Delayed graft function

Chronic renal allograft injury (CRAI) is a multifactorial clinical/pathological entity characterised by a progressive decrease in glomerular filtration rate, generally associated with proteinuria and arterial hypertension. Classical views tried to distinguish between immunological (sensitization, low HLA compatibility, acute rejection episodes) and non-immunological factors (donor age, delayed graft function, calcineurin inhibitors [CNI] toxicity, arterial hypertension, infections) contributing to its development. Defining it as a generic idiopathic entity has precluded more comprehensive attempts for therapeutic options. Consequently, it is necessary to reinforce the diagnostic work-up to add etiopathogenetic diagnosis in any case of graft dysfunction, specially transplant vasculopathy and transplant glomerulopathy, reserving the term interstitial fibrosis and tubular atrophy (IFTA) when a case of CRAI is unspecific and no clear contributing factors or a specific etiology is possible in diagnosis.

A promising way to increase the number of kidneys for transplantation is to expand the donor pool by including non-heart-beating donors (NHBDs). The centers involved in NHBD transplantation programs have reported a 16-40% increase in kidney transplants. A key issue with NHBD is the significantly higher rate of delayed graft function (DGF) and primary non-function (PNF) compared with that associated with heart-beating donor (HBD) transplants. However, although transplants from NHBD are associated with a greater incidence of early adverse events, long-term graft survival appears to be similar to that observed after transplants from HBDs. In addition, the use of extracorporeal membrane oxygenation and mechanical perfusion, the careful selection of recipients and donors, and an adequate therapeutic strategy may at least partially reduce the risk of PNF and DGF and improve transplant outcome.

Background: More than half the newly wait-listed patients for kidney transplantation in 2005 were older than 50 years, and 13% were older than 65 years. As waiting times for a deceased donor kidney increase, these older candidates are disadvantaged by rapidly deteriorating health, often resulting in death or removal from the wait list before transplantation. All adult kidney-only transplantations performed in recipients 60 years and older from 1996 to 2005 were included.

The purpose of this study was to define the incidence, dynamics, and profiles of anti-human leukocyte antigen antibodies (HLA-Abs) produced after kidney transplantation and their impact on graft outcome. A total of 72 first cadaver donor kidney recipients were prospectively monitored for the development of HLA-Abs using beadbased flow-cytometry assays (One Lambda FlowPRA tests). Sixteen recipients (22.2%) developed HLA-Abs after transplantation (class I, n ϭ 7; class IϩII, n ϭ 6; class II, n ϭ 3), in most cases (81.25%) within the first 2 weeks posttransplantation. A strong association between alloantibody presence and delayed graft function (Chi-square ϭ 7.659, p Ͻ 0.01), acute rejection (Chi-square ϭ 14.504, p Ͻ 0.001), chronic rejection (Chi-square ϭ 12.84, p Ͻ 0.001), and graft loss (Chi-square ϭ 20.283, p Ͻ 0.001) was found. Patients with higher alloantibody titers experienced acute rejections and even early graft loss, compared with those with lower titers for whom chronic rejections were more common. Immunologic complications occurred in recipients with both donor-specific and cross-reacting groups or non-donor-specific antibodies alone. A positive correlation (Pearson correlation, 0.245; p Ͻ 0.05) between HLA class I amino acid triplet incompatibility and alloantibody production was observed, mainly resulting from immunogenic triplotypes. Given the results obtained in this study, an alloantibody testing algorithm has been designed and implemented for routine monitoring and to define optimally the alloantibody reactivity in kidney transplant recipients.

Lack of an accepted definition for 'high immunological risk' hampers individualization of immunosuppressive therapy after kidney transplantation. For recipientrelated risk factors for acute rejection, the most compelling evidence points to younger age and African American ethnicity. Recipient gender, body mass, previous transplantation, and concomitant infection or disease do not appear to be influential. Deceased donation now has only a minor effect on rejection risk, but older donor age remains a significant predictor. Conventional immunological markers (human leukocyte antigen [HLA] mismatching, pretransplant anti-HLA alloantibodies, and panel reactive antibodies) are being reassessed in light of growing understanding about the role of donor-specific antibodies (DSA). At the time of transplant, delayed graft function is one of the most clear-cut risk factors for acute rejection. Extended cold ischemia time (≥24 h) may also play a contributory role. While it is not yet possible to establish conclusively the relative contribution of different risk factors for acute rejection after kidney transplantation, the available data point to variables that should be taken into account at the time of transplant. Together, these offer a realistic basis for planning an appropriate immunosuppression regimen in individual patients.

We studied the phenotype of late kidney graft failure in a prospective study of unselected kidney transplant biopsies taken for clinical indications. We analyzed histopathology, HLA antibodies and death-censored graft survival in 234 consecutive biopsies from 173 patients, taken 6 days to 31 years posttransplant. Patients with late biopsies (>1 year) frequently displayed donor-specific HLA antibody (particularly class II) and microcirculation changes, including glomerulitis, glomerulopathy, capillaritis, capillary multilayering and C4d staining. Grafts biopsied early rarely failed (1/68), whereas grafts biopsied late often progressed to failure (27/105) within 3 years. T-cell-mediated rejection and its lesions were not associated with an increased risk of failure after biopsy. In multivariable analysis, graft failure correlated with microcirculation inflammation and scarring, but C4d staining was not significant. When microcirculation changes and HLA antibody were used to define antibody-mediated rejection, 17/27 (63%) of late kidney failures after biopsy were attributable to antibody-mediated rejection, but many were C4d negative and missed by current diagnostic criteria. Glomerulonephritis accounted for 6/27 late losses, whereas T-cell-mediated rejection, drug toxicity and unexplained scarring were uncommon. The major cause of late kidney transplant failure is antibody-mediated microcirculation injury, but detection of this phenotype requires new diagnostic criteria.

Various factors determine the graft-and patient survival after transplantation. HLA-matching and immunological factors are of importance for the short-and long-term survival. Apart from these obvious determinants, nonimmunological factors play an important role in defining the baseline organ quality as well as the recipients' status. The influence of these parameters on graft-and patient survival is still underestimated and is a topic of debate. On account of the increasing acceptance of marginal-donor organs these events are of increasing importance for graft survival and long-term function. We review nonimmunological causes for deteriorated graft function and graft loss after solid organ transplantation.

Delayed graft function (DGF) has a negative effect on the results of living-donor kidney transplantation. To investigate potential risk factors for DGF. This prospective study included 200 consecutive living donors and their recipients between January 2002 and July 2007. Delayed graft function was defined as need for dialysis within the first postoperative week. Delayed graft function was diagnosed in 12 patients (6%). Intraoperative complications occurred in 10 donors (5%), and postoperative complications in 24 donors (13.5%). One-year kidney graft survival with vs without DGF was 52% and 98%, respectively (P < .002). In donors, 2 univariate risk factors for DGF identified were lower counts per second at peak activity during scintigraphy, and multiple renal veins. In recipients, only 2 or more kidney transplantations and occurrence of an acute rejection episode were important factors. At multivariate analysis, increased risk of DGF was associated with the presence of multiple re...

Introduction. Dual kidney transplantation (DKT), using extended criteria donor (ECD) grafts not suitable for single kidney transplantation (SKT), has been suggested to expand the kidney donor pool. Herein, we reviewed the long-term outcomes of DKT to assess its results versus a control group of 179 ECD SKTs. The allocation policy was based on a Remuzzi score obtained from a pretransplant biopsy. Materials and methods. We analyzed SKT in 179 (31.8%) and DKT in 41 (7.3%) of 563 cadaveric transplants from 2000 to 2008. Patients with DKT versus SKT showed mean recipient ages of 54 versus 51 years. We performed 17 ipsilateral and 24 bilateral DKT. The mean score was 2.78 for SKT and 4.3/4.6 for DKT. Results. Delayed graft function requiring dialysis occurred in 23 (56.1%) DKT and 70 (39.1%) SKT recipients. Primary nonfunction was observed in 1 (2.4%) DKT and 7 (3.9%) SKT recipients respectively. One DKT patient underwent monolateral transplantectomy. In the DKT versus SKT group, patient survivals were 92% versus 95%, 89% versus 93%, and 89 versus 91% at 12, 36, and 60 months, respectively (P ϭ .3). Graft survivals were 100% versus 94%, 95% versus 90%, and 89% versus 78% at 12, 36, and 60 months, respectively (P Ͻ .001). We observed a lower incidence of chronic allograft nephropathy (P ϭ .01) and a higher incidence of surgical adverse events (P ϭ .04) in DKT. Conclusions. ECD graft survival using DKT provided better results compared with SKT, despite the use of organs from higher-risk donors. At 5 years follow-up, DKT was a safe strategy to face the organ shortage. To optimize the use of available kidneys, the criteria for DKT require further refinement and standardization. Preimplantation evaluation must maximize transplant success and protect recipients from receiving organs at increased risk of premature failure.

Immunosuppressive protocols in dual kidney transplantation (DKT) are based on calcinerurin inhibitors (CNI). We wonder whether a CNI-free immunosuppression can improve outcome in older patients receiving a DKT with marginal donor organs. Thirty-six were treated with CsA, MMF and prednisone (CsA group) and 42 with rATG, SRL, MMF and prednisone (SRL group). Incidence of delayed graft function and acute rejection was 44% and 11% in the CsA group, and 40% and 8% in the SRL group. CMV infection incidence was low in both protocols. Three-year patient survival was 89% in the CsA and 76% in the SRL group. One-and 3-year graft survival after censoring for dead with a functioning allograft was 94.2% and 94% in CsA and 95% and 90% in SRL, respectively. Renal function was similar in both groups whereas proteinuria was higher in the SRL group. Uninephrectomy due to graft thrombosis or urinary-related complications was numerically higher in the SRL (21%) than in the CsA group (8%) (p = 0.13) and it was associated with renal failure and proteinuria. In DKT, a new induction immunosuppressive protocol based on rATG, SRL, MMF and prednisone does not offer any advantage in comparison to the old CsA, MMF and prednisone.

Adult dual kidney transplant is a strategy to overcome the imbalance between limited nephron mass supplied from an older donor and a recipient with a metabolic request. In our report, we review the literature and present our single-center experience. From June 2007 until July 2012, nine hundred twenty-eight single and seventeen dual kidney transplants from deceased donors were performed. The average donor was 71.5 ± 3.6 years of age with an average serum creatinine, creatinine clearance, and an average number of sclerotic glomeruli, 106.1 ± 44.2 μmol/L, 0.97 ± 0.37 mL/s, and 22.4 ± 14.2. Immediate graft function and acute rejection episodes were observed in 75% and 6% of patients. The overall patient survival rates at 1 and 2 years after transplant were 93%. The overall graft survival rates at 1 and 2 years were 88%. Previous studies and our single-center experience suggest that the dual transplant procedure may help improve results of kidney transplants from expanded criteria donor...

The pathogenesis of transplant glomerulopathy (TG) remains unclear, with evidence of human leukocyte antigen (HLA) antibodies as important contributors to the disease. We studied the risk factors and the associations of HLA antibodies in the development of TG. Sixty-one cases with morphologic features of TG were identified and compared with contemporaneous matched patients (without TG) from a 17-year period, all undergoing renal biopsy in a single center. Univariate risk factors for TG were previous glomerulitis [odds ratio (OR) 3.3, 95% confidence interval (95% CI) [1.2-9.4], p ϭ 0.025), delayed graft function (OR 2.3 [1.0 -5.1], p ϭ 0.042), HLA class I presensitization defined by Luminex solid-phase immunoassays (OR 5.0 [2.3-11.0]. p Ͻ 0.001), and de novo posttransplant development of donor HLA specific antibody (DSA) , p ϭ 0.002). Only DSA remained significantly associated with TG after adjustment (OR 3.8 [1.1-12.9], p ϭ 0.032). DSA was detected in Ͼ50% of TG patients, suggesting HLA antibodies play a critical role in TG pathogenesis. TG patients with DSA had increased risk of graft loss (median graft survival 4.4 -5.2 years), whereas patients with morphologic features of TG without DSA had similar graft survival compared with the non-TG group (median graft survival 15 years). Thus, DSA is a useful predictor for graft failure in TG patients.

In the last few decades, strategies to improve allograft survival after kidney transplantation have been directed to recipient-dependent mechanisms of renal injury. In contrast, no such efforts have been made to optimize organ quality in the donor. Optimizing deceased donor kidney quality opens new possibilities to improve renal allograft outcome. A total of 554 kidney biopsies were taken from donation after brain death (DBD) and donation after cardiac death (DCD) kidneys before donation, after cold ischemia and after reperfusion. Healthy living donor kidney biopsies served as controls. Transcriptomics was performed by whole genome microarray analyses followed by functional pathway analyses. Before organ retrieval and before cessation of blood circulation, metabolic pathways related to hypoxia and complement-and-coagulation cascades were the major pathways enhanced in DBD donors. Similar pathways were also enriched in DCD donors after the first warm ischemia time. Shortly after repe...

To test the effect of CIT, we excluded paired transplants with the same CIT (n = 3286). Of 14 230 recipients (7115 donors) the median difference in CIT was 5 h (Q1 = 3 h, Q3 = 9 h). Delayed graft function (DGF) was significantly more likely between pairs with greater CIT (35% vs. 31%, p < 0.001) including substantially higher rates for CIT differences ≥15 h (42%). Overall graft loss was not significantly different between recipients with higher CIT relative to paired donor recipients with lower CIT (p = 0.47) or for pairs with differences of 1-3 h (p = 0.90), 4-9 h (p = 0.41), 10-14 h (p = 0.36) or ≥15 h (p = 0.10). Results were consistent in multivariable models adjusted for recipient factors. Although increasing cold ischemia time is a risk factor for DGF among ECD kidney transplants, there is no effect on graft survival which may suggest an important utility for donor kidneys that may not currently be considered viable.

Most clinicians regard angioplasty with or without stent placement to be the treatment of choice for transplant renal artery stenosis (TRAS). However, published results regarding its effectiveness are heterogeneous. The aim of this study was to assess the safety and efficiency of TRAS endovascular therapy. All cases of TRAS admitted for treatment in our unit from January 2009 to December 2012 were reviewed retrospectively. The primary end point was the stenosis-free primary transplant renal artery patency. Secondary end points were freedom from reintervention, graft survival, postoperative serum creatinine level, blood pressure evolution, and the number of antihypertensive drugs pre- and postprocedure. A total of 17 patients (10 men, 7 women) presenting with TRAS were referred to our institution. During the early post-transplantation process (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;15 days), 35.2% of patients presented. The median time to presentation was 40 days. The predominant presentation was graft function alteration (82.3%). Percutaneous balloon angioplasty was performed in five patients (29.4%), while stenting was performed in the remaining 12 patients (70.6%). The stenosis-free primary patency rate and freedom from reintervention rate were 76.5% and 88.2%, respectively. The median follow-up was 19.6 months with 88.2% graft survival. There were no mortalities throughout the follow-up period. Serum creatinine levels decreased significantly from 186 μmol/L (range, 148-310 μmol/L) preoperatively to 160 μmol/L (range, 127-236 μmol/L at discharge (P = .0036). The glomerular filtration rates increased from 32.1 mL/min (range, 21.4-45.8 mL/min) to 41.7 mL/min (range, 27.5-52.4 mL/min; P = .004). Systolic and diastolic blood pressure varied from 140 mm Hg (range, 137-157 mm Hg) and 75 mm Hg (range, 70-80 mm Hg), to 135 mm Hg (range, 130-147 mm Hg and 80 mm Hg (range, 73-80 mm Hg), respectively (P = .11 and P = .36). The preoperative number of antihypertensive medications was 2 (range, 1-3) and remained unchanged (P = .33). The endovascular management of TRAS is safe and presents a high rate of technical success with low morbidity. Its impact on serum creatinine levels is significant in our experience. However, the blood pressure items do not seem to improve postoperatively.

Some patients demonstrate delayed recoveries after autologous hematopoietic stem cell transplantation despite infusion of an adequate number of CD34+ cells/kg and clinically stable status. Factors considered being possible predictors of this outcome in this context were explored. A total of 246 patients were evaluated in terms of engraftment. Delayed recovery was defined by white blood cell recovery time exceeding mean+1 SEM. Clinical factors and graft characteristics were examined. Comparisons between patients with normal or delayed engraftment were made. Proinflammatory cytokines and proteolytic enzyme quantification and CXCR4+ and CD44+ cell enumeration were performed on peripheral hematopoietic stem cells (PHSC) product samples of patients with delayed engraftment and patients with usual engraftment time. Sixteen patients, who received at least 3 × 10(6) CD34+ cells/kg without known clinical factors likely to affect engraftment, demonstrated a delayed recovery time of over 20 days. Some graft variables were found to be significantly increased in these patients by univariate analysis. One variable was the total number of nucleated cells cryopreserved and infused. Among the nucleated cells, the absolute number of granulocytes before and after cryopreservation also differed significantly between the two groups. A multivariate analysis showed that the main predictive factor for delayed recovery was the number of nucleated cells in the graft (p=0.0044). The influence of contaminating cells might be related to the release of elastase, matrix metalloproteinase-9, interleukin (IL)-1β, and IL-6 involved in stem cell homing. Therefore, the numeration of total nucleated cells and granulocytes should be considered as a possible quality control variable of PHSCs submitted for cryopreservation.

The University of Wisconsin (UW) solution is the most commonly used preservation solution. However, a new preservation solution-IGL-1-contains an inversion of K and Na concentrations and substitution of polyethylene glycol for hydroxyethyl starch in the UW solution. The present study is the first clinical experience on the outcome of kidneys preserved in IGL-1 solution. From June 2003 to June 2004, 119 cadaveric kidneys were retrieved and stored in IGL-1 solutions; among the 119 organs, this study includes 37 IGL-1-preserved kidneys that were locally transplanted versus 33 kidneys stored in University of Wisconsin (UW) solution that were also locally transplanted. The groups were comparable with regard to donor and recipient characteristics. Renal function outcome was evaluated by comparing delayed graft function (DGF) rates, the evolution of serum creatinine, daily urine output, and creatinine clearance. Biopsies were performed after reperfusion to evaluate apoptosis. The incidence of DGF was 5.71% among IGL-1 kidneys and 13.79% among UW kidneys. Creatinine values were significantly lower among the IGL-1 group from 2 to 14 days postoperative and at 1 month. Daily urinary output did not show any significant differences between the two groups. IGL-1 kidneys had a superior creatinine clearance during the first 15 postoperative days compared to UW kidneys. Kidneys preserved in IGL-1 solution showed fewer apoptotic cells compared to kidneys preserved in UW solution. This preliminary report suggests a superiority of IGL-1 for the immediate outcome of transplanted kidneys. Address reprint requests to Prof

Objective. The aim of this study was to assess the efficacy of inferior alveolar nerve (IAN) block combined with buccal infiltration for mandibular molars with irreversible pulpitis. Methodology. Eighty-four patients were randomly assigned to 3 groups of 28 patients each. Lidocaine 2% with 1:80,000 epinephrine was used for all injections. Group I patients received an IAN block with 1.8 mL of anesthetic. Group II patients received an IAN block using 3.6 mL. Group III patients received 1.8 mL as an IAN block and 1.8 mL as a buccal infiltration. A visual analogue scale was used to rate pain before anesthesia and discomfort experienced before and during access cavity preparation. Data were analyzed by chi-square, ANOVA, Kruskal-Wallis, and Mann-Whitney tests. Results. The success rates for groups I to III were 14.8%, 39.3%, and 65.4%, respectively. Group III had significantly better anesthesia compared with group I (P Ͻ .05).

Aim. Transplantations of kidneys from non-heart-beating donors (NHBD) are intended to increase the donor pool by 20% to 30%. Nevertheless the rate of primary nonfunction and delayed graft function is generally higher among this group of donors. The goal of this study was to assess whether kidney preservation by a pulsatile perfusion machine was able to limit the renal lesions due to ischemia reperfusion injuries as compared with static incubation. We have used a model of an autotransplanted kidney exposed to controlled warm ischemia in the pig to mimic the clinical conditions of NHBD. Material and Methods. Left kidneys from 11 large white pigs aged 4 weeks were harvested after vascular clamping of the renal vessels for 1 hour. Kidneys were preserved for 22 hours. Two groups were studied: the MPS static group (static incubation with Belzer MPS; n ϭ 6) versus the MPS RM group (renal perfusion with Belzer MPS; n ϭ 5). Kidneys were then autotransplanted into pigs after a right nephrectomy. The primary end point was animal survival rate at 1 month. Secondary endpoints were evolution of the plasma creatinine values, proteinuria, tubular sodium reabsorption, and histological features at 1 month.

The transplantation program in Bulgaria started in 1968 with renal transplantations to a child and adult woman. In 1986 the first heart transplantation was performed. To date a total of 10 heart transplants have been performed, including one combined heart/lung. A liver transplantation program was launched in 2005 with a total number of 16 transplantations-7 from living donors and 9 from deceased donors. The highest transplantation activity is registered in the field of renal transplantation. During the period 1980-2006, 462 Bulgarian recipients of kidney were transplanted in Bulgaria. The ratio between transplantations from deceased and living related donors is approximately 1:0.9. Annual transplantation activity varies among the years from 1 to 12 renal transplantations p.m.p./per year. The 1-(80.7% vs. 63.1%), 5-(57.86% vs. 39.0%) and 10-year (42.65% vs. 23.62%) graft survival rates are higher for recipients of living donor kidneys compared to those of deceased donor. In 1983 a

A prospective evaluation of the influence of methods of kidney storage prior to transplantation on long-term graft function has not been shown so far. A retrospective study undertaken in 415 patients in our department showed the benefit of machine perfusion (MP) on long-term results. The aim of the present study was to assess prospectively the long term function and survival of paired kidney allografts retrieved from the same donor, comparing the influence of cold storage (CS) and MP. 74 recipients included in the study received kidneys from 37 cadaveric donors. Kidneys were randomized to storage by CS or MP. There were no significant differences between the groups as to age, gender, duration of ESRD treatment, PRA titres, HLA compatibility and immunosuppressive regimens. At 10 years follow-up recipients of CS-stored kidneys returned to dialysis treatment twice as frequently as recipients of MP-stored kidneys (50% vs. 25%, p=0.02). Kidney storage by MP improves graft survival and re...

Background: To generate a robust predictive model of Early (3 months) Graft Loss after liver transplantation, we used a Bayesian approach to combine evidence from a prospective European cohort (Liver-Match) and the United Network for Organ Sharing registry. Methods: Liver-Match included 1480 consecutive primary liver transplants performed from 2007 to 2009 and the United Network for Organ Sharing a time-matched series of 9740 transplants. There were 173 and 706 Early Graft Loss, respectively. Multivariate analysis identified as significant predictors of Early Graft Loss: donor age, donation after cardiac death, cold ischaemia time, donor body mass index and height, recipient creatinine, bilirubin, disease aetiology, prior upper abdominal surgery and portal thrombosis. Results: A Bayesian Cox model was fitted to Liver-Match data using the United Network for Organ Sharing findings as prior information, allowing to generate an Early Graft Loss-Donor Risk Index and an Early Graft Loss-Recipient Risk Index. A Donor-Recipient Allocation Model, obtained by adding Early Graft Loss-Donor Risk Index to Early Graft Loss-Recipient Risk Index, was then validated in a distinct United Network for Organ Sharing (year 2010) cohort including 2964 transplants. Donor-Recipient Allocation Model updating using the independent Turin Transplant Centre dataset, allowed to predict Early Graft Loss with good accuracy (c-statistic: 0.76). Conclusion: Donor-Recipient Allocation Model allows a reliable donor and recipient-based Early Graft Loss prediction. The Bayesian approach permits to adapt the original Donor-Recipient Allocation Model by incorporating evidence from other cohorts, resulting in significantly improved predictive capability.

Urological complications after renal transplantation increase morbidity, delay graft function, and occasionally lead to graft and/or patient loss. The aim of this study was to analyze the causes of and therapeutic approaches to urological complications in renal transplantation as they related to patient outcomes. A series of 1525 consecutive renal transplantations were performed over a 24-year period. Renal grafts were obtained in 814 cases from living-related and in 711 from cadaveric donors. A Lich-Gregoire ureterovesical reimplantation technique with minimal bladder wall dissection was employed in all cases. Ureteral stents were routinely used in cadaveric transplants and exceptionally among living-related grafts. Urological complications were classified according to the mechanism and site of urinary tract involvement: graft ureteropelvic junction obstruction/stenosis (A), ureteral obstruction/stenosis (B), ureterovesical anastomosis obstruction/stenosis (C), urinary leakage (D), and other (E). Overall, we encountered 96 urological complications (6.3%). Group C complications occurred in 29 cases (30.2%), followed by 27 cases (28.1%) for group B patients, 25 cases (26.0%) for group D, 12 cases (12.5%) for group A, and 3 cases (3.1%) for group E patients. Surgical intervention was required in 49 (51.0%) of all urological complications. The others (n ϭ 47, 49.0%) were treated either conservatively or by minimally invasive procedures. A rapid diagnosis of urological complications, assisted by early posttransplant DTPA scans, routine ultrasonography, and especially prompt treatment, resulted in compensation of renal graft dysfunction in the vast majority (n ϭ 90, 93.8%) of cases. Surgical techniques of graft retrieval and reimplantation are of utmost importance to minimize the incidence of urological complications.

Background and objectives: Transplant "tourism" typically refers to the practice of traveling outside the country of residence to obtain organ transplantation. This study describes the characteristics and outcomes of 33 kidney transplant recipients who traveled abroad for transplant and returned to University of California, Los Angeles (UCLA) for follow-up.

Nonheart-beating donor (NHBD) kidneys are frequently associated with delayed graft function (DGF), with a deleterious effect on kidney function and allograft survival. The influence and the duration of DGF on the outcome of NHBD kidneys are assessed.

Introduction. Delayed graft function (DGF) is a common complication in kidney transplantation. We sought to evaluate possible correlates for DGF including intraoperative parameters, focusing on fluid replacement and central venous pressure (CVP) values among patients undergoing kidney transplantation at our center. Methods. One hundred fifty-five cadaveric donor transplantations performed at our center between 2001 and 2005 were selected for the study. We compared intraoperative parameters together with 15 other clinical and socio-demographic recipient and donor variables among patients experiencing DGF (n ϭ 58) versus those with immediate graft function (IGF; n ϭ 97). All significant variables at P Ͻ .05 upon univariate analysis were entered into a multivariate logistic regression model to identify risk factors for DGF.

Peritransplant risk factors influence short-term and long-term graft survival, and 1-year serum creatinine is known to predict long-term graft survival. To examine interrelationships between risk factors, renal function at 1 year, and long-term graft function in patients maintained on cyclosporine, we analyzed data collected from 10,692 de novo or maintenance renal transplant recipients in an ongoing international, prospective, observational study--Neoral-MOST (Multinational Observational Study in renal Transplantation). The effect of donor age, delayed graft function, acute rejection, donor type, panel-reactive antibodies, and previous graft on 1- and 5-year renal function and their relationship to 1-year serum creatinine was assessed. Donor age, delayed graft function, acute rejection, and donor type significantly increased the risk for serum creatinine &gt; 130 micromol/L at 1 year posttransplant, and 1-year serum creatinine was the strongest predictor of 5-year renal function. A...

The effect of de novo DSA detected at the time of acute cellular rejection (ACR) and the response of DSA levels to rejection therapy on renal allograft survival were analyzed. Kidney transplant patients with acute rejection underwent DSA testing at rejection diagnosis with DSA levels quantified using Luminex single-antigen beads. Fifty-two patients experienced acute rejection with 16 (31%) testing positive for de novo DSA. Median follow-up was 27.0 ± 17.4 months postacute rejection. Univariate analysis of factors influencing allograft survival demonstrated significance for African American race, DGF, cytotoxic PRA >20% (current) and/or >50% (peak), de novo DSA, C4d and repeat transplantation. Multivariate analysis showed only de novo DSA (6.6fold increased allograft loss risk, p = 0.017) to be significant. Four-year allograft survival was higher with ACR (without DSA) (100%) than mixed acute rejection (ACR with DSA/ C4d) (65%) or antibody-mediated rejection (35%) (p < 0.001). Patients with >50% reduction in DSA within 14 days experienced higher allograft survival (p = 0.039). De novo DSAs detected at rejection are associated with reduced allograft survival, but prompt DSA reduction was associated with improved allograft survival. DSA should be considered a potential new end point for rejection therapy.

Kidney donation after cardiac death has been popularized over the last decade. The majority of these kidneys are from controlled donors. The number of organs for transplantation can be further increased by uncontrolled donors after cardiac death. The outcome of uncontrolled compared to controlled donor kidney transplantation is relatively unknown. We compared the long-term outcome of kidney transplantation from uncontrolled (n = 128) and controlled (n = 208) donor kidneys procured in the Maastricht region from January 1, 1981 until January 1, 2008, and transplanted in the Eurotransplant region. The incidence of primary nonfunction and delayed graft function in both uncontrolled and controlled donor kidneys is relatively high (22% vs. 21%, and 61% vs. 56%, p = 0.43, respectively). Ten-year graft and recipient survival are similar in both groups (50% vs. 46%, p = 0.74 and 61% vs. 60%, p = 0.76, respectively). Estimated glomerular filtration rates 1 year after transplantation are 40 ± 16 versus 42 ± 19 mL/min/1.73 m 2 , p = 0.55, with a yearly decline thereafter of 0.67 ± 3 versus 0.70 ± 7 mL/min/1.73 m 2 /year, p = 0.97. The outcome of kidney transplantation from uncontrolled and controlled donors after cardiac death is equivalent. This justifies the expansion of the donor pool with uncontrolled donors to reduce the still growing waiting list for renal transplantation, and may stimulate the implementation of uncontrolled kidney donation programs.

It has been suggested that dual kidney transplantation (DKT) improves outcomes for expanded criteria donor (ECD) kidneys. However, no criteria for allocation to single or dual transplantation have been assessed prospectively. The strategy of DKT remains underused and potentially eligible kidneys are frequently discarded. We prospectively compared 81 DKT and 70 single kidney transplant (SKT) receiving grafts from ECD donors aged >65 years, allocated according to donor estimated glomerular filtration rate (eGFR): DKT if eGFR between 30 and 60 mL/min, SKT if eGFR greater than 60 mL/min. Patient and graft survival were similar in the two groups. In the DKT group, 13/81 patients lost one of their two kidneys due to hemorrhage, arterial or venous thrombosis. Mean eGFR at month 12 was similar in the DKT and SKT groups (47.8 mL/min and 46.4 mL/min, respectively). Simulated allocation of kidneys according to criteria based on day 0 donor parameters such as those described by Remuzzi et al., Andres et al. and UNOS, did not indicate an improvement in 12-month eGFR compared to our allocation based on donor eGFR.

Objective. To report clinical outcomes of kidney transplantation from cardiac death donors (DCD) in China, and to investigate its feasibility to expand the organ donor pool. Patients and methods. We retrospectively studied clinical data of 46 DCD kidneys from 31 donors from February 2007 to August 2011. Recipients were followed for patient and graft survival. Results. We discarded the organs from 3 of 29 (10.3%) DCD donors and 7 of 42 (16.7%) kidneys that displayed renal thrombosis. Of the 39 recipients engrafted with DCD kidneys successfully, the mean follow-up was 16 months, (range ϭ 50 days to 43 months). Delayed graft function (DGF) occurred in 15 (38.5%) recipients, who except one recovered within 3 months. Three biopsy-proven acute rejection episodes were observed in two recipients (5.1%). All patients survived through the follow-up. The graft survival rate was 97.4% at 12 months and 94.9% at 24 months. A 45-year-old male recipient who received a pair of grafts from a 6-year-old child survived with good renal function. Conclusion. Although kidney transplantations from DCD donors showed a higher rate of DGF with a longer duration of graft recovery, we achieved favorable short-term clinical outcome in terms of graft survival and function. Donation after cardiac death can expand the organ donor pool in China.

M ucha gente dice: "No hay que hablar mal de las iglesias legalistas, hay que unirse, debemos ser una sola iglesia." Y no estamos hablando de distintas opiniones o de maneras de ver o de interpretar las cosas, sino de mentiras. El legalista es una persona rígida que manipula a los demás usando el miedo y la culpa. Para manipular siempre se utilizan estas dos emociones, porque con culpa y miedo se puede llevar a una persona de las narices a cualquier lugar.

Early identification and prognostic stratification of delayed graft function following renal transplantation has significant potential to improve outcome. Mass spectrometry analysis of serum samples, before and on day 2 post transplant from five patients with delayed graft function and five with an uncomplicated transplant, identified aminoacylase-1 (ACY-1) as a potential outcome biomarker. Following assay development, analysis of longitudinal samples from an initial validation cohort of 55 patients confirmed that the ACY-1 level on day 1 or 2 was a moderate predictor of delayed graft function, similar to serum creatinine, complementing the strongest predictor cystatin C. A further validation cohort of 194 patients confirmed this association with area under ROC curves (95% CI) for day 1 serum (138 patients) of 0.74 (0.67-0.85) for ACY-1, 0.9 (0.84-0.95) for cystatin C, and 0.93 (0.88-0.97) for both combined. Significant differences in serum ACY-1 levels were apparent between delayed, slow, and immediate graft function. Analysis of long-term followup for 54 patients with delayed graft function showed a highly significant association between day 1 or 3 serum ACY-1 and dialysis-free survival, mainly associated with the donor-brain-dead transplant type. Thus, proteomic analysis provides novel insights into the potential clinical utility of serum ACY-1 levels immediately post transplantation, enabling subdivision of patients with delayed graft function in terms of long-term outcome. Our study requires independent confirmation.

Since 1996, our standard immunosuppressive protocol for simultaneous kidney-pancreas transplantation (SKPT) has been tacrolimus (TAC), mycophenolate mofetil (MMF) and steroids without antibody induction. When basiliximab and daclizumab, monoclonal antibodies directed against the interleukin-2 receptor (IL-2R), became available, we selectively added these agents to our standard protocol. The purpose of this prospective, open-la-be1 study was to evaluate the safety and efficacy of IL-2 receptor antagonists in SKPT. From April 1998 to August 1999,35 SKPTS were performed. One patient with delayed graft function received Thymoglobulin and was excluded; 17 received no induction, and 17 received IL-2R antagonists (9 basiliximab, 8 daclizumab) as induction. Demographic-and transplant characteristics were similar between the two groups. At 6 months, patient survival was 88 Yo (15/17) in the induction arm compared to 100 % (17/17) in the noinduction arm, P = NS. The 2 causes of death were sepsis and hemolytic uremic syndrome, and both patients died with functioning grafts. Deathcensored pancreas and kidney graft survival rates in the induction and the no-induction groups were 88 % vs. 100 YO respectively, in both groups. The incidence of acute rejection (kidney or pancreas) at 6 months did not differ between the two groups (35 Yo in both groups). Biopsy proven pancreas and kidney acute rejections were 35 % vs. 24 YO and 12 % vs. 12 % in the inductionand no-induction groups, respectively. The incidences of major infection and readmission did not differ between groups. TAC trough levels and mean daily doses of TAC, MMF and steroids did not differ between the two groups at 1,3, and 6 months. The incidence of event-free survival (no death, rejection, or graft loss) at 6 months was 59 YO (10/17) in the induction and 65 % (11117) in the noinduction group. Basiliximab and daclizumab appear to be safe in SKPT. However, the preliminary results of this study do not demonstrate a significant benefit in either reducing the incidence of acute rejection or improving outcomes at 6 months.

Increasing gap between demand and availability of human kidneys for transplantation has forced a re-evaluation of the limits on donor age acceptability. The present study included 74 patients who underwent kidney transplantation in University Clinical Centre Tuzla. In an observational cohort study we assessed impact of donor age on post transplant renal function by analyzing following parameters: 24 hour urine output, creatinine clearance (Cr Cl) and glomerular filtration rate (GFR). Depending on donor age recipients were allocated in to two groups. Group I included patients who received renal graft from donors age up to 55 years, and Group II encountered recipients who received renal graft from donors older than 55 years. Our goal was to determine whether donor age over 55 years significantly diminishes renal graft function in first seven post transplant days. No statistically significant difference was found between Group I and II regarding 24 hour urine output. From second to fif...

Sirolimus (SRL) is an antiproliferative agent inhibiting the mammalian target of rapamycin (mTOR) proposed as a non-nephrotoxic alternative to calcineurin inhibitors for the prevention of acute rejection in renal transplantation. Despite initial encouraging results, enthusiasm faded with large trials showing an increased risk of acute rejection with this molecule that did not provide superior graft function over cyclosporin or tacrolimus. Recent data showed that SRL, along with an immunosuppressive activity on CD4 þ T cells, exerts a paradoxical stimulatory effect on innate immunity, which may explain its incomplete control of alloimmune response. Moreover, SRL therapy is burdened by a concerning safety profile including high risk of delayed graft function and onset of proteinuria. This adds to many other adverse effects, including dyslipidemia, diabetes, myelosuppression, delayed wound healing, infertility, ovarian cysts, and mouth ulcers, that further limit the use of this molecule. Severe cases of interstitial pneumonia have also been reported with this therapy, raising additional concerns. Incomplete control of immune response, along with a poor tolerability, makes SRL far from being the ideal antirejection drug. Progressive restrictions of SRL indication in renal transplantation have, however, been paralleled by evidence showing mTOR abnormalities involved in many pathogenic conditions, thus opening the avenue to new possible applications of this molecule.

Purpose: Delayed graft function after live donor transplantation affects 5% to 10% of recipients regardless of procurement technique. This delay in function is associated with an increased risk of rejection and decreased graft survival. In the present study we critically assess allograft recovery to identify the risk factors related to delayed graft function.

Limited data are available for outcomes of simultaneous liver-kidney (SLK) transplantation using donation after cardiac death (DCD) donors. The outcomes of 12 DCD-SLK transplants and 54 SLK transplants using donation after brain death (DBD) donors were retrospectively compared. The baseline demographics were similar for the DCD-SLK and DBD-SLK groups except for the higher liver donor risk index for the DCD-SLK group (1.8 6 0.4 versus 1.3 6 0.4, P 5 0.001). The rates of surgical complications and graft rejections within 1 year were comparable for the DCD-SLK and DBD-SLK groups. Delayed renal graft function was twice as common in the DCD-SLK group. At 1 year, the serum creatinine levels and the iothalamate glomerular filtration rates were similar for the groups. The patient, liver graft, and kidney graft survival rates at 1 year were comparable for the groups (83.3%, 75.0%, and 82.5% for the DCD-SLK group and 92.4%, 92.4%, and 92.6% for the DBD-SLK group, P 5 0.3 for all). The DCD-SLK group had worse patient, liver graft, and kidney graft survival at 3 years (62.5%, 62.5%, and 58.9% versus 90.5%, 90.5%, and 90.6%, P 5 0.03 for all) and at 5 years (62.5%, 62.5%, and 58.9% versus 87.4%, 87.4%, and 87.7%, P < 0.05 for all). An analysis of the Organ Procurement and Transplantation Network database showed inferior 1-and 5-year patient and graft survival rates for DCD-SLK patients versus DBD-SLK patients. In conclusion, despite comparable rates of surgical and medical complications and comparable kidney function at 1 year, DCD-SLK transplantation was associated with inferior long-term survival in comparison with DBD-SLK transplantation.

Background: Several large series of laparoscopic donor nephrectomy (LDN) have been published, largely focusing on immediate results and short-term complications. The aim of this study was to examine the results of LDN and collect medium-term and long-term donor followup. Methods: We examined the results of two surgeons who performed 500 consecutive LDNs from 1996 to 2005. Prospective databases were reviewed for both donors and recipients to record demographics, medical history, intraoperative events, and complications. Patients were followed between 1 month and 9 years after surgery to assess for delayed complications, especially hypertension, renal insufficiency, incisional hernia, bowel obstruction, and chronic pain. Results: Left kidneys were procured in 86.2% of cases. Mean operative time was 3.5 h, and warm ischemia time averaged 3.4 min. Hand-assistance was used in 13.8%, and conversion rate was 1.8%. Intraoperative complication rate was 5.8% and was predominantly bleeding (93.1%). Most (86.2%) of the operative complications occurred during the initial 150 cases of a surgeon, compared with 10.3% in the subsequent 150 cases (p = 0.003). Operative time decreased by 87 min after the initial 150 cases (p < 0.001). Immediate graft survival was 97.5%. Delayed graft function occurred in 3.0% of recipients, and acute tubular necrosis occurred in 7.0%. Thirty-day donor complication rate was 9.8%. Mean donor creatinine was 1.24 on the first postoperative day, 1.27 at 2 weeks, and 1.24 at 1 year. At a mean followup of 32.8 months, long-term donor complications consisted of 11 cases of hypertension, 9 cases of prolonged pain or paresthesia, 2 incisional hernias, 1 small bowel obstruction requiring laparoscopic lysis of adhesions, and 1 hydrocele requiring repair.

Background: Laparoscopic donor nephrectomy (LDN) is becoming the standard of care for living donor nephrectomy. However, questions have been raised about the safety of LDN for the donor and about the potentially increased rates for ureteral complications experienced by the recipient. In this report, the authors review their 5-year experience with 253 living laparoscopic donor nephrectomies. Methods: A retrospective chart review was performed for 253 laparoscopic live donors. Graft function and survival were compared using recipient postoperative creatinine values up to 12 months. Results: The overall rate of complications in the investigated series was 10.3%. There were seven intraoperative complications (2.8%), three of which required open conversion. There were 19 postoperative complications (7.5%), three of which required reexploration for bleeding. The majority of complications were minor including 62% grade 1, 8% grade 2, 31% grade 3, and no grade 4 or 5 complications. There were no intraoperative complications in the right-sided donor group. There was a 5% complication rate for patients with a body mass index (BMI) exceeding 25. The findings showed that 11.2% of the recipients had slow graft function, and 4.4% had delayed graft function. Less than 1% of the recipients experienced ureteral stricture requiring permanent stent placement or reoperation. Overall, there was a 2% graft loss rate. Conclusions: The findings show a low rate of intraoperative and postoperative complications, most of which were minor complications. There was an increase in operative time and hospital stay in the right-sided group, but no increase in complication rate. There was no significant difference in outcome or complication rate for the overweight patients.

Background. Technical and medical advances over the past few years have produced an important increase in the functionality of renal allografts. The aim of this study was to identify the factors associated with allograft survival 15 years after transplantation in our series. Methods. A retrospective study of kidney transplantations was carried out at Reina Sofia Hospital in Cordoba from February 1979 to December 1997, with follow-up through June 2012. A subanalysis of the series was undertaken, and Kaplan-Meier analysis and Cox proportional hazards model regression used to achieve the main objective of the study. Results. A total of 487 renal allografts with a mean follow-up of 114 months were studied, of which 37% (n ¼ 180) survived for >15 years. Of the 180 patients, the main causes of graft failure were chronic allograft nephropathy in 29 (66%) and patient death in 13 (29.5%). Multivariate analysis identified the number of HLA mismatches (hazard ratio [HR] 1.25, 95% CI 1.01e1.56), panel reactive antibodies (HR 2.61, 95% CI 1.28e5.26), and delayed graft function (HR 11.25, 95% CI 1.33e95.28) as being significantly associated with graft loss after 15 years. Conclusions. The high immunologic risk of the patients was independently associated with graft loss. Delayed graft function was the most important factor in the speed of graft failure beyond 15 years.

An update is given about some factors leading to loss of renal allograft, especially in relation to the use of tacrolimus and cyclosporine. We discuss both immunological, such as suboptimal immunosuppression, acute rejection, and noncompliance, as well as nonimmunological factor's such as hypertension, hyperlipidemia, chronic toxic effects of immunosuppressants, older donors, and delayed graft function.

Introduction: Neutrophil gelatinase-associated lipocalin (NGAL) is a promising novel biomarker that correlates with the severity and outcome of acute kidney injury (AKI). However, its prognostic utility during the late course of AKI, especially in patients that require renal replacement therapy (RRT) remains unknown. The aim of this study was to evaluate the predictive value of serum NGAL in patients with established AKI at inception of RRT in the intensive care unit (ICU). Methods: Serum NGAL (ELISA methodology) was measured in 109 critically ill patients with AKI at inception of RRT in 7 ICUs of a tertiary care university hospital. The primary outcome studied was 28-day mortality. Secondary outcome measures were ICU length of stay, ventilator-free days, and renal recovery at day 28.