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Delayed graft function is a potentially challenging problem especially in cadaveric kidney transplant recipients. It adversely impacts long-term graft survival. It is rarely seen in living kidney transplants. Recovery of graft function usually occurs within a month. The chances of recovery of graft function diminish with further prolongation of delayed function. In fact, recovery of graft function after 3 months has rarely been described, we report herein recovery of graft function after 132 days of nonfunction in a living related kidney transplant.

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.

Background: In this study we sought to compare the long-term effects of anti-thymocyte globulin (ATG) and muromonab-CD3 (OKT3) as induction therapy after heart transplantation, with special regard to cardiac allograft vasculopathy (CAV), post-transplant infections, post-transplant non-skin cancers and patient survival., Methods: From 1988 to 1991, 25 heart transplant patients received OKT3 as induction treatment. Accordingly, 25 consecutive patients who received ATG and 25 consecutive patients without induction therapy were enrolled., Results: At a follow-up period of 13.4 +/- 4.6 years, time to onset of non-significant and significant CAV was 8.77 +/- 3.38 and 11.60 +/- 4.28 years, respectively, in the ATG group, which was significantly delayed compared with 5.71 +/- 3.08 and 7.44 +/- 2.74 years, respectively, in the non-induction group. In the OKT3 group, time to onset of non-significant and significant CAV (6.10 +/- 2.73 and 7.86 +/- 3.19 years, respectively) did not differ significantly from the non-induction group. Ten- and 15-year actuarial survival rates of ATG- and OKT3-treated patients were not significantly different from those of patients without induction treatment., Conclusions: Our study suggests the long-term advantage of ATG in prevention of cardiac allograft vasculopathy. In contrast, OKT3 failed to show such benefit. However, induction therapy with either ATG or OKT3 did not exhibit a significant beneficial effect on long-term patient survival.

Objective: To investigate the etiology and therapy of delayed graft function (DGF) recovery in renal transplant recipients., Methods: The clinical data were retrospectively analyzed in 15 renal recipients with DGF. All the 15 patients received hemodialysis along with pulse treatment against acute rejection (AR), or immunosuppressant adjustment, or in situ retransplantation after the resection of the original transplanted kidney according to different etiological factors., Results: Among the 15 patients, 8 developed AR, 5 showed acute renal tubular necrosis (ATN), 1 had grafting-associated renal vein embolism and 1 had acute cyclosporine nephrotoxication. The renal function recovered within 10 to 35 days after transplantation without complication during the follow-up period (0.5-3.0 years)., Conclusion: DGF is a common complication after kidney transplantation mainly due to the occurrence of AR and ATN. Good prognosis is expected if etiology-oriented therapy is performed properly and promptly.

Background: Older and marginal donors, increasingly used to overcome organ shortness, often have a cerebrovascular accident as cause of death and could have vascular lesions in their kidneys., Methods: In this literature study, we evaluated the predictive value of vasculopathy in the renal allograft at the time of transplantation, on the subsequent graft function., Results: Short-term graft survival rates do not seem to be diminished by suboptimal donor histology. When vasculopathy is clearly present at the time of transplantation, impaired kidney function is showed at 1-week posttransplantation, at hospital discharge, or at 3 months and an increased frequency of delayed graft function. The long-term graft survival rate, in the studies of Pokorna and Taub, was significantly lower in the group with arteriolosclerosis. Wang et al. concluded in their study that arterial fibrous intimal thickening is the single most important histological predictor of both graft loss and delayed graft function. However, Minakawa et al. observed no significant correlation between 1 or 2-year graft survival and vasculopathy score. Severe vascular lesions in the donor kidney do affect the level of kidney function in the later posttransplant period as described in different studies (follow-up till 7 years posttransplantation)., Conclusions: Data obtained from the studies of donor biopsies sustain the notion that vasculopathy is a major determinant of the short-term and the long-term outcome of the kidney allograft.

Background: The aim of our study was to examine, in a recent cohort of kidney transplant recipients who have received modern immunosuppressive therapy, the respective role of cold ischemia time (CIT) and delayed graft function (DGF) on acute rejection (AR) rates and long-term graft survival., Methods: We retrospectively reviewed the charts of 611 renal transplantations between 1996 and 2005. Most patients received a calcineurin inhibitor as maintenance therapy, either cyclosporine (43%) or tacrolimus (52%) and 76% of the patients received an antilymphocyte induction therapy. Study endpoints were DGF, first-year AR, and long-term graft survival. Uni- and multivariate analyses were performed to determine factors that may have influenced the study outcomes., Results: DGF was observed in 16.2% of patients. Both older donor age and longer CIT were significant risk factors for DGF. DGF rates were similar whether patients received a calcineurin inhibitor before transplantation or not. AR occurred in 16.5% of grafts during the first year. Independent predictors of AR by multivariate analysis were duration of dialysis, CIT, current panel-reactive lymphocytotoxic antibody more than 5%, and the number of human leukocyte antigen-A, B, and DR mismatches. Each hour of cold ischemia increases the risk of rejection by 4%. With respect to death-censored graft survival, three pretransplant parameters emerged as independent predictors of graft loss: younger recipient age, peak panel-reactive lymphocytotoxic antibody more than 5% and longer CIT. The detrimental effect of CIT on graft survival was entirely because of its propensity to trigger AR. When AR was added to the multivariate Cox model, CIT was no longer significant whereas first-year AR became the most important predictor of graft loss (Hazards ratio, 4.6)., Conclusion: Shortening CIT will help to decrease not only DGF rates but also AR incidence and hence graft loss. Patients with prolonged CIT should receive adequate immunosuppression, possibly with antilymphocyte preparations, to prevent AR occurrence.

Dialyzed delayed graft function (DGF) and nondialyzed slow graft function (SGF) both determine a large portion of the negative impact on patient and graft survival, on early acute rejection incidence, on tubulointerstitial fibrosis/tubular atrophy, and on graft function. In an era where expanded-criteria donors, including older donors, and non-heart beating donors are used to overcome organ shortage, the long-term results of kidney transplantation are influenced by the events occurring within the first 24 hr before and after the transplantation procedure. The ischemia-reperfusion injury is initiated in the brain-death donor and continues during preservation and engraftment of the transplant. The determinants of this DGF/SGF complex intervene in five chronologically related stages--donor tissue quality, brain death and related stress, preservation variables, immune factors, and recipient variables. For each of these five stages, therapeutic interventions or preventive measures are capable of partially reversing the expected dismal outcome of DGF/SGF; these measures are discussed in this article. Donor selection and pharmacologic modulations do have an effect on DGF/SGF.

Background: Since 1996, the allocation of grafts in France has been based on a hierarchical three-level system: national, regional and local. The objective of this study was to determine whether the shipment of cadaveric kidneys according to these new exchange rules affects allograft outcome in the Eastern region of France., Methods: This retrospective study analysed all renal transplants performed in the four centres of the French Eastern region during 3 years (1996 to 1998). All patients were followed up until death, return to dialysis, last information date or the end of June 2003. Information regarding the donors, recipients and treatments, as well as patient and graft outcome, was recorded. Factors associated with graft loss were analysed using Cox proportional hazard methods., Results: 542 transplants were analysed, 287 (53%) kidneys were transplanted locally, 229 (42.2%) kidneys coming from exchanges within the region and 26 (4.8%) from another region. There were statistically significant differences between the four centres for donors' and recipient' characteristics and for immunosuppressive treatment, but there was no difference between centres regarding patient survival (94.4% at 5 years), graft survival (83.7% at 5 years) or death-censored graft survival (87.8% at 5 years). Compared to locally transplanted grafts, shipped grafts had significantly better human leukocyte antigen (HLA) matching (2.5 +/- 1.3 versus 2.1 +/- 1.0 matches, P = 0.0005 but a longer cold ischaemia time (23.2 +/- 7.9 versus 19.2 +/- 7.8 h, P < 0.0001). Three independent factors were associated with a reduced graft survival: at least one acute rejection, delayed graft function and a shipped graft., Conclusion: The results of this study suggest that the shipment of cadaveric renal allografts in a regional distribution system is associated with better HLA matching but is a significant predictor of graft loss at 5 years. It would be advisable to restrict graft sharing to patients whose access to transplantation is limited, taking special care to avoid any additional factors having a detrimental effect on the outcome.

To determine whether microcirculatory changes following ischemia/reperfusion (I/R) may serve as predictors for subsequent graft dysfunction, we used noninvasive orthogonal polarization spectral (OPS) imaging to directly visualize and quantify cortical kidney microcirculation. In a total of 13 combined kidney/pancreas recipients, following reperfusion (5/30 min) microcirculatory parameters such as capillary diameter, functional capillary density (FCD) and red-blood-cell velocity (V(RBC)) of the renal graft were analyzed. From these parameters, a heterogeneity index (HI) and volumetric capillary blood flow (vCBF) were calculated. In addition, the extent of graft injury was determined by daily analysis of serum creatinine, blood urea nitrogen, C-reactive protein and systemic leukocyte count for 7 days post-transplant. At early reperfusion, a heterogeneous perfusion pattern with oscillating flow and scattered microvascular thrombosis of peritubular capillaries, resembling a 'no reflow', was observed. FCD was constant throughout the entire reperfusion period, whereas HI, capillary diameters, V(RBC) and vCBF increased. The latter showed a significant positive correlation with creatinine changes between days 1 and 3. So far our finding of a positive correlation of early microvascular changes (vCBF) and clinical parameters (creatinine) indicate a possible therapeutic implication of OPS imaging to predict early I/R-induced renal graft dysfunction., ((c) 2008 S. Karger AG, Basel.)

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 histopathology-based 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 transcriptome-based 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.

Aim: Many noninvasive techniques have been proposed for the early detection of chronic heart graft dysfunction. Diastolic dysfunction may precede systolic dysfunction, and often is prominent; therefore, the aim of the study was to investigate the clinical and prognostic value of a Doppler-derived index of both systolic and diastolic function in heart transplanted patients (Myocardial Performance Index, MPI)., Methods: The MPI was measured in 63 consecutive patients (mean age 55 years, 49 men and 14 women) in sinus rhythm with an orthotopic heart transplantation for at least 1 year (mean 5.3 years) and in 63 age and sex-matched controls. A complete clinical examination was performed at the time of enrollment and was repeated after 3 months., Results: At 3 months, 11 patients (17.5%) presented events (heart failure, hospitalisation or cardiac death). Patients were divided into 2 groups: Group A (52 patients) without events in the follow-up and Group B (11 patients) with events. The values of MPI in Group B (0.55+/-0.19) were significantly higher than values in Group A (0.34+/-0.18, P=0.001). Whereas the values of the index did not differ significantly between Group A and control group (0.34+/-0.18 vs 0.33+/-0.10, P=NS). In the univariate analysis, the population of heart transplanted patients was dichotomised in subgroups by a cut-off MPI of 0.47 and a cut-off ejection fraction (EF) of 50%. Nine patients (41%) with MPI=or>0.47 presented events, while only 2 patients (5%) with MPI<0.47 had any event (P<0.001; c2 12.9). Six patients (85%) with EF<50% had events, while only 5 patients (9%) with EF=or>50% had an event (P<0.001; c2 14). In the multivariate analysis only MPI (chi squared=22.6, P=0.018) and EF (chi squared=20.8, P=0.025) were significant independent predictors of heart failure or cardiac death. By looking at Kaplan-Meyer curves, MPI seems to be better than EF in the earlier detection of graft dysfunction., Conclusion: MPI, as a combined systolic and diastolic index, may detect graft dysfunction earlier than EF.

The survival and function of a kidney transplant are influenced by numerous immunological and nonimmunological factors. The aim of this study was to evaluate the role of a number of cadaveric donor parameters on transplanted kidney function, and in particular on the occurrence of delayed graft function (DGF) since DGF is one of the most important factors in long-term organ survival. This study looked at 143 patients who underwent kidney transplant of whom 32 displayed DGF. The creatinine levels in organ recipients, which were evaluated during a follow-up that ranged between 6 months and 4 years, were significantly higher among recipients who developed DGF after transplant (1.8 +/- 0.7 vs 1.4 +/- 0.4; P = .02). The following donor parameters were taken into consideration: history of diabetes and hypertension; creatinine levels; inotropie therapy; problems relating to hemodynamics (hypotension and/or cardiac arrest); and cold ischemia time. We observed that a donor history of hypertension (46.8% DGF vs 23.27% no DGF; P = .01) and high levels of donor creatinine prior to organ removal (1.9 +/- 1.2 mg/dL DGF vs 1.2 +/- 0.9 mg/dL no DGF; P = .007) were significant risk factors for DGF among kidney recipients. No significant differences were found for others factors between recipients with versus without DGF.

Background: In 2003, Irish and colleagues published a weighted nomogram designed to predict the risk of delayed graft function (DGF) in a given transplant. It was anticipated that the predictive nomogram would permit preemptive therapies or allocation decisions based on the risk of DGF. The potential for reducing unfavorable outcomes and expenses appeared significant. This nomogram, however, was developed using population data found in the United States Renal Data System and has not been prospectively validated., Methods: We evaluated the accuracy and utility of this nomogram in all cadaver renal transplants performed at a single transplant center. In addition, we correlated DGF with a variety of independent donor and recipient variables outside the established nomogram., Results: The average nomogram DGF risk was 0.41 (a 41% chance of DGF) among the 169 cases in our population. The mean was 0.45+/-0.14 (confidence interval: 0.40-0.49) for the 42 DGF-positive subjects, and 0.40+/-0.14 (confidence interval: 0.38-0.43) for the 127 DGF-negatives (t=1.80; P=0.07)., Conclusions: Although there was a trend showing the predictive value of the nomogram the overlap was tremendous, limiting the accuracy of the calculation for any single recipient. Prospective application of a nomogram on a case-by-case basis did not contribute meaningful information that could guide clinical decision-making regarding use, allocation or immunosuppressive regimen aimed at minimizing DGF.

Background: The clinical impact of chronic transplant glomerulopathy (CTG) on the outcome of kidney allograft receiving calcineurin inhibitors (CNIs) remains uncertain. A retrospective study of renal transplant recipients at Ospedale Maggiore of Milan was undertaken to evaluate the clinical outcome of patients with CTG., Methods: Among 666 biopsies taken at least 6 months after transplantation (Tx) in 498 transplant patients treated with CNIs, 28 cases (5.6%) of chronic transplant glomerulopathy (CTG) were identified and their clinical features at Tx, at follow-up and graft survival were compared with those of 56 controls transplanted in the same period and with kidney functioning 12 months after Tx. Clinical characteristics at biopsy and at 1 year after Tx were similar in the two groups., Results: After diagnosis graft function deteriorated in 22 patients (78.5%), while it remained stable in 6. Graft loss developed in 92 % of patients with proteinuria >2.5 g/day and in 33 % of those with lower proteinuria (P<0.005). In cases with more severe CTG the rate of graft loss was higher, though not significantly. Graft survival at 10 years was 48% in patients with CTG and 88% in controls (P<0.0001)., Conclusions: The incidence and clinical course of CTG do not seem to be modified by CNI-based immunosuppression. The evolution is unpredictable but the severity of glomerulopathy and proteinuria at follow-up are associated with progression to graft failure. Patients with CTG have a graft survival significantly worse than that of the general population of transplanted patients.

Objective: Early graft failure (EGF) is a life-threatening event still accounting for a significant percentage of early deaths after heart transplantation. We tested whether selected metabolic markers, including high-energy phosphate concentrations measured ex vivo in pre-transplant heart grafts by (31)P magnetic resonance spectroscopy (MRS) are related with early post-transplant outcome., Methods: During a 3-year period, 26 heart grafts harvested in the vicinity of the transplantation centre were studied. Evaluation of transplantability was done conventionally. (31)P MRS was performed ex vivo approximately 60min after aortic cross-clamp to quantify ATP, P(i) and PCr concentration ratios. A MRS-score was defined as a combination of intracellular pH (pHi) and the PCr/P(i) ratio. EGF was defined as the need to abnormally extend circulatory support or to use more than two inotropes before weaning the patient from CPB after transplantation. The grafts were attributed to three groups as follows: A1, transplanted with uneventful outcome (n=14); A2, transplanted with subsequent EGF (n=3) and B, not suitable for transplantation (n=9)., Results: Significant differences between groups existed for the following metabolic markers: PCr/ATP (P=0.013), PCr/P(i) (P=0.0004), pHi (P=0.0016) and MRS-score (P=0.0001). The sensitivity, specificity and positive likelihood ratio for EGF with a MRS-score