactically anticoagulating study patients with hypercoagulable states. A 2.6-fold reduction in the expected incidence of allograft thrombosis was observed in anticoagulated patients with hypercoagulable states.

Background Primary thrombosis and chronic allograft nephropathy are important causes of early and late graft loss, respectively, following renal transplantation. This study examined the potential for aspirin therapy to reduce these complications. Methods A consecutive series of 105 cadaveric renal transplants treated with aspirin 150 mg daily for the first 3 months after transplantation was compared with an untreated historical control group (n = 121). Protocol needle-core biopsies were performed on all transplants in both groups at 1 week and 12 months after transplantation. Needle-core allograft biopsies were performed at 3, 6 and 12 months after transplantation, and serum creatinine was measured at each outpatient attendance for the duration of follow-up. Results There was a significantly lower rate of primary allograft thrombosis in patients treated with aspirin (none of 105) compared with that in the control group (six (5 per cent) of 121; P = 0·03). There were no differences in renal function or 2-year allograft survival between the two groups. Aspirin-treated patients had a lower incidence of chronic allograft nephropathy at 1 year than controls although this did not reach statistical significance (16 versus 26 per cent; P = 0·075). There were no major bleeding complications in either group in association with peptic ulcer disease or following renal transplant biopsy. Conclusion Aspirin reduced the rate of early graft thrombosis of renal transplants in this series but did not improve renal function or graft survival. A trend towards a lower rate of chronic allograft nephropathy was noted with aspirin treatment. These findings require confirmation in a prospective randomized trial.

From January 1986 through December 1998, 175 adults received single kidneys from donors less than 60 months of age. Recipient age ranged from 16 to 66 years (mean 41.2 years), weight from 75 to 186 lb (mean 138 lb), and no exclusion was made for previous transplants, diabetes, or factors other than weight. Donor age ranged from 9 to 56 months (mean, 25.3 months), weight from 9 to 60 lb (mean, 28 lb), and cold ischemia time from 12 to 52 hours (mean, 32 hours). Donor kidneys were received en bloc and separated before transplantation. Surgical technique featured interrupted venous anastamosis, an aortic patch for the renal artery anastamosis, and urinary reconstruction with uretero-ureterostomy. Immunosuppression evolved through three phases, stressing avoidance of early rejection and prompt, vigorous treatment of rejection episodes. Current immunosuppression includes antibody induction, cyclosporine or tacrolimus, mycophenolate and steroids. Allograft survival rates have improved during the series: 1-, 3-, and 5-year actuarial allograft survival from 1986 to 1990 (n = 25 patients) was 60%, 44%, and 44%; from 1990 to 1995 ( n = 92 patients), 75%, 60%, and 54%; and from 1996 to the present, 1-year allograft survival has been 90%, with no graft losses to rejection. This current allograft survival rate is equivalent to that of patients receiving an organ from an adult donor age 18 to 45 years in our center. Surgical complications occurred in 10.8% of cases, the most serious being allograft thrombosis in 3.4%, most in kidneys from donors less than 24 months of age. Long-term allograft function and loss have not been different from recipients of adult kidneys. Single kidneys from donors less than 60 months of age can be used successfully in adult recipients with satisfactory long-term function and no significant increase in risk with current immunosuppression. A concerted effort should be made to recover and transplant younger kidneys as single units to increase organ availability and optimally use donor resources.

Dialysis modality and the risk of allograft thrombosis in adult renal transplant recipients.BackgroundRenal vascular thrombosis (RVT) is a rare but catastrophic complication of renal transplantation. Although a plethora of risk factors has been identified, a large proportion of cases of RVT is unexplained. Uremic coagulopathy and dialysis modality may predispose to RVT. We investigated the impact of the pretransplant dialysis modality on the risk of RVT in adult renal transplant recipients.MethodsRenal transplant recipients (age 18years or more) who were enrolled in the national registry between 1990 and 1996 (N = 84,513) were evaluated for RVT occurring within 30days of transplantation. Each case was matched with two controls from the same transplant center and with the year of transplantation. The association between RVT and 18 factors was studied with multivariate conditional logistic regression.ResultsForty-nine percent of all cases of RVT (365 out of 743) occurred in repeat transplant recipients with an adjusted odds ratio (OR) of 5.72 compared with first transplants (P < 0.001). There were a significantly higher odds of RVT in peritoneal dialysis (PD)-compared with hemodialysis (HD)-treated patients (OR = 1.87, P = 0.001). Change in dialysis modality was an independent predictor of RVT: switching from HD to PD (OR = 3.59, P < 0.001) and from PD to HD (OR = 1.62, P = 0.047). Compared with primary transplant recipients on HD (OR = 1.00), the highest odds of RVT were in repeat transplant recipients treated with PD (OR = 12.95, P < 0.001) and HD (OR = 4.50, P < 0.001). Other independent predictors of RVT were preemptive transplantation, relatively young and old donor age, diabetes mellitus and systemic lupus erythematosus as causes of end-stage renal disease, recipient gender, and lower panel reactive antibody levels (PRAs).ConclusionsThe strongest risk factors for RVT were retransplantation and prior PD treatment. Prevention of RVT with perioperative anticoagulation should be studied in patients who have a constellation of the identified risk factors.

Background. Renal transplantation and chronic renal failure are associated with an increased risk of venous thrombosis and myocardial infarction (MI). We investigated whether resistance to activated protein C due to a mutation in the factor V gene (FV Leiden/ FV506Q) may predispose patients to thrombosis. Methods. Three hundred patients who had undergone renal transplantation were genotyped for the FV mutation. Seventy-seven patients who had suffered thrombotic complications (42 venous, 28 arterial, and 7 both) were compared with 223 patients free of thrombosis. Results. Thirty-two patients had suffered early renal allograft thrombosis (30 venous), and 33 patients had suffered MI. A higher proportion of the patients with thrombosis, compared to those without, had a family history of arterial cardiovascular disease (42% vs. 26%, P=0.04). Eighteen (6%) patients were heterozygous for FV506Q and seven (39%) of these had suffered venous thrombosis (including four primary allograft thromboses), compared with 15% of the patients without the mutation (P

Objectives To determine factors associated with early pancreatic allograft thrombosis (EPAT). Thrombosis is the leading non-immunological cause of early pancreatic allograft failure. Multiple risk factors have been postulated. We hypothesized that recipient perioperative hypotension was a major risk factor and evaluated the correlation of this and other parameters with EPAT. Methods We retrospectively reviewed the records of the 118 patients who received a pancreatic allograft at our center between October 1992 and January 2010. Multiple donor and recipient parameters were analyzed as associates of EPAT by univariate and multivariate analysis. Results There were 12 episodes of EPAT, resulting in an incidence of 10.2%. On univariate analysis, EPAT was associated with perioperative hypotension, vasopressor use, and neuropathy in the recipient (p ≤ 0.04 for all). On multivariate analysis corrected for age, sex, and peripheral vascular disease, only vasopressor use retained a significant association with EPAT with a hazard ratio of 8.74 (CI 1.11–68.9, p = 0.04). Factors associated with vasopressor use included recipient ischemic heart disease, peripheral vascular disease, retinopathy or neuropathy, and any surgical complication. Conclusions Significant hypotension, measured by the need for perioperative vasopressor use was associated with EPAT, suggesting that maintenance of higher perfusion pressures may avoid this complication.

Aims: To review our single-center experience of preemptive anticoagulation for the prevention of allograft thrombosis in patients with hypercoagulable states. Material and methods: This is a retrospective cohort study. Included subjects were first-time kidney allograft recipients transplanted between 2003 and 2007 at a single center, with hypercoagulable states: prior venous thromboembolism, multiple vascular access thromboses, or identifiable thrombophilia. The predictor variable was preemptive anticoagulation and outcome variable was allograft thrombosis. Other risk factors for allograft thrombosis, characteristics of transplantation, and hemorrhagic complications were also examined. Results: Among this high-risk cohort (n=48), 16 received preemptive anticoagulation and 32 did not. The anticoagulated group included significantly more subjects with identifiable thrombophilia (50.0% vs. 0%; p < 0.001). One subject (6.3%) in the anticoagulated group and 6 (18.8%) without anticoagulation developed allograft thrombosis (p = 0.40). A perinephric hematoma was observed in 5 (31.3%) and 2 (6.3%) with and without anticoagulation, respectively (p = 0.03). Conclusions: Preemptive anticoagulation was associated with a non-significant trend towards decreased allograft thrombosis. It may be associated with increased risk of hemorrhage and should be considered cautiously in high-risk patients.

Background It has been described that patients on peritoneal dialysis (PD) suffer from thrombotic events (vascular access, deep venous thrombosis, and graft thrombosis) more frequently after transplantation than other recipients. We analyzed the incidence of allograft thrombosis among patients transplanted in a 6-year period (January 1, 2000, to December 31, 2005) to identify etiological factors, such as inherited thrombophilia. Materials and methods We performed 197 renal transplants in 189 patients, including 115 who had been on hemodialysis (HD), 44 on PD, and 30 preemptive. We recorded immunological and demographic data, studied graft and patient survivals, and evaluated the hypercoagulable state of those who experienced graft thrombosis. Results The mean age of the patients at transplantation was 49 years. There were no demographic or immunological differences between the three groups of patients, except for the number of previous blood transfusions and panel reactive antibodies (PRA) levels. Forty-seven grafts were lost in the first year; 14 suffered venous thrombosis, and there were 10 acute rejection epidoses (ARE), 7 death-censored graft failures, 3 chronic allograft nephropathies (CAN), 6 primary nonfunctions, 5 removed due to infection, 1 primary disease relapse, and 1 hemolytic-uremic syndrome. Of the 14 cases of thrombosis in 12 patients, 10 had been on PD and 4 on HD immediately before transplant. One-year graft and patient survivals were similar: 74% HD, 68% PD, 86% preemptive, and 93% HD, 95% PD, and 96% preemptive, respectively. The hypercoagulable state showed inherited thrombophilia patterns in some cases, but most of them were normal. Conclusion Renal graft thrombosis was responsible for graft lost in PD patients within the first year, while in the HD group it was ARE and in the preemptive cohort, death with a functioning graft. The hypercoagulable state pretransplant should be more accurately studied to identify thrombotic factors other than those which are inherited.

A patient with end-stage kidney disease is described, who lost his renal allograft in the early post-transplant period due to allograft renal vein thrombosis. Prior to transplantation, he had been treated by hemodialysis and lost several vascular accesses because of thrombosis. A search for potential thrombophilic factors disclosed a unique combination of increased clotting factor levels, i.e. FVIII, FIX, FXI and homocysteine. More common hereditary and acquired hypercoagulability factors have been excluded in this patient. While clotting factor deficiencies are well known causes of hemophilia, their levels should also be measured in the workup of transplant candidates with a history of multiple vascular access thrombosis.

Background Venous thrombosis remains an important cause of pancreatic graft loss. Nevertheless, reports are scarce of treatment alternatives to complete graft removal. We describe a case of surgical salvage of a partial pancreatic graft thrombosis. Methods We used descriptive retrospective analysis. Results A 36-year-old patient with juvenile-onset diabetes mellitus and previous living related renal transplant received a cadaveric pancreas transplant in the right iliac fossa with enteric exocrine drainage and standard vascular anastomosis. Two days after discharge from the hospital, he presented with severe right upper quadrant pain, nausea, vomiting, fever, and leukocytosis. He was taken to the operating room for exploration. The tail of the pancreas, which was kinked under the gallbladder, was necrotic and excised. The remainder of the pancreas looked normal. The patient recovered well from surgery and was discharged home 7 days later. Conclusions Partial pancreatectomy is an acceptable surgical alternative for incomplete graft thrombosis.

Renal allograft thrombosis remains a preventable cause of early allograft thrombosis. It should not be considered simply an unpredictable and poorly understood consequence of surgery. Extrapolated data from the general population and early data from renal patients supports the concept that the interplay of non-inherited hypercoagulability of renal disease with inherited thrombophilia, and the altered environmental milieu of transplantation predisposes to thrombosis (summarized in Figure 2). We should not accept the inevitability of a constant attrition of grafts to thrombosis and need to continue to identify risk factors and confirm appropriate screening and interventions for its prevention, almost certainly requiring collaborative multicentre trials. In the future, just as we now expand the specificity of HLA gene typing with molecular biology, genotyping for recognized thrombophilia genes in patients at risk will expand our ability to recognize and prevent thrombosis with targeted interventions drawn from the increasing array of anticoagulants now available. The contribution of thrombophilia to non-immune mechanisms of chronic allograft loss is also a potentially important but neglected area of research.

OLYCLONAL antilymphocyte agents have been widely used since the 1960s for induction therapy as well as for the treatment of allograft rejection in clinical organ transplantation. In addition to their role as induction agents, polyclonal antibodies are used in many centers in order to delay administration of nephrotoxic interleukin-2 (IL-2)‐ based agents such as cyclosporine (CyA) or tacrolimus until allograft function is established. Recent efforts have focused on selective use of polyclonal antibodies for recipient populations deemed to be at higher immunologic risk for allograft rejection. Many different preparations have been developed, using a range of hosts (primarily horse, rabbit, and goat) for the generation of antibody to either resting or stimulated lymphocytes or thymocytes. For many years, it was difficult to discern whether the use of polyclonal antilymphocyte agents in kidney transplantation was associated with a significant immunologic advantage. Recently, however, several large database analyses have demonstrated that polyclonal induction is associated with a significant increase in graft survival and a decreased risk of rejection in patients receiving kidney transplants. 1‐3 A large multicenter study of the use of polyclonal agents in the treatment of rejection demonstrated excellent reversal rates and low recurrence rates. 4 Outside of kidney transplantation, a number of series have documented favorable results using polyclonal antibodies in the treatment of liver, 5,6 pancreas, 7 and heart transplant recipients. 8 In specific patient populations, polyclonal antilymphocyte antibody preparations have been shown to be of particular benefit. This is especially true for pediatric renal transplant patients, who have been shown to derive immunologic benefit as well as a decreased incidence of allograft thrombosis when polyclonal agents are included as part of their immunosuppressive regimen, 9,10 and for recipients of repeat transplants. 11

Objective To identify renal transplant patients at a higher risk for allograft thrombosis and develop a risk stratification protocol for post-operative anticoagulation. Background According to the North American Pediatric Renal Transplant Cooperative Study data, vascular thrombosis is responsible for 12% of renal transplant failures. Congenital and acquired prothrombotic disorders have recently been found to play a major role in defining outcome of the renal transplants. Methods In 2007, we initiated universal screening for acquired and congenital thrombophilic risk factors for all renal transplant patients prior to transplant. They were assigned a risk category (Level I-IV) based on the presence of thrombophilic risk factors and their post-operative anticoagulation plan was pre-determined based on their risk level (Table). Low-dose unfractionated heparin drip was initiated a few hours after the transplant and titrated to achieve a 1.5 fold aPTT level. Anticoagulation was changed to low molecular weight heparin (LMWH) on day 2–4, when the risk of major bleed was over, and the serum creatinine had normalized. Result Nine patients have been screened and 8/9 were found to be at high risk for thrombosis (Level II or III). The prothrombotic risk factors identified were Prothrombin gene mutation (2), MTHFR (8), Lupus anticoagulant (2) and low protein S (2). Five patients have undergone renal transplant, and have been treated with LMWH post-operatively as per plan, with successful outcome. No patient has developed allograft thrombosis. 1/5 patients developed a peri-renal hematoma requiring evacuation, but completed prophylactic LMWH therapy. Conclusion Renal allograft thrombosis is preventable. Universal screening can stratify risk and allow an effective intervention to reduce that risk. Our Institution has developed a unique risk stratification protocol to identify patients at high risk for allograft thrombosis and prevent this complication by post-operative anticoagulation. Risk Categorization and Management Plan Risk Level Thrombophilia Management Level I Evidence of Thrombophilia (other than MTHFR) and previous thrombosis Heparin postoperatively and then LMWH bid for 6 months Level II Evidence of Thrombophilia (other than MTHFR), No history of thrombosis Heparin postoperatively, LMWH bid for 3 months, then qd for 3 months Level III MTHFR with normal homocysteine Heparin postoperatively, then LMWH qd for 3 months Level IV No evidence of thrombophilia No anticoagulation