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Vasodilatation vs. immunotherapy to prevent delayed graft function: delayed graft function as an indication of immune activation.

Delayed renal allograft function (DGF) is a factor for acute rejection and chronic allograft nephropathy. Cold ischemia time (CIT) is associated with an increased in DGF. Twenty patients receiving allografts with CIT>12 were enrolled in a double-blinded, randomized (1:1), placebo-controlled study to assess vasodilatation with fenoldopam (Abbott; dopamine-1 receptor agonist) on DGF. Fenoldopam infusion began at arterial anastomosis at 0.025 microg/kg/min and titrated to 0.1 microg/kg/min continued for 48 h postop (PO). Immunosuppression included steriods, MMF, and calcinurin inhibitors begun 36 h PO. Antibody induction (AI) using antithymocyte globulin (rabbit) (AT-G(r); Sangstat) was added halfway through the study to African-Americans and for PRA>40%. The need for dialysis, cumulative urine output (UOP), and creatinine (Cr) at PO day 7, 14, and 30 were compared. Eighteen patients completed the study drug infusion. Demographics of groups were not different. There was no difference between fenoldopam and controls for dialysis, UOP at 48 and 72 h, or Cr at 7, 14, or 30 days. There was a difference in UOP when AI (n=7) was compared to non-AI (n=11). At 48 h non-AI UOP 4796+/-3284 ml compared to AI UOP 8960+/-5130 ml (p=0.050). At 72 h, non-AI patients had UOP of 6824+/-4547 ml compared to AI patients with UOP of 12196+/-5868 ml (p=0.044). There was a trend to a lower Cr at day 7 for AI 2.7+/-2.1mg/dl compared to 4.9+/-3.0 mg/dl in non-AI (p=0.11). There was no difference in dialysis or Cr at day 14 and 30 between the AI and non-AI patients. AI with AT-G(r) significantly increases UOP in allografts with CIT>12 h, whereas vasodilatation did not. Therapy for DGF may include AT-G(r) AI.

Adult↗

Non-heart beating donor kidneys with delayed graft function have superior graft survival compared with conventional heart-beating donor kidneys that develop delayed graft function.

Delayed graft function may have an association with reduced graft survival, and nonheart-beating donor (NHBD) kidneys have higher rates of delayed graft function (DGF) than heart-beating donor (HBD) kidneys. This study compared outcome of renal transplants from HBDs who developed DGF, with NHBDs who developed DGF. All recipients of HBD and NHBD kidneys who developed DGF were identified during a 10-year period. All patients with graft primary nonfunction were excluded from analysis. Four hundred and fifty-six functioning transplants were performed. Delayed graft function occurred in 69 (17%) HBD and 55 (93%) NHBD kidneys. The grafts developing DGF were well matched for donor and recipient age. The rate of acute rejection was similar; [n = 16/69 (23%) HBD vs. n = 13/55 (24%) NHBD]. Cold ischaemia was 21 h in the HBD group and 17 h in NHBD group (p > 0.05). Serum creatinine was similar for both groups at 1.3 and 6 years (p > 0.05 for all time points). Graft survival in the NHBD recipients with DGF was significantly better at 3 years (84%) compared with recipients of a HBD renal transplant that developed DGF (73%) (p < 0.05), and at 6 years (62% survival for HBDs and 84% survival for NHBDs). This study shows that graft survival was better for NHBD kidneys up to 6 years after transplantation.

Adult↗

Improved results using OKT3 as induction immunosuppression in renal allograft recipients with delayed graft function.

Delayed graft function remains a major problem in cadaveric renal allograft transplantation. We have used 2 different immunosuppressive induction regimens in patients with delayed graft function. The first regimen, used in 40 patients from January 1985 to December 1986, consisted of CsA (8 mg/kg/day, orally within 48 hr of cadaveric renal transplantation regardless of graft function), azathioprine (1.5-2.5 mg/kg/day), and steroids (methylprednisolone 375 mg on day 0, then prednisone tapered to 30 mg/day by day 10 with slow tapering to 7.5-10 mg/day over the first 6 months after transplantation). A second regimen, used from January 1987 to March 1989, employed the same doses of azathioprine and steroids; however, OKT3 (5 mg i.v./day for 7-21 days) was administered in the 34 patients who had delayed graft function. CsA was withheld until ATN resolved. The use of OKT3 as induction immunosuppression in patients with ATN led to a significant increase in 1-year graft survival (80% vs. 55%) while markedly decreasing the incidence of rejection episodes (44% vs. 82%) and the duration of nonfunction (9.4 vs. 14.9 days). There were 5 CMV infections in patients treated with OKT3. Antibodies to OKT3 developed in only 1 of 34 patients treated with OKT3. Five of 7 patients who received a second course of OKT3 successfully reversed the rejection episode. Patient survival (89%) was the same in the 2 groups. The benefit of OKT3 on long-term graft survival appears to stem from elimination of early rejection episodes that may be difficult to diagnose in a poorly functioning allograft. We conclude that OKT3 induction provides superior results over CsA induction at doses given in renal allograft recipients with delayed graft function without a significant increase in morbidity or mortality and permits the reuse of OKT3 for treatment of rejection in most cases.

Antibodies, Anti-Idiotypic↗

Pathophysiology of reduced glomerular filtration rate in delayed graft function.

Delayed graft function is a form of postischemic acute renal failure. It lowers glomerular filtration rate in large part by depressing the glomerular transcapillary hydraulic pressure difference, the driving force for the formation of filtrate. Loss of proximal tubule cell polarity, impaired sodium reabsorption and tubuloglomerular feedback-mediated afferent arteriolar constriction are all implicated. A link between delayed graft function and chronic allograft injury is evident. The ensuing impairment of graft survival makes urgent the need for further elucidation of delayed graft function and a search for an effective therapy.

Acute Kidney Injury↗

Addition of sirolimus to cyclosporine delays the recovery from delayed graft function but does not affect 1-year graft function.

Delayed graft function (DGF) has long been identified as one of the main correlates of poor graft survival in cadaveric renal transplantation, but the factors that affect its onset and duration are not fully elucidated. The impact of two immunosuppressive protocols on the incidence and length of DGF among kidney transplant recipients of a suboptimal organ was evaluated. Patients were randomly treated with corticosteroids (CS); low-dose cyclosporine (CsA) and sirolimus (SRL; group 1; n = 42); or CS, full-dose CsA, and mycophenolate mofetil (group 2; n = 48). All recipients received immunoprophylaxis with basiliximab. After 3 mo, group 1 discontinued CsA and continued with SRL, whereas group 2 continued the same treatment. The incidence of DGF was similar in the two groups (group 1 = 52.4%; group 2 = 58.3%), whereas its duration was significantly higher in the group 1 (19.0 +/- 6.0 versus 10.3 +/- 3.2 d; P = 0.001). Both groups showed 100% actuarial graft and patient survival at 1-yr. Among DGF patients, serum creatinine (sCr) at discharge was significantly worse in group 1 (sCr, 3.0 +/- 1.0 versus 1.5 +/- 0.2 mg/dl; calculated creatinine clearance, 31.2 +/- 9.3 versus 61.1 +/- 10 ml/min; P = 0.001). During the first year, the former group displayed a significant improvement of graft function, such that at 1-yr, no difference could be measured between groups (sCr, 1.8 +/- 0.5 versus 1.7 +/- 0.4 mg/dl; calculated creatinine clearance, 51.5 +/- 10.2 versus 53.3 +/- 9.4 ml/min). In conclusion, in de novo renal transplanted patients, the administration of SRL, in combination with low-dose CsA, is associated with a delayed recovery from DGF but does not worsen 1-yr graft function.

Cyclosporine↗

Outcome of renal allografts from non-heart-beating donors with delayed graft function.

Delayed graft function (DGF) in renal transplantation using non-heart-beating donors (NHBDs) usually exceeds 80%. There is debate whether DGF in this subgroup is associated with poor long-term outcome. Between 1 January 1988 and 31 January 2000, 130 of 158 (82.3%) NHBD graft recipients with functioning grafts transplanted within our regional NHBD programme developed DGF. Overall graft survival and graft survival censored for recipient death was 113/130 (86.9%) versus 113/121 (93.4%) at year 1, 55/84 (65.5%) versus 55/64 (85.9%) at year 5 and 18/40 (45.0%) versus 18/28 (64.3%) at year 10 after transplantation. Seventeen grafts (13.1%) were lost due to rejection or graft nephropathy. Nine of these kidneys failed during the 1st year. Twenty-seven patients (20.8%) died with functioning grafts, eight within the 1st year after transplantation. In those patients who survived, DGF was associated with excellent long-term outcome in this study. The number of grafts lost due to recipient death exceeded those lost due to rejection or graft nephropathy.

Graft Survival↗

Creatinine reduction ratio on post-transplant day two as criterion in defining delayed graft function.

Delayed graft function (DGF) is a common complication after renal transplant, affecting its outcome. A common definition of DGF is the need for dialysis within the first week of transplantation, but this criterion has its drawbacks. We tried to validate an earlier and better defined parameter of DGF based on the creatinine reduction ratio on post-transplant day 2 (CRR2). We analyzed the clinical charts of 291 cadaver kidney recipients to compare the outcome of patients with immediate graft function (IGF), dialyzed patients (D-DGF) and nondialyzed CRR2-defined DGF patients (ND-DGF) and to identify risk factors for D-DGF and ND-DGF. Creatinine reduction ratio on post-transplant day 2 correlates significantly with renal function during the first year. Patients with IGF have significantly better renal function throughout the first year and better graft survival than patients with D-DGF and ND-DGF, while we found no differences either in renal function from days 30-365 or in graft survival between D-DGF and ND-DGF patients. Defining DGF by CRR2 allows an objective and quantitative diagnosis after transplantation and can help to improve post-transplant management. Creatinine reduction ratio on post-transplant day 2 correlates with renal function throughout the first year. The worse survival in the ND-DGF group is an important finding and a major advantage of the CRR2 criterion.

Adult↗

Calcium levels as a risk factor for delayed graft function.

BACKGROUND: Delayed graft function (DGF) occurs in up to 50% of renal transplants. Hypercalcemia and hyperparathyroidism are associated with impaired renal function. Little is known on the effects of serum calcium levels on DGF. This issue was addressed in the current study. METHODS: Patients receiving a cadaveric renal transplant between 1986 and 1996 were studied. Data on calcium metabolism and histologic characteristics of nephrocalcinosis, acute tubular necrosis (ATN), and acute rejection in biopsies taken within the first week were related to the occurrence of DGF. RESULTS: The incidence of DGF in a cohort of 585 cadaveric transplants was 31%. DGF correlated independently with serum calcium levels (odds ratio [OR] 1.14 [95% confidence interval (CI) 1.04-1.26] per 0.1 mmol/L). The use of calcium channel blockers before transplantation protected against DGF (OR 0.5 [95% CI 0.29- 0.87]). In this selected group, we found an association with histologic signs of ATN and DGF. However, most of the biopsies also had features of acute rejection or nephrocalcinosis. Nephrocalcinosis was found in 12 of 71 biopsies and was not associated with serum calcium levels or the occurrence of DGF. CONCLUSIONS: In this study, serum calcium levels were independently associated with DGF. This could not be explained by the presence of microscopic nephrocalcinosis. Therefore, DGF is attributed to high intracellular calcium levels. Because calcium supplementation and vitamin D analogues are commonly used in dialysis practice, hypercalcemia influences long-term graft outcome by its effect on DGF. The pretransplant use of calcium channel blockers has a protective effect on the occurrence of DGF.

Adult↗

A calcineurin inhibitor-sparing regimen with sirolimus, mycophenolate mofetil, and anti-CD25 mAb provides effective immunosuppression in kidney transplant recipients with delayed or impaired graft function.

Delayed graft function (DGF) after renal transplantation is a significant risk factor for early acute rejection and graft loss. Sirolimus (SRL) can be administered in the setting of DGF without exacerbating the impaired renal function after transplantation. We examined a calcineurin-sparing regimen using SRL during the early post-operative period in renal transplant patients with delayed or impaired graft function. A retrospective review of 14 consecutive kidney transplant recipients with delayed or impaired graft function who received SRL was performed. The immunosuppressive regimen consisted of daclizumab induction (2 mg/kg), SRL (5-15 mg load followed by 2 5 mg daily maintenance therapy), corticosteroids, and mycophenolate mofetil (MMF, 1.5-3 g/d). Patients were monitored for allograft function, acute rejection, graft survival, thrombocytopenia, and leukopenia. Serum levels of SRL were determined by high-performance liquid chromatography performed at an independent commercial laboratory. Donors were cadaveric in 13 cases and living related in one. The duration of follow-up was 0.5-5.2 months. Nine patients required hemodialysis after transplantation. The mean time to initiation of calcineurin inhibitors was 21 +/- 13 d. Average serum creatinine levels at the initiation of SRL and at 1 month after transplantation were 8.4 +/- 2.7 and 2.1 +/- 1.2 mg/dL, respectively. There were 2 patients (14%) who experienced acute rejection within the first month after transplantation -1 with type I (steroid therapy) and 1 with type II (anti-thymocyte therapy). Serum levels of SRL were initially undetectable in the 2 patients with acute rejection. No grafts were lost during the period of follow-up. Three patients developed thrombocytopenia (platelets < 100 x 10(9)) and no patients developed leukopenia. The combination of SRL with anti-CD25 mAb, MMF, and corticosteroids appears to provide effective non-nephrotoxic immunosuppression for kidney transplantation without the need for a lymphocyte-depleting regimen. However, it is important to monitor serum SRL levels to determine the optimal dosing regimen. Furthermore, long-term follow-up of these patients will be helpful to determine whether improved immunosuppression can be achieved with a fully calcineurin-sparing regimen using SRL.

Adult↗

Delayed graft function: risk factors and implications for renal allograft survival.

Delayed graft function (DGF) may be associated with diminished kidney allograft survival. We studied the risk factors that lead to nonimmediate function of a renal allograft and the consequences of DGF on short- and long-term renal transplant survival. Data from the U.S. Renal Data System were used to measure the relationships among cold ischemia time, delayed graft function, acute rejection, and graft survival in 37,216 primary cadaveric renal transplants (1985-1992). These relationships were investigated using the unconditional logistic and Cox multivariate regression methods. Cold ischemia time was strongly associated with DGF, with a 23% increase in the risk of DGF for every 6 hr of cold ischemia (P<0.001). Acute transplant rejection occurred more frequently in grafts with delayed function (37% vs. 20%; odds ratio=2.25, P=0.001). DGF was independently predictive of 5-year graft loss (relative risk=1.53, P<0.001). The presence of both early acute rejection and DGF portended a dismal 5-year graft survival rate of 35%. Zero-HLA mismatch conferred a 10-15% improvement in 1- and 5-year graft survival regardless of early functional status of the allograft. However, the 5-year graft survival rate in HLA-mismatched kidneys without DGF was significantly higher than that of zero-mismatched kidneys with DGF (63% vs. 51%; P<0.001). DGF independently portends a significant reduction in short- and long-term graft survival. Delayed function and early rejection episodes exerted an additive adverse effect on allograft survival. The deleterious impact of delayed function is comparatively more severe than that of poor HLA matching.

Adult↗

Immune Regulatory Signatures Associated with Different Recovery Durations of Delayed Graft Function after Kidney Transplantation.

Delayed graft function (DGF) is a common early complication of kidney transplantation characterized by immune activation. The duration of DGF may significantly affect long-term graft survival, yet the immune mechanisms underlying the different DGF durations remain unclear. Using a functional definition of delayed graft function (fDGF), defined as a failure of serum creatinine to decrease by at least 10% per day for three consecutive days within the first postoperative week, patients were stratified into short-term DGF (SDGF) and long-term DGF (LDGF) groups according to recovery periods. In this exploratory study, targeted proteomic analysis indicated that proteins enriched in SDGF were primarily involved in innate immune responses and acute inflammatory processes, including neutrophil chemotaxis and migration, whereas LDGF exhibited features related to adaptive immune responses and chronic inflammation, such as T-cell differentiation and activation. IL-7 and CCL20 were identified as candidate molecules potentially associated with different DGF durations. Targeted metabolomics revealed disturbances in amino acid metabolism, particularly alanine, aspartate, and glutamate metabolism, as well as in energy metabolism, including the tricarboxylic acid (TCA) cycle, which may be involved in LDGF. These findings provide preliminary insights into immune metabolic features associated with different DGF recovery durations.

Humans↗

Delayed graft function in kidney transplantation.

Delayed graft function is a form of acute renal failure resulting in post-transplantation oliguria, increased allograft immunogenicity and risk of acute rejection episodes, and decreased long-term survival. Factors related to the donor and prerenal, renal, or postrenal transplant factors related to the recipient can contribute to this condition. From experimental studies, we have learnt that both ischaemia and reinstitution of blood flow in ischaemically damaged kidneys after hypothermic preservation activate a complex sequence of events that sustain renal injury and play a pivotal part in the development of delayed graft function. Elucidation of the pathophysiology of renal ischaemia and reperfusion injury has contributed to the development of strategies to decrease the rate of delayed graft function, focusing on donor management, organ procurement and preservation techniques, recipient fluid management, and pharmacological agents (vasodilators, antioxidants, anti-inflammatory agents). Several new drugs show promise in animal studies in preventing or ameliorating ischaemia-reperfusion injury and possibly delayed graft function, but definitive clinical trials are lacking. The goal of monotherapy for the prevention or treatment of is perhaps unattainable, and multidrug approaches or single drug targeting multiple signals will be the next step to reduce post-transplantation injury and delayed graft function.

Animals↗

Delayed graft function does not influence long-term outcome in cadaver kidney transplants without mismatch for HLA-DRB1.

The currently study focused on the influence of delayed graft function on the long-term graft success rate in cadaver kidneys without any mismatches for HLA-DRB1. Donor-recipient HLA-DRB1 was determined by the significant two-locus linkages of HLA-B and -DRB1. The overall 5-year graft success rate was 88% in an HLA-DRB1-compatible group, significantly higher than the 69% in an HLA-DRB1 mismatch group (P < 0.05) and the 66% in an HLA-DR mismatch (P < 0.01). Delayed graft function was observed in 182 of 223 transplants. This high incidence of 82% is due to the fact that, in Japan, kidney procurement may only occur after cardiac arrest. The incidence did not differ in each group. The 5-year success rate for grafts with delayed function was 87% in the HLA-DRB1-compatible group, again significantly superior to the 68% in the HLA-DRB1 mismatch group and the 63% in the HLA-DR mismatch cases (P < 0.05). There was, thus, no difference in graft success rate for each group, with or without delayed graft function. Consequently, we feel that delayed graft function has no impact on the long-term outcome in transplants without mismatches for HLA-DRB1.

Adult↗

Delayed graft function in renal transplantation.

PURPOSE OF REVIEW: Delayed graft function is an important determinant of patient and graft survival. A complex of pathologic mechanisms intervenes in the pathophysiology of this outcome. This paper reviews the main processes involved in delayed graft function as they relate to five chronologically related stages: donor tissue quality, brain death and related stress, preservation variables, immune factors, and recipient variables. RECENT FINDINGS: Dialyzed delayed graft function and nondialyzed slow graft function both have a negative impact on graft survival and on the incidence of acute rejection. Expanded-criteria donors, older donors, and non-heart-beating donors are more frequently used. The long-term results of the use of well-selected non-heart-beating donors are surprisingly good. The process of ischemia/reperfusion injury is already initiated in the brain-death donor and continues during preservation of the graft. Graft-infiltrating T cells, heat shock proteins, and heme oxygenase-1 are implicated in the process. Modifications in immunosuppressive therapy and pharmacologic modulations have an effect on delayed graft function. Delayed graft function plays a part in the incidence of acute rejection, impaired graft function, and survival of patients and grafts. SUMMARY: This review discusses the current literature on several recent findings of pathophysiologic mechanisms of, and possible therapeutic interventions in, delayed graft function.

Age Factors↗

Use of enteric-coated mycophenolate sodium in de novo renal transplant recipients with high incidence of delayed graft function.

Patients with delayed graft function (DGF) are at risk of increased incidence for acute rejection episodes (ARE). Mycophenolate mofetil or induction therapy has produced a reduction in ARE incidence. An open, prospective, 3-month trial was performed in a group of Argentinian renal transplant recipients. We recruited 46 patients, 71.7% men, aged 41.7 +/- 13.8 years; including 36 (78.3%) recipients of cadaveric donors (CD) who were aged 43.4 +/- 15.5 years with a cold ischemia time of 19.4 hours +/- 5.4 minutes, and 10 (27.7%) recipients of living donors (LD) aged 37.8 +/- 12.9 years. HLA mismatches >or= 3 were observed in 58.4% of CD and in 7% of LD. All patients received two doses of basiliximab (20 mg each, days 0 and 4), cyclosporine microemulsion (CsA-ME) monitored by the second-hour concentrations (C2), enteric-coated mycophenolate sodium (EC-MPS; 720 mg twice a day, and steroids. A 58% incidence of DGF was observed. At the end of the third month the incidence of biopsy-proven ARE was 15%, with a median serum creatinine of was 1.54 +/- 0.42 mg/dL, including three grafts lost. Two patients died. No patient required EC-MPS dose discontinuation but 20% of patients required dose adjustments. The absence of discontinuations and the low incidence of dose adjustments of EC-MPS in this high-risk de novo population provided support of a suitable tolerability profile for this EC-MPS, and the possibility to impact efficacy results.

Adult↗

Effect of cyclosporine and delayed graft function on posttransplantation erythropoiesis.

The effect of delayed graft function and immunosuppressive drugs on posttransplant erythropoiesis was studied prospectively in 18 living-related (LR) and 84 cadaver-donor (CD) recipients. Eight of 18 LR and 20 of 84 CD recipients received antilymphoblast globulin (ALG) in addition to azathioprine and prednisone. Sixty-four CD recipients received cyclosporine (CsA) with prednisone. In the absence of rejection reticulocytosis began 6.7 +/- 0.2 days following graft implantation in azathioprine-only-treated LR recipients. This was lengthened by ALG to 9.4 +/- 0.3 and 9.9 +/- 0.7 days in LR and CD recipients, respectively, whose grafts functioned immediately. Delayed graft function prolonged onset of reticulocytosis to 15.9 +/- 0.9 days in ALG-treated but not in CsA-treated recipients (5.8 +/- 0.4 days). The shortest latency was noted in CsA-treated recipients (4.9 +/- 0.5 days) with immediately functioning grafts. The earlier onset of reticulocytosis of CsA-treated recipients was followed by statistically significant blunting of peak reticulocytosis, which correlated with a slower rate of correction of anemia (delta Hct = 0.19/day) compared with non-CsA-treated recipients (delta Hct = 0.34/day). Early rejection was associated with abrogation of reticulocytosis and correction of anemia without regard to immunosuppressive regimen) until rejection was reversed. Erythropoietin (EPO) was measured sequentially in 5 patients with immediate function. In 4 of 5 cases changes in EPO preceded those in reticulocytosis. EPO rose from a mean of 13 mU/ml pretransplant to a peak of 50 within 3 weeks and decreased to 18 mU/ml within 6 weeks of graft implantation. At six months posttransplant, normalized reticulocyte counts were only 55% higher (1.75 vs. 1.13%) but hematocrit had increased from 26 +/- 1% to 42 +/- 1%. Hematocrit varied inversely with serum creatinine, which was highest in CsA-treated patients with initial delayed graft function. We conclude that correction of anemia posttransplantation is driven by EPO but other factors may also be important, that neither ATN nor ALG-therapy have clinically important effects on erythropoiesis, and that CsA reduced "effective" erythropoiesis and influences correction of anemia--particularly if delayed graft function complicates the initial course posttransplantation.

Antilymphocyte Serum↗

Delayed graft function: immediate and late impact.

Delayed graft function remains a frequent problem after renal transplantation, which is often associated with subsequent graft failure. The major risks for delayed graft function are incurred during organ procurement, preservation, and transplantation, and are predominated by ischemic injury. The cofactors associated with delayed graft function that lead to subsequent poor outcome include early acute rejection as well as immunologic risk factors for rejection, such as presensitization, human leukocyte antigen mismatch, and previous loss of graft. Numerous diagnostic and therapeutic approaches have been assessed in recent years, but predicting or modifying adverse outcomes associated with delayed graft function in a given patient remains unreliable.

Graft Rejection↗

Impact of initial exposure to calcineurin inhibitors on kidney graft function of patients at high risk to develop delayed graft function.

We conducted a retrospective analysis of the influence of full doses of calcineurin inhibitors [8-10 mg kg-1 day-1 cyclosporine (N = 80), or 0.2-0.3 mg kg-1 day-1 tacrolimus (N = 68)] administered from day 1 after transplantation on the transplant outcomes of a high-risk population. Induction therapy was used in 13% of the patients. Patients also received azathioprine (2 mg kg(-1) day(-1), N = 58) or mycophenolate mofetil (2 g/day, N = 90), and prednisone (0.5 mg kg(-1) day(-1), N = 148). Mean time on dialysis was 79 +/- 41 months, 12% of the cases were re-transplants, and 21% had panel reactive antibodies > 10%. In 43% of donors the cause of death was cerebrovascular disease and 27% showed creatinine above 1.5 mg/dL. The incidence of slow graft function (SGF) and delayed graft function (DGF) was 15 and 60%, respectively. Mean time to last dialysis and to nadir creatinine were 18 +/- 15 and 34 +/- 20 days, respectively. Mean creatinine at 1 year after transplantation was 1.48 +/- 0.50 mg/dL (DGF 1.68 +/- 0.65 vs SGF 1.67 +/- 0.66 vs immediate graft function (IGF) 1.41 +/- 0.40 mg/dL, P = 0.089). The incidence of biopsy-confirmed acute rejection was 22% (DGF 31%, SGF 10%, IGF 8%). One-year patient and graft survival was 92.6 and 78.4%, respectively. The incidence of cytomegalovirus disease, post-transplant diabetes mellitus and malignancies was 28, 8.1, and 0%, respectively. Compared to previous studies, the use of initial full doses of calcineurin inhibitors without antibody induction in patients with SGF or DGF had no negative impact on patient and graft survival.

Adult↗