摘要:

Background.Nine years ago, a prospective trial began in all U.S. transplant centers to determine whether the results of renal transplantation would improve with the nationwide shipment of kidneys from cadaveric donors to HLA-matched patients. Since then, the stringency of criteria for HLA matching have been liberalized twice, from sharing only those kidneys that matched at all six HLA-A, -B, -DR antigens, to sharing phenotypically HLA-matched kidneys, and most recently to sharing zero HLA-mismatched kidneys.Methods.Data reported to the United Network for Organ Sharing Scientific Renal Transplant Registry from October 1987 to December 1986 were analyzed to examine the transplant results of nationally shared HLA-matched kidneys and the effects of changes to the HLA matching criteria on graft survival and the distribution of HLA-matched kidneys.Results.The overall 1-year graft survival rate of 5102 HLA-matched transplants was 88% compared with 81% for 58,207 recipients of kidneys with at least one HLA mismatch (P<0.001). HLA-matched kidneys had a projected 12-year graft half-life, 50% higher than the 8-year half-life of mismatched grafts (P<0.01). After the first change in the match criteria in August 1990, 1365 phenotypically matched kidneys with fewer than six HLA antigens identified had an 89% 1-year graft survival rate compared with 84% for 466 six antigen-matched kidneys transplanted before the change. After March 1995, 1067 zero HLA-mismatched kidneys that were not phenotypically identical nor six antigen matched, had a 1-year graft survival rate of 88%. Graft survival has not decreased as a result of these changes in the criteria for national sharing, despite an increase in the percentage of matched transplants from 2.5% during the six antigen-match era to 15.5% during the zero antigen-mismatch era.Conclusions.Changes to the United Network for Organ Sharing policy for national sharing of HLA-matched kidneys have increased the number of patients, and especially minority patients, who can benefit by receiving a well-matched graft without compromising the high graft survival rates provided by an HLA-matched kidney.

ISSN:0041-1337    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Background.We previously reported excellent outcome at 6 months after transplantation in recipients of expanded criteria donor kidneys that other local centers had declined, kidneys that nobody wanted (KNW), versus controls. We now report follow-up after 23 months.Methods.We retrospectively reviewed 27 donor and 24 recipient characteristics in 126 adult recipients of transplants from January 1, 1995, to November 25, 1996.Results.Donors of control kidneys versus KNW were younger and had significantly higher minimum 4-hr urine output. Recipients of control kidneys versus KNW had significantly more HLA matches and lower 3-month posttransplant serum creatinine levels. Patient and graft survival rates were similar between the control kidneys versus the KNW. We also compared the control kidneys and KNW with regard to prompt function or delayed graft function and satisfactory versus unsatisfactory function (unsatisfactory: serum creatinine ≥2.5 ml/dl or graft loss at 6 months) to identify donor and recipient characteristics associated with delayed graft function and unsatisfactory outcome. The incidence of rejection was significantly lower in control kidneys and KNW with satisfactory function versus control kidneys and KNW with unsatisfactory function.Conclusions.These data demonstrate: (1) similar graft survival at 12 months, (2) lower donor age, (3) higher minimum 4-hr urine output, and (4) more HLA matches in recipients of control kidneys versus KNW. Optimal outcome was achieved in recipients of control kidneys and KNW with prompt function and satisfactory function based upon serum creatinine in the first 6 months and in recipients with lower rates of rejection. Although outcome is dependent upon many donor and recipient variables, we believe that with careful donor and recipient selection, excellent outcome can be achieved using expanded criteria donor kidneys.

ISSN:0041-1337    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Background.There is a strong association between delayed graft function (DGF) and reduced graft survival (GS) of cadaveric renal transplants. This study was performed to identify donor characteristics that might predict adverse outcomes.Methods.We reviewed the folders of 509 consecutive organ donors for 586 renal transplant recipients receiving grafts between 1990 and 1995. A uniform immunosuppression protocol was employed.Results.The factors that did not alter the rate of DGF were procurement year, local versus shared organs, donor gender, race, hypotension, serum creatinine level and trend, blood transfusions, and vasopressor use and dose. The factors that did alter the frequency of DGF were cause of death(P=0.0053), donor age (P=0.0017), cold ischemic time (P=0.0009), anastomotic time(P=0.0012), combined cold ischemic time and anastomotic time (P=0.00018), and body mass index(P=0.009). All of the factors with the exception of body mass index were of comparable import when analyzed by multiple logistic regression. One-year GS of patients without DGF was 93.2%, and the GS of those with DGF was 76.6% (P<0.0001). However, none of the donor factors correlated with 1-year GS. Seventy-seven donors were the source of paired transplants performed by our program. Sixty percent were concordant for immediate function, 32% were discordant for DGF with equal numbers affecting the first or second graft, and in only 8% did DGF affect both grafts.Conclusions.Donor factors associated with DGF were increased ischemia, donor age, and cause of death. Although there is a close association between DGF and reduced GS, there is no association between these donor factors and GS. This seeming paradox suggests that unkonwn variables contribute heavily to early graft outcome.

ISSN:0041-1337    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Background.Despite great efforts to promote the donation of cadaveric organs, the number of organ transplantations in Japan is not increasing and a serious shortage of cadaveric organs exists. These circumstances have forced a widening of indications for kidney transplantation. For this purpose, ABO-incompatible living kidney transplantations (LKTs) have been performed. Although we have already reported the short-term results of ABO-incompatible LKT, there is no report of long-term results in such cases; anti-A and anti-B antibodies could cause antibody-induced chronic rejection and result in poor long-term graft survival. In this study, we have reviewed the long-term results of ABO-incompatible LKT and tried to identify the most important factors for long-term renal function in ABO-incompatible LKT.Methods.Sixty-seven patients with end-stage renal failure underwent ABO-incompatible living kidney transplantation at our institute between January, 1989, and December, 1995. The mean age was 34.9 years (range, 8-58 years), with 38 males and 29 females. Incompatibility in ABO blood group antigens was as follows: A1→O, 23 patients; B→O, 19 patients; A1B→A1, 7 patients; B→A1, 8 patients; A1→B; 4 patients; A1B→B, 4 patients; A1B→O, 2 patients. The number of HLA-AB, and -DR mismatches were 1.6±1.1 and 0.76±0.6, respectively. Plasmapheresis and immunoadsorption were carried out to remove the anti-AB antibodies before the kidney transplantation. In the induction phase, methylprednisolone, cyclosporine, azathioprine, antilymphocyte globulin, and deoxyspergualin were used for immunosuppression. Local irradiation of the graft was performed at a dose of 150 rad, on the first, third, and fifth days after transplantation. Splenectomy was done at the time of kidney transplantation in all cases.Results.Patient survival was 93% at 1 year and 91% at 8 years. Graft survival was 79% at 1, 2, 3, and 4 years, 75% at 5 and 6 years, and 73% at 7 and 8 years. Patient survival was not significantly different from that of ABO-compatible patients. However, graft survival was significantly different between ABO-incompatible grafts and ABO-compatible grafts. Specifically, ABO-incompatible transplant recipients experienced a significantly higher rate of early graft loss up to 3 years but showed an equivalent graft loss by year 4. Among 67 patients, 16 grafts were lost during the observation period. Loss was due to acute rejection in 5 patients, followed by chronic rejection in 5 patients and death with function in 3 patients, whereas immunosuppression was withdrawn in 3 patients due to nonimmunological reasons. Of 16 grafts lost, 15 were lost within 1 year after transplantation. Of the 67 patients, 5 died during observation. Three patients with functioning grafts died of uncontrolled bleeding due to duodenal ulcer, malignant lymphoma, and cerebral hemorrhage (one patient each). One patient died of ischemic colitis due to secondary amyloidosis and one patient of cerebral hemorrhage after graft loss due to humoral rejection. There was no fatal infectious complication, whereas 10 patients had non-tissue-invasive cytomegalovirus infection. The stepwise logistic regression model was employed to identify the most important factors for long-term renal function. Patients were subdivided into those with serum creatinine of less than 2.0 mg/dl (group 1, n=39) versus those with serum creatinine of more than 2.0 mg/dl (group 2, n=22) at one year after renal transplantation. Six patients were excluded because of death with functioning graft (three patients) and withdrawl of immunosuppression (three patients). Rejection episodes within 6 months were significantly frequent in group 2 compared with group 1 (P=0.0008). Odds ratio was 112-fold in the rejection episodes. Obviously, the high incidence of early humoral rejection is caused by ABO incompatibility, because ABO-incompatible grafts experience a higher rate of early rejection and graft loss compared with ABO-compatible grafts. This means that ABO incompatibility is, principally, the most important factor to affect graft function in ABO-incompatible LKT. Donors who were over 54 years old were also significantly frequent in group 2 compared with group 1, and the odds ratio was 12 in the donors who were over 54 years old. HLA-DR mismatches and pre-operative maximum anti-AB IgG showed a significant difference between group 1 and group 2. However, these differences were much less than those of donor age and rejection episodes. There were no significant differences between group 1 and group 2 in terms of recipient age, HLA-AB mismatches, anti-AB IgM antibody titers, incompatibility of blood type, and sex.Conclusions.ABO-incompatible living kidney transplantation offers an excellent long-term outcome and is an acceptable treatment for end-stage renal failure. Long-term renal function in ABO-incompatible LKT is primarily influenced by the occurrence of acute rejection episodes within 6 months, associated with ABO incompatibility and a higher donor age (over 54 years old).

ISSN:0041-1337    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Background.We reviewed the incidence of and risk factors for venous thromboembolic complications in our population of kidney (KTx) and simultaneous kidney-pancreas transplant (SPK) recipients.Methods.Information was collected retrospectively from a database on 1833 KTx and 276 SPK recipients who underwent transplant surgery between January 1985 and August 1995.Results.The incidence of deep venous thrombosis (DVT) was 6.2%(n=132), with significantly higher rates after SPK (18.1%) vs. KTx (4.5%)(P<0.001). The number of DVT episodes was highest in the first month; 17.5% occurred during this time. For KTx recipients, early thrombotic events were more common on the side of the graft(P=0.03); however, after 1 month, no correlation existed between the side of the graft and the side of DVT. For SPK recipients, DVT tended to be more common on the side of the pancreas (57%) vs. the kidney(43%) (P=0.10). By multivariate analysis, risk factors for DVT were: age >40 years (odds ratio [OR]=2.2,P<0.001), diabetes mellitus (DM) (OR=2.0,P=0.002), previous DVT (OR=4.4,P=0.001), and SPK transplant (OR=2.8,P<0.001). Pulmonary embolus (PE) was identified in 44 recipients (incidence, 2.1%) and was fatal in 13 (30%). The incidence was significantly higher in SPK (4.71%) vs. KTx recipients (1.69%)(P<0.01). The risk of death from PE was 0.5% in KTx recipients and 1.37% in SPK recipients (P=0.08). Risk factors for PE included DM (OR=2.6,P=0.005) and recent DVT (OR=8.9,P=0.0001).Conclusions.Based on risk and extrapolating from the general surgical literature, our recommendations for prophylaxis against DVT are use of graduated compression stockings for all recipients and, in addition, low-dose heparin for moderate and high-risk recipients (previous DVT, SPK, age>40 years, DM).

ISSN:0041-1337    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Background.Mycophenolate mofetil (MMF) significantly reduces the incidence of acute allograft rejection in renal transplant patients. The effect of adding MMF to the immunosuppressive regimen of patients with established rejection is unknown. The purpose of the current study was to compare the safety and efficacy of the addition of MMF to the treatment regimen of an early first acute cellular rejection.Methods.The study was a double-blind, double-dummy controlled clinical trial of 221 renal transplant recipients experiencing the first biopsy-proven rejection within 6 months of transplant performed at 15 U.S. and Canadian centers. A total of 113 patients received MMF (1.5 g twice daily) and intravenous corticosteroids, and 108 patients received azathioprine (AZA) (1-2 mg/kg/day) and intravenous corticosteroids. The intravenous corticosteroids in each group consisted of 5 mg/kg/day for 5 days followed by an oral steroid taper. End points for the study were the first use of antilymphocyte therapy, the number of courses of antirejection therapy given during the first 6 months, and graft and patient survival at 1 year.Results.At 6 months, 16.8% of the MMF-treated patients and 41.7% of the AZA-treated patients required at least one course of antilymphocyte therapy(P<0.0001). The number of patients requiring full courses of antirejection therapy for the treatment of rejection was less in the MMF-treated group (24.8%) versus the AZA-treated group (58.3%)(P<0.0001). The proportion of patients with the use of antilymphocyte therapy or treatment failure during the first 6 months was 29.2% vs. 51.9% (P=0.0006) in the MMF versus the AZA groups, respectively. By 1 year after enrollment, 10 patients (8.9%) in the MMF-treated group lost their graft or died versus 16 patients (14.8%) in the AZA-treated group. More patients in the MMF group withdrew because of an adverse event: 20 patients (17.7%) compared with 11 AZA-treated patients(10.2%).Conclusions.MMF administered in combination with pulse corticosteroids significantly decreases the subsequent use of antilymphocyte therapy in the treatment of acute renal allograft rejection. In addition to being a safe and effective prophylactic agent, MMF added to steroids improves the rate of reversal of acute rejection episodes.

ISSN:0041-1337    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Background.Multicenter clinical trials have shown that mycophenolate mofetil(MMF) reduces the risk of acute rejection, but it is unknown whether African-Americans constitute a subgroup of recipients less likely to benefit from MMF.Methods.This study compared the acute rejection rates within 6 months of kidney transplantation in MMF-treated transplant patients with those on azathioprine (AZA) at a single center. The study population consisted of 353 consecutive recipients of cadaver or living donor kidney transplants. African-Americans constituted 43% of the patients on AZA and 49% of the patients on MMF. Variables used in a Cox regression analysis included MMF immunosuppression, recipient race, type of transplant, delayed graft function, postoperative immune induction, average cyclosporine through level, and HLA mismatch.Results.Significantly fewer patients on MMF experienced a biopsy-proven rejection episode than those treated with AZA (24% vs. 42%, respectively; relative risk [RR]=0.57,P=0.001). This decrease in risk was greater in Caucasian transplant recipients (MMF vs. AZA: 16% vs. 46%, RR=0.35,P<0.001) than in African-American patients(32% vs. 36%, RR=0.88,P=0.6). Within each race stratum, the mean cyclosporine trough levels averaged over 2-week intervals were nearly identical for AZA- compared with MMF-treated patients. In the regression model, the effect of MMF on the incidence of rejection was again less in African-American than in Caucasian patients.Conclusions.Kidney recipients treated with MMF have a significantly lower risk of acute rejection within 6 months of transplantation than those given AZA. This reduction in risk is significantly less in African-American recipients than Caucasians.

ISSN:0041-1337    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Background.Studies using tacrolimus and corticosteroids or the combination of cyclosporine, mycophenolate mofetil, and corticosteroids have been shown to reduce the incidence of biopsy-proven acute rejection episodes in cadaveric kidney recipients compared with cyclosporine-based immunosuppression. The current study is a retrospective analysis of our experience with tacrolimus combined with mycophenolate mofetil and steroids as primary immunosuppression for kidney transplant recipients.Methods.In a retrospective analysis, 72 patients who received primary therapy with tacrolimus, mycophenolate mofetil, and corticosteroids (triple therapy) were compared with a control group of 98 kidney recipients who received tacrolimus and corticosteroids (double therapy).Results.There was a significant reduction in the incidence of biopsy-confirmed acute rejection in the triple therapy group (8.2%) compared with the double therapy group (21%;P=0.003). One-year patient and graft survival did not differ between groups. The incidence of posttransplant diabetes mellitus was 18% and 21% in the triple and double therapy groups, respectively. Leukopenia and gastrointestinal side effects were the most common cause for discontinuation of mycophenolate mofetil.Conclusions.The combination of tacrolimus with mycophenolate mofetil and corticosteroids is more effective at preventing early acute rejection than tacrolimus and corticosteroids alone. The use of mycophenolate mofetil was associated with a higher incidence of leukopenia and diarrhea, often leading to discontinuation of the drug.

ISSN:0041-1337    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Background.Mothers treated with cyclosporine (CsA) have previously not been allowed to breast-feed due to the reported accumulation of the drug in breast milk. The purpose of this study was to evaluate the consequences of allowing breast-feeding.Methods.Seven infants were breast-fed by mothers who had undergone kidney transplantation alone (n=5) or simultaneous kidney and pancreas transplants(n=2). In addition to CsA, all mothers received prednisolone at 5-7.5 mg/day and six mothers received azathioprine at 50-100 mg. CsA concentration was measured in the whole blood of mothers and babies and in breast milk. Serum creatinine was measured in babies 1 week after birth and after 4-12 months of breast-feeding.Results.Blood CsA levels ranged from 55 to 130 ng/ml in mothers (12-hr trough), 50 to 227 ng/ml in breast milk (mean for each woman), and was below the detection limit of 30 ng/ml in all infants. Breast milk concentration ranged from 87 to 440 ng/ml in 16 samples obtained at various time points from one mother. Infants' serum creatinine ranged from 25 to 54 μmol/L at 1 week after birth and 23-52 μmol/L after breast-feeding. All babies thrived.Conclusions.Breast-fed infants of mothers treated with CsA received less than 300 μg per day of CsA and absorbed undetectable amounts. There were no demonstrable nephrotoxic effects or other side effects. Thus, women with kidney transplants could be allowed to breast-feed.

ISSN:0041-1337    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Background.This article summarizes our 10-year multicenter experience with transplantation of 50 blood group A2and A2B kidneys into B and O patients.Methods.Since 1986, we have transplanted kidneys from 46 cadaver donors and 4 living donors who were blood group A2(47 donors) or A2B (3 donors) into 19 B and 31 O patients. In 1991, we began allocating these kidneys preferentially to B and O recipients who were selected based on a history of low (≤4) anti-A IgG isoagglutinin titers. Immunosuppression was no different from that used in ABO-compatible grafts.Results.The 1-month function rate before thus selecting the patients was 68%(19/28), but is now 94% (17/18). Two-year cadaver-donor graft survival with this selection method is 94%, compared with 88% for 640 concurrent and consecutive ABO-compatible transplants (log-rank, 0.15). All four living-related transplants are still functioning, with a mean follow-up of 71 months. Since we began allocating A2kidneys preferentially to B and O recipients, the percentage of the B patients who received A2or A2B kidneys has increased from 29% (8/28) to 55% (10/18).Conclusions.Transplantation of A2or A2B kidneys into B and O patients is clinically equivalent to that of ABO-compatible transplantation when recipients are selected by low pretransplant anti-A titer histories. This approach increases access of blood group B recipients to kidneys.

ISSN:0041-1337    

出版商:OVID    

年代:1998

数据来源: OVID