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BACKGROUND Prognostic models for 3-year mortality after kidney transplantation based on pre-transplant donor and recipient variables may avoid futility and thus improve donor organ allocation. MATERIAL AND METHODS There were 1546 consecutive deceased-donor kidney transplants in adults (January 1, 2000 to December 31, 2012) used to identify pre-transplant donor and recipient variables with significant independent influence on long-term survival (Cox regression modelling). Detected factors were used to develop a prognostic model for 3-year mortality in 1289 patients with follow-up of >3 years (multivariable logistic regression). The sensitivity and specificity of this model's prognostic ability was assessed with the area under the receiver operating characteristic curve (AUROC). RESULTS Highly immunized recipients [hazard ratio (HR: 2.579, 95% CI: 1.272-4.631], high urgency recipients (HR: 3.062, 95% CI: 1.294-6.082), recipients with diabetic nephropathy (HR: 3.471, 95% CI: 2.476-4.751), as well as 0, 1, or 2 HLA DR mismatches (HR: 1.349, 95% CI: 1.160-1.569) were independent and significant risk factors for patient survival. Younger recipient age ≤42.1 years (HR: 0.137, 95% CI: 0.090-0.203), recipient age 42.2-52.8 years (HR: 0.374, 95% CI: 0.278-0.498), recipient age 52.9-62.8 years (HR: 0.553, 95% CI: 0.421-0.723), short cold ischemic times ≤11.8 hours (HR: 0.602, 95% CI: 0.438-0.814) and cold ischemic times 11.9-15.3 hours (HR: 0.736, 95% CI: 0.557-0.962) reduced this risk independently and significantly. The AUROC of the derived model for 3-year post-transplant mortality with these variables was 0.748 (95% CI: 0.689-0.788). CONCLUSIONS Older, highly immunized or high urgency transplant candidates with anticipated longer cold ischemic times, who were transplanted with the indication of diabetic nephropathy should receive donor organs with no HLA DR mismatches to improve their mortality risk.

Outcome after living donor kidney transplantation is highly relevant, since recipient and donor were exposed to notable harm. Reliable identification of risk factors is necessary. Three hundred sixty-six living donor kidney transplants were included in this observational retrospective study. Relevant risk factors for renal impairment 1 year after transplantation and delayed graft function were identified with univariable and multivariable binary logistic regression and ordinal regression analysis. Eighty-four patients (26.6 %) suffered from renal impairment KDIGO stage ≥4 1 year post-transplant; median estimated glomerular filtration rate was 35.3 ml/min. In multivariable ordinal regression, male recipient sex (p

Background The timing of parathyroidectomy in kidney transplant candidates suffering from secondary hyperparathyroidism before versus early or late after transplantation remains controversial. Methods The short-term follow-up cohort comprised 66 patients with 1-year post-transplant follow-up, while the long-term follow-up cohort contained 123 patients. Risk-adjusted identification of independent risk factors for compromised renal graft function (KDIGO stage ≥ IV) was performed using multivariable regression analysis adjusted for propensity score logits for parathyroidectomy before versus after renal transplantation. Intra-individual matched-pairs analyses were used to identify significant effects of post-transplant parathyroidectomy on graft function as assessed by estimated glomerular filtration rate (eGFR) and paired t tests. Results Donor kidney function KDIGO stage III (P = .030; OR = 5.191, 95% CI: 1.100–24.508), donor blood group 0 (P = .005; OR = 0.176, 95% CI: 0.048–0.642), and post-transplant parathyroidectomy (P = .032; OR = 17.849, 95% CI: 1.086–293.268) were revealed as independent significant risk factors for compromised renal graft function in the short-term follow-up cohort using propensity score risk adjustment while post-transplant parathyroidectomy had no independent influence in the long-term follow-up cohort (P = .651). Parathyroidectomy after renal transplantation compromised graft function early after parathyroidectomy and at last follow-up in all post-transplant parathyroidectomy cases (P ≤ .004). Parathyroidectomy within the first post-transplant year was associated with compromised renal graft function until last follow-up (P = .004), while parathyroidectomy late post-transplant was not. Conclusion Parathyroidectomy should be conducted before transplantation or, if this is not possible, preferably after the first post-transplant year.

The concept of high-urgency (HU) renal transplantation was introduced in order to offer to patients, who are not able to undergo long-term dialysis treatment, a suitable renal graft in a short period of time, overcoming by this way the obstacle of the prolonged time spent on the waiting list. The goal of this study was to evaluate the patient and graft survivals after HU renal transplantation and compare them to the long-term outcomes of the non-high-urgency renal transplant recipients. The clinical course of 33 HU renal transplant recipients operated on at our center between 1995 and 2010 was retrospectively analyzed. The major indication for the HU renal transplantation was the imminent lack of access for either hemodialysis or peritoneal dialysis (67%). The patient survival of the study population was 67%, 56%, and 56%, whereas the graft survival was 47%, 35% and 35%, at 5, 10, and 15 years, respectively. In the comparison between our study population and the non-HU renal transplant recipients, our study population presented statistically significant(P<0.05)lower patient survival rates. The HU renal transplant recipients also presented lower graft survival rates, but statistical significance(P<0.05)was reached only in the 5-year graft survival rate.

Background Post-transplant lymphoproliferative disorder (PTLD) adversely affects patients’ long-term outcome. Methods The paired t test and McNemar’s test were applied in a retrospective 1:1 matched-pair analysis including 36 patients with PTLD and 36 patients without PTLD after kidney or liver transplantation. Matching criteria were age, gender, indication, type of transplantation, and duration of follow-up. All investigated PTLD specimen were histologically positive for EBV. Risk-adjusted multivariable regression analysis was used to identify independence of risk factors for PTLD detected in matched-pair analysis. The resultant prognostic model was assessed with ROC-curve analysis. Results Patients suffering with PTLD had shorter mean survival (p = 0.004), more episodes of CMV infections or reactivations (p = 0.042), and fewer recipient HLA A2 haplotypes (p = 0.007), a tacrolimus-based immunosuppressive regimen (p = 0.052) and higher dosages of tacrolimus at hospital discharge (Tac dosage) (p = 0.052). Significant independent risk factors for PTLD were recipient HLA A2 (OR = 0.07, 95 % CI = 0.01–0.55, p = 0.011), higher Tac dosages (OR = 1.29, 95 % CI = 1.01–1.64, p = 0.040), and higher numbers of graft rejection episodes (OR = 0.38, 95 % CI = 0.17–0.87, p = 0.023). The following prognostic model for the prediction of PTLD demonstrated good model fit and a large area under the ROC curve (0.823): PTLD probability in % = Exp(y)/(1 + Exp(y)) with y = 0.671 − 1.096 × HLA A2-positive recipient + 0.151 × Tac dosage − 0.805 × number of graft rejection episodes. Conclusions This study suggests prognostic relevance for recipient HLA A2, CMV, and EBV infections or reactivations and strong initial tacrolimus-based immunosuppression. Patients with risk factors may benefit from intensified screening for PTLD.

To investigate the influence of the type of liver graft donation on donor mortality and morbidity. The clinical course of 87 living liver donors operated on at our center between 2002 and 2009 was retrospectively analysed and data pertaining to all complications were retrieved. No donor mortality was observed and no donor suffered any life-threatening complication. Four donors (4.6%) developed biliary leakage, nine (10.3%) had to be readmitted to hospital and six (6.9%) required some or other type of reoperation related to the previous liver donation. Reoperations included incisional or diaphragmatic hernia repair (n = 4), biliary leakage repair (n = 1) and segmental colon resection combined with diaphragmatic hernia repair (n = 1). There was a statistically significant difference in hospital stay (P < 0.001), autologous blood transfusions (P < 0.001) and operating time (P < 0.005) when right lobe donations (Segments V-VIII) were compared with left lobe (Segments II-IV) and left lateral lobe (Segments II-III) donations, whereas no difference was found between these groups regarding hospital readmission, operative revisions and the incidence or severity of complications. Right lobe donation was associated with prolonged hospital stay, increased blood transfusions and prolonged operating time when compared with left and left lateral lobe donation, whereas donor mortality and morbidity did not differ between these groups.

BACKGROUND Increasing scarcity of donated liver grafts clearly demonstrates the desperate need for ongoing outcome analysis to improve patient and graft survival after liver transplantation. Coagulation is often severely deteriorated in patients suffering from liver disease, thus leading to bleeding complications after liver transplantation. MATERIAL AND METHODS We included 770 liver transplantations in this single-center retrospective analysis to identify independent risk factors for post-operative hemorrhage. The relevance of bleeding complications was assessed with special regards to coagulation-related variables. Multivariate regression analyses allowed weighing of different risk factors. RESULTS Post-operative hemorrhage leading to revision surgery was observed in 19.9% (n=153 cases) of cases and was revealed as an independent risk factor for mortality (p=0.014; HR: 1.457; 95%-CI: 1.081-1.964). Risk-adjusted multivariate regression analysis compiling all pre- and intra-operative donor and recipient variables revealed that only the number of transfused packed red blood cells (p

Summary Background Renal dysfunction is a major complication of long-term immunosuppressive therapy with calcineurin inhibitors (CNI) in liver-transplant recipients. We undertook a randomised study to assess the safety and efficacy of CNI withdrawal and replacement by mycophenolate mofetil. Methods 28 people who had had renal dysfunction attributable to suspected CNI toxicity after liver transplantation participated in the study. We replaced CNI with mycophenolate mofetil in a stepwise pattern in half the group (study patients); the other half (controls) stayed on CNI immunosuppression. Renal function, blood pressure, uric acid, and blood lipids were measured before and 6 months after study entry. Side-effects of medication and graft function were recorded throughout the study. Findings At the end of the study, mean (SD) serum creatinine had fallen by 44·4 (48·7) μmol/L in study patients compared with 3·1 (14·3) μmol/L in controls; a mean difference of 41·3 μmol/L (95% Cl 12·4–70·2). Moreover, systolic and diastolic blood pressure, and serum uric acid decreased significantly in the study group but not in the control group (mean [95% Cl] between group differences 10·8 mm Hg [3·0–18·6], 5·0 mm Hg [0·9–9·2], and 83·1 μmol/L [12·7–153·6], respectively). There were no changes in cholesterol or triglyceride concentrations in either group. Side-effects were reported by eight of the study patients. Three reversible episodes of acute graft rejection occurred in study patients during mycophenolate mofetil monotherapy, whereas none occurred in the control group. Interpretation Substitution of CNI by mycophenolate mofetil can improve renal function, blood pressure, and uric acid concentration of liver-transplant patients, but there is an increased rejection risk with mycophenolate mofetil monotherapy.

Background. Renal dysfunction caused by treatment with the calcineurin inhibitors (CNI) is a major problem in the long-term course after liver transplantation. Patients. In 22 liver graft recipients with renal dysfunction and stable graft function between 3 weeks and 12 years after transplantation, CNI were substituted by MMF at a final dose of 1.5-3 g/day between October 1996 and October 1998. Methods. In a prospective non-randomized study, the development of renal function, the side effects of MMF medication, and the stability of liver function were analyzed for a mean follow-up of 15 months. Results. (1) MMF was withdrawn in four patients for major side effects between 1 and 7 months after study entry; eight patients had minor side effects. (2) Six months after study entry, renal function had improved in 17 of the 22 study patients; mean serum creatinine ± SD (μmol/L) was 201±77 at entry and 153±65 after 3 months (P

The aim of this study was to evaluate the health-related quality of life of living liver donors after living-donor liver transplantation (LDLT).Health-related quality of life (HRQOL) in 55 living liver donors operated on at our center between 2002 and 2009 was assessed using the German Version of the 36-Item Health Survey (SF-36).Donors after full right-lobe hepatectomy (n=18) scored similarly to and without statistically significant difference from the German reference population, whereas donors after left lateral segmentectomy (n=37) revealed statistically significant higher average score values (P.005) in the categories of physical functioning, bodily pain, and general health compared with the German reference population. In the analysis between donors after full right-lobe hepatectomy and donors after left lateral segmentectomy no statistically significant difference was observed in any of the SF-36 categories. Postoperative complications of the donors and postoperative recipient mortality were particularly revealing regarding HRQOL. Donors who developed postoperative complications presented a lower HRQOL, especially in the categories of role physical, bodily pain, and social functioning, where statistically significant differences (P.005) were observed. Similarly, postoperative recipient mortality correlated with lower mean score values in all SF-36 categories, but a statistically significant difference (P.005) was reached only in the categories of role emotional and mental health.Donors did not regret their decision to donate, because HRQOL was not negatively affected by the donation procedure. Living liver donors scored as well as or even better than the German reference population, but it was clearly shown that the development of postoperative donor complications and the postoperative recipient mortality had a negative effect on the HRQOL of donors.

Background. Infusion of donor dendritic cells (DC) has been shown to prolong allograft survival in a number of models. However, many regimens that utilize donor DC do not consistently produced tolerance or long-term allograft survival. We hypothesized that one factor limiting the therapeutic effect of donor DC is their relative inability to traffic to recipient peripheral lymph nodes and inhibit the function of resident alloreactive T cells. Methods. Donor strain DC isolated from the spleens or bone marrow of Flt3L-treated mice were transferred intravenously into recipients at the time of skin grafting. Where indicated, recipients were treated with an anti-CD40L antibody and CTLA4-Ig. Results. Infusion of donor DC together with costimulatory blockade promoted donor-specific prolongation of skin allograft survival in mice. Perhaps due to their more immature phenotype, bone marrow DC trafficked more effectively to the spleen, bone marrow, and thymus and were associated with significantly longer allograft survival than were splenic DC. Neither population of DC trafficked well to peripheral lymph nodes. Consistent with our hypothesis, splenic but not lymph node T cells from DC-treated recipients displayed donor-specific hyporesponsiveness in vitro. Conclusion. These data suggest that one factor contributing to rejection following treatment with donor DC plus costimulation blockade is the persistence of donor-reactive T cells within the recipient's secondary lymphoid structures. Strategies to improve DC trafficking to these structures may enhance their therapeutic effect.

The development of protocols to induce a state of durable mixed allogeneic hematopoietic chimerism to confer robust donor-specific transplant tolerance has been a major focus of the transplant community for the past decade. High levels of mixed allogeneic hematopoietic chimerism across a full major histocompatibility complex (MHC) barrier can be achieved by total myeloablation and transfusion of host and donor bone-marrow cells or, as shown more recently, can be achieved with nonmyeloablative preconditioning regimes in combination with donor bone-marrow transfusions (2-4) or transfusion of purified hematopoietic stem cells (HSC) (5-7). Here we illustrate useful experimental techniques for the study of hematopoietic chimerism in rodents by describing a system in which chimerism can be induced using nonmyeloablative conditioning, short-term costimulation blockade, and transplantation of purified or cultured hematopoietic stem cells.

We reported stable mixed chimerism and specific tolerance to a fully allogeneic graft after a minimally myelosuppressive regimen including costimulation blockade (CB), donor bone marrow cells (BMC), and busulfan (Bu), a chemotherapeutic conditioning agent that makes niches for engraftment of BMC. For clinical application, the strategy may have the limitation of the number of donor BMC when a deceased donor offers transplants to multiple recipients. Herein, we examined whether donor splenocytes can serve as an alternative source to induce mixed chimerism and tolerance. When a C57BL/6 (H-2b) recipient was treated with CB (CTLA4-Ig and anti-CD154 mAb, on days 0, 2, 4, 6) and donor BALB/c (H-2d) BMC (2 x 10(7) cells on day 0) in the absence of Bu, survival of BALB/c skin graft was remarkably prolonged but not indefinite (median survival time [MST]: 138 days). The recipients never showed durable chimerism. When the recipient was treated with CB and donor splenocytes ([DST] 2 x 10(7) cells on day 0), survival was not indefinite either (MST: 114 days). When the dose of DST was increased to 2 x 10(8) cells, survival was further prolonged; two of six recipients had indefinite survival (MST: 132 days). Moreover, one recipient showed a low level of chimerism. When treated with CB, donor DST (2 x 10(7) cells on day 0) and Bu (20 mg/kg, day -1), six of seven recipients showed a stable, high level of chimerism and enjoyed tolerance of skin allografts. DST combined with CB and Bu may be an alternative source of hematopoietic stem cells to induce mixed chimerism and transplantation tolerance in our model.