Nephrol Dial Transplant (2002) 17: 884-886
© 2002 European Renal Association-European Dialysis and Transplant Association
Comparison of blood group versus HLA-dependent transplantation and its influence on donor kidney survival
1 Department of Urology and 2 Department of Medicine, University of Bonn, Bonn, Germany
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Abstract |
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Background. The advantages of organ allocation based on human leukocyte antigen (HLA) typing are controversial. This evaluation compares the results of HLA-dependent and non-HLA-dependent allocation in the transplantation of donor kidneys.
Methods. Seventy-seven donor kidney pairs explanted locally between 1984 and 1994 were examined. One half of each pair was transplanted locally in Bonn on the basis of criteria including blood group, waiting time and currently negative cross-match. The other half of these pairs was allocated in accordance with the Eurotransplant (ET) criteria.
Results. Cold ischaemia time was an average of 14.02 h in Bonn vs 24.18 h in the ET group (P<0.0001). The number of HLA mismatches was calculated and, for example, for locus A it was 1.13 in Bonn vs 0.73 in the ET group (P=0.0003). One-year graft survival for the locally transplanted kidneys was 92.2% and, for the ET kidneys, 90.9%. Five-year survival was 79.5% vs 81.7%, respectively. Patient survival after 1 year was 100% vs 97.4%, and after 5 years, 93.4% vs 93.1%.
Conclusion. The results show that it is possible to provide patients with a locally allocated kidney graft that enables good function after a short waiting period. This procedure avoids long cold ischaemia time and long waiting periods.
Keywords: HLA compatibility; kidney transplantation; local allocation; long-term kidney survival; long-term patient survival
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Introduction |
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The allocation of donor kidneys on the basis of human leukocyte antigen (HLA) compatibility, as is currently practiced by Eurotransplant (ET), is disadvantageous especially in small centres with short waiting lists because the chance of receiving a matching donor organ is reduced. HLA-independent transplantation of locally harvested organs was therefore introduced in Bonn. This procedure was in accordance with the results of the ‘Scandinavian Experience’ reported by Brynger et al. [1], who could not prove that HLA compatibility affected long-term organ function.
Until 1995, only blood group compatibility, place on the local waiting list at the time of announcement by ET and the currently negative cross-match were taken into account in Bonn. Only a small proportion of our patients received a donor organ arranged via ET. The procedure for allocation of donor organs in Bonn has been criticized because, like other authors [2], Opelz et al. [3] documented the positive influence of good HLA-compatibility on transplant function in large-scale studies.
This study is retrospective and was aimed at proving whether the long-term results of HLA-independent allocation of donor organs, combined with a responsible follow-up and care for patients, differ from the results of HLA-dependent allocation such as that practiced by ET.
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Subjects and methods |
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The study was conducted from January 1984 until December 1994 and focused particularly on the possible influence of HLA compatibility. A comparison was made between transplanted kidney pairs deriving from donors in Bonn or from assigned hospitals. One organ from each of these kidney pairs was transplanted in Bonn without regard for HLA compatibility. The other organ of the kidney pair was transplanted in other hospitals under the management of ET, taking HLA compatibility into account.
Data from donors and patients from Bonn were available in a Dbase database. The data from patients who had received the corresponding kidney in another hospital were investigated using the Transplantation Information System.
A questionnaire was sent out to any patients not transplanted in Bonn. Seventy-seven (83.7%) filled in the questionnaires, which served as the basis of the evaluation. Comparisons between the Bonn and ET patient groups were mainly with respect to the following variables: extent and effect of HLA mismatches, time of cold ischaemia, acute renal failure in the post-operative period, rate of rejection, short-term and long-term function of transplant and patient survival.
The statistical evaluation was carried out with the program SAS, Release 6.07 (SAS Institute Inc.). The patients were divided into the groups ‘Bonn’ (n=77) and ‘ET’ (n=77). When necessary, subgroups were set up. The basis for the evaluation was the comparison between the two groups.
Qualitative data were compared with the 
2 test and the Fischer test. The means of quantitative data were compared with a paired t-test. Transplant function and survival of patients were calculated according to Kaplan-Meier and performed graphically. The comparison was made using a log rank and the Wilcoxon test.
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Results |
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There were no significant differences between the mean ages at transplantation (40.8 vs 42.84 years) or the sex ratios (33.77 vs 36.36% female, 66.23 vs 63.64% male) in the Bonn group or the ET group. Similarly, there were no significant differences in the cytotoxic antibody statuses between the two groups.
A marked difference between the groups was seen in the average waiting periods before transplantation (Table 1
). Comparing the two groups, it is obvious that HLA mismatches in the ET group appear to be fewer than in Bonn (Table 1). In our centre, kidneys were transplanted after a significantly shorter cold ischaemia time than in the ET group (Table 1). The basic immunosuppression was carried out in Bonn with cyclosporin A and a steroid. In the ET group, patients also received azathioprine as a third therapy. An ATG prophylaxis for the first 7 post-operative days was administered to 47 patients in Bonn and 22 patients in the ET group.
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Of the 77 transplanted kidneys in each group, 67.53% (n=52) in Bonn and 58.44% (n=45) in the ET group started functioning intra-operatively or immediately post-operatively.
More rejections were seen in the Bonn group than in the ET group (Table 1
); a total of 23.4% (n=18) in Bonn and 27.3% (n=21) transplants in the ET group were lost. The most frequent reason for the loss of transplants in both groups was chronic rejection. Apart from immunological causes, death was the most common reason for the loss of transplants; in Bonn, a total of seven patients (9.1%) died, six of them still having functioning transplants. In the ET group, eight patients died, again with six of them having functioning transplants. Patient survival after 1 year was nearly 100% in Bonn and 97.4% in the ET group. After 5 years, the survival rate was 93.4% in Bonn and 93.1% in the ET group (no statistically significant difference).
The rate of transplant function according to Kaplan-Meier (Figure 1) shows no appreciable difference between the two groups (t-test, P=0.5617; Wilcoxon test, P=0.6168).
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Discussion |
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TopAbstractIntroductionSubjects and methodsResultsDiscussionEditor’s noteReferences |
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Half of the 154 kidneys from the 77 donors were locally transplanted in Bonn without consideration of HLA compatibility, and half in other hospitals under the administration of ET with particular consideration of HLA compatibility. The same donors provided kidneys for both study populations of patients. There were also no statistically significant differences between the characteristics of patients in Bonn and those in the ET group. However, the mean waiting period for transplantation in Bonn is less than a year. This is the result of a short waiting list and HLA-independent allocation of the locally harvested donor organs.
The expected statistically significant differences of mismatches can be put down to the criteria of organ distribution by ET. Cold ischaemia time in the Bonn group was 10 h shorter on average than in the ET group. This significant difference can be explained by the longer distances between harvesting location and the individual transplantation centre in the ET group.
A major problem is rejection in the post-operative period, because this endangers the success of transplantation. Evaluation of the data clearly shows that nearly twice the number of patients in the Bonn group had one or more rejections compared with the ET group. Diagnosis in patients with only one rejection is based exclusively on clinical criteria. Evaluation of the clinical criteria for diagnosis gives only a suggestion and is not a defined ‘score’ enabling a standardized diagnosis. It is possible that evaluation of clinical signs differs between transplantation centres as well as between physicians at a single centre. The 2 test, Wilcoxon test and logarithmic regression did not show a statistically significant correlation between the variables examined (pre-operative transfusions, cytotoxic antibodies, cold ischaemic time, HLA mismatches) (data not shown) and the occurrence of rejection either for the two groups together or for the two groups separately, probably because of a different management in immunosuppression.
The success of transplantation is best defined in terms of the rate of transplant function and patient survival rate. It is obvious that the rates of transplant function in the Bonn group and the ET group are almost the same after 1 and 5 years (Figure 1). These transplant function rates are consistent with data of Hariharan et al. [4] for renal transplantation in the United States. In large multicentre studies, Opelz et al. [3] and Takemoto et al. [2] found that success rates decreased as the numbers of HLA mismatches increased. They stated that the extent of HLA matching is the most important factor influencing the transplant function rate. In contrast, Alexander et al. [5], Brynger et al. [1] and Greenstein et al. [6] have shown that transplant function does not depend on the degree of HLA correspondence in large-scale multicentre studies.
Since allocation policy is not based on HLA compatibility in Scandinavian countries [1] and good results are attained nevertheless, the superiority of HLA-dependent allocation of donor organs is questionable. Moreover, Terasaki et al. [7] found that graft-survival from spouses with poor HLA matches is similar to that of parental-donor kidneys. Held et al. [8] reported that after a prolonged cold ischaemia time, the long-term function rates of maximally compatible transplants is only 4.4% better than those of transplants with one or more mismatches, showing the negative effect of a prolonged cold ischaemia time. Furthermore, the rate of patient survival was similar in the Bonn and the ET group and corresponds to reports in the literature [9,10]. However, the fact that our data does not show that HLA compatibility has any effect may be because we performed a retrospective investigation with a small number of patients. Larger series and prospective studies with a better comparability, especially with regard to immunosuppression, are more suitable for settling this question.
In conclusion, HLA-independent allocation shortens the waiting period and cold ischaemia time. With a more intensive immunosuppression, the same results might be obtained as in HLA-dependent allocation. As great a degree of HLA compatibility as possible and as short a period of cold ischaemia as possible are required to improve transplant success.
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Editor’s note |
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Please see also Controversy articles by G. Opelz (pp. 715–716) and R.A.P. Koene (pp. 717–718).
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Notes |
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Correspondence and offprint requests to: Dr Markus S. Gillich, Klinik und Poliklinik für Urologie, Universität Bonn, Sigmund Freud Strasse 25, D-53105 Bonn, Germany. Email: MGillich{at}t\|[hyphen]\|online.de
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References |
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TopAbstractIntroductionSubjects and methodsResultsDiscussionEditor’s noteReferences |
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- Brynger H, Persson H, Flatmark A et al. No effect of blood transfusions or HLA matching on renal graft success rate in recipients treated with cyclosporine-prednisolone or cyclosporine-azathioprine-prednisolone: the Scandinavian experience. Transplant Proc1988; 20: 261–263[Web of Science][Medline]
- Takemoto S, Terasaki PI, Cecka JM, Cho YW, Gjertson DW. Survival of nationally shared, HLA-matched kidney transplants from cadaveric donors. The UNOS Scientific Renal Transplant Registry. N Engl J Med1992; 327: 883–885[Web of Science][Medline]
- Opelz G, Wujciak T, Döhler B, Scherer S, Mytilineos J. HLA compatibility and organ transplant survival. Rev Immunogenet1999; 1: 334–342[Medline]
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Hariharan S, Johnson CP, Bresnahan BA, Taranto SE, McIntosh MJ, Stablein D. Improved graft survival after renal transplantation in the United States, 1988 to 1996. N Engl J Med2000; 342: 605–612
[Abstract/Free Full Text] - Alexander JW, Vaughn WK, Pfaff WW. Local use of kidneys with poor HLA matches is as good as shared use with good matches in the cyclosporine era: an analysis at one and two years. Transplant Proc1987; 19: 672–674[Medline]
- Greenstein SM, Schechner RS, Louis P et al. Evidence that zero antigen-matched cyclosporine-treated renal transplant recipients have graft survival equal to that of matched recipients. Transplantation1990; 49: 332–336[Web of Science][Medline]
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Terasaki PI, Cecka JM, Gjertson DW, Takemoto S. High survival rates of kidney transplants from spousal and living unrelated donors. N Engl J Med1995; 333: 333–336
[Abstract/Free Full Text] - Held PJ, Kahan BD, Hunsicker LG et al. The impact of HLA mismatches on the survival of first cadaveric kidney transplants. New Engl J Med1994; 33: 765–770
- Eigler FW, Albrecht KH, Niebel W, Kruschke A. Fortschritte der Nierentransplantation. Langenbecks Arch Chir1992; [Suppl]: 217–223
- Vanrenterghem Y, Waer M, Christiaens R, Roels L, Gruwez J, Michielson P. Long-term results after cadaver kidney transplantation have also improved over the last two decades. The Leuven Collaborative Group for Transplantation. Transplant Proc1991; 23: 1265–1266[Medline]
Accepted in revised form: 24.12.01
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