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Gerhard Opelz - One of the best experts on this subject based on the ideXlab platform.
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immunological relevance of creg matching in Cadaver Kidney transplantation
Transplantation, 2004Co-Authors: Gunter Laux, Gerhard OpelzAbstract:Background. On the basis of cross-reactive antibodies that react with different human leukocyte antigens (HLA) with shared epitopes, HLA-A and -B antigens can be assigned to cross-reactive groups (CREG). In the context of renal transplantation, it has been reported that matching for CREG results in improved graft outcome and reduces the requirement for rejection treatment. Because CREG matching also improves the equity of Kidney distribution to ethnic minorities, a CREG-based Cadaver Kidney allocation policy was introduced in the United States a few years ago. Methods. The authors reexamined the immunologic relevance of matching according to CREG using the data of the international Collaborative Transplant Study. A total of 91,917 patients who received a first Cadaver Kidney transplant between 1991 and 2002 formed the basis of this analysis. Results. The authors found that the underlying impact of matching for HLA antigens accounts entirely for the observed positive effect of CREG matching. For patients with a particular HLA antigen match grade, matching for CREG had no advantageous effect on graft outcome or rejection treatment. An immunologic basis for CREG matching could thus not be found in this large analysis of Cadaver Kidney transplants. Conclusions. The findings indicate that CREG matching for Kidney allocation is conceptually flawed from an immunologic viewpoint.
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critical evaluation of the amino acid triplet epitope matching concept in Cadaver Kidney transplantation
Transplantation, 2004Co-Authors: Gunter Laux, Joannis Mytilineos, Gerhard OpelzAbstract:Background. A computer-based approach for determining human leukocyte antigen (HLA) compatibility between Kidney donors and recipients on the basis of differences of amino acid sequences as motifs for immunogenic epitopes was proposed by Duquesnoy et al. The HLAMatchmaker algorithm focuses on HLA class I polymorphisms of serologically defined antigens encoded by the HLA-A and -B loci. HLA phenotypic mismatches that represent only a few mismatches at the amino acid triplet level are held to be not or only mildly immunogenic. This approach was proposed as being especially suitable for the allocation of donor Kidneys to highly sensitized patients. Methods. We reexamined this attractive concept using the data of the Collaborative Transplant Study. Intra- and interlocus comparisons for HLA-A and -B were performed according to the original HLAMatchmaker algorithm. To exclude the influence of HLA-DR, only transplants with no HLA-DR mismatch were considered. Patients who had one HLA-A and one HLA-B antigen mismatch were separated into subgroups, depending on the number of triplet mismatches as calculated by the HLAMatchmaker software. Separate analyses were performed for first transplants, retransplants, and patients with a panel-reactive antibody activity of 50% or more. A total of 16,997 white patients matched for HLA-DR who received a Cadaver Kidney transplant between 1991 and 2001 formed the basis of this analysis. Results. Application of the HLAMatchmaker method could not be shown to result in any statistically significant effect on graft survival. Conclusions. The HLAMatchmaker concept is theoretically attractive; however, it could not be shown to yield useful results in this analysis. Serologic HLA typing appears to provide an insufficient basis for applying epitope matching in clinical Kidney transplantation.
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a new epitope based hla dpb matching approach for Cadaver Kidney retransplants
Transplantation, 2003Co-Authors: Gunter Laux, Gerhard Opelz, Ariane Deufel, Ulrich Mansmann, Joannis MytilineosAbstract:Background. Several years ago a significant impact of matching for HLA-DPB1 alleles on the survival of Cadaver Kidney retransplants was shown. Here we report the results of a new approach, based on matching for HLA-DPB1 epitopes. Methods. The analysis is based on 1,478 patients who received a Cadaver Kidney retransplant between 1988 and 1998. DNA methodology (polymerase chain reaction, sequence-specific oligonucleotides) was used to perform HLA-DPB1 typing. Epitope matching was facilitated with the aid of sequence databases and computer calculations. Results. Matching for the HLA-DP epitopes A, B, E, and F, corresponding to the homonymous hypervariable regions of the second exon of the DPB1 gene, seems to have a greater influence on graft survival than matching for the epitopes C and D. Within a group of 529 retransplants with exactly one allelic HLA-DPB1 mismatch, a significantly better graft outcome was observed when less than two epitope mismatches were found, compared with the group with more than three epitope mismatches (at 2 years: 77.8% vs. 65.8%, P=0.0112). Importantly, patients with two DPB1 allele mismatches who had less than or equal to two epitope mismatches exhibited a significantly better graft outcome than recipients who had one HLA-DPB1 allelic mismatch but more than three epitope mismatches (at 2 years: 77.1% vs. 65.8%, P=0.0488). Conclusions. The findings indicate that the impact of HLA-DPB1 matching on the outcome of Kidney retransplants is a result of the predominant immunogenicity of certain epitopes of the HLA-DP molecule. Matching for immunogenic HLA-DPB1 epitopes seems to be functionally more relevant than classical matching at the allelic level.
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identification of highly responsive Kidney transplant recipients using pretransplant soluble cd30
Journal of The American Society of Nephrology, 2002Co-Authors: Caner Süsal, Steffen Pelzl, Bernd Dohler, Gerhard OpelzAbstract:ABSTRACT. The identification of high immunologic responders is desirable for the selection of appropriate immunosuppressive regimens. With the collaboration of 29 transplant centers in 15 countries, we investigated whether the pretransplant serum content of soluble CD30 (sCD30), a marker for the activation state of Th2-type cytokine producing T cells, is a useful predictor of Kidney graft outcome. Pretransplant sera of 3899 Cadaver Kidney recipients were tested for serum sCD30 concentration using a commercially available enzyme-linked immunosorbent assay kit. Subsequent Kidney graft survival was analyzed. The 5-yr graft survival rate in 901 recipients with a high pretransplant serum sCD30 (≥100 U/ml) was 64 ± 2%, significantly lower than the 75 ± 1% rate in 2998 recipients with low sCD30 ( P
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soluble cd30 as a predictor of Kidney graft outcome
Transplantation, 2002Co-Authors: Steffen Pelzl, Peter Schnülle, Constanze Schönemann, Bernd Dohler, Gerhard Opelz, Manfred Wiesel, Caner SüsalAbstract:BACKGROUND: In the present study, we investigated whether the soluble form of CD30 (sCD30), a marker for T helper 2-type cytokine-producing T cells, is increased in sera of potential Kidney graft recipients. We also investigated whether the pretransplantation serum sCD30 content is related to Kidney graft survival. METHODS: Pretransplantation sera of 844 Cadaver Kidney recipients from three transplant centers in Germany were tested for serum sCD30 content using a commercially available ELISA kit. RESULTS: Kidney graft recipients showed a significantly higher serum sCD30 content than healthy controls (P<0.0001). High sCD30 serum content was associated with graft rejection. The 2-year graft survival rate in recipients with a high pretransplantation serum sCD30 was 68+/-6%, significantly lower than the 86+/-1% rate in recipients with a low sCD30 (P<0.0001). Importantly, high sCD30 was indicative of an increased risk of graft loss even in recipients without lymphocytotoxic alloantibodies. CONCLUSION: These data show that an elevated pretransplantation serum sCD30 reflects an immune state that is detrimental for Kidney graft survival.
G Opelz - One of the best experts on this subject based on the ideXlab platform.
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prospective evaluation of pretransplant blood transfusions in Cadaver Kidney recipients
Transplantation, 1997Co-Authors: G Opelz, Yves Vanrenterghem, G Kirste, D W R Gray, T Horsburgh, J G Lachance, F Largiader, H Lange, K Vujaklijastipanovic, J AlvarezgrandeAbstract:A beneficial effect of pretransplant transfusions on graft survival was demonstrated in the early 1970s. In the mid-1980s, however, retrospective studies showed that transfusions had lost their graft-protective effect in the cyclosporine era. During the last 10 years, deliberate transfusion pretreatment of transplant patients has been discontinued. Within a collaborative project of 14 transplant centers, prospective recipients of Cadaver Kidney grafts were randomized to receive either three pretransplant transfusions or transplants without transfusions. The graft survival rate was significantly higher in the 205 transfusion recipients than in the 218 patients who did not receive transfusions (at 1 year: 90±2% vs. 82±3%, P=0.020; at 5 years: 79±3% vs. 70±4%, P=0.025). Cox regression analysis showed that this effect was independent of age, gender, underlying disease, prophylaxis with antilymphocyte antibodies, and preformed lymphocytotoxins. Transfusion pretreatment improves the outcome of Cadaver Kidney transplants even with the use of modern immunosuppressive regimens.
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a proposal for improved Cadaver Kidney allocation
Transplantation, 1993Co-Authors: T Wujciak, G OpelzAbstract:The allocation of Cadaver Kidneys for transplantation should have two objectives: a fair distribution of Kidneys among the waiting recipients and a high success rate. Currently, organ exchange organizations are following mainly a policy of success oriented allocation in that the Kidneys are distribu
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computer analysis of Cadaver Kidney allocation procedures
Transplantation, 1993Co-Authors: T Wujciak, G OpelzAbstract:Data of 32,000 donors were utilized for a computer simulation to analyze the effect of selection parameters on the outcome of Kidney transplants. If the HLA match grade is considered for organ allocation, the overall 1-year graft survival rate is up to 7% higher for first Cadaver transplants and up to 12% higher for second transplants than if HLA matching is disregarded. This solely success-oriented organ allocation method, however, leads to prolonged waiting times for patients with rare HLA phenotypes. We developed a selection procedure that yields results near the theoretical optimum: 95% of all patients can be transplanted with 0-2 HLA-A, -B, -DR antigen mismatches, the average waiting time decreases to 20 months, and no patient needs to wait longer for a transplant than 6 years. The overall graft survival rate is only 0.4% lower than the rate obtainable with strictly HLA-oriented allocation. The method prevents "poorly matchable" patients from accumulating on the waiting list. Additionally, the unfavorable race ratio in the North American recipient pool can be largely normalized.
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Analysis of HLA-DR matching in DNA-typed Cadaver Kidney transplants.
Transplantation, 1993Co-Authors: G Opelz, Joannis Mytilineos, H Dunckley, J Trejaut, Jeremy R Chapman, Gottfried Fischer, Sabine Scherer, Ingrid Fae, Derek Middleton, David A SavageAbstract:The effect of matching for HLA-DR antigens was analyzed retrospectively in 3455 Cadaver Kidney transplants that were typed by the DNA-RFLP method. HLA-DR matching improved the one-year graft survival rate significantly (P < 0.01). Importantly, in 718 first transplants in which the number of mismatches assigned by serological typing was different from that assigned by DNA typing, only the DNA results showed a significant impact of matching on graft outcome (P = 0.03). These results demonstrate that DNA typing is clinically relevant. We were unable to confirm that the HLA-DR6 specificity or the DR6-split DRB1*1302 are associated with poor graft survival.
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survival of dna hla dr typed and matched Cadaver Kidney transplants
The Lancet, 1991Co-Authors: G Opelz, Joannis Mytilineos, S Scherer, H Dunckley, J Trejaut, Jeremy R Chapman, D Middleton, David A Savage, Gottfried Fischer, J D BignonAbstract:The clinical value of serological HLA matching for Cadaver Kidney transplantation remains uncertain because the success rate for HLA-matched Cadaver transplants is lower than that of HLA-matched sibling grafts. Up to 25% of serological HLA-DR typings may be incorrect when compared with a more accurate DNA-RFLP method, and we have now examined whether incorrect HLA-DR typings account for the lower than expected success rates of HLA-matched Cadaver transplants. 58 transplant centres took part in this study and DNA was extracted from over 4000 samples of frozen tissue at the study centre. 8 laboratories then completed blind RFLP typing for HLA-DR. Serological typing data were reported by individual transplant laboratories. 29 of 107 transplants (27%) that were reported as HLA A, B, DR compatible and 76 of 273 (28%) transplants that were reported as HLA B, DR compatible according to serological typing were found to be HLA-DR mismatched by DNA typing. The one-year transplant success rate for DNA-matched HLA, A, B, DR grafts was 87% compared with 69% for mismatched grafts (p less than 0.02); the corresponding success rate for DNA-matched HLA B, DR grafts was 85% compared with 72% for mismatched grafts (p less than 0.01). Many transplants that were previously thought to be HLA matched are mismatched, and this finding may account for previously unexplained graft failures.
Joannis Mytilineos - One of the best experts on this subject based on the ideXlab platform.
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critical evaluation of the amino acid triplet epitope matching concept in Cadaver Kidney transplantation
Transplantation, 2004Co-Authors: Gunter Laux, Joannis Mytilineos, Gerhard OpelzAbstract:Background. A computer-based approach for determining human leukocyte antigen (HLA) compatibility between Kidney donors and recipients on the basis of differences of amino acid sequences as motifs for immunogenic epitopes was proposed by Duquesnoy et al. The HLAMatchmaker algorithm focuses on HLA class I polymorphisms of serologically defined antigens encoded by the HLA-A and -B loci. HLA phenotypic mismatches that represent only a few mismatches at the amino acid triplet level are held to be not or only mildly immunogenic. This approach was proposed as being especially suitable for the allocation of donor Kidneys to highly sensitized patients. Methods. We reexamined this attractive concept using the data of the Collaborative Transplant Study. Intra- and interlocus comparisons for HLA-A and -B were performed according to the original HLAMatchmaker algorithm. To exclude the influence of HLA-DR, only transplants with no HLA-DR mismatch were considered. Patients who had one HLA-A and one HLA-B antigen mismatch were separated into subgroups, depending on the number of triplet mismatches as calculated by the HLAMatchmaker software. Separate analyses were performed for first transplants, retransplants, and patients with a panel-reactive antibody activity of 50% or more. A total of 16,997 white patients matched for HLA-DR who received a Cadaver Kidney transplant between 1991 and 2001 formed the basis of this analysis. Results. Application of the HLAMatchmaker method could not be shown to result in any statistically significant effect on graft survival. Conclusions. The HLAMatchmaker concept is theoretically attractive; however, it could not be shown to yield useful results in this analysis. Serologic HLA typing appears to provide an insufficient basis for applying epitope matching in clinical Kidney transplantation.
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a new epitope based hla dpb matching approach for Cadaver Kidney retransplants
Transplantation, 2003Co-Authors: Gunter Laux, Gerhard Opelz, Ariane Deufel, Ulrich Mansmann, Joannis MytilineosAbstract:Background. Several years ago a significant impact of matching for HLA-DPB1 alleles on the survival of Cadaver Kidney retransplants was shown. Here we report the results of a new approach, based on matching for HLA-DPB1 epitopes. Methods. The analysis is based on 1,478 patients who received a Cadaver Kidney retransplant between 1988 and 1998. DNA methodology (polymerase chain reaction, sequence-specific oligonucleotides) was used to perform HLA-DPB1 typing. Epitope matching was facilitated with the aid of sequence databases and computer calculations. Results. Matching for the HLA-DP epitopes A, B, E, and F, corresponding to the homonymous hypervariable regions of the second exon of the DPB1 gene, seems to have a greater influence on graft survival than matching for the epitopes C and D. Within a group of 529 retransplants with exactly one allelic HLA-DPB1 mismatch, a significantly better graft outcome was observed when less than two epitope mismatches were found, compared with the group with more than three epitope mismatches (at 2 years: 77.8% vs. 65.8%, P=0.0112). Importantly, patients with two DPB1 allele mismatches who had less than or equal to two epitope mismatches exhibited a significantly better graft outcome than recipients who had one HLA-DPB1 allelic mismatch but more than three epitope mismatches (at 2 years: 77.1% vs. 65.8%, P=0.0488). Conclusions. The findings indicate that the impact of HLA-DPB1 matching on the outcome of Kidney retransplants is a result of the predominant immunogenicity of certain epitopes of the HLA-DP molecule. Matching for immunogenic HLA-DPB1 epitopes seems to be functionally more relevant than classical matching at the allelic level.
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clinical relevance of hla dpb locus matching for Cadaver Kidney retransplants a report of the collaborative transplant study
Transplantation, 1997Co-Authors: Joannis Mytilineos, Ariane Deufel, Gerhard OpelzAbstract:BACKGROUND Matching for the HLA class I loci A and B and for the HLA class II locus DRB is known to influence the survival rate of Kidney transplants. It is unknown whether matching for the HLA class II locus DPB also exerts an influence on graft outcome. METHODS The influence of matching for the HLA-DPB locus was analyzed based on DNA typing results obtained in more than 3600 first and 1300 repeat Cadaver Kidney transplants. RESULTS HLA-DPB mismatches had no deleterious influence on the outcome of first Cadaver transplants. However, the influence was statistically significant for retransplants. One-year graft survival rates were 83+/-2% with no mismatch (n=345), as compared with 76+/-2% with one mismatch (n=702, P=0.02), and 73+/-3% with two mismatches (n=258, P=0.003). The deleterious influence of HLA-DPB mismatches was particularly strong in retransplant recipients with >50% reactivity of preformed lymphocytotoxic antibodies, for which the 1-year graft survival rate was 70+/-4% with no mismatch, as compared with 69+/-3% with one mismatch (P=0.05) and 61+/-5% with two mismatches (P=0.003). CONCLUSIONS These results indicate that HLA-DPB is a clinically relevant histocompatibility locus in Cadaver Kidney retransplantation. It is proposed that prospective typing and matching for HLA-DPB should be implemented for Cadaver Kidney retransplants.
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analysis of hla dr split specificity matching in Cadaver Kidney transplantation a report of the collaborative transplant study
Transplantation, 1997Co-Authors: Gerhard Opelz, S Scherer, Joannis MytilineosAbstract:The influence of mismatches for HLA-DR "split" specificities was investigated in more than 8000 Cadaver Kidney transplants. HLA-DR typing was performed using DNA methodology. Among first transplants, mismatches defined by HLA-DR split specificities did not have a deleterious influence. Among retransplants, however, graft survival was significantly decreased if a mismatch was defined, considering split specificities in patients with no mismatch according to the "broad" definition (P=0.04) and also in grafts with two split mismatches, which showed only one mismatch according to the broad definition (P=0.03). Moreover, consideration of further "subsplit" specificities resulted in clinically relevant mismatches only among retransplants. These data indicate that the recognition of HLA-DR split specificity mismatches is fundamentally different in primary and regraft recipients. The results imply that recipients and donors of Kidney retransplants should be typed for HLA-DR split specificities and that these specificities should be considered for organ allocation.
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Analysis of HLA-DR matching in DNA-typed Cadaver Kidney transplants.
Transplantation, 1993Co-Authors: G Opelz, Joannis Mytilineos, H Dunckley, J Trejaut, Jeremy R Chapman, Gottfried Fischer, Sabine Scherer, Ingrid Fae, Derek Middleton, David A SavageAbstract:The effect of matching for HLA-DR antigens was analyzed retrospectively in 3455 Cadaver Kidney transplants that were typed by the DNA-RFLP method. HLA-DR matching improved the one-year graft survival rate significantly (P < 0.01). Importantly, in 718 first transplants in which the number of mismatches assigned by serological typing was different from that assigned by DNA typing, only the DNA results showed a significant impact of matching on graft outcome (P = 0.03). These results demonstrate that DNA typing is clinically relevant. We were unable to confirm that the HLA-DR6 specificity or the DR6-split DRB1*1302 are associated with poor graft survival.
Dinesh Ranjan - One of the best experts on this subject based on the ideXlab platform.
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impact of acute rejection episodes on long term graft survival following simultaneous Kidney pancreas transplantation
American Journal of Transplantation, 2003Co-Authors: Sudhakar K Reddy, Thomas D Johnston, Thomas Waid, Bruce A Lucas, Darcy Davies, Debra Ormond, Sony Tuteja, J W Mckeown, Dinesh RanjanAbstract:Although it is well established that acute rejection is one of the major risk factors for chronic graft loss following Kidney transplantation, its effect on long-term graft survival following simultaneous Kidney-pancreas transplants (SKPTs) is less well known. We analyzed a large cohort of SKPTs and Cadaver Kidney transplants reported to the United Network for Organ Sharing database during 1988–97, to determine the impact of acute rejection episodes on long-term Kidney and pancreas graft survival. Only patients whose Kidney and pancreas grafts had survived for at least 1 year were included. Other potential risk factors influencing long-term graft survival were included in the analysis. Of the 4251 SKPTs, 45% had no acute rejection, 36% had Kidney only rejection, 3% had pancreas only rejection, and 16% had both Kidney and pancreas rejection within the 1st year post transplant. The 5-year Kidney and pancreas graft survival rates adjusted for other risk factors were 91% and 85%, respectively; for those with no acute rejection episodes, 88% and 84%, respectively; for those with Kidney only rejection, 94% and 83%, respectively; for those with pancreas only rejection; and 86% and 78%, respectively, for those with both Kidney and pancreas rejection. The relative risk (RR) of Kidney graft failure was 1.32 when acute rejection involved the Kidney graft only, while the RR was 1.53 when the rejection involved both organs. We conclude that acute rejection episodes have a negative impact on the long-term Kidney graft survival in the SKPT population similar to that in the Cadaver Kidney transplant population. Patients who had acute rejection episodes of both Kidney and pancreas have the worst long-term graft survival.
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long term survival following simultaneous Kidney pancreas transplantation versus Kidney transplantation alone in patients with type 1 diabetes mellitus and renal failure
American Journal of Kidney Diseases, 2003Co-Authors: Sudhakar K Reddy, Don Stablein, S Taranto, Robert J Stratta, Thomas D Johnston, Thomas Waid, Wade J Mckeown, Bruce A Lucas, Dinesh RanjanAbstract:Abstract Background: Pancreas transplantation improves quality of life and prevents the progression of secondary complications of diabetes. Whether these benefits translate into a long-term survival advantage is not entirely clear. Methods: Using the United Network for Organ Sharing database, we analyzed long-term survival in 18,549 patients with type 1 diabetes and renal failure who received a Kidney transplant between 1987 and 1996. Patient survival was calculated using the Kaplan-Meier method. Proportional hazards models were used to adjust for effects of differences in recipient and donor variables between simultaneous Kidney-pancreas transplants (SKPTs) and Kidney-alone transplants. Results: SKPT and living donor Kidney recipients had a significant crude survival distribution advantage over Cadaver Kidney transplant recipients (8-year survival rates: 72% for SKPT recipients, 72% for living donor Kidney recipients, and 55% for Cadaver Kidney recipients). The survival advantage for SKPT recipients over Cadaver Kidney recipients diminished, but persisted after adjusting for donor and recipient variables and Kidney graft function as time-varying covariates. SKPT recipients had a high mortality risk relative to living donor Kidney recipients through 18 months posttransplantation (hazards ratio, 2.2; P
Antonio J. Matas - One of the best experts on this subject based on the ideXlab platform.
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delayed graft function in the absence of rejection has no long term impact a study of Cadaver Kidney recipients with good function at 1 year after transplantation
Transplantation, 1996Co-Authors: Christoph Troppmann, Kristen J. Gillingham, William D. Payne, Rainer W G Gruessner, David L Dunn, John S. Najarian, Antonio J. MatasAbstract:We previously reported that delayed graft function (DGF) in the absence of biopsy-proven acute rejection (Rej) had no effect on outcome of primary Cadaver Kidney transplantation (TX). By contrast, DGF in combination with Rej strongly predicted poor long-term graft survival. We asked whether this poor long-term outcome was due to early graft loss associated with DGF, or to an ongoing process leading to late graft loss. To answer this question, we studied a subset of 298 Cadaver Kidney transplant recipients who had not suffered early graft loss and had a serum creatinine level ≤2.0 mg/dl at 1 year after TX. The incidence of DGF (defined by dialysis during the first week after TX) in this subset was 19%. DGF was associated with cold ischemia time >24 hr (P=0.0003) and Rej (P=0.06). For grafts with versus without DGF, the incidence of late acute Rej (>1 year after TX) was similar. Actuarial graft survival was similar for Rej-free recipients with versus without DGF (P=0.9) and was worse for those with Rej and no DGF (P<0.02). Importantly, however, in out recipients who all had a serum creatinine level ≤2.0 mg/dl at 1 year after TX, the worst long-term outcome was noted in the subgroup with both DGF and Rej (P<0.0001). By multivariate analysis, DGF was also only a risk factor in combination with Rej (P=0.002, relative risk=3.7), while a 0-antigen HLA mismatch had no impact. Patient survival decreased for recipients with both DGF and Rej by univariate (P=0.009) and multivariate (P=0.02, relative risk=2.9) analyses. We conclude that DGF without Rej has no impact on long-term survival. However, out data for recipients with both DGF and Rej suggest that a chronic ongoing process leads to late graft failure. Further research is necessary to identify the exact pathophysiology of this process, which appears to be, at least in part, HLA antigen independent.
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delayed graft function in the absence of rejection has no long term impact a study of Cadaver Kidney recipients with good function at 1 year after transplantation
Transplantation, 1996Co-Authors: Christoph Troppmann, Kristen J. Gillingham, William D. Payne, Rainer W G Gruessner, David L Dunn, John S. Najarian, Antonio J. MatasAbstract:We previously reported that delayed graft function (DGF) in the absence of biopsy-proven acute rejection (Rej) had no effect on outcome of primary Cadaver Kidney transplantation (TX). By contrast, DGF in combination with Rej strongly predicted poor long-term graft survival. We asked whether this poor long-term outcome was due to early graft loss associated with DGF, or to an ongoing process leading to late graft loss. To answer this question, we studied a subset of 298 Cadaver Kidney transplant recipients who had not suffered early graft loss and had a serum creatinine level 24 hr (P = 0.0003) and Rej (P = 0.06). For grafts with versus without DGF, the incidence of late acute Rej (>1 year after TX) was similar. Actuarial graft survival was similar for Rej-free recipients with versus without DGF (P = 0.9) and was worse for those with Rej and no DGF (P < 0.02). Importantly, however, in our recipients who all had a serum creatinine level < or = 2.0 mg/dl at 1 year after TX, the worst long-term outcome was noted in the subgroup with both DGF and Rej (P < 0.0001). By multivariate analysis, DGF was also only a risk factor in combination with Rej (P = 0.002, relative risk = 3.7), while a 0-antigen HLA mismatch had no impact. Patient survival decreased for recipients with both DGF and Rej by univariate (P = 0.009) and multivariate (P = 0.02, relative risk = 2.9) analyses. We conclude that DGF without Rej has no impact on long-term survival. However, our data for recipients with both DGF and Rej suggest that a chronic ongoing process leads to late graft failure. Further research is necessary to identify the exact pathophysiology of this process, which appears to be, at least in part, HLA antigen independent.
