Medical research council trial of antilymphocyte globulin in renal transplantation. A multicenter randomized double-blind placebo controlled clinical investigation

A total of 173 patients who received live donor or cadaveric primary or secondary renal transplants at five British hospitals were entered into a randomized double-blind controlled clinical trial of equine antilymphocyte globulin (ALG) administered prophylactically to prevent rejection. The ALG was prepared in the early 1970s and used cultured human lymphoblasts as antigen. Following transplantation all patients were treated with a standard immunosuppressant regimen of steroids and azathioprine and, in addition, were given either 30 mg/kg ALG or placebo daily for 10 days by intravenous infusion. In comparison with more recently produced materials, the ALG employed in this study was of moderate potency in prolonging skin graft survival in monkeys. Primary graft failure occurred in 27 patients (15/86 ALG and 12/87 placebo). At three to five years after transplantation 50 of the remaining patients had died, almost all from diseases relating to their renal condition, and 25 more had suffered complete graft failure. No significant differences were found between patients treated with ALG and placebo in the numbers with functioning grafts during the 3 years following transplantation, in the time between transplantation and the first rejection episode, or in the number of episodes during the first six months after transplantation. This applied whether live or cadaveric grafts were employed. Within the first 6 months of operation, infection was given as a major contributory cause of death in 12 patients treated with ALG and in 5 who received placebo (P greater than 0.1). Infections were also slightly more common during the two weeks following transplantation in those receiving ALG (13/86 ALG, 10/87 placebo). As expected, graft survival was significantly better in patients who received live donor grafts (P = 0.001) and in patients with the least donor-recipient histocompatibility mismatches (P = 0.008). The results of this multicenter trial show no therapeutic benefit to renal graft recipients from the administration of ALG, and suggest that the risks of fatal infection may have been aggravated. Use of such equine ALG in similar dose regimens is therefore, not, justified in renal transplantation, especially if some part of the apparent effects on fatal infections is real. It is stressed that these findings are relevant only to the equine ALG used in this study, which was raised with cultured human lymphoblasts as the antigen, and to ALG prepared in a similar way and of similar potency. It should not be inferred that these results are applicable to ALG prepared in other ways.     

Single-center experience with renal transplantation in patients with Wegener's granulomatosis

Between 1980 and 1995, 13 patients with end-stage renal disease due to Wegener's granulomatosis received 14 renal transplants (10 cadaveric, 4 living related). The mean follow-up in the 13 successfully transplanted patients was 50 months (4–107 months). One patient had primary nonfunction and received another graft 4 months later. Three episodes of acute rejection occurred in two patients, and one of these patients lost her graft due to severe vascular rejection 4 months after transplantation. Two patients died with well-functioning grafts (one of metastatic cancer and one of sepsis). One patient presented with perisinusitis and had a mild recurrence of Wegener's disease. None of the patients developed recurrent disease in the transplanted organ. At the last follow-up, the mean creatinine ( ± SD) in the 12 patients with functioning grafts was 1.6 ± 0.6 mg/dl. We conclude that renal transplantation is an excellent treatment for renal failure due to Wegener's granulomatosis. Recurrence of the disease is uncommon in patients under immunosuppression, but careful monitoring is extremely important. Received: 1 July 1996 Received after revision: 6 September 1996 Accepted: 23 September 1996     

Low-dose maintenance prednisone and antilymphoblast globulin for the treatment of acute rejection. A steroid-sparing approach to immunosuppressive therapy

The purpose of this prospective randomized trial was to evaluate an immunosuppressive protocol involving reduced maintenance and antirejection steroid dosages in cadaver renal transplantation. The study comprises 23 first cadaver graft recipients who experienced an acute rejection episode. All patients received an initial 14-day course of antilymphocyte globulin (ALG) and azathioprine 1.5 to 2.0 mg/kg/day. In 11 patients (group 1), a low maintenance dose of prednisone (30 mg/day) was administered and first rejection episodes were treated with a second 10-day course of ALG. The remaining 12 patients (group 2) received high maintenance doses of prednisone (2 mg/kg/day with tapering) and intravenous methylprednisolone (IVMP) for first rejection episodes. Subsequent rejections in both groups were treated with high doses of steroids. In group 1, all first rejection episodes were reversed with ALG alone, 6 patients experienced no subsequent rejection, and 10 patients currently have a functioning graft. In Group 2, the first rejection episode was reversed with IMVP alone in 10 patients; in two patients in whom IVMP therapy was unsuccessful, ALG was then administered, and subsequent rejection reversal was effected. In group 2, 4 patients experienced no subsequent rejection, and 9 patients currently have a functioning graft. Patients in group 1 received significantly lower (P less than .01) cumulative steroid doses in the first six months following transplantation, which resulted in a reduced number of major infections, as compared with patients in group 2. We conclude that the steroid-sparing regimen of low maintenance prednisone and ALG for first rejection is as effective immunologically as the established high steroid protocol.     

The influence of acute rejection on long-term renal allograft survival: a comparison of living and cadaveric donor transplantation

BACKGROUND: We investigated whether recipients of living donor grafts who suffer an acute rejection progress to graft loss because of chronic rejection at a slower rate than recipients of cadaveric grafts. METHODS: A retrospective review was made of 296 renal transplantations performed at Mount Sinai Hospital. Only grafts functioning for at least 3 months were included in this analysis. Demographic variables of donor and recipient age, race, sex, and serum creatinine at 3 months after transplantation were compared between groups. RESULTS: Among the acute rejection-free cohort, the estimated 5-year graft survival was 90% for those receiving transplants from living relatives and 88% for those receiving cadaveric transplants (P=0.76). However, in grafts with early acute rejection, the 5-year survival was 40% for cadaveric recipients compared with 73% for living related graft recipients (P<0.014). Using the proportional hazards model, cadaveric donor source, older donor age, African American recipient race, and elevated 3-month serum creatinine were independent predictors of long-term graft loss caused by chronic rejection. The severity of acute rejection and recipient age had no impact on the risk of graft loss because of chronic rejection. CONCLUSION: These data indicate that the benefit of living related transplantation results from the fact that a living related graft progresses from acute to chronic rejection at a slower rate than a cadaveric graft. Furthermore, a cadaveric graft that is free of acute rejection 3 months after transplantation has an equal likelihood of functioning at 5 years as that of a graft from a living related donor.     

ALG和AHTG在肾移植术后急性肾功能衰竭中的应用

对１４例肾移植术后４８小时内出现肾功能衰竭的患者应用猪抗人胸腺细胞球蛋白（ＡＨＴＧ）和进口马抗人胸腺淋巴细胞球蛋白（ＡＬＧ）。结果发现７１．４％患者肾功能恢复，同期对照组仅４４．４％；一年内４０．０％患者出现排斥反应，而对照组为６２．５％；一年内排斥次数，肾功能恢复时间和进程等则与对照组无明显差异。肾移植术后早期肾功能衰竭的最常见原因为排斥因素，其次为急性肾小管坏死以及手术并发症。     

Kidney transplantation in Macedonia

During the last 10 years we performed 92 renal transplantations in our Skopje hospital (Macedonia), using 22 cadaver donors and 70 living donors. We also performed 15 explanations from cadavers and seven kidneys were allocated to former Yugoslavia. Standard surgical procedures were used for both living and cadaver donor explantations and transplantations. For living explantations, donors were matching in 66 cases (94.28%) and in four cases (5.7%) non-matching donors who however were relatives of the patient Explantations and transplantations took place only after all ethical- and legal-related problems had been solved. The minimum acceptable HLA mismatch was 50% with negative present or historical cross-match. A quadruple sequential immunosuppressive treatment was used, including either poly- or monoclonal globulins (thymoglobulin [ATG], lymphoglobulin [ALG], daclizumab, OKT-3) as an induction therapy and prednisolone, azathriopin and cyclosporin A as maintenance therapy. Rejection episodes were treated by pulse MP therapy or OKT-3 and increased doses of MMF if the patients were steroid-resistant. Kaplan-Meier survival curves showed that survival at 12, 36 and 60 month reached 90%, 75% and 60%, respectively. Survival was better after transplantation using a graft from a living donor than after transplantation using a graft from a cadaver donor (survival rates: 92%, 82% and 68% at 12, 36 and 60 months after surgery). Delayed graft functioning (DGF) was observed in 16 patients (17.3%), reaching 46.6% after transplantation of a graft from a cadaver donor and 10% after transplantation of a graft from a living donor. The relatively high percentage of DGF in the living donor program was due to the use of grafts from elderly donors (over 65 years of age). We registered 26 (29%) episodes of acute rejection that were predominantly histologically confirmed and further classified according to the BANFF criteria. Treatment of five steroid-resistant rejections proved to be successful. Neither early nor late surgical and medical complications were different from those reported in the literature. Despite the modest number of kidney transplantations, chronic renal failure has decreased in our region. The authors expect further improvement in this powerful therapeutic procedure thanks to links with regional and European transplant centers allowing better cooperation and organ sharing.     

Basiliximab (Simulect) in acute tubular necrosis high-risk kidney transplantation

BACKGROUND: Basiliximab (Simulect) therapy reduces acute rejection episodes in renal transplantation. Posttransplant acute tubular necrosis (ATN) is a predisposing factor for acute rejection and reduced graft survival. Anti-lymphocyte antibodies have been used to delay the use of calcineurin antagonists in patients receiving cadaveric renal transplants and to prevent acute rejection episodes. The aim of our study was to learn about the effects of Simulect on ATN in high-risk cadaveric renal transplantation recipients. MATERIALS AND METHODS: We studied 93 patients including, 45 who received Simulect (20 mg before transplantation and 20 mg at day 4 posttransplant and 48 patients who did not receive Simulect. All patients received mycophenolate mofetil, steroids, and cyclosporine (46%) or tacrolimus (54%). We defined ATN as the need for dialysis during the first week after transplantation. Risk factors for ATN were: cold ischemia time, donor and recipient age, donor cause of death as stroke, HLA matching, and panel-reactive antibodies. RESULTS: Among 54 patients who experienced ATN, 44% were in the Simulect group and 71% in the other group (P = .01). In the regression analysis, Simulect was shown to be a protective factor: 0.19 (0.05 to 0.62). Presence of de novo diabetes was more frequent in the group that did not receive Simulect (16 [33%] vs 6 [13%]; P = .02). Acute rejection episodes were similar in both groups: 2.5% in the Simulect group versus 4% in the other group (P = .34). CMV infections occurred in 15 patients (33%) from the Simulect group and in 20 patients (42%) in the other group. Seven patients died in the Simulect group, and five patients died in the other group. In general, Simulect was well tolerated and the degree of complications was similar in both groups. CONCLUSION: Simulect reduced the incidence of ATN among patients receiving a high-risk renal graft. It was well tolerated and no adverse effects were observed. The use of Simulect should be considered for patients receiving renal grafts at high risk for ATN.     

Improved efficacy of basiliximab over antilymphocyte globulin induction therapy in paediatric renal transplantation.

BACKGROUND: Basiliximab is a chimeric human/mouse monoclonal antibody directed against the alpha chain of the IL-2 receptor, CD25, which has been reported as successfully reducing rejection in adult renal transplant recipients. Reported clinical experience of basiliximab in paediatric renal transplantation is limited. METHODS: Using two intravenous doses on day 0 (pre-operatively) and day 4 with prednisolone and cyclosporin A (dual) maintenance immunosuppression in 42 children undergoing renal transplantation in our unit (SIM group), we have compared patient and graft outcome, rejection rates in the first 6 months, renal function and the incidence of Cytomegalovirus (CMV) infection with 42 consecutive children who previously received antilymphocyte globulin immunoprophylaxis with prednisolone, cyclosporin A and azathioprine (triple) maintenance immunosuppression (ALG group). The two groups were similar, including HLA mismatching, apart from age and size at transplantation (SIM=10.3+/-5.4 years vs ALG=12.4+/-4.2 years, P<0.05). RESULTS: One patient in the SIM group died from food inhalation with a functioning kidney and one patient in the ALG group from Pneumocystis pneumonia and post-transplant lymphoproliferative disorders with a rejecting graft. Both 1- and 2-year actuarial graft survivals were 93% for the SIM group and 86% for the ALG group (NS). Three grafts were lost in the SIM group-none from rejection (thrombosis 2, death 1)-and seven in the ALG group-three from rejection. Occurrence of biopsy documented rejection in the first 6 months after transplantation was 0.15+/-0.22 for the SIM group and 0.35+/-0.51 episodes per pt-month at risk for ALG treatment (P<0.04). Early rejection within 30 post-operative days occurred in only four SIM patients, three of whom had undergone retransplantation. Forty-seven per cent of rejection episodes occurred between days 30 and 44 in SIM treated patients. Switching to tacrolimus was similar in both groups; 24% of the SIM groups were prescribed triple therapy. Estimated glomerular filtration rate was 46.0 and 46.2 ml/min for SIM and ALG groups, respectively, six months after transplantation. Ten per cent of SIM and 19% of ALG treated patients developed clinically significant CMV infection (NS) but none of 16 (R(+)) SIM children had CMV infection compared with 8 out of 15 (R(+)) ALG patients (P<0.01). CONCLUSIONS: Basiliximab immunoprophylaxis and dual therapy reduces rejection episodes in the first six months and maintains graft survival and function after paediatric renal transplantation. Seventy-six per cent of children receiving basiliximab immunoprophylaxis were successfully maintained on long-term dual immunosuppression. This immunosuppressive protocol reduces CMV disease in CMV(+) recipients compared with ALG induction and triple therapy.     

The use of antilymphoblast globulin in the treatment of renal allograft rejection: a double-blind, randomized study.

A randomized, double-blind study comparing horse antilymphoblast globulin (ALG) (25 patients) with human IgG (20 patients) in addition to standard antirejection therapy was performed in recipients of first kidney transplants having their first rejection episodes. Patients received ALG (20 mg/kg/day) for 10 days, and a control group was given human IgG (20 mg/kg/day) for 10 days in addition to standard therapy. The groups were comparable with respect to HLA matching, age, time to onset of first rejection episode, and number of diabetics. The number of patients requiring transplant nephrectomy and/or dialysis, having a second rejection episode, having good late function, or dying did not differ in recipients of related kidneys receiving either ALG or human IgG. Recipients of cadaver kidney grafts had fewer (0.05 less than P less than 0.06) second rejection episodes if they received ALG during their first rejection episode. However, the number of patients requiring transplant nephrectomy and/or dialysis, having late good function, and dying did not differ significantly for recipients of cadaver kidneys. We conclude that ALG does not add significantly to standard antirejection therapy for the treatment of first rejection episodes.     

The Effect of Serum ALG Concentrations on Results Following Renal Transplantation

Seventy-three recipients of renal allografts from cadaver donors, and 121 recipients of kidneys from living related donors were studied to determine whether there were any differences in posttransplant results between patients that had a high average serum concentration of ALG (>/=800 microg/ml) during the two weeks of ALG therapy and patients that had low serum levels (/=800 microg/ml when high risk patients with diabetes mellitus were excluded. There were significantly also fewer rejection episodes at three months in recipients of living related kidney grafts that had serum ALG levels >/=800 microg/ml. When high risk diabetics or patients older than 40 were excluded from the related recipients, the number of rejection episodes was still significantly less in patients with high serum ALG levels. There was significantly less kidney loss 24 and more months posttransplant in recipients of kidneys from living related donors whether or not high risk patients were excluded. These results support previous reports from the University of Minnesota indicating ALG is a safe and effective immunosuppressive agent in renal allograft recipients.     

Clinical studies on 228 renal transplants

We studied patient survival and graft survival rates by dividing 228 renal transplants into seven groups according to their immunosuppressive regimen and the degree of histocompatibility. Both patient survival and graft survival rates of HLA identical sibling (Id Sib), living related transplantation with cyclosporin (CYA), transplantation with donor-specific transfusion and anti-lymphocyte globulin (DST.ALG) and cadaveric transplantation with cyclosporin (CYA.Cad) groups were better than those of living related transplantation with ALG, without DST (ALG), living related transplantation with azathioprine and steroid (Non-DST.Non-ALG) and cadaveric transplantation without cyclosporin (Conv.Cad) groups. The incidence and severity of acute rejection were lower in Id Sib, CYA, DST.ALG and CYA.Cad groups than in other groups. The incidence of infections was the highest in Conv.Cad group and that of fatal infections was higher in ALG, Non-DST.Non-ALG and Conv.Cad groups than in other groups. These results indicated that acute rejection and infection were two important factor that influenced the survival rates of these patients. Up to now, the graft survival rate of CYA.Cad group has been much improved as compared to that of Conv.Cad group and was better than those of ALG and Non-DST.Non-ALG groups. The fact urges us to promote more cadaveric renal transplantation in our country by virtue of ciclosporin.     

Role of splenectomy in renal transplantation

One hundred sixteen renal transplants in 99 patients were reviewed. Patients were divided into four groups: 53 live donor recipients with pretransplant splenectomy, 13 nonsplenectomized live donor recipients, 20 cadaver recipients with splenectomy, and 30 nonsplenectomized cadaver recipients. Nonsplenectomized live donor recipients had fewer rejection episodes per month of graft function (p < 0.005). Serum creatinine in functioning grafts showed no differences between splenectomized and nonsplenectomized patients. In 73 splenectomized patients there were 14 related septic and/or thromboembolic complications, 6 fatal. Mean daily azathioprine dosage was greater in splenectomized patients (p < 0.005). There were no hyperacute rejections of second transplants in splenectomized patients, while 2 occurred in 8 nonsplenectomized patients. Splenectomy prior to renal transplantation did not decrease the number of rejection episodes per month of graft function and was associated with a higher rate of septic and thromboembolic complications.     

Clinical experience in renal transplantation

In Shiga Prefecture, 378 chronic renal failure patients were registered at the end of 1981. In 1982, the Kidney Transplantation Group, composed of the department of Urology and the 1st division of Surgery, was organized in our hospital and 10 living related renal transplantations and 8 cadaver renal transplantations were performed between July 1982 and October 1984. As immunosuppressants, azathioprine, mizoribine, cyclosporine, prednisolone, methylprednisolone and ALG were used. Azathioprine was used mainly for living transplantation and cyclosporine mainly for cadaver transplantation. ALG was used only for the initial 3 living transplantations. Mizoribine was sometimes used in combination with azathioprine to reduce the dose of azathioprine and reduce its severe side effects. Seven episodes of acute rejection were experienced and all episodes were remitted by methylprednisolone pulse therapy. There were 20 major post-transplant complications in 13 recipients and among them 2 pulmonary infections were fetal (1 from aspergillus infection and 1 from cytomegalovirus infection). The 10 living related kidney transplantation recipients are all well and none have undergone hemodialysis. Three of the 8 cadaver renal transplantation are well without hemodialysis. One patient could not obtain diuresis. In addition to our experience of renal transplantation, the preoperative scheduled blood transfusion with combination of azathioprine administration, was briefly discussed.     

Improved Late Graft Survival and Half-Lives in Pediatric Kidney Transplantation: A Single Center Experience

We evaluated variables associated with improved late graft survival in 290 children transplanted between 11/1/1984 and 12/31/1997, and who had > 1 year graft survival. We studied the following variables: age, gender, race, primary disease (diseases prone to recurrence, i.e. hemolytic uremic syndrome, focal segmental glomerulosclerosis or oxalosis vs. others), primary vs. retransplant; donor source, acute tubular necrosis, acute rejection episodes in the first year, transplant era and discharge serum creatinine. Graft half-life was defined as the time taken for 1/2 of the grafts functioning at 1 year to fail. There were 205 living donor and 85 cadaveric transplant. The cumulative graft survival at 5 and 10 years was 88% and 75% for living donor, and 72% and 46% for cadaveric, respectively. Multivariate analyses showed a higher late graft survival to be associated with: no acute rejection episodes (risk ratio 0.16, p = 0.0001), age 2-5 years (risk ratio 0.24, p = 0.0007), living donor (risk ratio 0.46, p = 0.017), primary nonrecurrent disease (risk ratio 0.29, p = 0.001), Caucasian race (risk ratio 0.40, p = 0.006). A high half-life was seen with living donor transplant (21.3 years) and the age group 2-5 years (27.5 years). Further, living donor patients with no acute rejection episodes had the best half-life of 37.6 years, while children with hemolytic uremic syndrome, focal segmental glomerulosclerosis or oxalosis had the lowest overall half-life of 5.6 years. This study finds that living donor, no acute rejection episodes, age 2-5 years, Caucasian race and having a disease not prone to recurrence are strong predictors of late graft survival. Hence, preferential use of living donor and prevention of acute rejection episodes in the first year are key variables that can improve long-term renal graft survival in children.     

Prognostic factors affecting graft and patient survival in cadaveric and living kidney transplantation

Numerous studies have reported various prognostic factors that affect graft and patient survival in living and cadaveric donor kidney transplantation (KT). The purpose of this study was to evaluate the clinical outcomes and prognostic factors affecting graft and patient survivals in living and cadaveric donor KT. Between February 1995 and December 2001, 421 patients who had undergone cadaveric donor KT (group I: 216 cases, 51.3%) or living donor KT (group II: 205 cases, 48.7%), were retrospectively analyzed. Five-year overall graft survival rates in living was significantly better than that in cadaveric donor KT, respectively (P = .0234). There was no difference in patient survival rates between the two groups. Such factors as absence of rejection, female donor, female recipient, adult KT according to recipient age (>14 years), and donor serum creatinine level just before transplantation (< 2.5 mg/dL) were significantly associated with good graft survival among cadaveric donor KT, whereas two factors-absence of rejection and adult KT according to recipient age (>14 years)-influenced graft survival in living donor KT. In multivariate analysis, the only significant prognostic factor related to graft survival was the presence of rejection. In conclusion, we suggest that the presence of rejection is the only factor that impairs graft survival in both cadaveric and living donor KT, while other factors affected graft survival differently in the two groups.     

Intrarenal manometry in the diagnosis of acute rejection superimposed on acute tubular necrosis in renal transplantation

We used fine-needle intrarenal manometry as a guide for detection of acute rejection superimposed on protracted oliguric acute tubular necrosis occurring in the postoperative course of human renal transplantation. We followed intrarenal pressure (IRP) in 31 patients who received 32 renal transplants, 12 from living related donors and 20 from cadaveric donors. There were 19 rejection episodes and 10 episodes of transient cyclosporin A (CyA) nephrotoxicity. Nine patients had posttransplant acute renal failure. Levels of IRP (mmHg) in acute rejection were (mean +/- SD) 48.6 +/- 11.1, significantly higher (p less than 0.001) than the levels in CyA nephrotoxicity (28.2 +/- 5.21), acute tubular necrosis (24.5 +/- 5.5) and normal functioning grafts (26.4 +/- 6.63). Antirejection treatment was associated with return to normal of IRP after 10 days. Intrarenal manometry was performed routinely ever 2-3 days in patients who had postoperative acute renal failure. Increments in IRP were detected on the 7-10th postoperative day in 7 patients who had 10-25 days of post-transplant oliguria. Renal biopsy findings were compatible with acute rejection, and the patients responded to intravenous bolus of steroids. We suggest that fine-needle intrarenal manometry is a reliable test for the detection of acute rejection in circumstances when traditional parameters of altered renal function cannot be evaluated.     

A single-center experience of renal transplantation in thirteen Jehovah's Witnesses

The beneficial effects of pretransplant blood transfusions on the success rate of renal transplantation have been so overwhelmingly emphasized that there is virtually no information on the fate of grafts in nontransfused patients transplanted during the last decade. Since 1979, all patients who have undergone renal transplantation at the University of Minnesota have routinely received random blood transfusions except Jehovah's Witnesses. Jehovah's Witnesses refuse transfusions but will accept renal allografts. From 1979 to May 30, 1987, primary renal allografts were placed in thirteen nontransfused Jehovah's Witnesses; six patients received kidneys from mismatched living-related donors, two patients received HLA-identical sibling grafts, and five patients received cadaveric renal allografts. The range of follow-up of the thirteen patients was 3-93 months, with a mean of 45 months and a median of 50 months. The outcomes after renal transplantation in Jehovah's Witnesses were compared with those of a paired control group (n = 25) matched for age, date of transplant, donor source, and diabetic status. The overall three-year actuarial patient and graft survival rates of the Jehovah's Witnesses were 83 per cent and 66 per cent, versus 80 per cent and 77 per cent for the controls. Although the outcomes after renal transplantation in Jehovah's Witnesses were similar to those of the control group, the Jehovah's Witnesses had an increased susceptibility to rejection episodes. The cumulative percentage of incidence of primary rejection episodes was 77 per cent at three months in the Jehovah's Witnesses versus 44 per cent at 21 months in the matched control group. The consequence of early allograft dysfunction from rejection was particularly detrimental to Jehovah's Witnesses who developed severe anemia (hemoglobin (Hgb)* 4.5 g per cent)-two early deaths occurred in the subgroup with this combination of problems. The overall results suggest that renal transplantation can be safely and efficaciously applied to most Jehovah's Witnesses but those with anemia who undergo early rejection episodes are a high-risk group relative to other transplant patients.     

Role of donor age and acute rejection episodes on long-term graft survival in cadaveric kidney transplantations

Cadaveric donors can provide an effective solution to the problem of organ shortage, and many factors that may affect the functioning and survival of cadaveric kidneys have been studied. We aimed to clarify the impact of donor age and acute rejection episodes on long-term graft and patient survival in patients receiving cadaveric renal transplants. We retrospectively evaluated the long-term outcomes of 207 patients who had received cadaveric renal transplants between 1985 and 2004. Mean recipient age, HLA mismatch, mean donor age, delayed graft function (DGF), mean cold ischemia time, acute rejection episodes in the first 6 months after transplantation, and 1-, 3-, and 5-year graft survivals were evaluated. Two study groups were created according to donor age: group 1 (n = 126) was composed of patients receiving kidneys from donors younger than 50 years, and group 2 (n = 81) was composed of patients receiving kidneys from donors 50 years of age or older. Mean recipient age, HLA mismatch, and mean cold ischemia time between groups were not different. The DGF rate in group 1 was 40% (n = 50) and in group 2 was 46% (n = 37) (P > .05). The 1-, 3-, and 5-year survival rates of patients without acute rejection within the first 6 months after transplantation in group 1 (58/126; 46%) versus those in group 2 (46/81; 57%) were 95% versus 90%, 65% versus 60%, and 40% versus 35%, respectively (P > .05). The 1-, 3-, and 5-year graft survival rates of patients with acute rejection within the first 6 months in group 1 (n = 68) versus those in group 2 (n = 35) were 93% versus 89%, 71% versus 55%, and 44% versus 28%, respectively (P = .005). There was no significant difference in 1-, 3-, and 5-year survival rates between patients with DGF in both groups. Acute rejection episodes within the first 6 months after cadaveric transplantation, especially in patients receiving kidneys from donors older than 50 years, were shown to affect 5-year survival of the kidney graft. However, cadaver age alone had no negative effect on 5-year graft survival rates. Cadaveric donors older than 50 years may be a solution to the organ shortage in the treatment of end-stage renal disease.     

Use of anticoagulation in cadaver renal transplants

The effect of anticoagulation was studied in 92 consecutive cadaver renal transplants performed in 90 patients from 1977 to 1980. Patients were randomized to receive prophylactic anticoagulation with warfarin and antiplatelet drugs beginning on the second post-transplant day, or therapeutic heparin for acute rejection episodes with vascular involvement, only. These patients were later converted to long-term anticoagulation with warfarin and antiplatelet drugs. All first rejection episodes were diagnosed by percutaneous renal biopsy and scored as to the degree of cellular infiltrate and vascular change. Immunosuppression consisted of azathioprine, prednisone, methylprednisolone, and, in 19 patients, antilymphoblast globulin (ALG) given for 14 days post-transplant. Rejection episodes were treated in 76 patients. Severe rejection did not respond to any form of treatment and all these grafts failed in less than 3 months. Severe cellular rejection did not occur in ALG-treated patients. Heparin treatment improved the 3-month graft survival in patients with acute rejection and mild vascular changes but did not alter the results in any other category. Chronic rejection was not prevented by any method of anticoagulation. Bleeding complications occurred in 18.4% of patients receiving warfarin and 7.7% of the patients receiving heparin. Anticoagulation with heparin may be useful in the treatment of acute rejection with mild vascular changes. Biopsy-proven severe rejection accurately predicts early graft failure regardless of treatment and should prompt transplant nephrectomy.     

Outcome after transplantation of young patients with systemic lupus erythematosus: a report of the North American pediatric renal transplant cooperative study

BACKGROUND: The risk of progressing to end-stage renal disease in children with lupus glomerulonephritis is 18% to 50%. Published reports of transplantation secondary to end-stage renal failure in adult patients with systemic lupus erythematosus (SLE) demonstrate equivalent patient and graft survival. The purpose of this analysis is to compare patient and graft outcomes of pediatric SLE renal transplant recipients with an age-, race-, and gender-matched control group. METHODS: A retrospective analysis of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) database identified 100 renal transplants performed in 94 young SLE patients. A control group of 470 children having received 501 renal transplants was identified. RESULTS: The SLE cohort was primarily female (82%), non-Caucasian (61%), adolescents and differed from the control group in being less likely to be preemptively transplanted, in receiving longer pretransplant dialysis, and in being likely to have received more than five pretransplant transfusions. After transplantation, there were no differences seen in patient survival at 3 years (89% vs. 95%, SLE vs. control) or in overall graft failure rates (31% vs. 29%, SLE vs. control). There was a trend toward poorer graft survival in non-white SLE patients receiving living donor grafts compared with white SLE patients. An increased graft failure rate was seen among those SLE cadaveric transplant recipients receiving peritoneal dialysis before transplant compared with controls and compared with SLE patients receiving hemodialysis. No differences were seen in rates of acute tubular necrosis or overall acute rejection incidence, although there was a significant increase in the percentage of living donor SLE patients who experienced greater than four rejection episodes. There were nonsignificant trends toward increased graft loss due to patient death with a functioning graft as well as increased mortality secondary to infection in the SLE patients. CONCLUSIONS: The results of renal transplantation in young SLE patients are comparable to those seen in an age-, race- and gender-matched control group. The similar patient and graft survival is seen despite the SLE patients having an underlying disease with multiorgan involvement and despite receiving immunosuppression for potentially prolonged periods before transplantation. No outcome differences were seen except for an unexplained increase in the incidence of recurrent rejections (> or =4) in the living donor SLE patients as well as increased graft failure rate in those patients receiving cadaveric renal transplants after a period of peritoneal dialysis. The nonsignificant trends toward increased graft failures in non-white SLE patients receiving living donor grafts, increased graft loss secondary to death with a functioning graft, as well as the increased mortality due to infection deserve recognition and further study.