The large center variation in half-lives of kidney transplants.

Based on a log-linear model for analyzing multiple effects, center variation in the UCLA Transplant Registry is the most influential factor in early renal graft survival. Among 68 active centers accounting for 70% of all transplants between 1985 and 1989, the 1-year graft survival (adjusted for 15 covariates) varied from 60 to 90%. The long-term graft survival, as measured by the half-lives of the first cadaver donor transplants at these centers, based on a minimum of 4 years of follow-up data, varied from 3 to 26 years. Although there was some correlation (r = 0.24) of half-life with the 1-year graft survival rate at each center, in many instances, excellent centers had poor half-lives and average centers had excellent half-lives. From a Cox regression analysis on data from 6752 first cadaver-donor renal transplants surviving beyond 1 year (submitted to the UNOS data base), white female recipients of 0 HLA-AB-mismatched kidneys not requiring dialysis in the first week posttransplant had projected half-lives of 14.1 years, whereas black male recipients of 4 HLA-AB-mismatched kidneys requiring therapeutic dialysis had half-lives of 2.3 years. However, adjustment for these factors could only remove 17% of the total variability in the centers' half-lives. Consequently, any algorithm intended to judge a center's renal transplant capabilities should include, even after adjustment for covariates, some function of both 1-year graft survival and half-life beyond 1 year.     

Are blood transfusions beneficial in the cyclosporine era?

In patients treated with conventional immunosuppression (azathioprine and prednisone) after renal transplantation, there is a beneficial effect of pre-transplant blood transfusions on graft survival; in patients treated with cyclosporine, this effect may be lost. In 66 children who received living-related donor transplants after donor-specific transfusions (DST) and were treated with azathioprine-prednisone in our center, 1- and 5-year graft survival rates were 99% and 77% respectively. These rates were similar to those reported for children who did not receive DST but were treated with cyclosporine in other centers. There were 634 adult and pediatric recipients of cadaver transplants in our center who were treated with cyclosporine and prednisone (non-sequential therapy,n=89) or antilymphoblast globulin, azathioprine preduisone, and cyclosporin (sequential therapy,n=545). When all patients were considered, graft survival rates were higher in transfused than in non-transfused patients at 3–5 years, but in the sequential therapy group, there were no differences in graft survival rates between transfused and non-transfused patients. The results suggest that transfusions do not improve cadaver graft survival in patients receiving optimal cyclosporine therapy and that equally good related donor graft survival can be achieved with DST and conventional immunosuppression or no DST and cyclosporine.     

Analyses of the UNOS Scientific Renal Transplant Registry at three years--early events affecting transplant success.

The success of cadaveric renal transplants in the first year is determined largely by events that transpire during the transplant hospitalization. This conclusion is based upon analyses of data on 19,525 cadaver donor renal transplants performed since October 1987 and reported to the UNOS Scientific Renal Transplant Registry from more than 200 centers nationwide. Graft survival rates at 1 year differed by 20-30% depending upon whether or not the transplanted kidney functioned immediately and upon whether the patient required dialysis during the first week posttransplant, experienced rejection, or was discharged with a kidney that was functioning well. Recipients whose discharge serum creatinine level was less than 2.6 mg/dl or whose graft was functioning well at the time of discharge had 88% 1-year graft survival. A multistep logistic regression analysis showed cold ischemia time, transfusions, donor age and cause of death, HLA-DR mismatches, and peak sensitization to be significant factors in the first week. Prophylactic antilymphocyte antibodies (ALG/OKT3) reduced the incidence of rejection from 30% to 20% during the transplant hospitalization, but apparently only delayed rejection. By 6 months there was only a 3% reduction with ALG and a 5% reduction with OKT3 in the incidence of reported rejection and a 2% difference in 1-year graft survival. Although graft and patient survival are important measures of transplant success, graft survival is predicted upon both early and late events. The course of the transplant during the initial hospitalization and the quality of function at discharge were the strongest determinants of 1-year graft survival.     

The effect of center volume on pancreas transplant outcomes

BACKGROUND: Caseload often correlates with improved outcomes for several surgical procedures, including solid organ transplantation. Given the unique nature of pancreas transplantation and large variation in transplant center volumes, this study aims to determine whether center volume affects patient and graft survival after pancreas transplantation. METHODS: Registry data on all forms of whole organ pancreas transplants performed between 1995 and 2000 were obtained from the United Network for Organ Sharing. Patient and graft survival rates were followed until 2002. Center volume then was categorized as: low (< 10/year), medium (10-20/year), high (21-50/year), and very high (< 50/year). Cox proportional hazard regression models were developed to evaluate factors affecting pancreas transplant outcomes. RESULTS: Very-high-volume centers were more likely to do pancreas after kidney transplant, pancreas transplant alone, pancreas with kidney transplant, and repeat transplants, while other centers more frequently performed simultaneous pancreas-kidney transplants (P < .001). Very-high-volume centers were more likely to transplant older recipients and less likely to transplant minority or Medicaid patients. Low-volume centers tended to accept pancreatic allografts from younger donors and had the longest waiting times. In models adjusting for differences in patient population, there were no differences in patient survival. However, low-volume centers had a slightly increased risk of graft loss compared to other centers. Early graft loss was similar among all centers, but medium-volume centers were at increased risk for late graft loss. CONCLUSIONS: Low center volume is not associated with increased mortality after pancreas transplantation. Other factors appear to be more important than center volume in determining pancreas transplant outcomes.     

Comparison of Cadaveric Kidney Transplantation From In-center and External Center Donors

IntroductionRenal transplantation is the best treatment modality for end-stage renal disease. We investigated the effects of donor source on renal allograft and patient survival in deceased donor transplants.MethodsWe analyzed retrospectively 190 cadaver kidney transplants performed in our center from January 2000 to December 2009. Of these, 136 kidneys were harvested in our transplantation center and 54 were from external donors. Primary outcome of graft survival was assessed with the Kaplan–Meier method and the significance of possible variables was determined with the Cox proportional hazard model.ResultsThere was no difference between groups in the age of donor and recipient, recipient body mass index, duration of dialysis, or panel reactive antibody >30%. Twenty recipients lost their grafts (14 from external donors and 6 from internal donors). Graft survival at 1, 3, and 5 years was 99.2%, 97.3%, and 95.5% for in-center donors and 98.1%, 88.9%, and 86.2% for external donor transplants (P = .01). There was no difference in patient survival rates between the groups. Acute rejection episodes (hazard ratio [HR], 13.2; P < .001) and external hospital donor (HR, 9.3; P = .008) were independent factors associated with failure. Higher age of recipient was associated with increased patient death rate (HR, 1.2; P = .02).ConclusionGraft survival of cadaveric transplants from in-center donors was better than that of transplants from external center donors. Acute rejection episodes and location of harvest were significant factors for graft survival. Further study is needed to evaluate the effects of center-level factors on allograft outcomes.     

Effect of race on renal transplant outcome

Renal transplant outcome was compared in whites and blacks at a single center. All recipients transplanted between 1984 to 1991 were included in this study. White and black recipients were followed for a mean period of 37.6 (1-96) months. The age, sex, follow-up period, immunosuppressive protocol, number of retransplants, HLA mismatches and etiology of renal disease were comparable in the two races. Overall graft survival was lower in black recipients (p=0.0300). Graft survival in all cadaver (p=0.0520) and primary cadaver (p=0.1430) transplants was lower in blacks, though this was not statistically significant. Percentage of graft losses during the follow-up was higher in black 53/108 (49%), than white recipients 82/257 (32%)(p=0.002), as were cadaver graft losses due to rejection, 39/92 (42%) in blacks, 54/190 (28%) in whites (p=0.02). There was no significant difference in graft losses due to rejection between races in the 1 yr post transplant, but there were significantly more graft losses after 1 yr in blacks 16/83 (19%) compared to whites (16/156(10%)(p=0.05). In cadaver grafts functioning for 6 months, subsequent survival was lower in black recipients (p=0.0418). There was lower patient survival in blacks during the mean follow-up period of 37.6 months (1-96). In conclusion, lower graft survival in blacks can be partially explained by fewer LRD transplants in black recipients. Persistent lower graft survival in all black recipients and significantly more losses due to rejection beyond 1 yr may be related to immunological differences, poor compliance, or a combination of both.     

The 1989 report of the North American Pediatric Renal Transplant Cooperative Study

This report of the North American Pediatric Transplant Cooperative Study summarizes data contributed by 57 participating centers on 754 children with 761 transplants from 1 January 1989 to 16 February 1989. Data collection was initiated in October 1987 and follow-up of all patients is ongoing. Transplant frequency increased with age; 24% of the patients were less than 5 years, with 7% being under 2 years. Common frequent diagnoses were: aplastic/dysplastic kidneys (18%), obstructive uropathy (16%), and focal segmental glomerulosclerosis (12%). Preemptive transplant, i.e., transplantation without prior maintenance dialysis, was performed in 21% of the patients. Dialytic modalities pretransplant were peritoneal dialysis in 42% and hemodialysis in 25%. Bilateral nephrectomy was reported in 29%. Live-donor sources accounted for 42% of the transplants. Among cadaveric donors, 41% of the donors were under 11 years old. During the first post-transplant month, maintenance therapy was used similarly for live-donor and cadaver source transplants, with prednisone, cyclosporine, and azathioprine used in 93%, 83%, and 81%, respectively. Triple therapy with prednisone, cyclosporine, and azathioprine was used in 78%, 75%, and 75% of functioning cadaver source transplants at 6 months, 12 months, and 18 months as opposed to 60%, 63%, and 54% for live-donor procedures, with single-drug therapy being uncommon. Rehospitalization during months 1–5 occurred in 62% of the patients, with treatment of rejection and infection being the main causes. Additionally, 9% were hospitalized for hypertension. During months 6–12 and 12–17, 30% and 28% of the patients with functioning grafts were rehospitalized. Times to first rejection differed significantly for cadaver and live-donor transplants. The median time to the first rejection was 36 days for cadaver transplants and 156 days for live-donor transplants. Overall, 57% of treated rejections were completely reversible although the complete reversal rate decreased to 37% for four or more rejections. One hundred and fifty-two graft failures had occurred at the time of writing, with a 1-year graft survival estimate of 0.88 for live-donor and 0.71 for cadaver source transplants. In addition to donor source, recipient age is a significant prognostic factor for graft survival. Among cadaver donors, decreasing donor age is associated with a decreasing probability of graft survival. Thirty-five deaths have occurred; 16 attributed to infection and 19 to other causes. The current 1-year survival estimate is 0.94. There have been 9 malignancies.A list of all participating centers and the names of the investigators is printed on pages 552–553     

CAPD and renal transplantation

Continuous ambulatory peritoneal dialysis (CAPD) is believed to improve the immune competence of end-stage renal failure patients and to increase the risk of graft rejection following subsequent renal transplantation. At this centre, 220 consecutive renal transplants have been studied in patients treated by either CAPD or haemodialysis (HD). Patient and graft survival was not significantly different for the two treatment groups over a five year follow-up. When only first cadaver recipients were considered (152 grafts) one-year graft survival (non-immunological failures excluded) was 77 per cent for CAPD and 79 per cent for HD patients (P greater than 0.05). Time on dialysis and number of pre-operative transfusions were significantly greater for the HD patients (P less than 0.05). A group of HD and CAPD patients were identified as being matched for age, sex, HLA, A, B, DR antigen matches, pre-operative transfusions and time-on dialysis. One-year graft survival of the CAPD patients was 82 per cent and for the HD patients 61 per cent. Studies of patient lymphocyte function and plasma suppressive activity in vitro revealed no differences between CAPD and HD treated patients. CAPD is not an immunological risk factor in renal transplantation and its continued use in the preparation of patients for transplantation is recommended.     

Calculations on long-term graft and patient survival in human kidney transplantation.

Long-term survival rates of human kidney transplants were found to decline at constant rates following the second year after transplantation. The slopes of decline were statistically significantly different for cadaver, parent-to-child, and HLA-identifical sibling transplants, resulting in graft survival half-life times during the constant risk phase of 7.5, 11, and 34 years, respectively. The corresponding patient survival half-life times were 12, 19, and 36 years, respectively. A highly significant difference in long-term survival risk was found when seven transplant centers that had been selected on the basis of their good 1-year graft survival results were compared with seven centers known to have a poor 1-year survival rate. The cadaver graft half-life times during the constant risk phase were 3.3 years for the "poor" centers and 8.7 years for the "good" centers. Thus, although histocompatibility obviously is a main factor in determining long-term survival risk, additional factors such as clinical treatment regimen appear to be influential. Knowledge of the long-term risk constants for the different transplant categories can be applied for the projection of success rates as well as retransplant and dialysis needs.     

Center volume effects in pediatric renal transplantation

 An inverse relationship between mortality and center volume has been established for several surgical procedures. Given the distinctiveness of pediatric renal transplantation and the large variation in center volume, investigation for relationships between center volume and graft outcome was pursued using the North American Pediatric Transplant Cooperative Study database. Center volume groups were based on the total number of pediatric transplants reported from 1987 to 1995. Centers reporting >100, 51–100, or ≤50 transplants were grouped as high- (n=11), moderate- (n=28), or low-volume (n=65), respectively. Differences between groups included increasing rates of cadaver donor graft thrombosis (2.4%, 4.3%, and 5.7%, P<0.01) and acute tubular necrosis (ATN) (10.2%, 11.5%, and 14.0%, P<0.01) with decreasing center volume. Treatment differences included a higher rate of induction with an anti-T-cell antibody preparation in the larger-volume groups, 60.2%, 51.8%, and 39.2% (P<0.001). Decreasing graft survival for decreasing center size groups was noted at 3 months post transplant, 90.4%, 90.2%, and 88.4%. These differences were significant only with the exclusion of anti-T-cell induction from the proportional hazards model (relative risk=0.81 and =0.70 for the moderate- and high-volume groups, P<0.02). Superior graft survival in the high-volume centers noted at 3 months post transplant appears predominantly the result of lower rates of cadaver donor graft thrombosis and ATN. Analysis points to the need for low-volume centers to identify risk factors influencing these outcomes. Received: 13 May 1998 / Revised: 22 September 1998 / Accepted: 23 September 1998     

Pre-emptive transplants for patients with renal failure: an argument against waiting until dialysis

BACKGROUND: Pre-emptive kidney transplants have not been favored in some centers because of concern about possible increased noncompliance and allegedly inferior long-term results. We analyzed our experience with pre-emptive kidney transplants to determine whether such concerns are justified. PATIENTS AND METHODS: Between January 1, 1984, and June 30, 1998, we performed 1849 adult primary kidney transplants: 385 pre-emptive (recipients not undergoing dialysis, ND) and 1464 non-pre-emptive (recipients undergoing dialysis, D). Results were subdivided by donor source: cadaver (CAD) and living donor (LD). ND recipients tended to be younger, but otherwise, the two groups were similar. Posttransplantation quality of life in recipients was evaluated using the nationally standardized Short Form Health Survey (SF-36). The posttransplantation employment status of the recipients was also evaluated. RESULTS: The patient survival rate 5 years posttransplantation was significantly better for ND (vs. D) recipients for both CAD (92.6% vs. 76.6%, P=0.001) and LD (93.3% vs. 89.5%, P=0.02) transplants. The 5-year patient survival rate was significantly higher for ND recipients compared with recipients undergoing dialysis for < 1, 1-2, and > 2 years pretransplantation for both CAD (P=0.0005) and LD (P=0.0001) transplants. The graft survival rate 5 years posttransplantation was similar between ND and D recipients for CAD transplants, but significantly better for ND (vs. D) recipients of LD transplants (92.3% vs. 84.8%, P=0.006). For CAD transplants, the 5-year graft survival rate was not different when ND recipients were compared with recipients undergoing dialysis for < 1, 1-2, and > 2 years pretransplantation; for LD transplants it was significantly higher for ND recipients compared with recipients undergoing dialysis for < 1, 1-2, and > 2 years pretransplantation (P=0.04). The incidence of acute and chronic rejection was no different between ND and D recipients for either CAD or LD transplants, and it was also not affected by the pretransplantation time undergoing dialysis. Graft loss secondary to the recipient's discontinuation of immunosuppressive therapy (a crude estimate of compliance) was similar between ND and D recipients. Five years posttransplantation, the SF-36 scores regarding the recipient's quality of life and the employment status were similar for ND compared with D recipients, regardless of donor source. CONCLUSIONS: ND recipients do not seem to have higher rates of noncompliance than D recipients. Results for ND recipients seem to be superior than for D recipients, supporting the contention that renal failure patients should, if possible, undergo transplantation before dialysis.     

Living unrelated donors in kidney transplants: better long-term results than with non-HLA-identical living related donors?

BACKGROUND: Given the severe organ shortage and the documented superior results obtained with living (vs. cadaver) donor kidney transplants, we have adopted a very aggressive policy for the use of living donors. Currently, we make thorough attempts to locate a living related donor (LRD) or a living unrelated donor (LURD) before proceeding with a cadaver transplant. METHODS: We compared the results of our LURD versus LRD transplants to determine any significant difference in outcome. RESULTS: Between 1/1/84 and 6/30/98, we performed 711 adult kidney transplants with non-HLA-identical living donors. Of these, 595 procedures used LRDs and 116 used LURDs. Immunosuppression for both groups was cyclosporine-based, although LURD recipients received 5-7 days of induction therapy (antilymphocyte globulin or antithymocyte globulin), whereas LRD recipients did not. LURD recipients tended to be older, to have inferior HLA matching, and to have older donors than did the LRD recipients (all factors potentially associated with decreased graft survival). Short-term results, including initial graft function and incidence of acute rejection, were similar in the two groups. LURD recipients had a slightly higher incidence of cytomegalovirus disease (P=NS). We found no difference in patient and graft survival rates. However, the incidence of biopsy-proven chronic rejection was significantly lower among LURD recipients (16.7% for LRD recipients and 10.0% for LURD recipients at 5 years posttransplant; P=0.05). LRD recipients also had a greater incidence of late (>6 months posttransplant) acute rejection episodes than did the LURD recipients (8.6% vs. 2.6%, P=0.04). The exact reason for these findings is unknown. CONCLUSION: Although LURD recipients have poorer HLA matching and older donors, their patient and graft survival rates are equivalent to those of non-HLA-identical LRD recipients. The incidence of biopsy-proven chronic rejection is lower in LURD transplants. Given this finding and the superior results of living donor (vs. cadaver) transplants, a thorough search should be made for a living donor-LRD or LURD-before proceeding with a cadaver transplant.     

Outcomes of renal transplantation for recipients with lupus nephritis: analysis of the Organ Procurement and Transplantation Network database

Prior analyses of transplant outcomes in lupus transplant recipients have not consisted of multivariate analyses in the modern immunosuppressive era. Here, we compared patient and graft outcomes in lupus and non-lupus recipients transplanted between 1996 to 2000 using the United Network of Organ Sharing/Organ Procurement Transplant Network database. We evaluated the impact of recipient and donor demographic factors, time on dialysis and the initial immunosuppression regimen on rejection rates and transplant outcomes. Univariate analysis showed similar graft but better patient survival rates for primary lupus and non-lupus transplant recipients (5-year patient survival rates for lupus cohort 85.2% for deceased donor transplants and 92.1% for living donor transplants as opposed to 82.1% and 89.8% respectively for the non-lupus cohort; P=0.05 and 0.03) but similar patient survival rates for deceased donor retransplant patients. After controlling for confounding factors, no differences in patient or graft survival were seen between the two groups. No difference in acute rejection rates were observed in deceased donor transplants, but there was a small but significant increase in the risk of acute rejection in living donor lupus transplant recipients (hazard ratio=1.19, P=0.05). Risk of graft failure was lower for deceased donor recipients receiving MMF (five-year graft loss rate=29.6% for MMF vs. 40.2% for those not receiving MMF, P<0.0001), but no differences were seen among living donor recipients. Outcomes were similar regardless of type of calcineurin inhibitor, induction therapy, and time on dialysis. We conclude that lupus transplant recipients have outcomes generally equivalent to non-lupus transplant recipients.     

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.     

Long-term graft survival rate of zero-mismatch kidney transplants for HLA-DRB1

Abstract The study of a two-locus association between HLA-B and -DRB1 revealed a significant 43 linkage disequilibrium. Donorrecipient HLA-DRB1 was determined by these 43 linkages. Zeromismatch for HLA-DRB 1 had a significant effect on the graft survival rate in living related and cadaver transplants. The 5-year graft survival rate was 94% in the zero-mismatch group for HLA-DRB 1, 96% for related transplants, 92% for cadaver cases, and 94% in HLA identical siblings. A statistically significant difference was found between the zeromismatch group for HLA-DRB 1 and mismatch groups for HLA-DRB 1 or HLA-DR (P<0.01). The zero-mismatch group for HLADRB 1 had mismatches for HLA-A and/or HLA-B in 46 of 70 cases (66%). No significant differences in the rejection rate was observed between zero-mismatch and mismatch cases for HLA-A and/or -B in the zero-mismatch group for HLA-DRB l. In the second step, genotyping was conducted in 118 cases. The 5-year graft survival rate was 93% in the zero-mismatch group for HLA-DRB 1 and 86% in mismatch group (not a significant difference). We concluded that zero-mismatch transplant for HLA-DRB l had a better long-term graft survival rate regardless of HLA class I.     

Influence of hypercholesterolemia on patient and graft survival in recipients of kidney transplants

AIM: The aim of this retrospective, single centre study, was to study the effect of pre- and post-transplant serum total cholesterol (TC) on patient and graft survival. We also sought to see whether patients who had very high TC (>8 mmol/L) had a higher incidence of graft failure and patient mortality compared with those whose cholesterol was only moderately elevated. METHODS: Records of 935 cadaver kidney transplants between 1984 and 1998 were examined. Patients were placed into three groups based on TC level: <5.5 mmol/L (group 1), 5.5-8 mmol/L (group 2) and >8 mmol/L (group 3). The mean TC value from the first five post-transplant years was taken to seek a correlation between TC and post-transplant events. RESULTS: The mean graft follow-up was 66.9 +/- 50.1 months, ranging from 0.1 to 191 months, while mean patient follow-up was 83.8 +/- 50.1 months, ranging from 0.5 to 191.6 months. Pre-transplant TC was available in 201 patients (21.5%), and post-transplant data was available (for first 5 yr) in 655 patients (70%). During the study period, 220 patients (23.5%) had died, 285 (30.5%) of the grafts had failed during the follow-up, while 129 (13.8%) of the patients died with a functioning graft. We found significantly longer survival of patients having a pre-transplant TC below 5.5 mmol/L vs. patients whose pre-transplant TC was above 5.6 mmol/L (p = 0.02). We also compared patients who had very high pre-transplant TC (>8 mmol/L) level with those whose TC was moderately elevated (5.5-8 mmol/L) and found that there was no higher incidence of graft failure (p = 0.77) nor patient mortality (p = 0.83). No difference could be found in graft survival based on pre-transplant TC. We also did not find a detrimental influence of post-transplant TC on the patient or graft survival. Diabetes mellitus (p = 0.006) and age over 50 yr (p = 0.007) affected patient survival, while low cyclosporine levels (p = 0.02) and acute rejection episodes (p = 0.009) affected graft survival. The mode of dialysis and time on dialysis prior to transplantation did not affect patient and graft survival. CONCLUSIONS: We found significantly greater survival of patients having a pre-transplant TC below 5.5 mmol/L. No difference could be found in graft survival based on pre-transplant TC. Post-transplant TC did not adversely affect patient or graft survival.     

Does delayed kidney graft function increase the risk of chronic rejection?

Abstract  The impact of delayed graft function (DGF) on later renal graft loss due to chronic rejection was studied in a single center using uniform protocol for organ procure merit and post transplant patient care. DGF function was observed in 34 % of 829 consecutive first cadaveric renal transplants in adults and in 47 % of 169 retransplantations (P < 0.05). There were no significant differences in graft survival between groups with early graft function (EGF) and DGF, either in first transplantations or retransplantations. The half-life in EGF and DGF groups of first transplants was 12.3 years and 10.5 years, respectively, and of retransplantants was 8.0 years and 6.5 years, respectively. DGF was divided in three subgroups according to the day of onset. If graft function started during the first or second week after transplantation there were no significant differences in long-term graft survival rates compared with EGF. Only in re-transplants, if graft function started later than 2 weeks postoperatively, were long-term graft survival rates significantly lower when compared with EGF and the difference persisted if other causes of graft loss except chronic rejection were censored.     

A randomized controlled trial of cyclosporine withdrawal in renal-transplant recipients: 15-year results

BACKGROUND: In renal transplantation, the immunosuppressive efficacy of cyclosporine is counterbalanced by its nephrotoxicity. Although cyclosporine improves short-term graft survival, its long-term effects are unclear. METHODS: Recipients of first cadaver renal transplants were randomized into three groups between 1983 and 1986: azathioprine and prednisolone alone (AP, n = 158), long term cyclosporine alone (Cy, n = 166), and short-term cyclosporine followed by azathioprine and prednisolone (CyAP, n = 165). All groups received methylprednisolone induction. RESULTS: There were no significant differences in patient survival at 15 years (48 vs. 56 vs. 51%, P = 0.14), and 15-year graft survival (censored for death) in those patients in the CyAP group (47 vs. 44 vs. 59%, P = 0.06) was not significantly different statistically. When deaths or graft losses before 12 months were censored, the differences in 15-year graft survival between the groups were significant (58%, 51%, 70%, P = 0.01). The CyAP group also had lower mean serum creatinine at all time points beyond 3 months posttransplant out to 10 years (143 vs. 169 vs. 131 micromoles/L, P = 0.04). Per protocol analysis, after censoring patients at change in therapy, increased the observed differences in 15-year graft survival between the groups (54 vs. 38 vs. 65%, P = 0.01). CONCLUSION: Survival and function of first cadaveric kidney transplants is improved by use of short-term cyclosporine followed by azathioprine and prednisolone. Long-term cyclosporine use reduces long-term graft survival.     

Pancreas after kidney transplants

BACKGROUND: For certain uremic diabetic patients, a sequential transplant of a kidney (usually from a living donor) followed by a cadaver pancreas has become an attractive alternative to a simultaneous transplant of both organs. The purpose of this study was to compare outcomes with simultaneous pancreas-kidney (SPK) versus pancreas after kidney (PAK) transplants to determine advantages and disadvantages of the two procedures. METHODS: Between January 1, 1994, and June 30, 2000, we performed 398 cadaver pancreas transplants at our center. Of these, 193 were SPK transplants and 205 were PAK transplants. We compared these two groups with regard to several endpoints, including patient and graft survival rates, surgical complications, acute rejection rates, waiting times, length of hospital stay, and quality of life. RESULTS: Overall, surgical complications were more common for SPK recipients. The total relaparotomy rate was 25.9% for SPK recipients versus 15.1% for PAK recipients (P = 0.006). Leaks, intraabdominal infections, and wound infections were all significantly more common in SPK recipients (P = 0.009, P = 0.05, and P = 0.01, respectively, versus PAK recipients). Short-term pancreas graft survival rates were similar between the two groups: at 1 year posttransplant, 78.0% for SPK recipients and 77.9% for PAK recipients (P = not significant). By 3 years, however, pancreas graft survival differed between the two groups (74.1% for SPK and 61.7% for PAK recipients), although this did not quite reach statistical significance (P = 0.15). This difference in graft survival seemed to be due to increased immunologic losses for PAK recipients: at 3 years posttransplant, the incidence of immunologic graft loss was 16.2% for PAK versus 5.2% for SPK recipients (P = 0.01). Kidney graft survival rates were, however, better for PAK recipients. At 3 years after their kidney transplant, kidney graft survival rates were 83.6% for SPK and 94.6% for PAK recipients (P = 0.001). The mean waiting time to receive the pancreas transplant was 244 days for SPK and 167 days for PAK recipients (P = 0.001). CONCLUSIONS: PAK transplants are a viable option for uremic diabetics. While long-term pancreas graft results are slightly inferior to SPK transplants, the advantages of PAK transplants include the possibility of a preemptive living donor kidney transplant, better long-term kidney graft survival, significantly decreased waiting times, and decreased surgical complication rates. Use of a living donor for the kidney transplant expands the donor pool. Improvements in immunosuppressive regimens will hopefully eliminate some of the difference in long-term pancreas graft survival between SPK and PAK transplants.     

Impact of the delayed graft function in hypersensitized kidney transplant patients

AIM: The aim was to study the incidence, impact, and association of pretransplantation anti-HLA antibodies and delayed graft function (DGF) on the outcome of cadaver kidney transplants independent of the immunosuppressive therapy. METHODS: Data from 1325 cadaver donor kidneys (February 1975 to December 2002) included the variables of current and peak anti-HLA antibodies, presence of DGF, acute rejection (AR) episodes, patient survival, and graft half-life. RESULTS: DGF (need for dialysis in the first week posttransplantation) ranged between 15% and 40% with a mean of 30% in last 5 years. Eighty-five percent of the candidates on the waiting list for kidney transplants displayed <25% panel reactive antibody (PRA) at transplantation with 4.6% between 26% and 50%, 7.7% between 51% and 75%, and 1.5% >75%. Among the patients who developed DGF, 47% displayed AR compared an incidence of 30% among patients without DGF (P=.0026). The patients displaying >50% PRA (either current or maximum) showed a worse graft survival compared with patients with <50% PRA (log rank, P=.0000). DGF reduced graft survival (P=.04), the difference appearing in the early phase after transplantation. The best outcome was observed in the no DGF-no AR group (half-life, 11.6 years) and the worst results were in the hypersensitized patient groups: peak and current PRA >50% (half-lives of 2.4 and 2.2 years). A multivariate analysis showed that the presence of peak or current PRA >50% is the most important risk factor for graft loss. CONCLUSION: Sensitization is the key factor in graft outcome. Presensitization increases the risk of DGF and DGF increases the incidence of AR and both together produce the worst graft survivals.