Adult-size kidneys without acute tubular necrosis provide exceedingly superior long-term graft outcomes for infants and small children: a single center and UNOS analysis. United Network for Organ Sharing

BACKGROUND: Infants with end-stage renal disease are at highest risk for early graft loss and mortality of any subgroup undergoing renal transplantation. This study evaluates the influence of donor tissue mass and acute tubular necrosis (ATN) on graft survival and incidence of acute rejection episodes in infant and small child recipients of living donor (LD) and cadaver (CAD) adult-size kidneys (ASKs), pediatric CAD kidneys and combined kidney-liver transplants. Methods. Kidney transplants in infants and small children at a single center and those reported to the UNOS Scientific Renal Transplant Registry were analyzed. At Stanford, multi-variate analysis was conducted on 45 consecutive renal allograft recipients weighing < or = 15 kg, mean weight 11.2 +/- 2.6 kg. The UNOS Registry results in age groups 0-2.5 (n=548) and 2.5-5 years (n=743) were compared with age groups 6-12, 13-18, and the lowest risk adult group of 19-45 years. STANFORD RESULTS. Graft survival was 97.8 +/- 0.0 at 2 years and 84.6 +/- 0.1% at 8 years. The incidence of biopsy proven rejection was 8.8% in the first 3 months and 15.5% over the 8-year follow-up. None of the pediatric CAD kidneys had ATN. Rejection episodes were restricted to the pediatric CAD kidneys alone (3/3), with no kidney rejections in the combined pediatric CAD kidney-liver transplants (0/6; P=0.003). Four ASK transplants had ATN (1 postoperative and 3 late), and all predisposed to subsequent acute rejection episodes (4/4), whereas there were no rejection episodes in ASK transplants without ATN (0/32; P<0.001). At 3 years posttransplantation, mean serum creatinines were worse in ASKs with ATN (1.5 vs. 0.9 mg/dL; P<0.001) and in all grafts with rejection episodes (1.2 vs. 0.9 mg/dL; P<0.05). UNOS RESULTS: Among the 5 age groups studied, significantly better (P<0.001) long-term graft survival rates were observed in allograft recipients in the 2 youngest age groups with ASKs without ATN: 82 +/- 3% and 81 +/- 3% for LD and 70 +/- 7% and 78 +/- 4% for CAD recipients in the 0-2.5 and 2.5- to 5-year age groups, respectively, at 6 years after transplantation. Moreover, the projected graft half-lives after the 1st year in the LD groups without ATN were at least equivalent to those of HLA-identical sibling recipients ages 19-45 years: 26.3 +/- 5 and 29.3 +/- 6 years for the 0- to 2.5- and 2.5- to 5-year age groups, respectively, and 23.3 +/- 1 years for HLA-identical transplants. The graft half-lives for CAD recipients without ATN ages 0-2.5 and 2.5-5 yearswere equivalent or better than those for LD transplants without ATN in recipients aged 19-45 years: 15.4+/- 7 and 23.7 +/- 8 years versus 15.0 +/- 0.3 years. Mean serum creatinines were superior in the 2 younger recipient age groups compared with older age groups. CONCLUSIONS: Increased donor tissue mass of the ASK or kidney-liver transplants, in the absence of ATN, seems to confer a protective effect to infant and small child recipients of these allografts. This is manifested by a prolonged rejection-free state in the single center experience and enhanced graft survival and function in the UNOS analysis, comparable to HLA identical sibling transplants for LD infant and small child recipients and to LD adult results for CAD infant and small child recipients. To optimize this protective effect by whatever mechanism, absolute avoidance of ATN is essential in infant recipients of ASK or combined kidney-liver transplants.     

Simultaneous liver and renal transplantation in man

Advanced chronic renal failure has been thought of as a contraindication to liver transplantation. We present here seven cases of simultaneous kidney-liver transplant performed for combined end-organ failure. Six of the seven patients are alive with functioning grafts with follow-up of from 6 weeks to 32 months. In one case, the patient chronically rejected his liver graft (treated with successful retransplant) while maintaining good function in his kidney. The rate of acute rejection in the liver transplant was only 37.5% compared with 59.3% in the patients undergoing liver transplant only. There were no obvious rejections observed in the kidney transplants. These cases demonstrate the utility of simultaneous kidney-liver transplant in patients with combined kidney and liver failure. Advanced chronic renal failure should no longer be considered a contraindication to liver transplantation.     

Isolated heart and liver transplant recipients are at low risk for polyomavirus BKV nephropathy

BACKGROUND: BKV infection and nephropathy is a significant cause of allograft dysfunction in kidney transplantation. BKV viremia, rather than viruria, corresponds to BKV nephropathy. The prevalence of BKV viremia in non-renal solid organ transplants has not been systematically evaluated. METHODS: We determined prevalence of BKV viremia in kidney, combined kidney-heart, kidney-liver, kidney-pancreas, kidney-heart-liver, and heart and liver transplant recipients using BKV-PCR. RESULTS: Seven out of 173 (4%) kidney transplant recipients had BKV viremia, with BKV>2 x 10(5) copies/mL in 6/7 and 1.9 x 10(3) in the remaining one patient. BKV viremia was not found in 24 heart transplant recipients, whereas 1/37 (2.7%) liver transplants showed low copy numbers (< or =10(3)). BKV-PCR< or =10(3) copies/mL were also found in one of each combined kidney-heart and kidney-liver transplant recipients. BKV nephropathy was proven by biopsy in 4/6 patients with high BKV viral loads. All six patients showed renal dysfunction, requiring reduction in immunosuppression and antiviral therapy. All four patients with low BKV viral loads (1.9 x 10(3) or < or =10(3)) showed stable renal function after reduction of immunosuppression or no treatment, respectively. CONCLUSION: Higher BKV levels in plasma are associated with renal dysfunction. Kidney transplant recipients are at high risk compared with recipients of isolated heart or liver allografts, for development of BKV nephropathy.     

Significance of a T-lymphocytotoxic crossmatch in liver and combined liver-kidney transplantation

BACKGROUND: In contrast to kidney transplants a positive crossmatch is no contraindication for liver transplantation (OLT). In liver transplantation, antibody mediated rejections are rarely reported and a liver graft is suspected to have protective effects for kidney grafts when transplanted simultaneously. The aim of this study was to evaluate the effect of a positive crossmatch on outcome after OLT and combined liver and kidney transplantation (CLKTx). METHODS: We analyzed retrospectively the impact of a positive crossmatch on graft survival and rejection episodes after OLT (793pats) and CLKTx (18pats, 2.2%). Immunosuppression consisted of either Cyclosporine- or Tacrolimus-based regimens. RESULTS: A total of 50/811 (6%) of patients had a positive crossmatch, 45/793 (5.6%) with liver transplantation alone and 5/18 (28%) of patients with CLKTx. Follow-up ranged from 1 to 122.5 months (median 45.8 months). One- and 5-year graft survival rates of liver transplants alone with a positive crossmatch were 89.6% and 75.3%, respectively and were 88% and 77.5% in crossmatch negative recipients. Additionally, the incidence of acute and steroid-resistant rejection (44% and 15.5%) was not significantly increased in patients with a positive crossmatch when compared with patients with a negative crossmatch (38% and 19%). None of the patients with a positive crossmatch and CLKTx underwent a hyperacute-rejection episode after transplantation, and kidney graft survival 100%. CONCLUSIONS: In conclusion, a positive crossmatch is no contraindication for OLT and CLKTx. Furthermore, not having to wait for results of donor/recipient crossmatching can shorten cold ischemia time and may improve the clinical outcome.     

Graft-protective role of high pretransplantation IgA-anti-Fab autoantibodies: confirmatory evidence obtained in more than 4000 kidney transplants. The Collaborative Transplant Study

BACKGROUND: Preliminary studies showed an excellent success rate of kidney grafts in patients with high pretransplantation serum levels of IgA autoantibodies directed against the Fab region of the human IgG molecule. METHODS: With the collaboration of 30 centers from around the world, we attempted to verify the role of IgA-anti-Fab autoantibodies in kidney transplantation in an entirely new series of 4316 cadaveric kidney transplants, with special consideration of presensitized and poorly HLA-matched recipients. RESULTS: In agreement with previously published preliminary findings, 147 recipients with a high pretransplantation IgA-anti-Fab of >1000 had a 2-year kidney graft survival rate of 88+/-3% (+/- SE), compared with an 80+/-1% rate in 851 recipients with a low IgA-anti-Fab of <60 (P = 0.02). Even in patients at an increased risk of graft rejection, high pretransplantation IgA-anti-Fab autoantibody activity was associated with superior graft survival. Among 815 presensitized patients, 31 had a high pretransplantation IgA-anti-Fab activity of >1000 and their 2-year graft survival rate was 94+/-4%, in contrast to a 71+/-4% rate in 165 presensitized recipients with a low IgA-anti-Fab of <60 (P = 0.02). Of 2294 recipients who received a kidney with > or =3 HLA-A+B+DR mismatches, 79 recipients had a high pretransplantation IgA-anti-Fab of >1000 and a 2-year graft survival rate of 90+/-4%, as compared with a 79+/-2% rate in 459 patients with a low IgA-anti-Fab of <60 (P = 0.04). CONCLUSIONS: The present study confirms that kidney graft recipients with high pretransplantation IgA-anti-Fab activity have excellent graft survival, and it extends this observation to presensitized recipients and poor HLA matches.     

ABO-incompatible kidney transplantation using both A2 and non-A2 living donors

BACKGROUND: Given the scarcity of cadaveric organs, efforts are intensifying to increase the availability of living donors. The current study assessed the feasibility of using ABO-incompatible living-donor kidneys to expand the donor pool. METHODS: The authors performed 18 ABO-incompatible living-donor kidney transplants between May 1999 and April 2001. Ten patients received living-donor kidneys from A2 and eight patients received kidneys from non-A2 blood group donors. Immunosuppression consisted of Thymoglobulin antibody induction, tacrolimus, mycophenolate mofetil, and prednisone. Eight non-A2 and two A2 kidney recipients also received a pretransplant conditioning regimen of four plasmapheresis treatments followed by intravenous immunoglobulin and splenectomy at the time of transplantation. Antidonor blood group antibody titer was measured at baseline, pretransplant, at 1- to 3-month and 1-year follow-up, and at the time of diagnosis of antibody-mediated rejection. RESULTS: No hyperacute rejection episodes occurred. One-year graft and patient survival rates in the 18 ABO-incompatible recipients were only slightly lower than those of 81 patients who received ABO-compatible kidney transplants during the same period (89% vs. 96% and 94% vs. 99%, respectively). Glomerular filtration rate and serum creatinine levels did not differ between the groups. Antibody-mediated rejection occurred in 28% of ABO-incompatible recipients, and was reversible with plasmapheresis, intravenous immunoglobulin, and increasing immunosuppression in all patients except one. CONCLUSIONS: ABO-incompatible living donor kidney transplants can achieve an acceptable 1-year graft survival rate using an immunosuppressive regimen consisting of Thymoglobulin induction, tacrolimus, mycophenolate mofetil, and prednisone combined with pretransplant plasmapheresis, intravenous immunoglobulin, and splenectomy.     

Kidneys from Deceased Donors: Maximizing the Value of a Scarce Resource

Donor age is a significant risk factor for graft loss after kidney transplantation. We investigated the question whether significant graft years were being lost through transplantation of younger donor kidneys into older recipients with potentially shorter lifespans than the organs they receive. We examined patient and graft survival for deceased donor kidney transplants performed in the United States between the years 1990 and 2002 by Kaplan-Meier plots. We categorized the distribution of deceased donor kidneys by donor and recipient age. Subsequently, we calculated the actual and projected graft survival of transplanted kidneys from younger donors with the patient survival of transplant recipients of varying ages. Over the study period, 16.4% (9250) transplants from donors aged 15-50 were transplanted to recipients over the age of 60. At the same time, 73.6% of donors above the age of 50 were allocated to recipients under the age of 60. The graft survival of grafts from younger donors significantly exceeded the patient survival of recipients over the age of 60. The overall projected improvement in graft survival, by excluding transplantation of younger kidneys to older recipients, was approximately 3 years per transplant. Avoiding the allocation of young donor kidneys to elderly recipients, could have significantly increased the overall graft life, by a total 27,500 graft years, between 1990 and 2002, with projected cost savings of about 1.5 billion dollars.     

Long-term analysis of combined liver and kidney transplantation at a single center

OBJECTIVE: To analyze use of combined liver and kidney transplantation (CLKT) for patients with chronic primary diseases of both organs and for patients with hepatorenal syndrome. DESIGN: Retrospective case series. SETTING: Multiorgan transplantation service in a large university medical center. PATIENTS: A total of 98 patients underwent 99 CLKTs during a 16-year period; 76 had primary renal diseases, and 22 had hepatorenal syndrome. Patients receiving isolated liver and kidney transplants were analyzed for comparison. MAIN OUTCOME MEASURES: Patient and graft survival, rejection rates, and need for hemodialysis before and after transplantation. RESULTS: Overall patient survival was 76%, 72%, and 70% at 1, 3, and 5 years, respectively; liver graft survival was 70%, 65%, and 65%; and kidney graft survival was 76%, 72%, and 70%. No risk factors analyzed for recipients or donors were associated significantly with early posttransplantation mortality or graft loss. In 28 patients who received monoclonal antibody induction therapy with interleukin 2 blockers, there were significantly fewer episodes of acute liver rejection. For patients with hepatorenal syndrome, CLKT did not confer a survival advantage over liver-only transplantation (1-year patient survival was 72% vs 66%; P = .88). The 1-year acute kidney rejection rate in the adult CLKT group was 14% vs 23% in a 5-year cadaveric renal transplantation cohort (P<.01). CONCLUSIONS: First, CLKT is indicated in patients with dual organ disease and achieves excellent results. Second, CLKT for hepatorenal syndrome is indicated in patients receiving hemodialysis for longer than 8 weeks and confers advantages in patient survival and use of hospital resources. Third, the liver is immunoprotective for the kidney.     

Successful results after 5 years of tacrolimus therapy in ABO-incompatible kidney transplantation in Japan

In Japan, living donor kidney transplantation accounts for about 80% of all kidney transplants. This is in contrast to the United States and Europe, where transplantation of organs from cadaveric or brain-dead donors is more common. This study analyzed the results of 5 years of experience with tacrolimus in Japan, focusing on the efficacy of the drug in improving patient and graft survival in patients who underwent transplantation with ABO-incompatible kidney grafts. Of the 1542 evaluable patients, 1281 patients received grafts from living donors. Of these, 177 patients received kidneys from ABO-incompatible donors and 981 patients received kidneys from ABO-compatible donors. Graft survival rates in ABO-incompatible recipients ranged from 90.7% at 1 year to 80.5% at 5 years. Subsequent graft survival rates in ABO-compatible recipients were 98.1% and 92.9%, respectively (P < .001 between groups). Patient survival rates at 5 years were 93.2% in ABO-incompatible recipients and 98.1% in ABO-compatible recipients. The rejection rate for kidneys from ABO-compatible donors was 27.8%, while for ABO-incompatible donors the rejection rate was 45.2%. The excellent outcome from this study demonstrates that even suboptimal ABO-incompatible donors can be used successfully as a source of kidneys when using tacrolimus as the immunosuppressive regimen. This may go some way to addressing the shortage of kidney donors in Japan.     

Analysis of the United Network for Organ Sharing database comparing renal allografts and patient survival in combined liver-kidney transplantation with the contralateral allografts in kidney alone or kidney-pancreas transplantation

BACKGROUND: Combined liver-kidney transplantation (LKT) is the accepted treatment for patients with liver failure and irreversible renal insufficiency. Controversy exists as to whether simultaneous LKT with organs from the same donor confers immunologic and graft survival benefit to the kidney allograft. This study compares the outcomes of simultaneous LKT with the contralateral kidneys used for kidney alone transplantation (KAT) or combined pancreas-kidney transplantation (PKT) to understand the factors that account for the differences in survival. METHODS: From October 1987 to October 2001, LKTs with organs from 899 cadaver donors were reported to the United Network for Organ Sharing; 800 contralateral kidneys from these donors were used in 628 KAT and 172 PKT recipients. These 800 paired control patients were the basis of this analysis. RESULTS: Graft and patient survival rates were lower among LKT recipients compared with KAT (P<0.001) and PKT recipients (P<0.001), because of a higher patient mortality rate during the first 3 months posttransplant. Among human leukocyte antigen-mismatched transplants, LKT recipients demonstrated the highest 1-year rejection-free survival rate (LKT 70%, KAT 61%, and PKT 57% ) (P=0.005 vs. KAT, P=0.005 vs. PKT). There was a lower incidence of renal graft loss resulting from chronic rejection among LKT recipients (LKT 2% vs. KAT 8% vs. PKT 6%, P<0.0001). CONCLUSIONS: Patients undergoing LKT exhibit a higher rate of mortality during the first year posttransplant compared with patients undergoing KAT and KPT. Analysis of the data indicates an allograft-enhancing effect of liver transplantation on the renal allograft.     

Positive donor and negative recipient cytomegalovirus status is a detrimental factor for long-term renal allograft survival

Abstract In 524 allogeneic cadaveric kidney transplants, the impact of cytomegalovirus (CMV) donor/recipient status on the incidence of CMV infection, CMV disease, early and long-term graft, and patient survival have been analyzed with respect to rejection episodes. Most CMV infections (59%) and diseases (17%) were found in CMV-negative recipients of CMV-positive kidneys. The 1-year function rate of CMV-positive kidneys (75%) dropped about 10% below that of CMV-negative organs (85%), and in the case of CMV-negative recipients an additional graft loss of more than 10% happened within the 4th and 5th years (5-year graft survival pos./neg.: 56%). This detrimental effect was exaggerated if it coincided with antibody-treated rejection episodes.     

Combined liver and kidney transplantation

Patients with end-stage renal and hepatic failure may be treated with combined liver and kidney transplantation (CLKTx). We reviewed the indications and outcomes of 16 CLKTx performed at the University of Minnesota between 1980 and 1994. The majority of the recipients (87.5%) were young patients affected by congenital hepatic anomalies and concomitant end-stage renal failure. Fourteen were treated with cyclosporin-based immunosuppression and had an excellent outcome: with an average of 6 years of follow-up, patient survival was 85.7%, liver graft survival 85.7%, and kidney graft survival 72%. The incidence of rejection episodes was similar to the rate of rejection in our solitary kidney and liver transplants. In conclusion, our experience supports the value of CLKTx in treating patients with simultaneous failure of both organs or with congenital enzymatic hepatic deficits leading to renal failure.     

Ten years of training community urologists and general surgeons to do cadaver kidney retrievals

We trained 82 community hospital cadaver kidney retrieval teams during a 10-year period ending June 30, 1987. During the last 5 years of that period the concept of multiple organ retrieval was introduced into the training sessions and 429 cadaver kidney grafts were retrieved. Of those kidneys 292 were transplanted at our hospital, and the function of 220 cadaver kidney grafts retrieved by the community hospital teams was compared to that of 72 retrieved by the transplant center retrieval team. Of the cadaver kidney transplants 114 were from multiple organ donors. There was no significant difference in 1-month serum creatinine nadir of surviving grafts (2.1 +/- 1.8 versus 1.9 +/- 1.7 mg. per dl.), 6-month serum creatinine level (1.7 +/- 0.8 versus 1.6 +/- 0.6 mg. per dl.), 12-month serum creatinine level (1.8 +/- 0.9 versus 1.6 +/- 0.6 mg. per dl.) and 5-year actuarial graft survival (44.8 +/- 4.1 versus 52.4 +/- 7.5%), with the community hospital data presented first. The delayed graft function rate was significantly higher in the recipients of cadaver kidney grafts retrieved by community hospital teams (54 versus 35%), which was reduced by the in situ flush technique. There was no significant difference in delayed graft function rate (48 versus 40%) for the 114 cadaver kidney transplants retrieved from multiple organ donors by either community hospital or transplant center teams. With continuing education and quality control, community hospital retrieval teams can provide kidneys satisfactory for transplantation, even when working with multiple organ retrieval teams.     

Antithymocyte globulin induction therapy in hepatitis c-positive liver transplant recipients

It is unclear whether antithymocyte globulin (ATG) induction therapy in hepatitis C-positive (HCVpositive) liver transplant recipients influences the risk of developing recurrent HCV disease. Multiple acute rejection episodes and high-dose steroids and/or OKT3 used to treat acute rejection increase the risk of graft loss from HCV. We studied the impact of ATG induction on graft and patient survival in HCVpositive liver transplants performed since 1990. Recipients who died or lost their grafts within 1 month of transplantation were excluded. Second, third, and fourth grafts were excluded, as were patients with stage III or IV hepatocellular carcinoma. There were 443 cadaveric liver transplants in adult recipients, of whom 142 (32%) were HCV positive. The incidence of biopsy-proven acute rejection was less in patients who received ATG induction, 34.2% (ATG induction) versus 66.6% (no ATG induction) (P = .01). ATG induction did not influence the risk of graft loss from HCV-related disease (P ≤ .75). When only HCV-related graft loss was considered, 10-year graft survival for HCV-positive recipients was 74% (ATG induction) versus 68.2% (no ATG induction). Whether ATG induction was given or not had no significant impact on either overall graft survival (P = .39) or patient survival (P = .11) in HCVpositive recipients. Presented at the Fifth Biennial Meeting of the American Hepato-Pancreato-Biliary Association, Fort Lauderdale, Florida, April 14–17, 2005     

Influence of HLA matching on survival of second kidney transplants in cyclosporine-treated recipients

In an analysis of over 4000 cyclosporine-treated recipients of second kidney transplants we observed a strong effect of HLA matching in living-related and cadaver transplants. In contrast to the results obtained in first cadaver transplants, second cadaver transplants benefited substantially from matching for HLA-A locus antigens. The strongest effect of matching was found when HLA-A, HLA-B, and HLA-DR antigens were analyzed together: 214 second grafts with no mismatch had a survival rate of 82 +/- 3% at two years in contrast to a 49 +/- 4% rate in 149 grafts with 6 mismatches (P less than 0.0001, log rank). Patients whose first graft functioned for more than 1 year had a significantly higher second graft survival rate than patients with shorter first graft duration. Because the effect of HLA matching is particularly strong in patients with less than 1 year first graft duration, it is suggested that HLA well-matched kidneys should be allocated to them with priority.     

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

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

The transfusion effect in cadaver kidney transplants--yes or no

The transfusion effect in first cadaver kidney transplants was re-examined at the UCLA Transplant Registry. One-year graft survival rates were 71% for non-transfused patients, which improved to 75% (P less than 0.05) with a single transfusion, 77% (P less than 0.01) with 2, and 78% (P less than 0.01) with 3 and 4 transfusions. One-year graft survival rates did not improve further with additional transfusions but remained at the same level. Thus, the transfusion effect clearly does exist, and 2 to 4 transfusions are sufficient to obtain the maximum beneficial transfusion effect. Patients with zero HLA-DR mismatched transplants had no blood transfusion effect. Transfusions improved the 1-year graft survival rate by 8% for transplant recipients with 1 DR-mismatched grafts (P less than 0.01) and by 10% with 2 DR-mismatched grafts (P less than 0.01). The transfusion effect was greater in Black than White recipients; however, the 77% 1-year graft survival rate for transfused Black recipients of zero DR-mismatched kidneys did not differ from that of transfused comparably matched Whites. We conclude that transfusion protocols should not be abandoned unless patients receive zero DR-mismatched kidneys.     

Kidney graft failure and presensitization against HLA class I and class II antigens

BACKGROUND: It is well known that kidney transplant recipients with preformed lymphocytotoxic antibodies against HLA antigens have an increased graft rejection rate. However, the individual contribution of anti-HLA class I and class II antibodies to this phenomenon is poorly understood. We investigated the clinical relevance of preformed anti-HLA class I and class II antibodies on graft outcome in more than 4000 kidney recipients. METHODS: Pretransplant sera of 4136 cadaver kidney recipients from 28 transplant centers were tested in ELISA for IgG-anti-HLA class I and IgG-anti-HLA class II antibodies. The influence of antibody reactivity on graft survival was analyzed. RESULTS: Four hundred eighty of the anti-HLA class I antibody-positive recipients had a graft survival rate at 2 years of 77+/-2%, compared with an 84+/-1% rate in 3656 anti-HLA class I antibody-negative recipients (P<0.0001), and 770 anti-HLA class II-positive recipients had a graft survival rate of 79+/-2%, compared with an 84+/-1% rate in 3366 anti-HLA class II-negative patients (P<0.0001). Importantly, good 2-year graft survival rates of 85+/-3% and 84+/-2%, respectively, were observed in 206 anti-HLA class I-positive/class II-negative and 496 anti-HLA, class I-negative/class II-positive recipients. In contrast, the 274 recipients positive for both types of antibodies showed a poor graft survival rate of 71+/-3% (P<0.0001). Among 853 patients who received a well-matched kidney (0 or 1 HLA-A+B+DR mismatch), sensitization against either class I or class II, or both, had no deleterious effect. However, in 113 class I and class II antibody-positive patients who received a kidney with > or =3 HLA-A+B+DR mismatches, the 2-year graft survival rate was only 60+/-5%. CONCLUSION: Presensitization of first kidney transplant recipients against either HLA class I or class II is of no clinical consequence, whereas sensitization against both HLA class I and class II results in increased rejection of HLA mismatched grafts.     

Improving access to kidney transplantation without decreasing graft survival: long-term outcomes of blood group A2/A2B deceased donor kidneys in B recipients

BACKGROUND: The transplantation of blood group A2/A2B deceased donor kidneys into B recipients could improve access to transplantation for blood group B recipients. However, this practice is controversial, and long-term data are lacking. This study analyzed the long-term outcomes of A2/A2B deceased donor kidneys transplanted into selected B recipients. METHODS: We retrospectively assessed the outcomes (graft survival, transplant rates, and acute rejection) of deceased-donor kidneys using an allocation system that transplanted A2/A2B donors into B recipients with low anti-A blood group antibody titers between 1994 and 2003. Patients received conventional immunosuppression without any specific antibody reduction procedures. We further assessed the impact this system had on access to transplantation by blood group. RESULTS: Of 1,400 kidney transplants, 56 (4.0%) were A2/A2B to B recipients. The system reduced waiting time for all B recipients, even shorter than for blood group A recipients (median waiting times of A2/A2B to B transplants=182 days vs. B to B transplants=297 days; and A to A=307 days). Although there was a trend toward increased acute rejection in A2/A2B to B transplants, the actuarial 7-year death censored graft survival was 72% for B recipients regardless of donor type. CONCLUSIONS: Transplanting A2/A2B deceased donor kidneys into B recipients leads to an equalization of waiting time between blood groups with similar patient and graft survival using conventional immunosuppression. This protocol could lead to more equal access to kidney transplantation in blood group B recipients.     

Renal transplantation in diabetic patients with or without simultaneous pancreatic transplantation 1986: data from the EDTA Registry

This report summarises the outcome of 90 combined kidney/pancreatic grafts performed in Europe in 1986. Data for the combined kidney/pancreas grafts were obtained by a special questionnaire. The one-year patient and kidney graft survival is compared to the results of a group of 389 patients with diabetic nephropathy on the EDTA Registry data file who received kidney grafts alone. The recipients of combined kidney-pancreas grafts were younger, whereas a greater proportion of males received kidney graft alone. Patient survival at one year after transplantation was similar: 89% in recipients of combined transplants compared to 90% in recipients of kidney grafts alone. Kidney graft survival was 78% at one year for recipients of combined grafts versus 76%. It is concluded that pancreas transplantation has little effect on the fate of concomitant kidney grafts. The procedure should-in experienced hands and in selected patients-be almost as safe as kidney grafting alone.