Delayed graft function

Renal transplantation remains the treatment of choice kidney transplant survival. for end-stage renal disease (ESRD) in regards to patient Background. Improvements in long-term kidney graft sursurvival [1]. A recent analysis of the UNOS/OPTN transvival have been recently noted. However, the reasons for this plant database, confirmed that long-term renal graft surwere unclear. This study examined post-transplant renal function within the first year as an independent variable influencing vival measured as graft half-life has improved from 1988 long-term survival. to 1996 [2]. Many risk factors are known to influence long-Methods. The influence of demographic characteristics (age, term graft survival. Among these include: recipient age, sex, race); transplant variables (cadaver versus living donor, race, presence of diabetes, delayed graft function (DGF),

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.

Background: Neutrophil gelatinase associated lipocalin (NGAL) is a biomarker of kidney injury. We examined plasma levels of NGAL in a cohort of 57 kidney allograft recipients (Tx group, 39 ± 13 years), a uraemic group of 40 patients remaining on the waiting list (47 ± 11 years) and a control group of 14 healthy subjects matched for age, sex and body mass index (BMI). The kidney graft recipients were studied at baseline before transplantation and 3 and 12 months after transplantation and the uraemic group at baseline and after 12 months. Methods: NGAL was measured using a validated in-house Time-Resolved Immuno-flourometric assay (TRIFMA). Repeated measurements differed by < 10% and mean values were used for statistical analyses. Spearman rank order correlation analysis and the Kruskal-Wallis non-parametric test were used to evaluate the association of NGAL concentrations with clinical parameters. Results: Plasma NGAL levels before transplantation in the Tx and uraemic groups were significantly higher than in the healthy controls (1,251 μg/L, 1,478 μg/L vs. 163 μg/L, p < 0.0001). In the Tx group NGAL concentrations were associated with serum creatinine (R = 0.51, p < 0.0001), duration of end-stage renal failure (R = 0.41, p = 0.002) and leukocyte count (R = 0.29, p < 0.026). At 3 and 12 months plasma NGAL concentrations declined to 223 μg/L and 243 μg/L, respectively and were associated with homocysteine (R = 0.39, p = 0.0051 and R = 0.47, p = 0.0007).

Static cold storage is generally used to preserve kidney allografts from deceased donors. Hypothermic machine perfusion may improve outcomes after transplantation, but few sufficiently powered prospective studies have addressed this possibility.

Background. The term delayed graft function (DGF) is commonly used to describe the need for dialysis after receiving a kidney transplant. DGF increases morbidity after transplantation, prolongs hospitalization and may lead to premature graft failure. Various definitions of DGF are used in the literature without a uniformly accepted technique to identify DGF. Methods. We performed a systematic review of the literature to identify all of the different definitions and diagnostic techniques to identify DGF. Results. We identified 18 unique definitions for DGF and 10 diagnostic techniques to identify DGF. Conclusions. The utilization of heterogeneous clinical criteria to define DGF has certain limitations. It will lead to delayed and sometimes inaccurate diagnosis of DGF. Hence a diagnostic test that identifies DGF reliably and early is necessary. Heterogeneity, in the definitions used for DGF, hinders the evolution of a diagnostic technique to identify DGF, which requires a gold standard definition. We are in need of a new definition that is uniformly accepted across the kidney transplant community. The new definition will be helpful in promoting better communication among transplant professionals and aids in comparing clinical studies of diagnostic techniques to identify DGF and thus may facilitate clinical trials of interventions for the treatment of DGF.

Background. There is mounting evidence from experimental and clinical studies that the quality of organs from cadaver donors may be influenced by events occurring around the time of brain death, and that these may affect transplant outcome. The aim of this study is to investigate the influence of donor factors on renal allograft outcome in a homogeneous cohort of 518 patients transplanted in a single centre over a 9 year period. Methods. Endpoints of the study were delayed graft function (DGF), acute rejection (AR), 1 year graft survival and long-term survival of those grafts that reached 1 year. Multivariate analysis was performed to determine factors that may have influenced the graft outcome indicators. Results: DGF was the major predictor of graft failure overall with cold ischaemia time (CIT) as an important independent factor. The level of histocompatibility did not influence graft survival. DGF was the major factor affecting 1 year graft survival (P<0.0005) with effects persisting beyond 1 year. DGF was significantly influenced by CIT, donor age, female kidney into male recipient and donor creatinine (P<0.05). Other donor factors and factors associated with donor management were not risk factors for DGF, rejection episodes or graft survival. The risk factors for a number of AR episodes were HLA-DR mismatch and DGF (P<0.005). When grafts surviving for 1 year were considered, only CIT, recipient age and creatinine at 1 year (P<0.05) were found to affect graft survival significantly.

The purpose of this study was to analyze the possible effects of machine perfusion (MP) versus cold storage (CS) on delayed graft function (DGF) and early graft survival in expanded criteria donor kidneys (ECD). As part of the previously reported international randomized controlled trial 91 consecutive heartbeating deceased ECDs -defined according to the United Network of Organ Sharing definition -were included in the study. From each donor one kidney was randomized to MP and the contralateral kidney to CS. All recipients were followed for 1 year. The primary endpoint was DGF. Secondary endpoints included primary nonfunction and graft survival. DGF occurred in 27 patients in the CS group (29.7%) and in 20 patients in the MP group (22%). Using the logistic regression model MP significantly reduced the risk of DGF compared with CS (OR 0.460, P = 0.047). The incidence of nonfunction in the CS group (12%) was four times higher than in the MP group (3%) (P = 0.04). One-year graft survival was significantly higher in machine perfused kidneys compared with cold stored kidneys (92.3% vs. 80.2%, P = 0.02). In the present study, MP preservation clearly reduced the risk of DGF and improved 1-year graft survival and function in ECD kidneys.

SiR-Wijnen and colleagues (April 29, p 1067) report the long-term outcome of renal transplantation from non-heartbeating (NHB) donors. Although the 57 kidneys were harvested by a single unit, transplantation and subsequent management was undertaken in 21 centres throughout Europe. Cold ischaemia times therefore varied between centres. The Guy's Hospital experience of NHB renal transplantation is different, in that organs have been harvested and transplanted at a single centre that has consistent protocols and a short cold ischaemia time. We report our experience of this technique. 44 NHB renal transplants were done between 1988 and 1993. Causes of organ donation were: primary intracerebral malignant disease (5), subarachnoid haemorrhage (5), stroke (8), trauma (14), and cerebral anoxia (12). Kidneys were allocated on the basis of ABO compatibility, clinical need, and waiting time, with little weight attached to HLA tissue matching. Mean donor and recipient ages were 47 years (range 14-80) and 43 years (22-72), respectively. Mean warm ischaemia time was 30 min (15-65), whereas cold ischaemia times were consistently less than 24 h. Details of organ harvesting were as previously reported.' Patient survival at 1, 3, and 5 years with NHB donors was 93%, 88%, and 88%, and graft survival was 64%, 49%, and 49%, respectively (figure). These results are similar to those obtained by Wijnen and co-workers, and to those from an equivalent analysis of heart-beating (HB) donors in the South Thames region.' The mean durations of delayed graft function and number of days in hospital were greater in the NHB than HB donors (21 vs 8 days and 29 vs 17 days, respectively; p<005), but this was not reflected in an increased frequency of primary non-function. Mean serum creatinine at mean 49 month follow-up (range 19-88) was 153 (SE 11'5) /lmol/L.

Aberrant promoter hypermethylation of several known or putative tumor suppressor genes occurs frequently during the pathogenesis of human cancers and is a promising marker for cancer detection. We investigated the feasibility of detecting aberrant DNA methylation in the urine and serum samples of renal cancer patients. We examined the tumor and the matched urine and serum DNA for aberrant methylation of nine gene promoters (CDH1, APC, MGMT, RASSF1A, GSTP1, p16, RAR-␤2, and ARF) from 17 patients with primary kidney cancer by quantitative fluorogenic real-time PCR. An additional 9 urine samples (total, 26) and 1 serum sample (total, 18) also were tested from renal cancer patients. Urine from 91 patients without genitourinary cancer and serum from 30 age-matched noncancer individuals were used as controls. Promoter hypermethylation of at least two of the genes studied was detected in 16 (94%) of 17 primary tumors. Aberrant methylation in urine and serum DNA generally was accompanied by methylation in the matched tumor samples. Urine samples from 91 control subjects without evidence of genitourinary cancer revealed no methylation of the MGMT, GSTP1, p16, and ARF genes, whereas methylation of RAR-␤2, RASSF1A, CDH1, APC, and TIMP3 was detected at low levels in a few control subjects. Overall, 23 (88%) of 26 urine samples and 12 (67%) of 18 serum samples from cancer patients were methylation positive for at least one of the genes tested. By combination of urine or serum analysis of renal cancer patients, hypermethylation was detected in 16 of 17 patients (94% sensitivity) with high specificity. Our findings suggest that promoter hypermethylation in urine or serum can be detected in the majority of renal cancer patients. This noninvasive high-throughput approach needs to be evaluated in large studies to assess its value in the early detection and surveillance of renal cancer.

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.

ABSTRACT. Delayed graft function (DGF) is the need for dialysis in the first week after transplantation. Studied were risk factors for DGF in adult (age ≥16 yr) cadaveric renal transplant recipients by means of a multivariable modeling procedure. Only donor and recipient factors known before transplantation were chosen so that the probabilities of DGF could be calculated before transplantation and appropriate preventative measures taken. Data on 19,706 recipients of cadaveric allografts were obtained from the United States Renal Data System registry (1995 to 1998). Graft losses within the first 24 h after surgery were excluded from the analysis (n = 89). Patients whose DGF information was missing or unknown (n = 2820) and patients missing one or more candidate predictors (n = 2951) were also excluded. By means of a multivariable logistic regression analysis, factors contributing to DGF in the remaining 13,846 patients were identified. After validating the logistic regression model, ...

Background. Severe ischemia/reperfusion (IR) injury is a risk factor for delayed graft function. Delayed graft function remains difficult to predict, and it currently relies primarily on serum creatinine (SCr), urine output, and occasionally on graft biopsy. 1 H-NMR (nuclear magnetic resonance spectroscopy) based metabolomics was used to establish IR-specific metabolic markers in both blood and kidney tissue. These markers were compared to SCr and graft histology.

Background. Everolimus is a proliferation-signal inhibitor which was introduced for heart transplant recipients in 2004. To date, there are only sparse data about long-term calcineurin inhibitor (CNI)-free immunosuppression using everolimus. Methods. After heart transplantation, patients receiving everolimus were consecutively enrolled. Reasons for switching to everolimus were side effects of CNI immunosuppression, such as deterioration of kidney function and recurrent rejection episodes. All 60 patients underwent standardized switching protocols, 42 patients completed 24-month follow-up. Blood was sampled for lipid status, renal function, routine controls, and levels of immunosuppressive agents. On days 0, 14, and 28, and then every 3 months, echocardiography and physical examination were performed. Results. After switching to everolimus, most patients recovered from the side effects. Renal function improved significantly after 24 months (creatinine, 2.1 Ϯ 0.6 vs 1.8 Ϯ 1 mg/dL; P Ͻ .001; creatinine clearance, 41.8 Ϯ 22 vs 48.6 Ϯ 21.8 mL/min; P Ͻ .001). Median blood pressure increased from 120.0/75.0 mm Hg at baseline to 123.8/80.0 mm Hg at month 24 (P values .008 and .003 for systolic and diastolic pressures, respectively). Tremor, peripheral edema, hirsutism, and gingival hyperplasia markedly improved. Levels of interleukin-6 were stable between baseline and 24-month levels. Temporary adverse events occurred in 8 patients [13.3%: interstitial pneumonia (n ϭ 2), skin disorders (n ϭ 2); reactivated hepatitis B (n ϭ 1), and fever of unknown origin (n ϭ 3)]. Conclusion. CNI-free immunosuppression using everolimus is safe, with excellent efficacy in maintenance of heart transplant recipients. Arterial hypertension and renal function significantly improved. CNI-induced side effects, such as tremor, peripheral edema, hirsutism, and gingival hyperplasia, markedly improved in most patients.

Chronic rejection accounts for most renal allograft losses after the first year posttransplantation. On March 24 and 25, 1997, a roundtable of five transplant surgeons, two nephrologists, and one pathologist assembled in Dallas, Texas, to review critical issues surrounding chronic renal allograft rejection. This article summarizes the presentations and relevant discussions of this meeting regarding the cause of chronic rejection, clinical diagnoses, risk factors, future prospects for intervention strategies, and general recommendations for the transplant community. Growing evidence indicates that chronic rejection is the aggregate sum of irreversible immunologic and nonimmunologic injuries to the renal graft over time. A history of acute rejection episodes and inadequate immunosuppression, likely attributable to inconsistent cyclosporine exposure or poor patient compliance, are among the most recognizable immunologic risk factors for chronic rejection. Donor organ quality, delayed graft function, and other donor and recipient variables leading to reduced nephron mass are nonimmunologic factors that contribute to the progressive deterioration of renal graft function. Clinical management of renal transplant recipients should incorporate both immunologic-and nonimmunologic-based intervention strategies aimed at minimizing risk factors to thwart the progression of chronic rejection and improve long-term allograft and patient survival. 1999 by the National Kidney Foundation, Inc.

Transplant renal artery stenosis (TRAS) is a common complication of kidney transplantation but attempts to identify predisposing risk factors for TRAS have yielded conflicting results. In order to determine the predisposing factors for transplant (TRAS), we retrospectively reviewed the records of 29 renal allograft recipients with TRAS treated with percutaneous transluminal angioplasty (PTA). The TRAS group was compared with a case-control group of 58 patients. Predisposing factors for TRAS included CMV infection (41.4% vs. 12.1% p = 0.0018) and initial delayed graft function (DGF) (48.3% vs. 15.5% p = 0.0018), respectively in the TRAS and the control group. Acute rejection occurred more frequently in patients from the TRAS group (48.3%) compared with the control group (27.6%), although the difference was not significant (p = 0.06). In a multivariate analysis, only CMV infection (p = 0.005) and DGF (p = 0.009) appear to be significantly and independently associated with TRAS. The long-term graft survival was significantly higher in the control group, compared with the TRAS group (p = 0.03). Our study suggests that CMV infection and DGF are two reliable risk factors for TRAS. Despite treatment by PTA with primary successful results, TRAS significantly affects long-term graft outcome. † These authors contributed equally to this study.

Our aim was to analyze the short- and long-term function of kidneys procured from non- heart-beating donors (NHBD) by means of three techniques: in situ perfusion (ISP), total body cooling (TBC) and normothermic recirculation (NR). Fifty-seven potential NHBD were included. Mean warm ischemia time was 68.9 ± 35.6 min. Forty-four kidneys were obtained from donors perfused with ISP, 8 with TBC, and 8 with NR. Eighteen kidneys (32 %) started functioning immediately, 29 (52 %) showed delayed graft function (DGF) and 9 (16 %) showed primary non function (PNF). The actuarial graft survival rate was 76.4 % at 1 year and 56 % at 5 years. The patient survival rate was 89.3 % at 5 years. Incidence of DGF and PNF was significantly lower in kidneys perfused with NR than those with ISP or TBC (P < 0.01). Duration of DGF was shorter in kidneys obtained through TBC than in kidneys obtained with ISP (P < 0.05). In conclusion, NR reduces the incidence of DGF and may be considered the method of choice for kidney procurement from NHBD.

Five preventable causes of kidney graft loss in the 1990s: A tic and intensive care, and treatment and prevention of single-center analysis. infectious diseases). Background. Despite improvements in immunosuppressive In spite of these advances, grafts continue to fail. In protocols and patient care, kidney allografts continue to fail. 1991, we reviewed the causes of graft loss at our insti-We studied causes of graft loss for primary kidney transplants tution in the 1980s versus the 1970s [1]. We noted that in the 1990s to determine major causes and potential interventions. graft loss to acute rejection and to infectious death had Methods. Causes of graft loss were reviewed for 1467 primarkedly decreased, but that chronic rejection and carmary kidney transplants done at our institution between Janudiovascular death had become the major causes of graft ary 1, 1990, and December 31, 1999. Graft loss for that entire loss. This observation led to clinical studies in which we population was studied and then the causes of loss selectively showed that an acute rejection episode is the major risk examined at Ͻ1 year, 1 to 5 years, and Ͼ5 years post-transplant. factor for biopsy-proven chronic rejection [2, 3], that the Finally, causes of loss in the 1990s versus the 1980s were compared. incidence of early post-transplant acute rejection could Results. Five major causes of graft loss were noted in the be reduced by maintaining higher immunosuppressive 1990s: thrombosis, acute rejection (either alone or combined drug levels [4, 5], and that a decreased incidence of with delayed graft function or infection), chronic rejection, acute rejection is associated with a decreased incidence death with function, and noncompliance. In the first year postof chronic rejection [6]. transplant, thrombosis (25%) and death with function (41%) During the last ten years, patient care and immunosupwere the major causes of graft loss. After the first year, chronic rejection and death with function predominated. For recipients pressive protocols have changed significantly. Numerous dying with graft function, cardiovascular disease was the major new immunosuppressive agents have been approved for cause of death. induction and maintenance therapy and for treatment Conclusions. This study identified the five major causes of of rejection. However, because of improved transplant kidney graft loss in the 1990s. Different interventions are reoutcome, acceptance criteria for transplant candidates quired to decrease loss from each of these causes. Future rehave been expanded. Older as well as higher-risk candisearch needs to be directed at such interventions.

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.

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.

Background. Several groups have demonstrated that non-heart beating donation is a viable source of organs for transplantation. However, the theoretically worse graft function and survival of the kidneys obtained from non-heart beating donors (NHBDs) is still a matter of debate that has led to consider them as marginal donors for kidney transplantation. Methods. In this report, we compare the outcome and course of 83 kidney transplants from NHBDs with those corresponding to 3177 adult cadaveric heart beating donor (HBD) transplants performed over the same period in our country. Graft and patient survival were estimated by means of Kaplan-Meier analysis. In addition, groups were compared using Cox proportional regression. Results. The delayed graft function (DGF) rate was higher on NHBD transplants than in HBD kidneys (58.8 vs 28.9%, P<0.0001). However, in 1998, where the highest number of NHBD transplants was performed, graft function estimated by serum creatinine levels at 3 months and 1 year, was significantly better in the NHBD transplant group (1.42±0.45 vs 1.66±0.66 and 1.45±0.59 vs 1.62±0.64, respectively, P ¼ 0.01 and 0.07). Graft survival at 2 years was 97%, 95% at 4 years and 84% at 6 years for NHBDs and 97, 90 and 84%, respectively, for HBDs. Interestingly, DGF was a risk factor for worse graft survival in HBDs but not on NHBDs. Conclusions. We conclude that, in our study, both graft function and graft survival of NHBD kidney transplants are at least similar to those from HBD transplants. Therefore, NHBDs should be considered as a viable source of non-marginal kidneys for transplant.

Initial graft function following liver transplantation is a major determinant of postoperative survival and morbidity. Primary graft nonfunction (PNF) is uncommon; however, it is one of the most serious and life-threatening conditions in the immediate postoperative period. The risk factors associated with PNF and short-term outcome have been previously reported, but there are no reports of long-term follow-up after retransplant for PNF. At our institution, 52 liver transplants had PNF (2.22%) among 2,341 orthotopic liver transplants in 2,130 patients from 1984 to 2003. PNF occurred more often in the retransplant setting. Female donors, donor age, donor days in the intensive care unit, cold ischemia time, and operating room time were significant factors for PNF. Patient as well as graft survival of retransplant for PNF was not different compared to retransplant for other causes. However, PNF for a second or third transplant did not demonstrate long-term survival, and hospital mortality was 57%.

The purpose of this investigation was to compare outcomes in the immediate posttransplant period for hemodialysis (HD) and peritoneal (PD) dialysis patients who received cadaveric renal transplantation. Data were obtained from the United Network of Organ Sharing on all cadaveric graft recipients who were dialysis-dependent at the time of transplantation between April 1994 and December 1995. Baseline characteristics were compared between groups, and multivariate logistic regression was performed with outcome measures including urine production in the first 24 h posttransplantation (U24), requirement for dialysis in the first week posttransplant (FWDIAL), and treatment for acute rejection during the initial hospitalization. The odds of oliguria (not producing urine in the first 24 h) were 1.49 (1.28 to 1.74) times higher in HD versus PD patients. After adjustment for other comorbid conditions including age, gender, race, HLA mismatch, time on dialysis, panel-reactive antibodies, and c...

We studied the effect of initial graft function and acute rejection on graft survival in 1047 cadaveric renal transplantations during 1991-1997 with a constant policy of donor selection, graft allocation, and immunosuppression. The overall 1-and 5-year patient survival rates were 96 % and 88 % , and the 1-and 5-year graft survival (GS)

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.

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.

Donor age was identified recently as a major factor that determines long-term outcome after transplantation, but the mechanism that is responsible for increased graft loss of old donor kidneys is unknown. The influence of donor age on graft survival was assessed retrospectively in 514 consecutive first cadaveric transplants that were treated with cyclosporine maintenance immunosuppression. Donor age &gt; or =50 yr (relative risk [RR] = 1.7; 95% confidence interval [CI], 1.2 to 2.6), acute rejection (RR = 2.0; 95% CI, 1.3 to 3.0), and type of rejection (RR = 3.3; 95% CI, 2.0 to 5.3) had a significant impact on graft survival. However, when subsets of patients who entered subsequent intervals after transplantation were analyzed, donor age was not an independent predictive factor of graft loss. Donor age (RR = 1.53; 95% CI, 1.19 to 1.98), human leukocyte antigen-DR mismatch (RR = 2.28; 95% CI, 1.78 to 2.92), and recipient age (RR = 1.34; 95% CI, 1.05 to 1.72) were associated significan...

To counter the shortage of kidney grafts in France, a non heart beating donor (NHBD) program has recently been implemented. The aim of this study was to describe this pilot program for kidney retrieval from "uncontrolled" NHBD meaning those for whom attempts of resuscitation after a witnessed outof-hospital cardiac arrest (CA) have failed (Maastricht 1 and 2), in a centre previously trained for retrieval from brain dead donors.

Background. The prevalence of obesity is increasing globally and is associated with chronic kidney disease and premature mortality. However, the impact of recipient obesity on kidney transplant outcomes remains unclear. This study aimed to investigate the association between recipient obesity and mortality, death-censored graft loss and delayed graft function (DGF) following kidney transplantation. Methods. A systematic review and meta-analysis was conducted using Medline, Embase and the Cochrane Library. Observational studies or randomized controlled trials investigating the association between recipient obesity at transplantation and mortality, death-censored graft loss and DGF were included. Obesity was defined as a body mass index (BMI) of ≥30 kg/m 2 . Obese recipients were compared with those with a normal BMI (18.5-24.9 kg/m 2 ). Pooled estimates of hazard ratios (HRs) for patient mortality or death-censored graft loss and odds ratios (ORs) for DGF were calculated. Results. Seventeen studies including 138 081 patients were analysed. After adjustment, there was no significant difference in mortality risk in obese recipients [HR = 1.24, 95% confidence interval (CI) = 0.90-1.70, studies = 5, n = 83 416]. However, obesity was associated with an increased risk of death-censored graft loss (HR = 1.06, 95% CI = 1.01-1.12, studies = 5, n = 83

Little is known regarding the molecular phenotype of kidneys with AKI because biopsies are performed infrequently. However, all kidney transplants experience acute injury, making early kidney transplants an excellent model of acute injury, provided the absence of rejection, because donor kidneys should not have CKD, post-transplant biopsies occur relatively frequently, and follow-up is excellent typically. Here, we used histopathology and microarrays to compare indication biopsies from 26 transplants with acute injury with 11 pristine protocol biopsies of stable transplants. Kidneys with acute injury showed increased expression of 394 transcripts associated with the repair response to injury, including many epithelium-like injury molecules tissue, remodeling molecules, and inflammation molecules. Many other genes also predicted the phenotype, including the acute injury biomarkers HAVCR1 and IL18. Pathway analysis of the injury-repair transcripts revealed similarities to cancer, development, and cell movement. The injury-repair transcript score in kidneys with acute injury correlated with reduced graft function, future renal recovery, brain death, and need for dialysis, but not with future graft loss. In contrast, histologic features of acute tubular injury did not correlate with function or with the molecular changes. Thus, the transcripts associated with repair of injury suggest a massive coordinated response of the kidney parenchyma to acute injury, providing both an objective measure for assessing the severity of injury in kidney biopsies and validation for many biomarkers of AKI.

Background. Ischemia-reperfusion injury after organ transplantation is a major cause of delayed graft function. We showed earlier that antisense oligodesoxynucleotides (ODN) for intercellular adhesion molecule-1 (ICAM-1) ameliorate reperfusion injury after acute ischemia. This study tested the hypothesis that antisense ODN for ICAM-1 prevents ischemia-reperfusion injury and facilitates immediate graft function in a rat autotransplantation model.

Small molecule selectin ligand inhibition improves outcome in genesis of renal ischemia-reperfusion injury (IRI) have ischemic acute renal failure. most commonly utilized the model of renal artery clamp-Background. The pathophysiologic and potential therapeuing. Post-ischemic renal injury in this model has been tic role of selectins in renal ischemia-reperfusion injury (IRI) shown to be very similar to human ischemic renal injury, is not fully understood, due in part to redundancy in the roles including that secondary to cold kidney storage prior to of individual selectins. We hypothesized that blockade of ligands for all three selectins using a novel small molecule (TBC-1269) transplantation [5, 6]. However, a recent review also has would improve the course of renal IRI by overcoming redunemphasized differences between experimental animal dancy issues. This was investigated in a rat model of renal IRI. and human acute renal failure [7]. Methods. Rats were treated with TBC-1269 either during Several studies have shown that ischemia-reperfusion or post-IRI. The effects of TBC-1269 were investigated in two can stimulate renal expression of leukocyte adhesion models of renal IRI: moderate IRI (30 minutes bilateral renal artery clamping) and severe IRI (45 minutes clamping). The molecules [8, 9]. Previous studies have demonstrated combination of anti-E-and anti-P-selectin antibodies also was that antibody blockade of the CD11/CD18 receptor on investigated in rats subjected to moderate IRI. Renal function, leukocytes significantly attenuated renal IRI in rats histological injury and mortality were assessed.

Background. The effect of hydroxyethyl starch (HES) on early allograft function was examined retrospect-Osmotic nephrosis-like histological lesions have been ively in a cohort of 119 renal transplantations realized noticed in kidney transplant recipients when hydroxyby local organ exchange between four cooperating ethyl starch (HES ) was used for fluid resuscitation of centres.

Previous studies aimed at identifying the causes, risk factors, and outcome of kidney transplant recipients with delayed graft function (DGF) have yielded controversial results. We retrospectively analyzed the causes and risk factors for DGF in 263 cadaveric kidney transplantations from November 1988 to March 1997 in one center. Causes of DGF were assessed by postoperative graft evolution and graft biopsy.

Improved assessment of donor organ quality at time of transplantation would help in management of potentially usable organs. The transcriptome might correlate with risk of delayed graft function (DGF) better than conventional risk factors. Microarray results of 87 consecutive implantation biopsies taken postreperfusion in 42 deceased (DD) and 45 living (LD) donor kidneys were compared to clinical and histopathologybased scores. Unsupervised analysis separated the 87 kidneys into three groups: LD, DD1 and DD2. Kidneys in DD2 had a greater incidence of DGF (38.1 vs. 9.5%, p < 0.05) than those in DD1. Clinical and histopathological risk scores did not discriminate DD1 from DD2. A total of 1051 transcripts were differentially expressed between DD1 and DD2, but no transcripts separated DGF from immediate graft function (adjusted p < 0.01). Principal components analysis revealed a continuum from LD to DD1 to DD2, i.e. from best to poorest functioning kidneys. Within DD kidneys, the odds ratio for DGF was significantly increased with a transcriptomebased score and recipient age (p < 0.03) but not with clinical or histopathologic scores. The transcriptome reflects kidney quality and susceptibility to DGF better than available clinical and histopathological scoring systems.

Hypertension (HTN) and diabetes mellitus (DM) predispose to systemic atherosclerosis with renal involvement. The prevalence of HTN and DM in cadaveric renal donors (affected donors) and the results of transplantation are unknown. We investigated these issues with national data from the US Renal Data System. A total of 4,035 transplants from affected donors were matched 1:1 with unaffected controls according to donor age and race, recipient race, and year of transplantation. Graft and patient survival were estimated. Among the 25,039 solitary renal transplantations performed between July 1, 1994, and June 30, 1997, cadaveric renal transplants from donors with HTN accounted for 15%, and donors with DM, 2%. Programs with 1-year cadaveric renal graft survival rates greater than 90% had 50% less affected donors compared with programs having 1-year cadaveric renal graft survival rates of 85% or less. Compared with donor-age-matched controls, transplants from affected donors were at minimally increased risk for primary nonfunction, delayed graft function, and acute rejection. Three-year graft survival rates were 71% in affected donor organs and 75% in controls (P = 0.001). Compared with controls, duration of HTN was an independent risk factor for graft survival (3-year graft survival rates, 75% versus 65%; relative risk = 1.36 for HTN >10 years; P < 0.001). A substantial fraction of cadaveric renal donors have preexisting HTN. Programs transplanting fewer affected donor kidneys had better than average results. Because the negative impact of donor HTN and DM on transplant outcome was of moderate degree except when the duration of donor HTN was greater than 10 years, use of affected donors should not be discouraged, but graft and patient survival analyses should account for their presence.

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.

The pathogenesis of primary graft dysfunction (PGD), a serious complication of lung transplantation, is poorly understood. Human studies and rodent models have shown that collagen type V (col[V]), stimulates IL-17-dependent cellular immunity after lung transplantation. Objectives: To determine whether patients with end-stage lung disease develop pretransplant col(V)-specific cellular immunity, and if so, the impact of this response on PGD. Methods: Trans-vivo delayed-type hypersensitivity (TV-DTH) assays were used to evaluate memory T-cell responses to col(V) in 55 patients awaiting lung transplantation. Pa O 2 /FI O 2 index data were used to assess PGD. Univariate risk factor analysis was performed to identify variables associated with PGD. Rats immunized with col(V) or irrelevant antigen underwent lung isografting to determine if prior anti-col(V) immunity triggers PGD in the absence of alloreactivity. Measurements and Main Results: We found that 58.8% (10/17) of patients with idiopathic pulmonary fibrosis, and 15.8% (6/38) of patients without idiopathic pulmonary fibrosis tested while on the wait list for a lung transplant were col(V) DTH positive. Col(V) reactivity was CD4 + T-cell and monocyte mediated, and dependent on IL-17, IL-1b, and tumor necrosis factor (TNF)-a. Pa O 2 /FI O 2 indices were impaired significantly 6-72 hours after transplantation in col(V)-reactive versus nonreactive patients. Univariate risk factor analysis identified only preoperative TV-DTH to col(V) and ischemic time as predictors of PGD. Finally, in a rat lung isograft model, col(V) sensitization resulted in significantly lower Pa O 2 /FI O 2 , increased local TNF-a and IL-1b production, and a moderate-to-severe bronchiolitis/ vasculitis when compared with control isografts. Conclusions: The data suggest that activation of innate immunity by col(V)-specific Th-17 memory cells represents a novel pathway to PGD after lung transplantation.

Utilization and long-term outcomes of kidneys from donors with elevated terminal serum creatinine (sCr) levels have not been reported. Using data from the Scientific Registry of Transplant Recipients from 1995 to 2007, recipient outcomes of kidneys from adult donors were evaluated stratified by standard criteria (SCD; n = 82 262) and expanded criteria (ECD; n = 16 978) donor type and by sCr ≤1.5, 1.6–2.0 and >2.0 mg/dL. Discard rates for SCDs were ascertained. The relative risk of graft loss was similar for recipients of SCD kidneys with sCr of 1.6–2.0 and >2.0 mg/dL, compared to ≤1.5 mg/dL. For ECD recipients, the relative risk of graft failure significantly increased with increasing sCr. Of potential SCDs, the adjusted risk of discard was higher with sCr >2.0 mg/dL (adjusted odds ratio [AOR] 7.04, 95% confidence interval [CI] 6.5–7.6) and 1.6–2.0 mg/dL (AOR 2.7; CI 2.5–2.9) relative to sCr ≤1.5 mg/dL. Among potential SCDs, elevated terminal creatinine is a strong independent risk factor for kidney discard; yet, when kidney transplantation is performed elevated donor terminal creatinine is not a risk factor for graft loss. Further research is needed to identify safe practices for the optimal utilization of SCD kidneys from donors with acute kidney injury.

Initial graft function is a major factor influencing the clinical outcome after liver transplantation (LTX), but a reliable method for assessing and predicting graft dysfunction directly after LTX is not available. Ninety-nine patients undergoing deceaseddonor LTX were studied in a prospective pilot study to evaluate the LiMAx test, the indocyanine green test, and conventional biochemical parameters with respect to their sensitivity and prognostic power for the diagnosis of initial graft dysfunction. Patients suffering from initial graft dysfunction (defined as technical complications or primary nonfunction (n ¼ 8)) had significantly decreased LiMAx readouts (43 6 18 versus 184 6 98 lg/kg/hour, P < 0.001) immediately after LTX. Univariate analysis also showed significant differences for serum bilirubin, ammonia, glutamate dehydrogenase, and the international normalized ratio (P < 0.05), but multivariate analysis revealed LiMAx as the single independent predictor of initial dysfunction (P ¼ 0.008) with an area under the receiver operating characteristic curve (AUROC) of 0.960 (95% confidence interval ¼ 0.921-0.998, P < 0.001). In addition, the diagnosis of primary nonfunction (n ¼ 3) was evaluated with LiMAx and aspartate aminotransferase (AST) activity on the first postoperative day. The calculated AUROC values were 0.992 (0.975-1.0, P ¼ 0.004) for LiMAx and 0.967 (0.929-1.0, P ¼ 0.006) for AST. By a combination of test results obtained directly after LTX and on the first day, LiMAx indicated primary nonfunction with a sensitivity of 1.0 (0.31-1.0) and a positive predictive value of 1.0 (0.31-1.0), whereas AST classification showed a sensitivity of 0.67 (0.13-0.98) and a positive predictive value of 0.29 (0.05-0.70). In conclusion, the assessment of initial graft function using the LiMAx test might be effective for identifying critical complications that could threaten graft survival within 24 hours after LTX. Liver Transpl 16:172-180,

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.