Risk factors for chronic rejection after pediatric liver transplantation

BACKGROUND: Chronic rejection is a major cause of graft failure and a frequent reason for retransplantation after pediatric liver transplantation. Identification of risk factors for chronic rejection in pediatric transplant recipients is vital to understanding the pathogenesis of chronic rejection and may help prevent further graft loss. METHODS: The study population consisted of 285 children with 385 liver transplants performed at University of Chicago between 1991 and 1999. Logistic regression analysis was used to evaluate risk factors for chronic rejection, including age, sex, race, type of graft (living related vs. cadaveric), native liver disease, acute rejection episodes, cytomegalovirus (CMV) infection, and posttransplant lymphoproliferative disease (PTLD). RESULTS: The chronic rejection rate was significantly lower in recipients of living-related grafts than in recipients of cadaveric grafts (4% vs. 16%, P=0.001). African-American recipients had a significantly higher rate of chronic rejection than did Caucasian recipients (26% vs. 8%, P<0.001). Numbers of acute rejection episodes, transplantation for autoimmune disease, occurrence of PTLD, and CMV infection were also significant risk factors for chronic rejection. However, recipient age, gender, donor-recipient gender mismatch, and donor-recipient ethnicity mismatch were not associated with higher incidence of chronic rejection CONCLUSION: We have identified a number of risk factors for chronic rejection in a large group of pediatric liver allograft recipients. We believe that donor-recipient matching for gender or race is not likely to reduce the incidence of chronic rejection. The elucidation of the mechanisms by which living-related liver transplantation affords protection against chronic rejection may provide insight into the immunogenetics of chronic rejection and help prevent further graft loss.     

Similar risk profiles for post-transplant renal dysfunction and long-term graft failure: UNOS/OPTN database analysis

BACKGROUND: Renal dysfunction measured by serum creatinine (>1.5 mg/dL) at 1 year post-transplant correlates with long-term kidney graft survival. The purpose of this study was to compare the risk factors for elevated serum creatinine (SCr) >1.5 mg/dL at 1 year post-transplantation, and for long-term graft failure. METHODS: Between 1988 and 1999, 117,501 adult kidney transplants were reported to Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS). Of these, 96,091 were functioning at 1 year and SCr was available on 85,135 transplants. Donor and recipient demographics (age, sex, and race), transplant [living vs. cadaveric, previous transplantation, panel reactive antibody (PRA), human leukoocyte antigen (HLA) mismatch, cold ischemic time (CIT) and post-transplant delayed graft function (DGF), use of azathioprone vs. mycophenolate mofetil (MMF), cyclosporine A (CsA) vs. tacrolimus (Tac)], induction antibody, acute rejection within 1 year variables were used in the logistic regression model to estimate odds ratio (OR) for elevated 1 year serum creatinine (SCr). A Cox proportional hazard model was used to estimate the relative risk (RR) for long-term kidney graft failure with and without censoring for death with a functioning graft. RESULTS: Five-year actuarial graft survival for living donor transplant with SCr >1.5 and 1.5 mg/dL) declined from 54.5% in 1988 to 42.3% in 1999. There was a strong concordance between the key variables, such as cadaveric transplant, increasing CIT, HLA mismatch, DGF, and acute rejection, recipient race (black), younger age, and nondiabetics status; and donor race (black) and older age for elevated SCr and long-term graft failure. CONCLUSION: Donor (age), race (black), recipient race (black), immunologic variables (HLA mismatch, DGF, acute rejection) were identified as important risk factors for elevated SCr at 1 year post-transplantation and long-term graft failure. Elevated SCr should be used as a short-term marker for predicting long-term transplant survival.     

Living related kidney donors over 60 years old

The lack of available cadaveric organs for transplantation has resulted in an increased number of kidney transplants from living donors. During a period of 6 years, 149 kidney transplantations were performed from living related donors in our institute, 33.5% of whom were older than 60 years of age. In this study we examined the survival of patients and grafts as well as the graft function in 50 patients with transplants from donors over 60 years (mean age 65 years) as compared with those of 99 patients with transplants from donors younger than 60 years (mean age 47 years). There were no significant differences in the course of donor nephrectomy, postoperative complications, or remnant kidney function. However, delayed graft function occurred more frequently in recipients of transplants from older donors. Improvement in graft function was also slower in recipients of kidneys from older donors, with significant differences in serum creatinine levels observed during the first 12 months after transplantation. More frequent acute complications and more progressive chronic graft failure, irrespective of the causes, occurred during the 1st post-transplant year in recipients with grafts from older donors. Five-year patient survival (77% vs 92%) and kidney graft survival differed significantly for the same period with worse results for patients receiving grafts from older donors. It may be concluded that kidney grafts from donors older than 60 years — and especially those older than 70 years — may be used for living related kidney transplantation, but with precautions.     

Causes of long-term graft failure in renal transplantation

Summary A single-center experience of 980 consecutive renal transplant recipients treated with cyclosporine (CyA) was reviewed to analyze the causes of renal allograft loss and the factors affecting long-term renal survival in CyA-treated kidney transplants. In all, 217 grafts were lost during the observation period, with the most common causes of graft loss being chronic rejection (96 cases, 44%), death with a functioning graft (52 cases, 24%), glomerulonephritis (28 cases, 13%), and acute rejection (20 cases, 8%). The actuarial 10-year survival of patients with living and cadaveric grafts was 93% and 91%, respectively. The actuarial 10-year survival of living and cadaveric grafts was 70% and 63%, respectively. Patients were divided into two groups, namely a graft-survival group (n=763) and a graft-loss group (n=217). There was no significant difference between the two groups in terms of sex, donor source, donor age, recipient age, duration of hemodialysis, retransplants, transfusions, presensitization, of HLA match. There was no difference between the graft-survival group and the graft-loss group in the mean CyA dose given or the mean CyA trough level measured at any time following transplantation. Acute rejection episodes occurred in patients from the graft-survival group (55%) as compared with those from the graft-loss group (83%; P<0.00001). These data suggest that long-term graft survival in CyA-treated kidney transplant patients is primarily influenced by the occurrence of rejection episodes rather than by the drug dose or the duration of CyA administration. CyA nephrotoxicity was not the major risk factor for long-term graft survival in CyA-treated renal transplants.     

Intermediate outcomes of dual renal allografts: the University of Washington experience

PURPOSE: The increased survival advantage of renal transplantation with end stage renal disease combined with an increasing incidence of renal disease fuel an increasing disparity between supply and demand for transplantable kidneys. Despite efforts to increase cadaveric organ donation through education and publicity, the number of cadaveric kidneys transplanted has not increased and in the last year was surpassed by kidneys transplanted from living donors. In an effort to maximize cadaver organ donors use of kidneys from expanded criteria donors has been investigated. In select cases both donor kidneys have been transplanted into a single recipient, which is called dual renal transplant. We report on the 4-year dual renal transplant graft and patient outcomes and compare these to age matched single cadaver kidney transplants. MATERIALS AND METHODS: A retrospective review of 10 dual renal transplant recipients and 10 age matched single cadaver kidney recipients was performed. All patients underwent transplantation at our university between January 1996 and February 1998. Mean followup was 4.1 years (range 2.5 to 5.1) for the dual kidney recipients and 3.6 (0.0 to 5.5) years for the control group. RESULTS: Of the 10 dual renal transplant recipients 7 remain alive and 3 died of nontransplant related causes. Of the 10 single recipients 8 are alive, 1 died of postoperative complications and 1 died of nontransplant related causes. When censored for death with a functioning graft, 7 of 10 dual grafts are functioning at followup with a mean creatinine clearance of 39.4 ml. per minute (range 16.1 to 65.9) and mean serum creatinine of 2.0 mg./dl. (1.1 to 3.9). If not censored for death with a functioning graft, 50% of dual grafts are functioning. Of the 3 graft losses 2 were due to recurrent disease and 1 was attributed to chronic rejection. In the control group 8 of 10 grafts are functioning at current followup (regardless of censoring for death with a functioning graft) with a mean creatinine clearance of 48.7 ml. per minute (range 23.4 to 66.5) and mean serum creatinine of 1.6 mg./dl. (1.2 to 2.4). Of the 2 graft losses 1 resulted from postoperative complications and 1 was due to chronic rejection. CONCLUSIONS At the 4-year followup patients undergoing dual renal transplant have comparable graft function, incidence of graft loss and survival compared to the control group. However, because of our small sample size, differences in the 2 groups may be significant in a larger study. Additional studies need to be conducted to determine if this practice represents an acceptable use of kidneys from expanded criteria donors.     

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.     

Comparison of survival probabilities for living-unrelated versus cadaveric renal transplant recipients

Any attempt to improve organ donation would be of benefit due to the growing shortage of cadaveric sources for transplantation. OBJECTIVE: We compared the graft survivals and possible predictive variables among renal transplant recipients with organs from living unrelated (LURD) versus cadaveric donors (CD). METHOD: Among 104 consecutive renal transplants performed from July 1992 to February 2003, 41 were from LURD and 24 from CD. Immunosuppressive regimens were based on cyclosporine and steroids with mycophenolate mofetil added after 1998. Patient and graft survivals were estimated using the Kaplan-Meier method and compared using log-rank tests. The significance level of predictive variables was analyzed with the Cox proportional hazard model. The follow-up period was 2 to 127 months (median 46 months). RESULTS: Eight recipients lost their grafts (six from LURD and two from CD) due to four chronic rejections, one acute rejection, one recurrence of primary disease, and one death with a functioning graft. The graft survival rates at 1, 3, 5, and 7 years were 97.6%, 91.9%, 88.5%, and 82.2% for LURD transplants versus 95.5%, 90.9%, 90.9%, and 90.9% for CD transplants, respectively (P > .05). Delayed graft function and donor age (>55 years old) were statistically significant predictors of graft survival among LURD transplants. Donor age (>55 years old) and multiple preoperative transfusion history were significant in CD transplants. CONCLUSION: LURD transplant survival was similar to that of CD transplants in our series. LURDs are an excellent source of organs to expand the donor pool.     

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.     

Outcome of renal transplantation in children less than two years of age.

Twenty-two renal transplants were performed in 21 children less than two years of age at Children's Hospital. Fourteen were from living related donors and eight were from cadaveric donors. The five year patient and graft survivals of these recipients were compared to all other pediatric recipients between two and 18 years of age who received renal transplants over the same time period. Five year graft survival for recipients less than two years of age was 86% following living-related donor transplantation and 38% following cadaver donor transplantation. Older pediatric recipients aged between two and 18 years had a five year graft survival of 73% following living-related donor renal transplantation, which was similar to that for recipients less than two years of age. Although older cadaveric recipients had a comparable five year graft survival to younger recipients, at 42%, the patterns of graft loss were different. Graft failures in young recipients occurred within the first seven months post-transplant, whereas the older recipient's grafts failed more gradually. Actuarial five-year patient survival in recipients less than two years of age was 86% following living-related donor renal transplantation and 70% following cadaver-donor renal transplantation. Recipients less than two years of age had a poorer patient survival than older recipients following both living-related donor renal transplantation (P = 0.06) and cadaver-donor renal transplantation (P less than 0.05). These findings suggest that the graft survival of living-related donor renal transplantation in recipients less than two years of age is better than that of cadaver-donor renal transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cadaveric kidney transplantation in children < or =20 kg in weight: long-term single-center experience

BACKGROUND: We report long-term follow-up data on cadaveric kidney transplantation in children < or =20 kg in weight. METHODS: Between January 1990 and October 2003, we performed 19 cadaveric renal transplants in 19 children < or =20 kg in weight. Mean age at transplantation was 4.7 years (range 18 months to 9 years). Mean weight at transplantation was 14.4 kg (range 9 to 20 kg). Nine patients had preemptive kidney transplantation, whereas 10 were maintained on renal replacement therapy before the transplant operation. RESULTS: Actuarial 1-, 3-, 5-, and 10-year patient survival rates were 89.5%, 89.5%, 89.5%, and 82%, respectively. Actuarial 1-, 3-, 5-, and 10-year graft survival rates were 79%, 73%, 73%, 65%, respectively. Three patients died. Eight grafts failed. Cause of graft failure was death with a functioning graft in 3 patients, chronic rejection in 1, acute cellular rejection in 1, vascular rejection in 1, hemolytic-uremic syndrome in 1, and unknown in 1. CONCLUSIONS: Our results indicate the success of cadaveric kidney transplantation in the very small child with results comparable to living related donor transplantation.     

Factors contributing to long graft survival in non-heart-beating cadaveric renal transplantation in Japan: a single-center study at Kitasato University

A total of 107 cadaveric kidneys from non-heart-beating donors (NHBDs) have been transplanted between 1974 and 2000 at Kitasato University Hospital, Sagamihara, Japan. The patient survival of the 107 recipients of cadaveric renal transplants at 1, 5 and 10 yr was 0.857, 0.770 and 0.746, respectively. The 50% graft survival was 3.8 yr. The 5 and 10-yr graft survival was 0.457 and 0.337, respectively. Twenty of the 107 recipients of non-heart-beating cadaveric renal transplantation had graft survival longer than 10 yr. Of these 20 patients, 14 survivors still maintain functioning renal grafts and two died with functioning graft, although the remaining four reverted to dialysis because of chronic rejection and nephropathy. The average graft survival of these 20 patients at the time of study was 13.3 yr and the longest was 21.4 yr. The average serum creatinine level at 10 yr after transplantation was 1.63 mg/dL, almost identical to that at 5 yr post-transplant. The donors aged on average 40.2 yr; 13 were male and seven were female. The youngest donor was 9-yr-old and the oldest was 66. The graft survival was significantly better in the group with donor age younger than 55 yr (Log-rank: p=0.007). The average weight of the renal graft was not different between the long and shorter graft survival groups. The average warm ischemic time and total ischemic time were 9.7 and 539.7 min, respectively. The duration of post-transplant acute tubular necrosis averaged 9.2 days. These parameters tended to be shorter than those in recipients with graft survival >10 yr, but with no statistical significance. The mean numbers of acute rejection (AR) episode within 3 months after transplantation were 0.25 +/- 0.66 and 0.92 +/- 0.90 (p=0.020) in long survival and shorter survival groups, respectively. Long survivors had a significantly lower incidence of AR. Two of 20 cases received conventional immunosuppression with prednisolone, azathioprine and mizoribin, and 18 had prednisolone and calcineurin inhibitor (CNI). Kaplan-Meier analysis showed a significant contribution of CNI to graft survival (p=0.036). However, the graft survival reduction rate after 1 yr post-transplant did not differ between conventional and CNI immunosuppression. These data suggest that renal grafts retrieved with proper organ procurement procedures from NHBDs may survive long-term and help to overcome donor shortage.     

The effect of donor age, recipient age, and HLA match on immunologic graft survival in cadaver renal transplant recipients.

We retrospectively analyzed 526 primary cadaver recipients transplanted at a single center to identify pretransplant variables that predict long-term survival with multivariate analysis. All recipients received at least three random blood transfusions and were treated under a quadruple-therapy protocol consisting of ALG, azathioprine, prednisone, and cyclosporine. Of 526 consecutive transplants, 86 grafts were lost from acute or chronic rejection. Thirteen grafts were lost for nonimmunologic reasons and 35 recipients died with a functioning graft. A total of 273 patients (52%) experienced at least one episode of acute rejection. Donor age ranged from 3 to 64 years, with 62% of donors less than 30 years of age and 9% of donors over 50 years of age. Donor age was not predictive of long-term graft survival and neither was the difference between donor and recipient age. Recipient age was predictive of subsequent immunologic graft less, with younger recipients at greater risk (P = 0.011). The rate of first rejection was also inversely related to recipient age, with younger recipients rejecting earlier (P = 0.0001). The degree of DR mismatch was the only other significant predictor of long-term graft success (P = 0.013). Transplant survival correlated with the degree of DR mismatch: 2 DR mismatch was the worst, 1 DR mismatch was intermediate and 0 DR mismatch was the best (P = 0.02). A, B, AB, and BDR did not influence long-term graft outcome. In our center, donor age does not predict graft failure. Younger recipients have a higher rate of early rejection and, combined with a poor DR match, are at higher risk for long-term graft failure.     

Living donor kidney transplantation: the effects of donor age and gender on short- and long-term outcomes

BACKGROUND: The influence of donor age and sex on acute rejection episodes and short- and long-term graft survival in living donor (LD) kidney transplantation has not been well characterized. METHODS: This prospective cohort study includes 739 first time LD transplantations with median follow-up time of 55.1 months. Death censored graft survival according to donor age and sex was compared with Kaplan-Meier plots. Cox regression was performed to estimate the association between different risk factors and graft survival and acute rejection episodes. RESULTS: Graft survival was not affected by donor age above 50 years as long as these recipients did not experience an early acute rejection episode. Acute rejection episodes increased in recipients of grafts from donors > or =65 years (P=0.009). Donor age > or =65, recipient age less than 50 years, human leukocyte antigen (HLA)-DR matching, and female donor gender were risk factors for early acute rejection episodes. In multivariate analysis donor age > or =65 years was a risk factor for graft loss in all time periods after transplantation. During the first 5 years after transplantation a steroid resistant rejection episode was an additional risk factor. More than 5 years after transplantation male donor gender was the only additional risk factor for graft loss. CONCLUSION: These results support the continued use of older male and female living donors who meet carefully constructed medical criteria and who are highly motivated to donate. Furthermore, donor age seems to be a more important predictor of graft loss than donor sex.     

Microchimerism and renal transplantation: doubt still persists

OBJECTIVE: We sought to study microchimerism in a group of kidney transplant recipients. MATERIALS AND METHODS: In this study, the peripheral blood microchimerism (PBM) after renal transplantation was retrospectively evaluated in 32 male-to-female recipients of living unrelated or cadaveric donor renal transplants. Using a nested polymerase chain reaction (PCR) amplification specific for SRY region of the Y chromosome, microchimerism was detected with a sensitivity of 1:1,000,000. Recipients were compared according to the presence of PBM, acute and chronic rejection episodes, type of allotransplant, recipient and donor age at transplantation, previous male labor or blood transfusion, allograft function (serum creatinine level), and body mass index. RESULTS: Among 32 recipients, 7 (21.9%) were positive for PBM upon multiple testing at various posttransplant times. All microchimeric recipients had received kidneys from living unrelated donors. No significant difference was observed with regard to other parameters. In addition the acute rejection rate in the microchimeric group was 3 (42%) versus 4 (16%) in the nonmicrochimeric recipients (not significant). CONCLUSION: Our results suggested better establishment of microchimerism after living donor kidney transplantation. However, doubt persists concerning the true effect of microchimerism after renal transplantation. It seems that microchimerism alone has no major protective role upon renal allograft survival.     

The effect of donor gender on graft survival

Differences in actuarial graft survival according to donor gender have been reported for renal allografts and for cardiac and hepatic allografts, but for the latter in small series with limited biostatistical power. Using the large database of the Collaborative Transplant Study (CTS), this study is an evaluation of graft survival according to donor and recipient gender for renal (n = 124,911), cardiac (n = 25,432), and hepatic (n = 16,410) transplants. Confounders, such as calendar year, geographical area, race, donor and recipient age, HLA mismatch, cold ischemia time, and others, as well as interaction terms were taken into consideration. Death-censored actuarial renal allograft survival from female compared with male donors was less in female recipients and even more so in male recipients. The donor gender-associated risk ratio for graft loss was 1.15 in female recipients and 1.22 in male recipients. The age-gender interaction term was statistically significant, the gender effect being more pronounced for younger (16 to 45 yr) compared with older (>45 yr) donors. Serum creatinine concentrations 1 yr after transplantation were also higher for recipients with kidney grafts coming from female donors irrespective of recipient gender. For first cardiac transplants, graft survival was inferior when the donor was female and the recipient male, but no statistical difference according to donor gender was demonstrable in female recipients. For first hepatic transplants overall, no significant differences according to donor gender were noted. The proportion of recipients who had treatment for rejection crisis during the first year was higher for male recipients of kidneys from female donors compared with male donors. No difference according to donor gender was demonstrable in female recipients. For cardiac and hepatic grafts, no significant effect of donor gender on the proportion of patients treated for rejection episodes was noted. The data show that adverse effects of female donor gender for different organs is much less uniform than reported in the past. An important confounder is donor age. A gender effect on graft survival is also observed for cardiac allografts. Therefore, in addition to potential "nephron underdosing," further pathomechanisms must play a role, possibly differences in immunogenicity according to donor gender.     

Simultaneous pancreas-kidney transplantation and living related donor renal transplantation in patients with diabetes: is there a difference in survival?

OBJECTIVE: To compare the outcome of simultaneous pancreas-kidney transplantation (SPK) and living related donor renal transplantation (LRD) in patients with diabetes. SUMMARY BACKGROUND DATA: It remains unanswered whether diabetic patients with end-stage renal failure are better served by LRD or SPK. METHODS: Using a longitudinal database, data from all diabetic patients receiving LRD or cadaveric renal transplants or SPKs from January 1986 through January 1996 were analyzed. Patient and graft survival, early graft function, and the cause of patient and graft loss were compared for 43 HLA-identical LRDs, 87 haplotype-identical LRDs, 379 SPKs, and 296 cadaveric renal transplants. RESULTS: The demographic composition of the SPK and LRD groups were similar, but because of less strict selection criteria in the cadaveric transplant group, patients were 10 years older, more patients received dialysis, and patients had been receiving dialysis longer before transplantation. Patient survival was similar for the SPK and LRD groups but was significantly lower for the cadaveric renal transplant group. Similarly, there was no difference in graft survival between SPK and LRD recipients, but it was significantly lower for recipients in the cadaveric renal transplant group. Delayed graft function was significantly more common in the cadaveric renal transplant group. Discharge creatinine, the strongest predictor of patient and graft survival, was highest in the SPK group and lowest in the HLA-identical LRD group. The rate of rejection within the first year was greatest in SPK patients (77%), intermediate in the haplotype-identical LRD and cadaveric transplant groups (57% and 48%, respectively), and lowest (16%) in the HLA-identical LRD group. Cardiovascular disease was the primary cause of death for all groups. Acute rejection, chronic rejection, and death with a functioning graft were the predominant causes of graft loss. CONCLUSIONS: This study demonstrates that there was no difference in patient or graft survival in diabetic patients receiving LRD or SPK transplants. However, graft and patient survival rates in diabetic recipients of cadaveric renal transplants were significantly lower than in the other groups.     

Chronic allograft nephropathy uniformly affects recipients of cadaveric,nonidentical living-related,and living-unrelated grafts

BACKGROUND: Chronic allograft nephropathy (CAN) remains a major barrier to long-term allograft survival. The authors retrospectively compared the development of CAN in recipients of cadaveric (CAD), living-related donor (LRD), and living-unrelated donor (LURD) transplants at their center. METHODS: The authors retrospectively examined the impact of various factors on the incidence of CAN using univariate and multivariate proportional hazards analysis in a single-center kidney transplant population. RESULTS: Between 1 January 1990 and 31 May 2000, 2,140 kidney-alone transplants were performed at the authors' center. The overall 5-year incidence of biopsy-proven CAN was 12.2% (n=203). Risk factors for CAN included the number of transplants (P=0.0001), acute rejection (P=0.0001), panel reactive antibody (P=0.0001), discharge creatinine (P=0.0001), 1-year creatinine (P=0.0015), delayed graft function (P=0.007), total human leukocyte antigen (HLA)-B and -DR mismatches (P=0.0005), recipient age (P=0.003), black donor race (P=0.001), black recipient race (0.0457), donor age (P=0.0053), cold storage time (P=0.019), and cytomegalovirus infections (P=0.002). Interestingly, although the LRD HLA-identical recipients had a significantly lower incidence of CAN (P=0.0015), the incidence of CAN in CAD and HLA-nonidentical LRD recipients did not differ. Graft survival was significantly worse in CAD recipients compared with all other groups (P<0.001). CONCLUSIONS: These results demonstrate the importance of immunologic and nonimmunologic factors on the development of CAN. The disparities in overall graft survival, despite the similarities in CAN rates, suggests that other factors, in addition to CAN, influence the increase in graft loss in CAD transplant recipients.     

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.     

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.     

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.