Long-term effect of splenectomy versus no splenectomy in renal transplant patients. Reanalysis of a randomized prospective study

In 1980 we determined the patient and renal allograft survival in 299 kidney transplants recipients who, between 1976 and 1979, were randomized to splenectomy (n = 146) versus nonsplenectomy (n = 152), and who were treated with antilymphocyte globulin-azathioprine-prednisone for immunosuppression. The preliminary analysis showed significantly (P less than .05) better (10% overall, 12% for cadaver, 14% for nonidentical-related) graft survival rates at two years in splenectomized recipients. The splenectomized patients had higher white blood counts and received more azathioprine and less prednisone. We concluded that splenectomy had a beneficial effect for at least the first two years posttransplant without a detrimental effect on patient survival. Splenectomy, however, remains controversial. Thus, we reanalyzed the original cohort 7 years after the study began and 4 years after the last patient was entered. The reanalysis showed that the differences in graft survival rates between splenectomized and nonsplenectomized recipients were no longer significant. There were more late deaths from sepsis in the splenectomized group, although the overall patient survival rates were similar in splenectomized and nonsplenectomized recipients. Splenectomy modestly improved graft survival for the first few years, but the eventual fate of the graft was determined by other factors. The dominant influence on graft survival rates was the source of the kidney (at 6 years in splenectomized recipients the functional survival rate of grafts from HLA-identical siblings was 24% higher than that of grafts from HLA-mismatched relatives, which in turn was 24% higher than that of grafts from cadaver donors; in nonsplenectomized recipients the difference in 6-year function rates between HLA-identical and mismatched related grafts was 34%, and between mismatched related and cadaver grafts was 16%. Between 1979 and 1983, we performed pretransplant splenectomies in all recipients of renal allografts from HLA-mismatched related or cadaver donors. Two-year graft survival rates were 81% and 68%, respectively, in azathioprine-treated recipients, 7% and 12% higher than in the splenectomized patients in the randomized trial. (ABSTRACT TRUNCATED AT 400 WORDS)     

Lessons learned from ABO-incompatible living donor kidney transplantation: 20 years later

From June 1982 to November 1989, 39 ABO-incompatible living kidney transplants were performed in 38 recipients. Pretransplant therapies included platelets donor transfusion (21/39), 2 to 5 plasmapheresis sessions (39/39), cyclosporin A with or without azathioprine (33/39) along with polyclonal Abs (36/39) and splenectomy at the time of transplantation (37/39). The last patient who received 2 ABO-incompatible transplants was previously splenectomized (end-stage renal failure due to a cortical necrosis following a traumatic spleen rupture). Three other patients who did not undergo a splenectomy at the time of transplantation were not included in that series but hyperacutely rejected their transplants during the first postoperative week. The 31 ABO-incompatible living related donor graft recipients are alive. Graft loss occurred from acute and/or hyperacute rejection in 5 cases (none below 15 years of age) and from chronic rejection in 8 cases. By contrast, among the 8 ABO-incompatible living unrelated donor graft recipients, only one renal graft is still functioning 20 years later. Graft survival rates are better in the group of patients < 15 years (100%, 89%, 78%, and 78% at 2, 5, 10, and 15 years respectively) compared with the group > 15 years (77%, 77%, 64%, and 59% respectively; NS). Today, 20 years later, prospective randomized studies testing different steps in the preparation protocol are still lacking. Plasmaphereses were replaced by double filtration plasmapheresis and immunoadsorption. Splenectomy seems to be a prerequisite for successful ABO-incompatible living kidney transplantation but IV Ig globulins and rituximab are currently being successfully used without splenectomy along with the new immunosuppressive drugs. As the procedure remains unchanged, it might be reserved to patients where cadaver graft could not be a valuable alternative, especially for recipients < 15 years of age with a living related ABO-incompatible donor.     

Race as a risk factor in cadaver kidney transplantation.

Recipients of 93 first-cadaver kidney transplants were studied for the effect of recipient and donor race on graft and patient survival. Both graft and patient survival were lower for black recipients than for whites. The difference was not explained by racial mismatch between donor and recipient. Black recipients had more rejection episodes and more instances of bacterial pneumonia. Pretransplant splenectomy reduced the likelihood of rejection episodes for black recipients and increased their rate of graft survival.     

Effect of splenectomy on first cadaver kidney transplants.

A prospective study was begun in January 1975 to evaluate the effect of splenectomy on graft and patient survival in recipients of first cadaver kidney transplants. Ninety-two cases were evaluated. Splenectomy increased the survival of both grafts and recipients. The benefit from splenectomy compensated readily for the perioperative morbidity of splenectomy and the long-term increased risk of sepsis from certain bacteria for the asplenic patient. Splenectomy exerted its effect by reducing the incidence and intensity of rejection episodes. It was not clear whether the observation resulted from a direct immunosuppressive effect of splenectomy or from the increased tolerance to azathioprine observed in asplenic recipients. Finally, splenectomy negated an effect of race that had been observed earlier for survival of cadaver transplants and recipients.     

Evaluation of flowcytometric crossmatching in renal allograft recipients.

Forty-four cadaver renal allograft recipients who had flowcytometric cross-match (FCXM) testing and sequential quadruple immunosuppression were studied with respect to the number of rejection episodes and the functional viability of the graft in the first year after transplantation. Fourteen of these patients had antibodies to donor T cells by FCXM. All were negative by conventional crossmatch. Multiple-regression analysis with HLA mismatches, panel-reactive antibody (PRA) percentage, flowcytometric channel shifts and transplant number as independent variables revealed that transplant number and high PRA (> 50%) impacted (p < 0.05) on serum creatinine at 1 month and 1 year, and graft survival at 1 year. In first transplants, a positive FCXM had no impact on 1-year graft survival rates; however, in retransplants, a positive FCXM and/or high PRA had a significant negative impact on 1-year graft survival. This study indicates that the FCXM should be utilized for retransplant patients, and in patients with a high PRA, in an attempt to improve graft survival for these high-risk recipients.     

Laparoscopic Versus Open Renal Procurement for Pediatric Recipients of Living Donor Renal Transplantation

Despite reports demonstrating the safety of laparoscopic donor nephrectomy (LDN) for pediatric recipients of renal transplants, recent evidence has challenged using LDN for recipients 5 years of age or younger. We retrospectively reviewed the records of all pediatric recipients of living donor renal transplants from September 2000 through August 2004. We compared those who received allografts recovered by LDN (n = 34) with those recovered by open donor nephrectomy (ODN, n = 26). Outcomes of interest included operative complications, postoperative renal function, the incidence of delayed graft function or episodes of acute rejection and long-term graft function. Donor and recipient demographic data were similar for the LDN and ODN groups. Serum creatinine and calculated creatinine clearance were not significantly different between groups both in the early postoperative period and at long-term follow-up (p > 0.142). Rates of delayed graft function and acute rejection did not differ between groups. Among recipients aged 5 years old or younger stratified by donor technique (9 LDN, 5 ODN recipients), no difference was noted in graft outcomes both early and long-term (p > 0.079). At our center, pediatric LDN recipients have graft outcomes comparable to those of ODN recipients. At experienced centers, we recommend continued use of LDN for pediatric recipients of all ages.     

Renal transplantation between living-related sibling pairs matched for zero-HLA haplotypes

The functional survival rates of kidney grafts from zero-HLA haplotype-matched sibling pairs are similar to one-haplotype-matched pairs and superior to cadaver grafts. From January 1980 to March 1988, 318 primary renal transplants from sibling donors (151 matched for two, 130 for one, and 37 for zero HLA haplotypes), and 352 cadaver graft transplants were performed at the University of Minnesota. The renal graft survival rates at two years were 94%, 91%, and 94% for the 2, 1, and 0-haplotype pairs versus 75% for cadaver graft recipients (P less than 0.04). When analyzed across the different immunosuppression protocols the same trends held up, similar graft functional survivals for 1- and 0-haplotype-matched pairs both being superior to cadaver graft recipients. The graft functional survival rates at two years of recipients of 0-haplotype-matched sibling donor grafts (n = 37) was 94% versus 80% for recipients of cadaver donor grafts matched for greater than or equal to 4 HLA antigens. In addition, for recipients of 0-haplotype-matched grafts, hospital stay was shorter, fewer patients required dialysis posttransplant, and, despite a slightly higher incidence of rejection episodes (51% versus 40%, P = ns), the creatinine values one year posttransplant were significantly lower (1.5 mg/dl versus 1.9 mg/dl, P less than 0.02) than those of recipients of cadaver grafts matched for greater than or equal to 4 HLA antigens. These data support the use of cadaver grafts for patients not having a willing sibling donor, and the use of all willing sibling donors, whether or not they are a zero-haplotype match, for patients fortunate to have that family commitment.     

Renal transplantation for end-stage polycystic kidney disease

From 1963 to 1984, 56 renal transplants were performed in 51 patients with end-stage renal failure due to autosomal dominant polycystic kidney disease (ADPKD). There were 49 cadaver and 7 living-related transplants. Overall patient and graft survival was 88 per cent and 66 per cent at one year, 59 per cent and 49 per cent at five years, respectively. There was no significant difference in patient or graft outcome with cadaver versus living-related donor kidneys. One-year graft success with and without pretransplant bilateral nephrectomy (BN) was 78 per cent versus 58 per cent, respectively (n.s.). Patient survival after return to dialysis after graft loss was not compromised by the earlier performance of BN. In patients who did not undergo pretransplant BN, there were no complications from the retained native kidneys after transplantation. In cadaver recipients, the two-year graft success rate with and without preliminary blood transfusions was 54 per cent versus 61 per cent, respectively (n.s.). Cadaver graft survival with and without adjunctive antilymphocyte globulin (ALG), excluding 3 recipients managed with cyclosporine, was 88 per cent versus 50 per cent at one year, and 70 per cent versus 32 per cent at five years, respectively (p less than 0.05). This beneficial effect of ALG was still evident when only transfused cadaver recipients were analyzed and was achieved with no resulting compromise in patient survival. Follow-up computerized tomography (CT) scanning of the transplant kidney in 10 recipients with a long-term (1-9 years) functioning allograft showed no evidence of recurrent ADKPKD.     

Living Donor Renal Transplantation Using Alemtuzumab Induction and Tacrolimus Monotherapy

Alemtuzumab was used as an induction agent in 205 renal transplant recipients undergoing 207 living donor renal transplants. All donor kidneys were recovered laparoscopically. Postoperatively, patients were treated with tacrolimus monotherapy, and immunosuppression was weaned when possible. Forty-seven recipients of living donor renal transplants prior to the induction era who received conventional triple drug immunosuppression without antibody induction served as historic controls. The mean follow-up was 493 days in the alemtuzumab group and 2101 days in the historic control group. Actuarial 1-year patient and graft survival were 98.6% and 98.1% in the alemtuzumab group, compared to 93.6% and 91.5% in the control group, respectively. The incidence of acute cellular rejection (ACR) at 1 year was 6.8% in the alemtuzumab group and 17.0% (p < 0.05) in the historic control group. Most (81.3%) episodes of ACR in the alemtuzumab group were Banff 1 (a or b) and were sensitive to steroid pulses for the treatment of rejection. There was no cytomegalovirus disease or infection. The incidence of delayed graft function was 0%, and the incidence of posttransplant insulin-dependent diabetes mellitus was 0.5%. This study represents the largest series to date of live donor renal transplant recipients undergoing alemtuzumab induction, and confirms the short-term safety and efficacy of this approach.     

Risk factors on graft survival of living donor kidney transplantation

Living donors have always been the basic resources of transplantation in our country, where cadaveric harvesting is still hampered for various reasons. OBJECTIVE: The aim of this study was to compare graft survival rates between living unrelated donor (LURD) and living related donor (LRD), to assess the potential risk factors for the graft survival, and to discuss the role of LURD. METHOD: From October 1991 to February 2003, 77 living donor renal transplants were performed: 41 were LURD and 36 were LRD transplants. The analyzed variables were donor relationship, recipient age and sex, donor age and sex, HLA-DR mismatching, nonspecific blood transfusion history of donor, acute rejection episodes, repeated rejection episode (more than 3 times), delayed graft function, recurred primary disease, and immunosuppressive regimen. Graft survival rate was assessed with the Kaplan-Meier method and the significance of possible variables with the Cox proportional hazard model. RESULTS: Eleven recipients lost their grafts (6 from LURD and 5 from LRD), most of them are due to chronic rejection (n = 7). Overall 3-, 5- and 10-year graft survival in live donors were 92.8%, 86.6%, and 76.9%, respectively. Graft survival at 3, 5, and 10 years being 91.9%, 88.5%, and 74.7% for the LURD versus 94%, 84%, and 78.8% for LRD transplants (P > .05). Acute rejection episodes, especially more than 3 times (risk ratio [RR] = 11.1) and preoperative multiple transfusion history (RR = 4.2) were significant factors on graft survival in our series. CONCLUSION: Acute rejection episodes markedly decreased the long-term graft survival in live donor renal transplants. The use of LURD transplants provides graft survival comparable with LRD transplants and proper management to acute rejection is essential for long-term graft survival.     

Estimated donor glomerular filtration rate is the most important donor characteristic predicting graft function in recipients of kidneys from live donors

We hypothesized that predictors of outcome in live donor transplants were likely to differ significantly from deceased donor transplants, in which cold ischaemia time, cause of donor death and other donor factors are the most important predictors. The primary aim was to explore the independent predictors of graft function in recipients of live donor kidneys (LDK). Our secondary aim was to determine which donor characteristics are the most useful predictors. A retrospective analysis was undertaken of all patients receiving live donor (n = 206) renal transplants at our institution between 31 May 1994 and 15 October 2002. Twelve patients were excluded from the analysis. Follow-up was completed on all patients until graft loss, death or 22 November 2003. We explored predictors of Nankivell glomerular filtration rate (GFR) at 6 months by multivariate linear regression. In the 194 patients studied, the mean recipient 6-month Nankivell GFR was 59 +/- 15 ml/min/1.73 m(2). Independent predictors of recipient GFR in at 6 months were donor Cockcroft-Gault GFR (CrCl; beta 0.16; CI 0.13 to 0.29; P < 0.0001), steroid resistant rejection (beta-6.07; CI -12.05 to -0.09; P = 0.006) and delayed graft function (DGF) (beta-10.0; CI -19.52 to -0.49; P = 0.039). Renal function in an LDK transplant recipients is predicted by donor GFR, episodes of steroid resistant rejection and DGF. Importantly, donor Cockcroft-Gault GFR is the most important characteristic for predicting the recipient renal function.     

Splenectomy and renal allograft survival in the rat

The effect of splenectomy on renal allograft survival is not clear. In the rat, spleens isolated from recipients with functioning grafts have been shown to be a major source of cells that are capable of suppressing the rejection response (suppressor T lymphocytes). Thus the removal of the spleen in these allograft recipients could be detrimental to renal allograft survival. This study investigates this hypothesis, and looks for the presence of suppressor cells in other lymphoid organs apart from the spleen. In the rat renal allograft model, donor Lewis spleen cells given to DA recipients intravenously 1 week before transplantation of a Lewis kidney leads to indefinite allograft survival (median survival time (MST) greater than 100 days). Splenectomy before or after pretreatment with donor spleen cells failed to abrogate this effect (MST greater than 100 days). Experiments were performed in which cells or serum were prepared from long-term surviving splenectomized animals which had already been pretreated and transplanted, and then were injected into untreated recipients (adoptive transfer experiments). This was done to determine if cells capable of suppressing graft rejection were present in lymphoid organs outside the spleen in these splenectomized recipients. Thus the IV transfer of 10(8) lymph node cells harvested from splenectomized DA recipients with a long-term surviving LEW graft (LTS), into untreated but lightly irradiated (200 rad) DA recipients resulted in indefinite survival of a fresh Lewis kidney (MST greater than 100 days). In contrast, adoptive transfer of normal DA lymph node cells was ineffective (MST 13 days). Thus splenectomy is not necessarily detrimental to graft survival, as cells capable of preventing graft rejection are found in other lymphoid organs, such as lymph nodes, in splenectomized recipients.     

A single institution, randomized, prospective trial of cyclosporin versus azathioprine-antilymphocyte globulin for immunosuppression in renal allograft recipients.

Between September 26, 1980 and December 31, 1983, 230 splenectomized, transfused renal allograft recipients were randomized to treatment with either cyclosporin-prednisone (N = 121, 68 diabetic and 53 nondiabetic recipients; 73 cadaver and 48 related donor grafts) or azathioprine-prednisone-antilymphocyte globulin (N = 109, 61 diabetic and 48 nondiabetic recipients; 69 cadaver and 40 related donor grafts). The results were analyzed on March 31, 1984. Actuarial patient survival rates at 2 years were 88% in the cyclosporin and 91% in the azathioprine groups (p = 0.649). Graft survival rates at 2 years were 82% in all cyclosporin and 77% in all azathioprine-treated recipients (p = 0.150); the corresponding figures in the recipients of related donor grafts were 87% vs. 83% (p = 0.656), and in the recipients of cadaver donor grafts were 78% vs. 73% (p = 0.178). The 2-year graft survival rates were 81% in cyclosporin and 74% in azathioprine-treated diabetic recipients (p = 0.150) and 83% in cyclosporin and 81% in azathioprine-treated nondiabetic recipients (p = 0.604). Within the cyclosporin and azathioprine treatment groups, the differences in graft survival rates between diabetic and nondiabetic recipients were not significant (p = 0.822 and 0.423, respectively). Although there were no significant differences in graft survival rates, the cumulative incidence of rejection episodes within the first post-transplant year was significantly lower in the cyclosporin (34%) than in the azathioprine (60%) treated recipients (p = 0.001). In recipients of technically successful cadaver kidney grafts, the incidence of acute tubular necrosis (ATN) was 31% in cyclosporin and 30% in azathioprine-treated recipients (p = 0.822). Graft survival rates in azathioprine- and cyclosporin-treated recipients who did or did not undergo ATN were 72% vs. 89% (p = 0.011). The mean (+/- S.D.) serum creatinine levels (mg/dl) at 1 year were higher in cyclosporin (2.0 +/- 0.6) than in azathioprine (1.5 +/- 0.5) treated recipients (p = less than 0.001). A reduction in cyclosporin dose because of nephrotoxicity was required in 96 of the cyclosporin-treated patients (70%), and 25 were switched to treatment with azathioprine (21%). The incidence of all infections in cyclosporin-treated patients was approximately half of that in azathioprine-treated patients, and only nine per cent of the cyclosporin-treated patients were diagnosed to have cytomegalovirus infections during the first post-transplant year vs. 28% in azathioprine-treated patients (p = 0.002).(ABSTRACT TRUNCATED AT 400 WORDS)     

Immunologic and nonimmunologic factors: different risks for cadaver and living donor transplantation

BACKGROUND: There is a debate about the relative contribution of immunologic (rejection) and nonimmunologic (limited nephron mass) factors in long-term graft survival. METHODS: Using multivariate analysis, we studied the association of the following variables with outcome: delayed graft function (DGF), acute rejection, recipient race (black vs. nonblack), donor age (<50 vs. > or =50), donor race, and donor and recipient gender. Because of the association between DGF and rejection, recipients were grouped as follows: DGF, rejection; DGF, no rejection; no DGF, rejection; no DGF, no rejection. Data were analyzed on 1199 first kidney transplants in adults (752 living donor, 447 cadaver donor) done between January 1, 1985 and December 31, 1996. Two analyses were done: first, all transplants; second, only those with > or =1 year survival. For both, there was no difference in risk factors if death with function was or was not censored. RESULTS: For all cadaver transplant recipients, risk factors were acute rejection, DGF plus rejection, black recipient race, and donor age > or =50. For living donor recipients, only acute rejection was a risk factor. When only 1-year graft survivors were considered, risk factors were the same: for cadaver recipients, risk factors were acute rejection, DGF plus rejection, black recipient race, and donor age > or =50; for living donor recipients the risk factor was rejection. CONCLUSION: We found immunologic factors (rejection with or without DGF) to be significant in both living donor and cadaver donor transplants. Nonim. munologic factors (donor age, recipient race) were significant only in cadaver donor transplants.     

Renal transplantation in the older recipient

From 1976 to 1983, 13 living related and 54 cadaver renal transplants were done in 62 patients more than 50 years old. Patients with no coronary or myocardial disease upon coronary angiography were selected preferentially for transplantation. Over-all 1-year patient and graft survival rates were 88 and 70 per cent, respectively. Among cadaver recipients graft survival was improved (p less than 0.001) when prophylactic antilymphoblast globulin was used. There were fewer steroid-related complications (p less than 0.001) in recipients managed with a low dose rather than a high dose maintenance prednisone regimen. With careful patient selection and a steroid-sparing immunosuppressive regimen, renal transplantation can be done safely in older recipients with no increased risk of death or graft loss.     

Long term results of living donor kidney transplantation: graft and patient survival

Donor kidney transplantation's graft and patient survivals are better than cadaver donor's. In Spain, living donor kidney transplantation hardly accounts for 1% of transplant activity in comparison to 60% in United States. Accordingly to bibliography, the experience of the Renal Transplant Unit of the Hospital Clinic de Barcelona has demonstrated better graft and receptor survival for living donor recipients. The analysis of 184 living donor kidney transplants and 1678 cadaver donor transplants performed between 1978 and 2002 showed that graft survival was higher in the group of living donors (p < 0.01). At the same time, graft survival was clearly better in receptors of HLA haploidentical grafts (n=142) (p < 0.05). The introduction of new and better immunosuppressive drugs, as well as better diagnostic and therapeutic management of acute rejection, prophylaxis for infections, and control of complications have contributed to better results. The absence of acute rejection between 1978 and 1983 was 45.1%, between 1984 and 1998 was 57.3% and 84.7% between 1999 and 2003. In conclusion, these results demonstrate better graft and patient survival for living donor kidney transplants in comparison with cadaver donor receptors. Altogether with the low risk involved for donors should incentivate authorities, professionals, and patients to promote these therapeutic option by means of adequate information and wider diffusion. Living donor kidney transplantation should contribute together with cadaver kidney transplantation to lessen our long waiting lists, because they are not excluding options.     

2,500 living donor kidney transplants: a single-center experience

OBJECTIVE: To review a single center's experience and outcome with living donor transplants. SUMMARY BACKGROUND DATA: Outcome after living donor transplants is better than after cadaver donor transplants. Since the inception of the authors' program, they have performed 2,540 living donor transplants. For the most recent cohort of recipients, improvements in patient care and immunosuppressive protocols have improved outcome. In this review, the authors analyzed outcome in relation to protocol. METHODS: The authors studied patient and graft survival by decade. For those transplanted in the 1990s, the impact of immunosuppressive protocol, donor source, diabetes, and preemptive transplantation was analyzed. The incidence of rejection, posttransplant steroid-related complications, and return to work was determined. Finally, multivariate analysis was used to study risk factors for worse 1-year graft survival and, for those with graft function at 1 year, to study risk factors for worse long-term survival. RESULTS: For each decade since 1960, outcome has improved after living donor transplants. Compared with patients transplanted in the 1960s, those transplanted in the 1990s have better 8-year actuarial patient and graft survival rates. Death with function and chronic rejection have continued to be a major cause of graft loss, whereas acute rejection has become a rare cause of graft loss. Cardiovascular deaths have become a more predominant cause of patient death; infection has decreased. Donor source (e.g., ideally HLA-identical sibling) continues to be important. For living donor transplants, rejection and graft survival rates are related to donor source. The authors show that patients who had preemptive transplants or less than 1 year of dialysis have better 5-year graft survival and more frequently return to full-time employment. Readmission and complications remain problems; of patients transplanted in the 1990s, only 36% never required readmission. Similarly, steroid-related complications remain common. The authors' multivariate analysis shows that the major risk factor for worse 1-year graft survival was delayed graft function. For recipients with 1-year graft survival, risk factors for worse long-term outcome were pretransplant smoking, pretransplant peripheral vascular disease, pretransplant dialysis for more than 1 year, one or more acute rejection episodes, and donor age older than 55. CONCLUSIONS: These data show that the outcome of living donor transplants has continued to improve. However, for living donors, donor source affects outcome. The authors also identify other major risk factors affecting both short- and long-term outcome.     

Kidney transplantation by use of splenectomy and transfusions, cadaver haplotype matching, suppressor cell assays, and T-cell monitoring

We attempted to modulate several determinants of the host immunologic profile to improve kidney transplant survival: (1) genotype matching of the cadaver donor with the recipient, (2) assessment in recipients of living related donors (LRD) for predisposition to generate suppressor cells in mixed lymphocyte culture (MLC), (3) pretransplant splenectomy and transfusions, and (4) posttransplant immunologic monitoring. Between January, 1979, and July, 1980, 48 primary renal transplants were performed and followed up between 6 and 24 months. Pretransplant splenectomy was performed, and transfusions were administered in 38 of 48 and 48 of 48 patients, respectively. Donors and recipients of 10 of 11 cadaveric transplants were genotyped and selected for one HLA haplotype identity. All 10 proved to also be one DR antigen matches. There were no cadaveric kidney losses, but one surgical antibody to T cell subtest were used to modulate rejection therapy. The LRD group (n = 37) included 13 HLA-identical, seven haploidentical low MLC reactors, and 17 haploidentical high MLC reactors. Three deaths occurred (diabetes and myocardial infarction, stroke, and pancreatitis). A three-component coculture assay was used in the LRD group before transplantation to determine the capacity to generate specific and nonspecific MLC suppressor cells. Suppressor cells were seen in 17 patients given standard immunosuppression postoperatively without rejection episodes. However, in 20 patients incapable of generating suppressor cells, seven biopsy-proved rejection episodes occurred. There were no kidney losses, with 44 of 48 surviving recipients demonstrating normal renal function.     

Improved patient and primary renal allograft survival in uremic diabetic recipients

From January 1968 to December 1981, 470 uremic diabetic patients received primary renal allografts at the University of Minnesota. Until 1979, the patient and graft survival rates were less good in diabetic than in nondiabetic recipients. Since 1979, the results in diabetics have been at least equal to those achieved in nondiabetic patients. Two-year actuarial patient and graft survival rates in diabetic renal allograft recipients were, respectively, 71 and 66% from 1968 to 1976 (n = 156), 78 and 64% from 1976 to 1979 (n = 187), and 88 and 82% from 1979 to 1981 (n = 127). Improved survival rates were seen in all donor source and recipient age categories. For comparison, the 2-year patient and graft survival rates in nondiabetic renal allograft recipients who received transplants between 1979 and 1981 (n = 162) were 92 and 79%. Changes associated with improved survival rates included performance of pretransplant splenectomy on all patients except those receiving grafts from HLA-identical siblings, deliberate transfusions of blood from greater than or equal to 5 random donors at least 1 month before transplantation, intensive insulin therapy for diabetic management post-transplant, and less vigorous treatment of repetitive rejection episodes. The current results show that diabetic recipients are no longer at higher risk than nondiabetics for graft or patient loss, at least during the first 2 years after transplantation.     

Adverse effect of splenectomy on the survival of patients with more than one kidney transplant

Risk factors associated with death were identified in a cohort of patients who received 2 or more kidney transplants. Data on 19 variables were collected by chart review on 774 patients who received allografts between 1973 and 1980 at any one of 3 hospitals in Philadelphia. 124 of the patients received two or more transplants and were followed for a minimum of 1.5 years. Modified life table analyses of single variables indicated that 7 factors--splenectomy, donor source, age, transplant hospital, number of HLA mismatches, donor sex, and survival time of the prior graft--were significantly related to patient survival. Using all 19 variables, the proportional hazards model was fit to the data. The characteristics most related to survival were splenectomy (P less than .001), donor source (P = .0022), and age (P = .0015). The other 4 factors that were significant on univariate analysis were not significant in this multivariate analysis. The relative risk of death was 5.5 for patients who had had a splenectomy compared with those who had not had a splenectomy. Patients who had received more than one transplant were compared with patients who had received only one transplant, and a subset of recipients of primary transplants who returned to dialysis after primary graft failure. Survival of patients who had received one transplant was approximately the same as that of the retransplanted population. When the proportional hazards model was fit to the populations that received one transplant and compared with the model for the retransplanted group, only age and donor source were common to all three models. The effect of splenectomy on survival was significant for the total population of primary transplant recipients but had no effect on the survival of the subset of recipients whose kidney grafts had failed and were returned to hemodialysis. Infection accounted for 45% of the deaths among splenectomized, retransplanted patients. A higher percentage of septic deaths occurred in patients whose grafts were functioning at the time of death when compared with patients who had returned to dialysis after secondary graft failure. Although retransplantation alone is not associated with an increased mortality, retransplantation in splenectomized patients carries a high risk of death.