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Renal transplants with delayed graft function show decreased renal function despite monitoring with postabsorptive levels.

Cyclosporine (CyA) monitoring with postabsorptive levels can predict the risk of an acute rejection episode (ARE). Large doses of CyA are needed to obtain adequate drug exposure. The impact of this strategy on renal function, especially in patients with delayed graft function (DGF), is unknown. We report our experience comparing C3 (3-hour postdose) monitoring with a historical series of cadaveric renal transplants. Sixty-three consecutive patients who received cadaveric renal transplants were followed for 1 year. Group A (historical n = 31) patients received 6 mg/kg/d CyA with the dose adjusted according to the trough level (target, 250-350 ng/mL), group B (study n = 32) received 10 mg/kg/d CyA with dose adjustments based upon C3 (target, 1100-1500 ng/mL). All patients received cyclosporine prednisone and a third agents. The general characteristics of the donors and recipients were comparable. The incidence of biopsy-proven ARE at 1 year in group A was 42% and 19% in group B (P <.05). Patients achieving C3 levels >1000 ng/mL at 1 week displayed significantly lower ARE rates (8% vs 50%; P <.05). The rate of DGF was similar in both groups, but the duration was longer in group B (15 vs 21 days, P <.05). The serum creatinine (SCr) level was significantly higher in group B at 3 months (1.47 mg/dL group A vs 1.76 mg/dL group B; P <.05). Patients in group B with DGF showed significantly higher SCr values at 1 year (1.18mg% vs 2.03 mg%; P <.05). C3 level monitoring of CyA yields excellent results in terms of decreased ARE, but an increased SCR was observed among patients with DGF.

Creatinine↗

Comparison of outcomes after delayed graft function: sirolimus-based versus other calcineurin-inhibitor sparing induction immunosuppression regimens.

BACKGROUND: Sirolimus (SRL) may increase the incidence of or prolong delayed graft function (DGF) after cadaveric renal transplantation. This study compares transplant outcomes of SRL-based induction immunosuppression (IS) with other calcineurin-inhibitor (CNI) sparing regimens in the DGF setting. METHODS: Adult cadaveric renal-transplant recipients who received transplants between January 1, 1997 and June 30, 2001 and experienced DGF (n=132) were divided into three groups by induction IS: A, depleting antibody (n=41); B, SRL (n=49); and C, neither (n=42). All recipients also received steroids and mycophenolate mofetil with delayed initiation of CNIs when good renal function returned. Patient survival, graft survival, and time to rejection within 1 year of transplantation were assessed by Kaplan-Meier analysis. One-year graft function was compared using Kruskal-Wallis and Fisher's exact tests. RESULTS: The SRL group had longer DGF duration (P=0.01). The three groups had comparable patient (P=0.27) and graft survival (P=0.69), but the depleting antibody group experienced less rejection (P=0.004). There were no clinically significant differences in 1-year graft function. CONCLUSIONS: In our analysis of a large and modern cohort of adult cadaveric transplant recipients with DGF, induction immunosuppression with a depleting antibody preparation reduced rejection, whereas SRL prolonged DGF duration. All three CNI-sparing induction IS regimens resulted in comparable patient survival, graft survival, and graft function.

Adult↗

Donor age and delayed graft function as predictors of renal allograft survival in rejection-free patients.

BACKGROUND: Transplant recipients of kidneys harvested from old donors have a high incidence of delayed graft function (DGF) and a poor graft outcome. This result is partly explained by the increased incidence of acute rejection in patients suffering from DGF. However, the long-term impact of donor age and DGF in rejection free renal transplants is not well established. The aim of the present work is to evaluate the impact of donor age and DGF on long-term outcome in renal transplants with or without acute rejection. PATIENTS: We review all cadaveric kidney transplants performed in our centre between April 1984 and December 1995 treated with a cyclosporin-based immunosuppression. RESULTS: Five hundred and ninety-five patients were included. The overall incidence of DGF was 29.1%, and this event was associated with an increased donor age and cold ischaemia time. Univariate and multivariate analysis showed that graft loss was associated with acute rejection (relative risk (RR) 2.24, 95% confidence interval (CI) 1.62-3.01); DGF (RR 1.83, 95% CI 1.32-2.54); donors >50 years (RR 1.65, 95% CI 1.13-2.38); and retransplantation (RR 1.52, 95% CI 1.01-2.31). In rejection-free patients there were two independent predictors of graft failure: donor >50 years (RR 2.40, 95% CI 1.45-4.01); and DGF (RR 2.42, 95% CI 1.53-3.84). CONCLUSIONS: Regardless of the presence of acute rejection, delayed graft function amplifies the detrimental effect of advanced donor age on long-term graft outcome.

Adult↗

Perioperative blood pressure control, delayed graft function, and acute rejection after renal transplantation.

BACKGROUND: Blood pressure (BP) control immediately after renal transplantation is poorly understood, with patients experiencing both high and low BP levels. Donor kidneys lack the ability to autoregulate their blood flow, meaning high pressures are directly translated to the graft endothelium, whereas reduced perfusion may augment ischemic injury. We hypothesize that early BP control may therefore influence the early alloimmune response. METHODS: A total of 276 patients undergoing primary cadaveric renal transplantation who received cyclosporine-based therapy were followed; standard transplant variables were identified. BP was serially recorded before, during, and after reperfusion until 50 hr after surgery. Variables predicting acute rejection and delayed graft function were identified using Cox and logistic regression models. RESULTS: The mean (SD) BP after surgery was 161(19) mm Hg systolic and 73(12) mm Hg diastolic. Forty-two percent had perioperative hypertension defined by conventional parameters. Increasing postoperative systolic BP, measured as standardized area-under-the-curve, was associated with an increased risk for acute rejection (hazard ratio [per mm Hg]=1.008), independent of other covariables including the preoperative BP level. Diastolic BP was inversely associated with the risk of delayed graft function (odds ratio [per mm Hg]=0.956). CONCLUSIONS: Early hypertension is common after renal transplantation. Early BP control has the potential to influence the risk of allograft rejection and delayed graft function.

Adult↗

Organ sharing for good HLA-A,B, and DR matching improves cadaver renal graft survival in SEOPF: retrospective and prospective studies considering delayed graft function, race, center effects, cyclosporine, and other factors.

1. HLA matching is associated significantly with factors including CsA use, ALS use, recipient race, prior graft loss, presensitization, preservation time and most strongly, with organ sharing. However, HLA match is not directly associated with delayed graft function. 2. By univariate and multivariate analyses, good HLA matching provides significant benefits in graft survival regardless of CsA use, organ source or other potentially confounding factors. 3. HLA-A,B, and DR matching have independent and essentially equivalent benefits on graft survival in CsA-treated patients, whereas HLA-A,B matching has a greater benefit in non-CsA-treated patients. 4. Organ sharing, per se, provides no direct detrimental effect on graft survival by univariate or multivariate analysis. 5. By multivariate and univariate analyses, shared/well-matched kidneys provide significantly better graft survival than local/poorly matched kidneys. 6. Delayed graft function is associated in a complex relationship with organ sharing, prior graft failure, presensitization, and CsA use. 7. The increased rate of delayed graft function associated with organ sharing is overcome by the benefit of good HLA matching. 8. Since April 1986, purposeful organ sharing at SEOPF centers for good HLA matching has been associated with improved graft survival, especially in patients at high risk due to presensitization or prior graft failure.

Actuarial Analysis↗

Sub-clinical acute rejection detected using protocol biopsies in patients with delayed graft function.

Acute rejection in renal transplants is difficult to diagnose when patients have delayed graft function (DGF) in the early post-transplant period. In this study protocol, renal transplant biopsies were performed in an attempt to detect sub-clinical acute rejection episodes. Eighty-three patients were eligible for the study, of whom 33 had DGE All had protocol renal transplant biopsies performed under ultrasound control at 7 days post-transplant, and those with DGF had further biopsies weekly until the graft functioned. All histologically confirmed acute rejection episodes were treated. Sub-clinical acute rejection was detected in 6/33 (18%) patients with DGF compared to 2/50 (4%) in the other patients (P < 0.05). Borderline rejection was present in 4/33 (12%) and 4/50 (8%) patients, respectively. Because of the high detection rate of sub-clinical acute rejection and the low morbidity of renal transplant biopsies, their use is recommended in patients with DGF.

Acute Disease↗

Outcome of nonheart-beating donor kidneys with prolonged delayed graft function after transplantation.

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. All recipients of an NHBD kidney in the period 1993-2003 were reviewed. Excluded from analysis were patients with primary nonfunction (PNF). One hundred and five patients with a functioning NHBD graft were reviewed: 23 (22%) had immediate function (group 1), 40 (38%) had DGF < or = 2 weeks (group 2), 31 (30%) had DGF 15 days to 4 weeks (group 3) and 11 (10%) had DGF for > 4 weeks (group 4). Creatinine clearance at 3 months was higher in groups 1 and 2 versus group 4 (p = 0.015 and p = 0.006, respectively) and was higher in group 2 versus group 4, at 1 year (p = 0.01). Graft survival was 95%, 98%, 97% and 89%, respectively, at 1 year and 95%, 85%, 77% and 89%, respectively, at 5 years, which was not significantly different. The duration of DGF in NHB kidneys has a negative effect on creatinine clearance, but no effect on graft survival.

Adult↗

Pharmacokinetics of mycophenolic acid in renal transplant patients with delayed graft function.

The pharmacokinetics of mycophenolic acid (MPA), the immunosuppressant form of the prodrug mycophenolate mofetil (MMF), and the primary glucuronide metabolite, MPAG, were characterized in renal transplant patients with delayed graft function using random effects piecewise linear models. Eight patients were evaluated after receiving their first and subsequent daily oral doses of 1.5 g mycophenolate mofetil twice daily on study days 1 (n = 8), 7 (n = 8), 14 (n = 5), 21 (n = 2), and 28 (n = 7). The area under the concentration-time curve from zero to 12 hours (AUC0-12) for MPA, MPAG, MPA free fraction, and free MPA were analyzed in serial plasma samples using validated high-performance liquid chromatography and ultrafiltration procedures. Random effects piecewise linear models, fit by maximum likelihood methods, were applied to AUC0-12 of MPA and MPAG, MPA free fraction, AUC0-12 of free MPA, and serum creatinine concentration, the index of renal function used in this study. Two hemodialysis sessions did not lower MPA plasma concentration, although some MPAG was removed. The AUC0-12 of MPA increased as a function of time, although it was not possible to fit a statistical model to the data due to considerable among-patient variation in the pattern of increase with time. The AUC0-12 of MPAG, MPA free fraction, and AUC0-12 of free MPA reached maximal values on day 7; each of these parameters had unique day 1 to 7 positive slope values and unique day 7 to 28 negative slope values. The average creatinine concentration was maximal at day 1 and a unique negative slope was obtained between days 7 and 28. Thus, this study provides statistical models for the alteration of AUC0-12 of MPAG, MPA free fraction, AUC0-12 of free MPA, and serum creatinine in renal transplant patients with delayed graft function. These results provide evidence that renal dysfunction is associated with altered pharmacokinetics of MPA, particularly increased AUC0-12 of MPAG, MPA free fraction, and AUC0-12 of free MPA. The perturbed pharmacokinetics normalized with improving renal function.

Adult↗

Risk factors for delayed graft function after renal transplantation and their significance for long-term clinical outcome.

Abstract. Delayed graft function (DGF) remains a grieving complication after renal transplantation. In this study, we examined various factors related to organ donation, transport, and transplantation for their influence on the incidence of DGF and on long-term prognosis. The incidence of DGF, renal function after 5 years, and allograft survival were analyzed in 200 kidneys transplanted in Düsseldorf as well as in 193 partner kidneys transplanted at 43 other centers. The main risk factors for DGF were donor age, cold ischemia time (CIT) and organ shipment. DGF itself, as well as donor age, influenced the long term prognosis. A significant relationship between the partner organs regarding clinical outcome was demonstrated. Non-immunological factors strongly influence the clinical results after renal transplantation. Organs of older donors have a limited long-term prognosis. To minimize additional risks, prevention of DGF, especially by reducing CIT, should be regarded as of paramount importance.

Adult↗

Cyclosporine prolongs delayed graft function in kidney transplantation: are rabbit anti-human thymocyte globulins the answer?

BACKGROUND: Cyclosporine (CsA) nephrotoxicity may prolong duration of anuria in renal transplant patients with delayed graft function (DGF). Thus, many Transplant Centers tend to delay CsA treatment in order to accelerate renal function recovery. METHODS: In this single-center, retrospective analysis we compared the outcomes of 40 renal transplant patients with DGF given a CsA-based (n = 17) regimen since the day of transplant or a CsA-sparing regimen (n = 23) based on early treatment with rabbit anti-human thymocyte globulin (RATG) and delayed CsA administration. We studied all patients with DGF who received a first or second graft at the Bergamo Transplant Center from January 1992 to March 2000. RESULTS: Patients given RATG as compared to those on CsA had significantly shorter duration of anuria (11.0 +/- 5.6 vs. 19.6 +/- 8.9 days; p < 0.005) and of initial hospitalization (17.4 +/- 4.3 vs. 27.4 +/- 10.4 days; p < 0.001). Throughout the whole study period, 4 patients on RATG as compared to 6 on CsA had an acute rejection episode (p > 0.05). However, no patient on RATG as compared to 4 on CsA had an acute rejection during the anuria period (p < 0.05). Costs including hospitalization, dialysis treatment and study drugs were significantly lower in RATG than in CsA patients (EUR 29,944 +/- 7,281 vs. 36,795 +/- 13,656; p < 0.05). CONCLUSIONS: In renal transplant patients with DGF, early RATG treatment with delayed CsA administration accelerated renal function recovery and patient discharge, prevented occult rejections throughout the anuria period and significantly decreased the treatment costs.

Adult↗

The detrimental effects of delayed graft function in cadaver donor renal transplantation.

Data collected prospectively on over 3800 cadaveric renal transplants performed between June 1977 and July 1982 by the 41 member institutions of the South-Eastern Organ Procurement Foundation were analyzed to determine the influence of delayed graft function (DGF) on patient and graft outcome. Approximately 35% of first graft recipients and 47% of regrafted patients were found to have DGF, as determined by the necessity for dialysis at one week posttransplant. First-graft recipients with DGF tended to include more black recipients, patients with higher peak levels of panel reactive antibody (PRA), less use of antilymphocyte serum (ALS) posttransplant, slightly longer organ preservation times and the more frequent use of organs by ice alone. Multivariate (Cox) regression analysis considering DGF simultaneously with ten other potentially confounding variables showed a highly significant association between DGF and overall graft loss from all causes (P less than 10(-5], irreversible graft rejection (P less than 0.001) as well as patient death (P = 0.012). The differences in graft survival between first graft recipients with DGF (n = 961) versus those without DGF (n = 1769) at one and four years posttransplant were 46% +/- 2 vs. 60% +/- 1 and 28% +/- 3 vs. 40% +/- 2, respectively. The detrimental effect of DGF was highly significant irrespective of the source of donor organs or the type of preservation used. For first transplant recipients who recovered good graft function by one month following DGF (n = 564), there was a significant decrease in eventual graft survival, as compared with patients who had graft function at one month but no prior history of DGF (n = 1407; P = 0.008). However, patients with history of DGF who had good graft function at six months (n = 361) showed no significant difference in longer-term graft survival when compared with similar patients with good graft function at six months but no history of DGF (n = 912). Interestingly, first transplant recipients with DGF were found to have significantly better graft survival if they had received bilateral native nephrectomy at least one month prior to transplantation. These results indicate that delayed graft function following cadaver donor renal transplantation provides a significant risk for eventual graft and patients survival that is principally manifested during the first six months posttransplant. In addition, patients who recover graft function following DGF appear to also remain at higher risk for early graft loss, while pretransplant bilateral native nephrectomy may afford some protection against the detrimental effects of DGF.

Female↗

Effect of delayed graft function in hypersensitized kidney transplant recipients.

There is increased evidence about the deleterious effect of delayed graft function (DGF) in both short- and long-term kidney graft outcome. Among the mechanisms involved in the production of DGF, immune factors play a role, especially in the level of hypersensitization. From the 1389 patients transplanted at our hospital until November 2004, it has been found that the presence of moderate and high levels of sensitization, as measured by panel-reactive antibodies, is a risk factor for suffering from DGF. Further, DGF was associated with poor graft survival, and the risk was even higher when DGF was combined with moderate/high panel-reactive antibodies. Recent data demonstrate the usefulness of intravenous immunoglobulins in the management of hypersensitized patients in terms of short-term outcome. It remains to be demonstrated whether this therapy is able to ameliorate the higher ischemic injury that kidneys undergo from these immunologically high-risk patients.

Desensitization, Immunologic↗

Basiliximab (Simulect) in renal transplantation with high risk for delayed graft function.

BACKGROUND: Basiliximab (Simulect) is effective in reducing episodes of acute rejection in renal transplantation. Delayed graft function (DGF) predisposes to acute rejection and shortens graft survival. The aim of this study was to determine the effects of basiliximab in renal transplantation recipients at high risk for DGF. METHODS: We studied 87 patients (mean age, 59 years), 42 of whom received basiliximab, 20 mg before transplantation and 20 mg on day 4. This cohort was compared with 45 patients without basiliximab. All received cyclosporine (51%) or tacrolimus (49%), mycophenolate mofetil, and steroids. DGF was defined as the requirement for dialysis within the first week after transplantation or failure to improve preexisting renal function. High-risk factors for DGF were cold ischemia time, recipient and donor age, non-heart-beating donor, HLA matching, and panel reactive antibody (PRA). RESULTS: The incidence of DGF was 18 (43%) in the basiliximab group versus 28 (62%) in the other patients (P = .07). When allografts from non-heart-beating donors were excluded, this incidence was 14 (38%) in the basiliximab group versus 28 (62%) in the other patients (P = .04). Regression analysis showed basiliximab to be a protective factor: 0.26 (range, 0.09-0.76). Basiliximab was well tolerated, and complications were similar in both groups. CONCLUSIONS: Basiliximab reduced the incidence of DGF in patients who received a high-risk allograft. It was well tolerated, and no adverse events were reported. The use of basiliximab may be considered in patients receiving an allograft who are at high risk for DGF.

Antibodies, Monoclonal↗

Incidence of delayed graft function in cadaveric kidney transplants in Brazil: a multicenter analysis.

To evaluate the frequency of delayed graft function (DGF) in kidney transplant centers in Brazil, we sent a questionnaire requesting information on the number of cadaveric donor kidney transplants performed during the years 2000, 2001, and 2002, the number of early nonfunctioning grafts, and the number of patients on dialysis during the first posttransplant week with subsequent recovery. Among all centers performing more than 50 kidney transplants during the last year of evaluation, 6, performing 612 cadaveric kidney transplants during the study period, replied to the questionnaire. Sixty procedures (9.7%) resulted in nonfunctioning grafts, while 312 (55.6%) patients required dialysis during the first Ptx week: 216 (53.9%) in 2000, 189 (62.3%) in 2001, and 216 (51.6%) in 2002. The frequency of DGF during the study period was higher than that noted by several previous foreign studies. To better evaluate the possible causes of this finding, a more extensive and focused study is warranted.

Brazil↗

Deleterious effects of delayed graft function in cadaveric renal transplant recipients independent of acute rejection.

BACKGROUND: In cadaveric renal transplantation, delayed graft function (DGF) correlates with poor long-term graft survival; however, whether its effects are independent of acute rejection is controversial. We wished to study the effect of DGF on graft survival, controlling for acute rejection, discharge creatinine, and human leukocyte antigen match. METHODS: We analyzed 27,096 first cadaveric donor renal transplants reported to the UNOS Scientific Renal Transplant Registry between January 1994 and November 1997. DGF was defined as dialysis need in the first week. Acute rejection was recorded for initial hospitalization and within 6 months. Kaplan Meier survival curves were analyzed with the log rank test. RESULTS: DGF increased the incidence of acute rejection before discharge (8% without DGF; 25% with DGF, P<0.01) and any acute rejections by 6 months (25% without DGF, 42% with DGF, P<0.01). Without early rejection, DGF reduced 1-year graft survival from 91 to 75% (P<0.0001) and graft half-life from 12.9 to 8.0 years. In kidneys with acute rejection within 6 months, DGF decreased 3-year graft survival from 77 to 60% and graft half-life from 9.4 to 6.2 years (P<0.001). With a discharge creatinine of less than 2.5 mg/dl, the difference in graft half-life between no DGF and no rejection (13.4 years) and DGF with rejection (9.8 years) was significant (P<0.001). Increased donor age and cold ischemia time additionally decreased graft survival, whereas a good human leukocyte antigen match could not overcome the deleterious effects of DGF or acute rejection. CONCLUSIONS: DGF is an important independent predictor of poor graft survival. Newer immunosuppressive strategies must minimize nonimmune and immune renal injury if long-term graft survival is to improve.

Acute Disease↗

Delayed graft function is characterized by reduced functional mass measured by (99m)Technetium-mercaptoacetyltriglycine renography.

BACKGROUND: The mechanism that underlies delayed graft function (DGF) is still poorly defined. Previous studies using tubular function tests have shown that postischemic injury to the renal transplants results in profound impairment of paraimmunohippurate (PAH) extraction through the tubules. METHODS: Using (99m)Technetium-mercaptoacetyltriglycine ((99m)Tc-MAG3) renography and tubular function slope (TFS), a study of the tubular uptake of (99m)Tc-MAG3 was undertaken in a prospective study of renal transplant recipients with immediate graft function (IGF) and those with DGF. RESULTS: A total of 37 consecutive recipients of a cadaveric graft and 5 kidneys from living donors was evaluated within 48 hours after transplantation and in week 2, months 3 and 6, and 3 years after transplantation. In addition to the protocol scans, recipients with DGF were examined every other day until function was resumed. Repeated measurement two-way analysis of variance and a change point analysis were performed to determine the difference in the follow-up of TFS values between the two groups. Fourteen patients were classified as having DGF and 28 immediate graft function. In the DGF group, the initial TFS value was significantly lower than in the immediate graft function group (0.54 [+/-0.01] and 1.75 [+/-0.16], respectively; P=0.002), a difference that persisted for up to 3 years. Change point analysis revealed that the postischemic tubular excretion improved with time in both groups in the first 3 to 4 weeks, but both groups remained different up to 3 years after transplantation. Multivariate analysis revealed that only the cold ischemic time was an independent risk factor for a low TFS value. After the initial recovery from postischemic injury, the TFS may be used as a marker for functional renal mass. CONCLUSION: We propose that the tubular defect in DGF, as defined by (99m)Tc-MAG3 renography, is irreversible and may be a marker of initial graft function.

Adult↗

Utility of a mathematical nomogram to predict delayed graft function: a single-center experience.

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.

Adult↗

Effect of delayed graft function on short- and long-term kidney graft survival.

Delayed graft function (DGF) has been identified as a predictor of poor long-term graft survival, but whether its effects are independent of rejection or final serum creatinine level is controversial. Based on the results of 57,025 first cadaver transplants reported to the UNOS Registry, we showed that: 1. Early acute rejection significantly lowered one-year graft survival rates by 8-9% in kidneys with early function (EF) (89% vs 80%; p < 0.001) or with DGF (72% vs 64%; p < 0.001). 2. DGF significantly lowered short- and long-term graft survival in patients without rejection (EF-1-yr graft survival rate of 89%, t1/2 of 9.5 years vs DGF-72% 1-yr graft survival rate, t1/2 of 6.7 years; p < 0.001). 3. Even when the discharge serum creatinine level was < 2.0 mg/dl with no rejection, DGF lowered graft survival (EF-1-yr graft survival rate of 93%, t1/2 of 10.4 years vs DGF-90% 1-yr graft survival rate, t1/2 of 7.6 years; p < 0.001). 4. Acute rejection, elevated discharge serum creatinine level (2-6 mg/dl) and older donor age (46-60 yrs) each lowered one-year graft survival rates in a stepwise fashion. There was exceptionally poor graft survival of kidneys from donors aged 46-60 with DGF, whether or not early acute rejection was present (with rejection-1-yr graft survival rate of 61%, t1/2 of 5.6 yrs vs no rejection-1-yr graft survival rate of 71%, t1/2 of 5.3 yrs). 5. Increasing cold ischemia time only decreased graft survival when there was no DGF and no rejection and had no significant effect on long-term graft survival. 6. Among recipients of HLA-matched cadaver kidneys, DGF lowered short- and long-term graft survival, even in the absence of early rejection (EF-1-yr graft survival rate of 93%, t1/2 of 14.8 yrs vs DGF-1-yr graft survival rate of 76%, t1/2 of 7.8 yrs). 7. DGF was associated with higher rates of acute rejection but impaired long-term graft survival even when rejection was absent and discharge creatinine was normal. These data support the hypothesis that DGF leads to an injury response that can reduce graft survival through antigen dependent and antigen independent mechanisms.

Adult↗