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BACKGROUND There has been, to our knowledge, no reports on LifeCycle Pharma tacrolimus (LCPT) taken during pregnancy after simultaneous pancreas-kidney transplantation (SPK). Here, we report a 25-year-old female SPK recipient who gave birth to a healthy infant in posttransplant month 32. We analyzed the long-term graft function, obstetric/neonatal course, LCPT dosage, tacrolimus (TAC) levels, concomitant medication, and complications. CASE REPORT Her medical history consisted of type 1 diabetes with chronic nephropathy, arterial hypertension, and atypical haemolytic uremic syndrome with critical deterioration of her general condition requiring clinically indicated early termination of her first pregnancy prior to SPK. SPK was performed according to surgical standards. The immunosuppressive prophylaxis consisted of thymoglobulin, mycophenolate mofetil, standard TAC formulation, and steroids. Due to rapid TAC metabolism, the patient was converted from a standard TAC formulation to LCPT in the first month posttransplant. Her long-term immunosuppression, including the obstetric and peripartal course, consisted of LCPT, prednisolone, and azathioprine. She was normotensive without antihypertensive medication and maintained excellent function of both grafts during the observation period of 48 months posttransplant. All (mostly infectious) complications were reversible, especially temporary polyoma viremia within normal renal function, and 2 episodes of urosepsis. No relapse of her pretransplant episode of atypical haemolytic uremic syndrome occurred posttransplant. Her child is in good health at the age of 12 months without any malformations. CONCLUSIONS This case suggests that pregnancy after SPK under LCPT is feasible. Further studies are needed to expand the empirical knowledge surrounding tacrolimus.

Background The relationship between nutrition and liver disease is relevant for the outcome after surgery. Patients with liver cirrhosis characteristically show protein-energy malnutrition with decreased levels of branched-chain amino acids (BCAA) and increased levels of aromatic amino acids. Materials and Methods We conducted a prospective controlled clinical trial including 57 patients after liver transplantation or major liver resection surgery in order to test the effect of early postoperative nutrition on the outcome and nutrition profile of these patients. The test group received a dietetic program composed of ingredients naturally rich in BCAA (BCAA group), and the control group received standard hospital meals. Patient survival, liver function tests, subjective well-being, and a nutritional status including amino acid profiles were analyzed immediately and 14 days after major liver surgery (secondary end points). General health and well-being were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (primary end point). Results In-depth analysis of amino acid profiles was performed for patients undergoing liver resection (n = 21) and liver transplantation (n = 36). Interestingly, amino acid profiles did not correlate with body mass index or the Model for End-Stage Liver Disease score. Patients scheduled for liver transplantation showed significantly lower levels of BCAA pretransplant compared to patients undergoing liver resection. Patients in the liver resection subgroup were more likely to benefit from the BCAA cuisine in terms of significantly higher food intake and subjective rating. The clinical liver function tests, however, did not show statistical difference between the BCAA group and the control group in the examination period of 14 days. Conclusion Our specifically designed BCAA-enriched diet resulted in greater patient satisfaction and compliance with nutrition. A larger trial or longer-term follow-up may be required to identify an effect on survival, recovery, surgical complications, protein profiles, and amino acid profiles.

With a later onset of diabetes complications and thus increasing age of transplant candidates, many centers have extended upper age limits for pancreas transplantation. This study investigates the effect of recipient and donor age on outcomes after pancreas transplantation.We retrospectively analyzed 565 pancreas transplants performed at two Eurotransplant centers. The cohort was split at a recipient and donor age of 50 and 40 years, respectively. Median recipient age in old patients (≥50 years; 27.2%) was 54 years and 40 years in young patients (

Background Normothermic machine perfusion (NMP) bears the potential for significant prolongation of liver preservation before transplantation. Although safety and feasibility have been recently published, no data are available describing the significant challenges of establishing NMP programs outside clinical studies. We herein present our experience and propose a multidisciplinary approach for liver NMP in the clinical routine. Methods In February 2018, liver NMP was introduced for routine use in marginal organs, logistic challenges, and complex recipients at our institution. In a multidisciplinary effort among transplant coordinators, perfusionists, transplant surgeons, anesthesia, nurses, blood bank as well as laboratory staff, a clinical routine was established and 34 NMP cases were performed without critical incidents or organ loss. Results Nine livers were discarded due to poor organ quality and function observed during NMP. Twenty-five livers were successfully transplanted after preservation of up to 38 h. The extended criteria donors rate was 100% and 92% in discarded and transplanted livers, respectively. Nighttime procedures and parallel transplantations were eventually omitted. Graft and patient survival was 88% at 20 mo. No cholangiopathy was observed despite the use of extended criteria donor organs in 92% of cases. Conclusions NMP in a multidisciplinary approach enables a safe prolongation of liver preservation and overnight organ care. A first field test of NMP indicates safety and benefit of this approach.

Summary Donor cardiac arrest and cardiopulmonary resuscitation (CACPR) has been considered critically because of concerns over hypoperfusion and mechanical trauma to the donor organs. We retrospectively analyzed 371 first simultaneous pancreas–kidney transplants performed at the Medical University of Innsbruck between 1997 and 2017. We evaluated short‐ and long‐term outcomes from recipients of organs from donors with and without a history of CACPR. A total of 63 recipients received a pancreas and kidney graft from a CACPR donor. At 1, and 5‐years, patient survival was similar with 98.3%, and 96.5% in the CACPR and 97.0%, and 90.2% in the non‐CACPR group (log rank P = 0.652). Death‐censored pancreas graft survival was superior in the CACPR group with 98.3%, and 91.4% compared to 86.3%, and 77.4% (log rank P = 0.028) in the non‐CACPR group, which remained statistically significant even after adjustment [aHR 0.49 (95% CI 0.24–0.98), P = 0.044]. Similar relative risks for postoperative complications Clavien Dindo > 3a, pancreatitis, abscess, immunologic complications, delayed pancreas graft function, and relative length of stay were observed for both groups. Donors with a history of CACPR are, in the current practice, safe for transplantation. Stringent donor selection and short CPR durations may allow for outcomes surpassing those of donors without CACPR.

Chronic immunosuppression is associated with an increased risk of malignancy. The main objective of this study is to evaluate the incidence and effect of post-transplant malignancies (PTMs) following pancreas transplantation. The 348 first pancreas transplants performed between 1985 and 2015 were retrospectively analyzed in this study. Incidences of PTMs, as well as patient and graft survival, were evaluated. Out of 348 patients, 71 (20.4%) developed a PTM. Median time to diagnosis was 130 months. Thirty-six patients (50.7%) developed skin cancers (four patients with melanoma, 32 with NMSCs). Solid organ malignancy occurred in 25 (35.2%), hematologic malignancy in ten patients (14.1%). Affected patients were transplanted earlier [2000 (IQR 1993−2004) vs. 2003 (IQR 1999−2008), p &lt, 0.001]. No differences in induction therapy were seen, both groups demonstrated comparable patient and graft survival. Pancreas transplant recipients with solid organ and hematologic malignancies had a three- and six-fold increased hazard of death compared to those with skin cancers [aHR 3.04 (IQR 1.17–7.91), p = 0.023, aHR 6.07 (IQR 1.87–19.71), p = 0.003]. PTMs affect every fifth patient following pancreas transplantation. Skin cancers are the most common malignancies accounting for 50% of all PTMs. These results underscore the importance of close dermatologic follow-up.

In contrast to well-published data with acceptable long-term results in large cohorts of single renal transplant recipients aged >65 y (lit.), combined pancreas-kidney transplantation in recipients >50 y is discussed controversially. Some groups have identified older recipients as a high-risk group, demonstrating decreased patient and graft survival in this population.1-4 Nevertheless, several centers have reported results for pancreatic transplantation in older patients as being comparable to those for younger recipients with the age cutoff ranging from 50 to 60 y.5-10 At our center, we have long-term experience with a total of 655 pancreas transplants performed between 1979 and August 2020, whereby 21 recipients were over 60 y of age; the oldest was age 69 and in remarkably good general condition with good mental adherence and a strong wish to undergo simultaneous kidney-pancreas transplantation (SPK). We retrospectively analyzed patient, pancreas, and kidney graft survival, graft function, and complications at month 38 posttransplant.

The aim of our prospective clinical trial was to test a tissue staining technique (real-time confocal analysis [RTCA]) as a rapid assessment tool for donor kidney quality and function in human kidney transplantation.Tools for objective graft tissue viability assessment before kidney transplantation are lacking. RTCA has recently been established and tested in a pilot study using rodent kidneys.RTCA was performed in kidney biopsies stained with SYTO16/PI and WGA. A score between -3 (100% nonviable) and +3 (100% viable) describes the sum of viable cells divided by the number of nonviable cells per examined area (glomerulus, proximal, and distal tubules). The primary study endpoint was the delayed graft function (DGF).Seventy-one kidney transplant recipients were transplanted. The median recipient and donor age were 58.5 and 57 years, respectively. Cold ischemia time was 13.6 ± 4.7 hours; anastomosis time was 30.8 ± 8.7 minutes (mean ± SD). Overall, 23 (33.8%) patients developed DGF. The RTCA score was significantly lower in kidneys developing DGF -0.43 ± 1.78 versus no DGF 0.91 ± 2.17, P = 0.01. The Remuzzi score did not differ between DGF and no DGF, P = 0.13. Remuzzi score and RTCA score correlate inversely significantly; P = 0.004. In the multivariate analysis, solely RTCA score was revealed as a significant independent factor predicting DGF; P = 0.015, Wald = 5.95, odds ratio = 0.72, 95% confidence interval = 0.55 to 0.94.Our data demonstrate that RTCA is feasible and clinically meaningful. The RTCA score predicts DGF and is a valid option to be applied in renal transplantation.

Retrospective analysis of the long-term results of a randomized controlled trial comparing alemtuzumab (ALEM) and antithymocyte globulin (ATG) as induction therapy in simultaneous pancreas-kidney transplantation (SPK) to address individualized long-term immunosuppression. Between 2006 and 2010 a total of 30 SPKs were randomized to treatment with ALEM plus tacrolimus (TAC) monotherapy (Group A, n=14) versus ATG induction plus TAC, mycophenolate mofetil (MMF) and steroids (Group B, n=16), followed by individualized long-term immunosuppression. We here present the long-term results for graft survival, graft function, and major complications. The 9-year patient survival rates in Groups A and Group B were 92.9% and 86.7% respectively; pancreas graft survival was 75.0% and 65.0% respectively; renal graft survival was 83.1% and 93.8% respectively. Long-term graft function was excellent with a creatinine of 1.5 mg/dL and 1.4 mg/dL, fasting glycemia of 104 mg/dL and 102 mg/dL, hemoglobin (Hb) A1c of 5.4 g% and 5.6 g% in Group A and Group B, respectively. Major complications were comparable in both groups. Good long-term results for patient, pancreas graft and kidney graft survival were achieved in both groups with individually adapted maintenance immunosuppression. ALEM is a valid induction therapy.

Hypothermic machine perfusion (HMP) has been introduced as an alternative to static cold storage (SCS) in kidney transplantation, but its true benefit in the clinical routine remains incompletely understood. The aim of this study was to assess the effect of HMP vs. SCS in kidney transplantation. All kidney transplants performed between 08/2015 and 12/2019 (n = 347) were propensity score (PS) matched for cold ischemia time (CIT), extended criteria donor (ECD), gender mismatch, cytomegalovirus (CMV) mismatch, re-transplantation and Eurotransplant (ET) senior program. A total of 103 HMP and 103 SCS instances fitted the matching criteria. Prior to PS matching, the CIT was longer in the HMP group (17.5 h vs. 13.3 h, p &lt, 0.001), while the delayed graft function (DGF) rates were 29.8% and 32.3% in HMP and SCS, respectively. In the PS matched groups, the DGF rate was 64.1% in SCS vs. 31.1% following HMP: equivalent to a 51.5% reduction of the DGF rate (OR 0.485, 95% CI 0.318&ndash, 0.740). DGF was associated with decreased 1- and 3-year graft survival (100% and 96.3% vs. 90.8% and 86.7%, p = 0.001 and p = 0.008) or a 4.1-fold increased risk of graft failure (HR = 4.108, 95% CI: 1.336&ndash, 12.631, p = 0.014). HMP significantly reduces DGF in kidney transplantation. DGF remains a strong predictor of graft survival.

Living kidney donation represents the optimal renal replacement therapy, but recent data suggest an increased long-term renal risk for the donor. Here, we evaluated the risk for reduced estimated glomerular filtration rate (eGFR), death, and major cardiovascular events such as nonfatal myocardial infarction or cerebrovascular event including TIA (transient ischemic attack) and stroke in 225 donors, who underwent pre-donation examinations and live donor nephrectomy between 1985 and 2014 at our center. The median follow-up time was 8.7 years (1.0&ndash, 29.1). In multivariate analysis, age and arterial hypertension at baseline were significantly associated with a higher risk of adverse renal outcomes, such as (1) eGFR &lt, 60 mL/min/1.73 m2 (age per year: HR (hazard ratio) 1.05, 95% confidence interval (CI) 1.03&ndash, 1.08, hypertension: HR 2.25, 95% CI 1.22&ndash, 3.98), (2) eGFR &lt, 60 mL/min/1.73 m2 and a decrease of &ge, 40% from baseline (age: HR 1.08, 95% CI 1.03&ndash, 1.13, hypertension: HR 4.22, 95% CI 1.72&ndash, 10.36), and (3) eGFR &lt, 45 mL/min/1.73 m2 (age: HR 1.12, 95% CI 1.05&ndash, 1.20, hypertension: HR 5.06, 95% CI 1.49&ndash, 17.22). In addition, eGFR at time of donation (per mL/min/1.73 m2) was associated with a lower risk of (1) eGFR &lt, 60 mL/min/1.73 m2 (HR 0.98, 95% CI 0.97&ndash, 1.00) and (2) eGFR &lt, 45 mL/min/1.73 m2 (HR 0.95, 95% CI 0.90&ndash, 1.00). Age was the only significant predictor for death or major cardiovascular event (HR 1.08, 95% CI 1.01&ndash, 1.16). In conclusion, arterial hypertension, lower eGFR, and age at the time of donation are strong predictors for adverse renal outcomes in living kidney donors.

Contains fulltext : 226016.pdf (Publisher’s version ) (Closed access) In several deceased donor kidney allocation systems, organs from elderly donors are allocated primarily to elderly recipients. The Eurotransplant Senior Program (ESP) was implemented in 1999, and since then, especially in Europe, the use of organs from elderly donors has steadily increased. The proportion of ≥60-year-old donors reported to the Collaborative Transplant Study (CTS) by European centers has doubled, from 21% in 2000-2001 to 42% in 2016-2017. Therefore, in the era of organ shortage it is a matter of debate whether kidney organs from elderly donors should only be allocated to elderly recipients or whether

Primary focal segmental glomerulosclerosis (FSGS) recurs in up to 55% of patients after kidney transplantation. Herein we report the successful management of recurrent FSGS. A 5‐year‐old boy with primary FSGS received a deceased donor renal transplant. Immediate and fulminant recurrence of FSGS caused anuric graft failure that was resistant to plasmapheresis and rituximab. After exclusion of structural or immunologic damage to the kidney by repeated biopsies, the allograft was retrieved from the first recipient on day 27 and transplanted into a 52‐year‐old second recipient who had vascular nephropathy. Immediately after retransplantation, the allograft regained function with excellent graft function persistent now at 3 years after transplant. After 2 years on hemodialysis, the boy was listed for kidney retransplantation. To prevent FSGS recurrence, pretreatment with ofatumumab was performed. Nephrotic range proteinuria still occurred after the second transplantation, which responded, however, to daily plasma exchange in combination with ofatumumab. At 8 months after kidney retransplantation graft function is good. The clinical course supports the hypothesis of a circulating permeability factor in the pathogenesis of FSGS. Successful ofatumumab pretreatment implicates a key role of B cells. Herein we provide a description of successful management of kidney failure by FSGS, carefully avoiding waste of organs., Successful management of recurrent primary focal segmental glomerulosclerosis after kidney transplantation includes retransplantation of an allograft that failed in the first recipient due to disease recurrence into a second recipient and ofatumumab pretreatment before kidney retransplantation in the patient with fulminant recurrence of focal segmental glomerulosclerosis in the first graft.

Background Pancreas retransplantation is still a controversial option after loss of a pancreatic graft. This article describes the experience of pancreas retransplantation at a high‐volume centre. Methods This was a retrospective observational study of all pancreas retransplantations performed in a single centre between 1997 and 2013. Pancreatic graft loss was defined by the return to insulin dependence. Risk factors for graft loss as well as patient and graft survival were analysed using logistic and time‐to‐event regression models. Results Of 409 pancreas transplantations undertaken, 52 (12·7 per cent) were identified as pancreas retransplantations. After a median follow‐up of 65·0 (range 0·8–174·3) months, 1‐ and 5‐year graft survival rates were 79 and 69 per cent respectively, and 1‐ and 5‐year patient survival rates were 96 and 89 per cent. During the entire follow‐up, 22 grafts (42 per cent) were lost. Patient survival was not associated with any of the donor‐ or recipient‐related factors investigated. Five‐year graft survival was better after simultaneous kidney–pancreas retransplantation than pancreas retransplantation alone: 80 per cent (16 of 20) versus 63 per cent (20 of 32) (P = 0·226). Acute rejection (odds ratio 4·49, 95 per cent c.i. 1·59 to 12·68; P = 0·005) and early surgical complications (OR 3·29, 1·09 to 9·99, P = 0·035) were identified as factors with an independent negative effect on graft survival. Conclusion Pancreas retransplantation may be considered for patients whose previous graft has failed., Good outcome in selected patients

Background Several studies in solid organ transplantation have shown a correlation between donor and recipient sex mismatch and risk of graft loss. In this study, we aimed to analyze the impact of donor and recipient sex matching on patient and pancreas graft survival in a large single‐center cohort. Methods We retrospectively analyzed all first simultaneous pancreas‐kidney transplants performed between 1979 and 2017 at the Medical University of Innsbruck. Results Of 452 patients, 54.6% (247) received a sex‐matched transplant. Patient survival (P = .86), death‐censored pancreas graft survival (dcPGS, P = .26), and death‐censored kidney graft survival (dcKGS, P = .24) were similar between the sex‐matched and sex‐mismatched groups. Patient survival and dcPGS at 1, 5, and 15 years were 95.9%, 90.0%, and 62.1% and 86.1%, 77.1%, and 56.7% in the sex‐matched group and 93.6%, 86.2%, and 62.4% and 83.1%, 73.3%, and 54.3% in the sex‐mismatched group. Sex matching led to a lower odds of severe postoperative complications (41.2% vs 49.0%; OR 0.57, 95%CI 0.33‐0.97; P = .038); however, no increased odds of other adverse postoperative outcomes was detected. Conclusion Our study demonstrates that sex matching reduced the odds of postoperative complications but did not impact other early and late outcome parameters in our cohort.

BACKGROUND In kidney transplantation, the association of cold ischemia time (CIT), anastomosis time (AT), and delayed graft function (DGF) is particularly detrimental in grafts from marginal donors; however, actual cut-off criteria are still debated. MATERIAL AND METHODS Data from patients65 years (n=193) and patients65 years (n=1054) transplanted between 2000 and 2010 were retrospectively analyzed regarding the age-dependent impact of ischemia times and DGF. RESULTS Overall death censored graft survival was inferior for ECD/DCD organs. Graft survival was significantly impaired by DGF in younger and older recipients. The multivariate analysis revealed an age-dependent profile of risk factors for DGF. In younger patients, multiple risk factors were identified while in patients65 years, only CIT and AT were correlated with DGF. Marginal grafts with a CIT769 min had a comparable outcome to any SCD organ; extended CIT770 min worsened ECD/DCD survival significantly. Similarly, AT longer than 26 min was associated with a significantly impaired survival of ECD/DCD grafts. In a Cox regression analysis with penalized splines, this increased risk of graft loss was not linear: CIT beyond 800 min and AT beyond 20 min were cut-off values associated with worse outcomes in marginal organs. CONCLUSIONS Thus, risk factors for DGF are age-dependent; keeping ischemia times below these thresholds offers outcome of ECD/DCD organs comparable to SCD organs.

Donor organ quality affects long term outcome after renal transplantation. A variety of prognostic molecular markers is available, yet their validity often remains undetermined. A network-based molecular model reflecting donor kidney status based on transcriptomics data and molecular features reported in scientific literature to be associated with chronic allograft nephropathy was created. Significantly enriched biological processes were identified and representative markers were selected. An independent kidney pre-implantation transcriptomics dataset of 76 organs was used to predict estimated glomerular filtration rate (eGFR) values twelve months after transplantation using available clinical data and marker expression values. The best-performing regression model solely based on the clinical parameters donor age, donor gender, and recipient gender explained 17% of variance in post-transplant eGFR values. The five molecular markers EGF, CD2BP2, RALBP1, SF3B1, and DDX19B representing key molecular processes of the constructed renal donor organ status molecular model in addition to the clinical parameters significantly improved model performance (p-value = 0.0007) explaining around 33% of the variability of eGFR values twelve months after transplantation. Collectively, molecular markers reflecting donor organ status significantly add to prediction of post-transplant renal function when added to the clinical parameters donor age and gender.

Despite a continuously growing knowledge of the impact of factors on kidney graft function, such as donor age, body mass index, and cold ischemia time, few data are available regarding anastomosis time (AT) and its impact on long-term results. We investigated whether surgical AT correlates with patient and graft survival after kidney transplantation performing a retrospective analysis of 1245 consecutive deceased donor kidney transplantations between 01/2000 and 12/2010 at Innsbruck Medical University. Kaplan-Meier and log-rank analyses were carried out for 1- and 5-year patient and graft survival. AT was defined as time from anastomosis start until reperfusion. Median AT was 30 min. Five-year survival of allografts with an AT >30 min was 76.6% compared with 80.6% in the group with AT

The development of de novo renal cell carcinoma (RCC) in a transplanted kidney is a rare condition. Currently, this is the second case report of a 41-year-old man in whom carcinoma of a renal allograft was detected by contrast-enhanced ultrasound (CEUS). An abdominal CT scan was not conclusive enough to differentiate between septal enhancement of a cyst and a low vascularized tumor. CEUS confirmed a solid, homogeneously enhancing but hypoechoic and hypovascular lesion compared to the surrounding kidney parenchyma without septal enhancement. Therefore, the patient underwent nephron-sparing surgery (NSS), affirming papillary RCC type 2. Graft function remained unchanged postoperatively; 12 months after NSS, no local recurrence or distant metastasis was described. CEUS seems to be a minimally invasive and efficient imaging option if other diagnostic tools cannot clearly exclude RCC, with the advantage of wide-ranging use, especially in cases of impaired renal function.

Background Some hemodialysis patients develop arteriovenous (AV) fistulas with high flows. This volume overload can result in high-output cardiac failure. To date, predisposing access flow rates are unknown. Methods A retrospective study of all kidney-transplant recipients at the Medical University of Innsbruck (MUI) from 2005 to 2010 included 797 patients with the following criteria: previous hemodialysis with a native AV fistula or a graft, sufficient function of the kidney transplant up to the time of the data analysis, and follow-up care at the MUI. Results Twenty-nine of the 113 patients (25.7%) needed an AV fistula closure, mostly because of symptoms of cardiac failure. The mean shunt flow in the intervention group was 2197.2 mL/min, whereas the mean shunt flow in the non-intervention group was only 850.9 mL/min. Shunt closures were most frequently made in patients with upper-arm shunts (41.7%). Conclusion The necessity of shunt closure is not a rarity. Patients who underwent an AV fistula ligature had high access flows with about 2200 mL/min. As the symptoms of cardiac failure greatly improved after shunt closure, patients with high access flow may benefit from such an intervention.

Summary Surgeries performed during the night are associated with higher complication rates. The aim of this study was to determine the impact of nighttime surgery on the outcome after kidney transplantation. In all, 873 deceased donor kidney transplants were retrospectively analyzed and grouped according to the time of surgery: daytime (8 am to 8 pm, n = 610) versus nighttime (8 pm to 8 am, n = 263). Statistical analysis compared patient/graft survival, rate of delayed graft function (DGF), acute rejection rate, and surgical complications. One and 5-year patient and graft survival did not differ between daytime and nighttime transplants. DGF occurred in 31.1% of daytime compared to 37.6% of nighttime procedures (P = 0.06). Acute allograft rejection was observed in 22.6% of daytime compared to 18.3% in nighttime graft recipients (P = 0.15). Nighttime procedures were associated with 22.4% complications compared to 22.1% in daytime procedures (P = 0.92). Most importantly, if transplantations were postponed until the next morning, cold ischemia time (CIT) would have increased from 16.6 h to 24.6 h (P

BACKGROUND Simultaneous pancreas-kidney (SPK) transplantation is widely accepted as an optimal therapeutic option for patients with type 1 diabetes mellitus (T1DM) and end-stage renal disease, but the indication for patients with type 2 diabetes mellitus (T2DM) is still controversially discussed. METHODS Twenty-one T2DM recipients of a first combined pancreas-kidney graft performed at our center during a 9-year period were retrospectively analyzed with regard to demographic characteristics; cardiovascular risk factors; surgical, immunological, and infectious complications; and patient and graft survivals and compared with T1DM recipients (n=195) and 32 T2DM patients who received a kidney transplant alone (KTA) during the same period. RESULTS Patient survival at 1 and 5 years was 96.9% and 91.6% for the T1DM group, 90.5% and 80.1% for the T2DM group, and 87.1% and 54.2% for the T2DM KTA group, respectively (P

BACKGROUND In adult liver transplantation, arterial conduits have been associated with increased risk for vascular complications and inferior outcome. MATERIAL AND METHODS Complication rates and outcomes of adult patients undergoing liver transplantation in our center between 1990 and 2012 were analyzed retrospectively. Characteristics, transplantation-related factors, and survival rates of patients with conduit grafts (n=43) were compared to patients with a standard arterial anastomosis (n=904) by univariate and multivariate analysis. RESULTS Patients in the conduit group were younger but had a significantly higher proportion of high-urgency and re-transplantations. While patient survival was comparable between the groups, graft survival was inferior for patients with a conduit (1-year, 5-year, and 10-year survival, control vs. conduit group: 87.3%, 78.8% and 71.5% vs. 72.4%, 63.8%, and 41.8%, respectively, p=0.008). In univariate analysis, an arterial conduit was associated with more arterial and biliary complications. However, an arterial conduit was not an independent risk factor for graft or patient survival in a Cox regression analysis. CONCLUSIONS An arterial conduit is associated with more vascular complications, yet a conduit per se does not influence graft survival. The inferior outcome may reflect the complex situation of the sicker liver transplant patients needing a non-standard arterial anastomosis.

Highlights • Pretransplant DSA have a deleterious impact on graft survival only in the presence of high pretransplant serum levels of sCD30. • The majority of patients with pretransplant DSA might be transplanted safely without special pretreatment measures. Kidney transplantation in the presence of donor-specific HLA antibodies (DSA) is associated with a high failure rate due to antibody-mediated rejection. Many centers avoid transplantations if DSA are present. Others perform such transplantations after removal of DSA by apheresis under potent immunosuppression. We provide strong evidence that DSA positive recipients reject their grafts at a high rate only if the immune activation marker sCD30 is also high, suggesting that T-cell help from an activated immune system is necessary for pretransplant DSA to exert a deleterious effect on the graft. High-risk patients with DSA and sCD30 may benefit from special treatment measures. The presence of DSA alone may not be deleterious., Background It is an unresolved issue why some kidney transplant recipients with pretransplant donor-specific HLA antibodies (DSA) show a high transplant failure rate, whereas in other patients DSA do not harm the graft. We investigated whether help from preactivated T-cells might be necessary for DSA to exert a deleterious effect. Methods The impact of pretransplant DSA and immune activation marker soluble CD30 (sCD30) on 3-year graft survival was analyzed in 385 presensitized kidney transplant recipients. Findings A deleterious influence of pretransplant DSA on graft survival was evident only in patients who were positive for the immune activation marker sCD30. In the absence of sCD30 positivity, 3-year graft survival was virtually identical in patients with or without DSA (83.1 ± 3.9% and 84.3 ± 2.8%, P = 0.81). A strikingly lower 3-year graft survival rate of 62.1 ± 6.4% was observed in patients who were both sCD30 and DSA positive (HR 2.92, P

BACKGROUND We investigated the safety and efficacy of Campath induction and tacrolimus (TAC) maintenance therapy compared to ATG induction with TAC +MMF + steroids in de novo kidney-pancreas transplanted patients. MATERIAL/METHODS 14 patients (Group A) received Campath 30 mg + methylprednisolone 500 mg before revascularization followed by TAC monotherapy, and 16 patients (Group B) ATG 8 mg/kg with TAC + MMF+ steroids (withdrawn at month 3). TAC trough levels (ng/mL) of 12-15 were aimed for in both groups until month 6 and thereafter 6-12. RESULTS 1-year patient survival was 100% in both groups; kidney and pancreas survival in Group A was 93% each. In Group B 1-year kidney and pancreas survival was 100% and 87%, respectively. A total of three pancreas grafts were lost due to thrombosis of the graft vein within the first month. The only kidney loss was due to initial non-function. All biopsy-proven acute rejections of renal transplants (n=3 in Group A, n=0 in Group B) were reversible. No acute pancreas graft rejection was demonstrated. Infectious complications, lipid metabolism and blood pressure were comparable in both groups, as were other adverse events. No tumor occurred. At 12 months 13 patients in each group were steroid-free; the mean serum creatinine level was 1.44 mg/dL in Group A and 1.33 mg/dL in Group B. All patients were exogenous insulin-free. CONCLUSIONS At one year efficacy and safety of Campath +TAC monotherapy were comparable to those of ATG + TAC + MMF + steroids in a limited number of combined kidney-pancreas transplant recipients.

Kidney retransplantation is often associated with a higher immunological risk than is primary renal transplantation. Faced with increasing organ shortage and growing waiting lists, results of kidney retransplantation are of particular interest. Fifty-six third and fourth kidney transplants were analyzed retrospectively. Parameters included patient and donor demographics, operative details, incidence of surgical, immunological and infectious complications and patient and graft survival. Patients receiving third kidney grafts had 1- and 5-year patient/graft survival rates of 97.4%/72.9% and 88.9%/53.6%, respectively. Episodes of acute rejection and delayed graft function were observed in 44% and 49% of these patients. Fourth kidney transplantation was associated with 1- and 2-year patient/graft survival rates of 84.8%/68.5% and 63.6%/47%, respectively. Acute rejection and delayed graft function occurred in 33% and in 60% of cases. Acceptable patient and graft survival may be achieved after third and fourth kidney transplantation. Graft losses in this sensitized population are mainly because of rejection. Profound immunosuppression may lead to major infectious problems.

Introduction: Delayed graft function (DGF) as a consequence of ischemia reperfusion injury (IRI) is associated with a decrease in long-term allograft survival. Heme oxygenase-1 (HO-1) is a stress responsive gene that is highly expressed in multiple pathological processes. The aim of our study was to analyze whether HO-1 protein levels in human kidney transplants during IRI correlate with the incidence of DGF. Methods: Kidney biopsies were obtained from 27 kidney allografts at two time points: at the end of cold storage and shortly after reperfusion. Samples were analyzed for HO-1 protein levels by Western blot. Results: Heme oxygenase-1 protein levels were significantly higher in post-reperfusion biopsies (39.4 vs. 13.7 arbitrary units, p = 0.001). In pre-reperfusion biopsies no association was observed between HO-1 protein levels and DGF. In post-reperfusion biopsies, higher levels of HO-1 protein were measured in kidneys with DGF (53.7 vs. 36.2 arbitrary units, p = 0.064). DGF kidneys showed a significantly higher increase from pre- to post-reperfusion in HO-1 protein (42.0 vs. 18.7 arbitrary units, p = 0.025). Conclusion: Heme oxygenase-1 protein levels shortly after allograft reperfusion are closely related with initial graft function. Assessment thereof may be considered a valuable tool to predict DGF.

The immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO) is activated by interferon-gamma (IFN-gamma) and via tryptophan depletion, suppresses adaptive T cell-mediated immunity in inflammation, host immune defense, and maternal tolerance. Its role in solid organ transplantation is still unclear. Therefore, we investigated the usefulness of IDO-mediated tryptophan catabolism in the evaluation of kidney allograft rejection. Blood, urine, and tissue samples were collected from 34 renal transplant patients without rejection and from nine patients with biopsy-confirmed episodes of acute rejection (n=12). Concentrations of kynurenine and tryptophan in serum and urine were analyzed by high-pressure liquid chromatography. Kynurenine to tryptophan ratio (kyn/trp) was calculated to estimate IDO activity. Immunostaining for IDO was performed on renal biopsies. Neopterin was assessed using radioimmunoassay. Kyn/trp and neopterin were detectable at low levels in serum of healthy volunteers and were increased in non-rejecting allograft recipients. Serum levels of kyn/trp were higher in recipients with rejection compared to non-rejectors as early as by day 1 post-surgery. Rejection episodes occurring within 13+/-5.9 days after transplantation were accompanied by elevated kyn/trp in serum (114+/-44.5 micromol/mmol, P=0.001) and urine (126+/-65.9 micromol/mmol, P=0.02) compared to levels during stable graft function. Kyn/trp correlated significantly with neopterin suggesting an IFN-gamma-induced increase in IDO activity. Immunostaining showed upregulation of IDO in rejection biopsies, localized in tubular-epithelial cells. Non-rejected grafts displayed no IDO expression. Acute rejection is associated with simultaneously increased serum and urinary kyn/trp in patients after kidney transplantation. Thus, IDO activity might offer a novel non-invasive means of immunomonitoring of renal allografts.

UNLABELLED Extremely few reports have been published on experience with multiple combined pancreas-kidney re-transplantation including long-term results. We here analyze our experience with two patients following successful combined pancreas fourth-kidney third and pancreas third-kidney second transplantation. METHODS Patient and graft survival as well as graft function and major complications were recorded. Patient 1 (women, 47 years) underwent combined pancreas fourth-kidney third transplantation after previous removal of the first and second renal and the second pancreatic grafts. Patient 2 (men, 51 years) underwent combined pancreas third-kidney second transplantation after nephrectomy of the first renal graft. Immunosuppression consisted of induction with alemtuzumab and maintenance with tacrolimus, mycophenolate mofetil/mycophenolic acid and steroids. RESULTS After a follow-up of 44 and 49 months, respectively, both patients are doing well with stable graft function. Leukopenia, thrombocytopenia, bacterial sepsis, and chronic hepatitis C as major complications were controllable. CONCLUSIONS Multiple pancreas-retransplantations combined with simultaneous renal transplantation are feasible. Meticulous immunosuppression, careful monitoring, and excellent patient adherence are of crucial importance.

The association of donor-specific HLA antibodies (DSA) with kidney graft failure has been addressed previously ; however, the majority of studies were based on small numbers of patients with graft failure. We investigated 83 patients with failed kidney transplants for a possible association of de novo development and persistence or loss of pre-existing DSA with graft failure. Single Antigen Bead assay-detected DSA and non-DSA antibodies were compared between patients with graft loss and matched controls with functioning grafts. The incidence of weak de novo DSA or non-DSA at a mean fluorescence intensity of 500 or higher was higher in the graft loss than in the nonrejector group (76% vs 40%, P < 0.001). Because of the low number of patients developing de novo DSA, the DSA results did not reach statistical significance (only 22% of patients with graft loss developed de novo DSA). However, at all cutoffs, there was a significantly higher rate of graft loss in patients with de novo non-DSA. The incidence of strong pretransplant DSA that persist after transplantation was higher in the graft loss group (10% vs 1%, P = 0.034). When C1q-binding ability in sera of rejectors and nonrejectors with posttransplant de novo or persistent DSA was compared, none of the nonrejectors demonstrated C1q positivity, whereas 43% of patients with graft loss showed C1q-positive antibodies, although not necessarily donor-specific (P < 0.001). Our data show that the posttransplant presence of persisting or de novo HLA antibodies, especially if C1q binding, is associated with graft loss, even if the antibodies are not specific for mismatched donor HLA.

Fungal infections still represent a serious complication after organ transplantation. Early diagnosis and aggressive treatment are crucial. Because of the many diagnostic problems involved, we present a case of mucormycosis - primarily affecting the paranasal sinuses with later intracranial extension - in a highly immunized recipient of a third renal transplant. Although fungal infection was suspected from various imaging techniques, only the detection of typical fungal hyphae in the infected tissue was diagnostic. Neither the blood tests and cerebrospinal fluid examinations performed nor cultures from maxillary sinus fluid were of any diagnostic help. Surgical debridement from a transnasal as well as an intracranial approach and systemic amphotericin B together with the discontinuation of immunosuppression after removal of the rejected graft were able to save the patient. This case stresses the importance of early diagnosis that can only be made from tissue biopsies and allows appropriate timely treatment.

The highly atherogenic lipoprotein(a) [Lp(a)] is significantly elevated in patients with renal disease. It is discussed controversially whether Lp(a) concentrations decrease after renal transplantation and whether the mode of immunosuppressive therapy influences the Lp(a) concentrations. In a prospective study the Lp(a) concentrations before and on average 48 months after renal transplantation were measured in 145 patients. The determinants of the relative changes of Lp(a) concentrations were investigated in a multivariate analysis. Patients treated by CAPD showed a larger decrease of Lp(a) than hemodialysis patients, reflecting their markedly higher Lp(a) levels before transplantation. The relative decrease of Lp(a) was higher with increasing Lp(a) concentrations before transplantation in combination with an increasing molecular weight of apolipoprotein(a) [apo(a)]. That means that the relative decrease of Lp(a) is related to the Lp(a) concentration and the apo(a) size polymorphism. With increasing proteinuria and decreasing glomerular filtration rate, the relative decrease of Lp(a) became less pronounced. Neither prednisolone nor cyclosporine (CsA) had a significant impact on the Lp(a) concentration changes. Azathioprine (Aza) was the only immunosuppressive drug which had a dose-dependent influence on the relative decrease of Lp(a) levels. These data clearly demonstrate a decrease of Lp(a) following renal transplantation which is caused by the restoration of kidney function. The relative decrease is influenced by Aza but not by CsA or prednisolone.

OBJECTIVE To describe the evolution of pancreas transplantation from 1979 to 2011. The aim was to examine factors influencing long-term patient and graft survival, surgical methods, and risk factors influencing organ performance after transplantation. BACKGROUND Pancreas transplantation has become the therapy of choice for patients suffering insulin-dependent diabetes and end stage renal failure. METHODS Retrospective analysis of 509 consecutive pancreas transplants (442 simultaneous pancreas and kidney [SPK], 20 pancreas transplanted alone [PTA], and 47 pancreas transplanted after kidney [PAK]), performed at the University Hospital Innsbruck. The data were statistically analyzed using the Kaplan-Meier method and log-rank test. RESULTS After overcoming initial immunological and technical problems between 1979 and 1988 (5-year pancreas graft survival rate, 29.7%), pancreas transplantation evolved during the second decade (1989-1996; 5-year pancreas graft survival rate, 42.2%). Technical changes, optimized immunosuppression, careful pretransplant evaluation, and improved graft monitoring have become standard in the last decade and result in excellent 5-year patient (94.3%), kidney (89.4%), and pancreas (81.5%) graft survival. Five-year graft survival was superior in SPK (68.8%) compared with PAK (62.5%) and PTA (16.4%). SPK retransplantation can be carried out safely with 5-year patient (87.5%) and pancreas graft (75.0%) survival. Overall 5-year patient survival after loss of the first pancreas graft is significantly better in patients who underwent retransplantation (89.4% vs. 67.9%, P = 0.001). Long-term pancreas graft survival is independent of donor body mass index, sex, and cause of death, anastomosis time and the number of human leukocyte antigen (HLA) mismatches, recipient age, body mass index, sex, current panel reactive antibodies, and waiting time. Significant risk factors for reduced graft survival are cold ischemia time and donor age. CONCLUSIONS During the last 32 years, many problems in pancreas transplantation have been overcome and it may currently represent the therapeutic gold standard for some patients with diabetes and end stage renal failure.

BACKGROUND Obesity is increasingly impacting the overall health status and the global costs for health care. The increase in body mass index (BMI) is also observed in kidney allograft recipients and deceased organ donors. METHODS In a retrospective single-center study, we analyzed 1132 deceased donor kidney grafts, transplanted at our institution between 2000 and 2009 for recipient and donor BMI and its correlation with delayed graft function (DGF). Recipients/donors were classified according to their BMI ( 30 kg/m(2)). DGF was defined as requirement for one dialysis within the first week after transplantation. RESULTS Overall DGF rate was 32.4%, mean recipient BMI was 23.64 ± 3.75 kg/m(2), and mean donor BMI was 24.69 ± 3.44 kg/m(2). DGF rate was 25.2%, 29.8%, 40.9%, and 52.6% in recipients with BMI less than 18.5, 18.5 to 24.9, 25 to 29.9, and more than 30 kg/m, respectively (P

Background. It is a matter of debate whether alloantibodies should be monitored in all kidney transplant recipients in order to combat antibody-mediated graft loss. Methods. In the Collaborative Transplant Study Serum Project, there were 64 patients with graft loss on whom a posttransplant serum 1-year before failure was available, as well as recipient and donor DNA for complete HLA typing, including HLA A, B, C, DRB1/3/4/5, DQA1, DQB1, DPA1, or DPB1 antigens, which allowed the precise definition of donor-specific antibodies (DSA). We compared the incidence of Luminex Single Antigen (SA)-detected DSA and non-DSA antibodies in these patients with graft failure and in matched controls with functioning grafts (non-rejectors). Positivity cut-offs at 500, 1000, 2000, 3000, and 5000 MFI (mean fluorescence intensity) were analyzed systematically. Results. At cut-off 500, as many as 95% of patients with graft loss and 94% of patients without graft loss showed evidence of Luminex-detected HLA antibodies. The incidence of DSA in patients with and without graft failure was with 44% and 36%, respectively, not significantly different between the two groups. However, with increasing cut-offs the difference between the two patient groups became more pronounced. When MFI of 5, 000 was used as cut-off for Luminex positivity, 64 patients with graft loss had a higher incidence of DSA or non-DSA antibodies than patients without graft loss (total: 59% vs. 36% ; p=0.013 ; class I: 50% vs. 31%, p=0.047 ; class II: 33% vs. 14%, p=0.021 ; DSA: 19% vs. 9%, p=0.20 ; non-DSA: 56% vs. 33%, p=0.013). Importantly, as many as 67% of Luminex-positive patients with graft loss were also positive in ELISA screening, whereas this rate was only 17% in the non-rejector group. In 51 patients with graft loss, we also had a pretransplant serum which allowed the evaluation of de novo antibody production after transplantation. The rate of de novo antibodies was higher in the graft loss group than in the non-rejector group (total DSA or non-DSA: 35% vs. 14%, p=0.020 ; class I: 29% vs. 10%, p=0.023 ; class II: 18% vs. 4%, p=0.051 ; DSA: 8% vs. 6%, p=n.s. ; non-DSA: 33% vs. 14%, p=0.034). Interestingly, at the low cut-off 500, as many as 45% of patients in the non-rejector group lost their preexisting DSA during the posttransplant course, as compared to only 25% in the graft loss group (p=0.062). Conclusion. Our data indicate that the posttransplant presence of strongly reactive HLA antibodies, especially if de novo produced, is associated with graft loss. It appears that not all Luminex-detected antibodies are detrimental. Many patients lose pretransplant weakly reactive donor-specific antibodies after transplantation and these antibodies are not associated with graft loss.

Kidney retransplantation is often associated with a higher immunological risk than is primary renal transplantation. Faced with increasing organ shortage and growing waiting lists, results of kidney retransplantation are of particular interest. Fifty-six third and fourth kidney transplants were analyzed retrospectively. Parameters included patient and donor demographics, operative details, incidence of surgical, immunological and infectious complications and patient and graft survival. Patients receiving third kidney grafts had 1- and 5-year patient/graft survival rates of 97.4%/72.9% and 88.9%/53.6%, respectively. Episodes of acute rejection and delayed graft function were observed in 44% and 49% of these patients. Fourth kidney transplantation was associated with 1- and 2-year patient/graft survival rates of 84.8%/68.5% and 63.6%/47%, respectively. Acute rejection and delayed graft function occurred in 33% and in 60% of cases. Acceptable patient and graft survival may be achieved after third and fourth kidney transplantation. Graft losses in this sensitized population are mainly because of rejection. Profound immunosuppression may lead to major infectious problems.

Introduction: To asses safety of LLDN and post-transplant graft function of kidneys from extended criteria donors. Materials and methods: Retrospective review of all LLDN between 03/2004 and 10/2009. Side of nephrectomy was determined by renal function and vascular anatomy. Extended criteria[for full text, please go to the a.m. URL], 128. Kongress der Deutschen Gesellschaft für Chirurgie

Thrombotic complications following pancreas transplantation are still the most common cause of nonimmunologic graft loss. The aim of this study was to analyze pancreatic graft function after partial arterial graft thrombosis and the investigation of the pancreatic arterial anatomy with regard to intraparenchymal anastomoses. We retrospectively analyzed the data for 175 consecutive pancreas transplants performed between January 2002 and October 2007. Selective Y-graft angiography was performed in 10 and rubber-milk injection in 5 fresh pancreas specimens. Thrombosis of one leg of the Y-graft was diagnosed in 18 (10.3%) patients. Only one of these patients with thrombosis of the splenic artery required exogenous insulin. Sufficient graft perfusion was demonstrated in all of the remaining grafts. One graft was lost due to acute rejection. In all specimens angiography showed an excellent perfusion of the pancreaticoduodenal arcade, even after selective cannulation of the splenic artery. Arterial collaterals between the gastroduodenal, splenic artery and the superior mesenteric artery were demonstrated. Our results demonstrate that global perfusion of the pancreatic graft and sufficient graft function is sustained after the thrombotic occlusion of one branch of the Y-graft by a complex system of intraparenchymal anastomoses. These anatomical findings may have consequences for resection strategies in pancreas surgery.

We report a transplant of the left lateral liver segments with two arteries for a pediatric recipient from a live donor. A six-month-old female patient was diagnosed with liver cirrhosis secondary to biliary atresia and scheduled for LDLT (father as donor). Left lateral hepatectomy was performed at the donor site. The dissection of the left HA, which divided immediately after its origin, showed two branches for segments II and III. The artery for segment III was anastomosed to the recipient HA. The artery for segment II was too short for direct anastomosis with the gastroduodenal artery. After an unsuccessful attempt to use of the recipient's saphenous vein, the recipient's IMV was used as an interposition graft. No post-operative complications were observed. The outcome of this case demonstrates that left lateral segments with two arteries can be successfully used if proper surgical techniques are applied. From this experience we can recommend the IMV as an alternative to the saphenous vein for an interposition graft.

Delayed graft function (DGF) as a consequence of ischemia reperfusion injury (IRI) is associated with a decrease in long-term allograft survival. Heme oxygenase-1 (HO-1) is a stress responsive gene that is highly expressed in multiple pathological processes. The aim of our study was to analyze whether HO-1 protein levels in human kidney transplants during IRI correlate with the incidence of DGF.Kidney biopsies were obtained from 27 kidney allografts at two time points: at the end of cold storage and shortly after reperfusion. Samples were analyzed for HO-1 protein levels by Western blot.Heme oxygenase-1 protein levels were significantly higher in post-reperfusion biopsies (39.4 vs. 13.7 arbitrary units, p = 0.001). In pre-reperfusion biopsies no association was observed between HO-1 protein levels and DGF. In post-reperfusion biopsies, higher levels of HO-1 protein were measured in kidneys with DGF (53.7 vs. 36.2 arbitrary units, p = 0.064). DGF kidneys showed a significantly higher increase from pre- to post-reperfusion in HO-1 protein (42.0 vs. 18.7 arbitrary units, p = 0.025).Heme oxygenase-1 protein levels shortly after allograft reperfusion are closely related with initial graft function. Assessment thereof may be considered a valuable tool to predict DGF.