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Saudi Journal of Kidney Diseases and Transplantation
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Year : 1994  |  Volume : 5  |  Issue : 3  |  Page : 359-364
The impact of non-HLA factors on renal graft survival


Department of Internal Medicine and Nephrology, Zagazig University Hospital, Zagazig, Egypt

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   Abstract 

Several non-HLA factors such as, age, sex, blood group, and cytomegalovirus (CMV) carrier state of both the donor and the recipient are known to influence renal allograft survival. In a retrospective study on 150 living related donor renal transplant patients, we evaluated the effect of the above mentioned factors on graft survival. Patients were divided into two groups, according to immunosuppression protocols. Group 1 (n=120) patients were on triple therapy with cyclosporin-A, azathioprine and prednisolone whereas those in Group 2 (n=30) were on conventional therapy with azathioprine and prednisolone. In Group 1, the patients aged < 45 years had graft survival rates 100%, 94% and 83% at 1,2 and 3 years, whereas the rates were 87%, 87%, 68% respectively in those aged > 45 years (P < 0.06). Sex of neither the donors nor the recipients affected graft survival. Patients with blood group B had poor graft survival among Group 2 patients (P < 0.05). However, the patients with blood group B in Group 1 had significantly superior graft survival rates than the patients with the same blood group in Group 2 (P < 0.01). No significant difference in the graft survival rates was found between the two groups in relation to other blood groups. Also, there was no significant difference in the graft survival of the CMV negative and the CMV positive (IgG) recipients in both the study groups.

Keywords: Renal transplantation, Renal allograft survival, Blood Groups, HLA, Cyclosporin, Cytomegalovirus.

How to cite this article:
Hassan AA, Amin EM, Amer AI, Omar EL, Aly MH. The impact of non-HLA factors on renal graft survival. Saudi J Kidney Dis Transpl 1994;5:359-64

How to cite this URL:
Hassan AA, Amin EM, Amer AI, Omar EL, Aly MH. The impact of non-HLA factors on renal graft survival. Saudi J Kidney Dis Transpl [serial online] 1994 [cited 2020 Feb 23];5:359-64. Available from: http://www.sjkdt.org/text.asp?1994/5/3/359/41165

   Introduction Top


It is known that matching for HLA-A, -B, and -DR improves graft survival in recipients treated with conventional immunosuppression [1] . Matching for HLA-B and -DR has been proven to be important in patients on cyclosporin (CyA) therapy [1],[2],[3] Apart from this there are several non.-HLA factors that might affect graft survival such as, Pre-transplant blood transfusions [4],[3],[6] , age of the donor [7],[8] , age of the recipient [9],[10] , sex of the donor as well as the recipient [11],[12],[13] , blood group [14],[15] , and cytomegalovirus (CMV) status of the donor as well as the recipient [16],[17]

We conducted this study to evaluate the effect of these non-HLA factors on the graft survival in patients receiving conventional immunosuppressive therapy as well as in patients receiving CyA therapy.


   Subjects and Methods Top


One hundred and fifty consecutive renal transplant patients from HLA haplo-identical living donors performed at transplant centers of Al-Salem Mohandaseen, Ibn Sina Specialized, and Al-Mataria Teaching Hospitals, Cairo, Egypt, between December 1986 and December 1991, were included in the study.

Patients were divided into two groups according to their immunosuppressive protocol. Group 1 consisted of 120 consecutive patients on triple immunosuppressive therapy with CyA, azathioprine and corticosteroids while Group 2 consisted of 30 consecutive patients on conventional immunosuppressive therapy with azathioprine and corticosteroids [Table 1].

In Group 1, there were 84 males and 36 females with a mean age of 35.6 + 10.5 years (range 8-50 years). The mean follow-up period of these patients was 23 + 15.8 months. In Group 2, there were 22 males and eight females with a mean age of 34.9 + 7.5 years (range 18-45 years). The mean follow-up period was 20.4 8.6 months.

Most of the patients had received third party blood transfusions as treatment of anemia while on dialysis and all but three patients received blood transfusion at the time of surgery as well. In addition, 25 patients in Group 1 had received DST. However, DST protocol was discontinued because some patients developed specific antibodies.

IgG and IgM antibodies tested and had been managed in the following manner:

* CMV IgM positive recipients were not transplanted until seroconversion to negative.

* CMV IgM positive donors were excluded from donation.

* CMV IgG positive (CMV IgG +ve) recipients received kidneys from CMV IgG + ve or CMV -ve donors.

CMV negative (CMV -ve) recipients received kidneys only from CMV -ve donors.

All transplants were performed using ABO compatible donors. The upper age limit for the donors was 55 years.


   Statistical Analysis Top


Probabilities of actuarial patient and graft survivals were estimated using the method described in the Combined Report of the European Dialysis and Transplant Association, XIV, 1983. Significance of the differences among survival curves were calculated using Mantel Cox test. For comparison of the proportions of patients in different groups, Chi square or Fisher's exact probability tests were used. Student's " t " test was used for paired observations to compare the mean values of the study groups.


   Results Top


Overall patient and graft survival rates

The overall patient and graft survival rates were significantly better in Group 1 compared to Group 2 (P < 0.05 and P <0.01 respectively) [Figure 1].

Graft survival rates according to the recipient age

In Group 1, the actuarial graft survival rates for patients below the age of 45 years were 100%, 94%, 83%, and 79% at 12, 24, 36 and 48 months respectively, while they were 87%, 87% and 68% at 12, 24 and 36 months respectively for patients above 45 years. The differences were not statistically significant. All patients in Group 2 were below 45 years.

Graft survival according to the sex of the donor and the recipient

No statistically significant differences were observed when donors and recipients were matched or mismatched for sex.

Graft survival according to blood groups

There was no significant difference in the graft survival rates in Group 1 in relation to various blood groups. In Group 2, patients with blood group A or O had better graft survival rate compared to those with AB or B. Patients with blood group B in Group 2 had the poorest graft survival rates (P <0.05) [Figure 2]. However, the recipients with blood group B in Group 1 had better graft survival rates when compared to patients with the same blood group in Group 2 (P < 0.001) [Figure 3].

Blood transfusion and graft survival rates

Since all the patients had received third party transfusion the effect of blood transfusion and graft survival could not be assessed in our study patients.

CMV status and graft survival rates

Graft survival rates were compared between the CMV IgG +ve and CMV -ve recipients in both the groups. In Group 1, the actuarial graft survival rates of the CMV -ve recipients were 100%, 90% and 78% whereas in the CMV IgG +ve recipients, the graft survival rates were 100%, 80% and 57% at 33, 36 and 54 months respectively. In Group 2, the graft survival rates of the CMV -ve recipients were 100% at 21 months and 85% at 30 months, while those of CMV IgG + ve recipients were 100% at 3 months and 60% at 30 months. Although the graft survival rates seem superior in the CMV -ve recipients, the differences were not statistically significant.


   Discussion Top


Although HLA matching is a prime factor influencing post-transplant graft survival, there are several other factors which also affect graft survival [2],[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17] . In this study, use of CyA improved both patient and graft survival, a well known advantage of the use of CyA in renal transplant recipients.

Another factor that is thought to influence allograft survival is the age of the recipient. Early experience in transplantation indicated that recipients of older age-group had higher mortality rates compared to the younger age group, leading to exclusion of such elderly patients as potential recipients for renal transplantation [9]. However, the effect of the donor and the recipient age on the outcome of the kidney transplant seems to have changed over the years. In more recent studies, the difference in the mortality rates of the older age-group, compared with the younger age group recipients was smaller [10] . In our study, we did not find any effect of recipient age on the graft survival rates.

Several studies have considered the influence of the sex of the donor and the recipient on allograft survival [11],[12],[13] . In the past, it was also suggested that there might be sex linked histocompatibility antigens in humans [12] . One study suggested that male to male transplants did better than male to female or female to male transplants [13] . However, others could not confirm these data [11] . Our results were in keeping with the observation that neither the donors' nor the recipients' sex affected the overall graft survival.

Only a few studies have analyzed the effect of the recipient blood group on renal graft survival. Some have reported that the blood group O recipients had better graft survival compared to recipients with other blood groups [14] . Others have pointed out that the effect of HLA matching is influenced by the ABO blood group of the recipient only in recipients with blood group other than group O [15] . In our study, the effect of the blood groups was seen in patients on azathioprine and prednisolone, in whom the patients with blood groups A or O had better graft survival rates compared to those with blood groups AB or B. The patients with blood group B had the poorest graft survival rates. However, among the patients on CyA, this effect of blood group B was not seen. A well designed study with a large number of patients may give further information on the role of CyA in improving the graft survival in patients with blood group B.

The influence of third-party blood transfusions in patients receiving cadaveric [18] as well as live related [19] donor kidney renal transplantations who are on conventional immunosuppression is well established. However, pre-transplant blood transfusion has lost its importance in recent years with the usage of CyA [20] . We could not assess the effect of this factor among our patients.

Cytomegalovirus continues to be a major problem in solid organ and in bone marrow transplantation [16],[17] . It seems to play a role in the development of vascular rejection after renal transplantation [21] . Matching of the donors and the recipients according to CMV status has been found to have an influence on the graft and patient survival. Recipients of organs from CMV antibody negative donors have been reported to have better graft survival rates, especially if they were CMV negative [22],[23] . Others have found an identical risk of active CMV disease, whether or not the donor or the recipient had CMV antibody detected in their sera [14],[16] . In our study, we did not find a statistically significant difference in the graft survival rates between the CMV + ve (IgG) and CMV -ve recipients regardless of the immunosuppressive regimen.

Thus, among the several non-HLA factors that could affect the renal graft survival, we found an effect only in relation to recipients' blood groups, in addition to the well known advantage of CyA. Other factors did not show any significant effect in our group of patients.

 
   References Top

1.Hassan AA, Khalil R, Amin EM, Amer AI, Ayaad MA, Aly MH. The role of HLA in renal transplantation. N Egyptian J Med 1992;7(6):1497-501.  Back to cited text no. 1    
2.Mendez R, et al. The effect of HLAmatching on graft outcome in Sandimmune (SIM) treated kidney recipients. Transplant Proc 1988;(S1) 20:28-30.  Back to cited text no. 2    
3.Cicciarelli J. HLA matching and cyclosporine immunosuppression: a strong correlation. ancet 1986;1:267.  Back to cited text no. 3    
4.Gardner B, Harris KR, Tate DG, et al. The effect of pretransplant blood transfusions on renal allograft survival in patients on cyclosporin. Transplant Proc 1984;16:1172-3.   Back to cited text no. 4  [PUBMED]  
5.Opelz G. Comparison of random transfusions with DST for pretreatment of HLA haplotype matched related donor kidney transplant recipients. Transplant Proc 1985;17(6):2357-61.  Back to cited text no. 5    
6.Sommer BG, Ferguson RM. Mismatched living, related donor renal transplantation: a prospective, randomized study. Surgery1985;98:267-74.  Back to cited text no. 6  [PUBMED]  
7.Lloveras J. The elderly donor. Transplant Proc 1991;23:2592-5.   Back to cited text no. 7  [PUBMED]  
8.Sautner T, Cotzinger P, Wamser P, Gnant M, Steininger R, Muhlbacher F. Impact of donor age on graft function in 1180 consecutive kidney recipients. Transplant Proc 1991;23:2598-601.  Back to cited text no. 8    
9.Simmons RL, Kjellstrand CM, Buselmier TJ, Najarian JS. Renal transplantation in high risk patients Arch Surg 1971;103:290-8.  Back to cited text no. 9    
10.Okiye SE. Primary renal transplantation in patients 50 years of age or older. Transplant Proc 1983;15:1046.  Back to cited text no. 10    
11.Opelz G, Terasaki PI. Influence of sex on histocompatibility matching in renal transplantation. Lancet 1977;2:419-21.  Back to cited text no. 11  [PUBMED]  
12.Oliver RT. Are there Y-Linked histocompatibility antigens in man? Eur J Immunol 1974;4:519-20.  Back to cited text no. 12  [PUBMED]  
13.Descamps B, N'Guyen AT, Kreish H.Tests of immunologic competence. New insights into im-munologic selection of human cadaver renal allograft recipients based on immune response capacity criteria. Transplant Proc 1978;10:497-500.  Back to cited text no. 13    
14.Tosey S. In: Terasaki PI (ed): Clinical Transplants 1984, UCLA. Tissue typing lab. Los Angeles 1984;246-48.  Back to cited text no. 14    
15.Cecka M. ABO blood group antigens and kidney transplant. In: Terasaki PI (ed): Clinical kidney transplants 1985, UCLA tissue typing laboratory. Los Angeles, 1985;179.  Back to cited text no. 15    
16.Rocha E, Campos HH, Rouzioux C, et al. Cytomegalovirus infections after kidney transplanation: identical risk whether donor or recipient is the virus carrier. Transplant Proc 1991;23:2638-40.  Back to cited text no. 16  [PUBMED]  
17.Muller GA, Braun N, Einsele H, Muller CA. Human cytomegalovirus infection in Transplantation. Nephron 1993;64:343-53.  Back to cited text no. 17    
18.Salavatierra O. Advantages of continued use of kidney transplant from living donors. Transplant Proc 1985;17(2):18.  Back to cited text no. 18    
19.Opelz G, Mickey MR, Terasaki PI. Blood transfusions and kidney transplants: remaining controversies. Transplant Proc 1981;13:136-41.  Back to cited text no. 19  [PUBMED]  
20.Opelz G. The role of HLA matching and blood transfusions in the cyclosporin era. Collaborative transplant study. Transplant Proc 1989;21:609-12.  Back to cited text no. 20    
21.Tenschert W, Dittmer R, Harfmann P, et al. Vascular rejection of renal allografts is linked to CMV IgG, positive organ donor.Transplant Proc 1991;23:2641-2.  Back to cited text no. 21  [PUBMED]  
22.Battegay EJ, Mihatsch MJ, Mazzucchelli L, et al. Cytomegalovirus and kidney. Clin Nephrol 1988;30:239-47.  Back to cited text no. 22  [PUBMED]  
23.Barsoum R, Yassa HE, El-Khashab O, et al. Endemic cytomegalovirus (CMV) infection and renal transplantation in Egypt. A multicenter retrospective study. In: Abstracts of The Second Congress of the Arab Society of Nephrology and Renal Transplantation 1991;54.  Back to cited text no. 23    

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Correspondence Address:
Ahmed Adel Hassan
Consultant Nephrologist, Jeddah Kidney Center, P.O. Box 50505, Jeddah 21533, Saudi Arabia

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PMID: 18583765

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    Introduction
    Subjects and Methods
    Statistical Analysis
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