Objectives: The aim of this study was to report the results of 30 years of experience at the first kidney transplant center in Tunisia.
Materials and Methods: All kidney transplants performed at the center between June 1986 and June 2016 were included. The study period was divided into 3 decades. Recipient and donor data and follow-up information were obtained from a local database and patient medical records. Comparative analyses were performed using the t test for continuous variables and the χ2 test for qualitative variables. Patient and graft survival rates were calculated according to the actuarial method, and comparison of survival curves was performed according to the log-rank test.
Results: The mean age of recipients was 32.7 ± 11.5 years (range, 6-65 y) with a gender ratio of 2.2. Duration of prekidney transplant dialysis varied from 2 months to 20 years (median, 27.5 mo); 1.7% of patients underwent transplant preemptively. Kidneys were recovered from deceased donors in 21.2% of cases and from living donors in 78.8%. The proportion of deceased donors dropped from 27.4% during the period 2006-2010 to 12.9% during the period 2011-2015 (P < 0.04). Patient survival rates at 1, 5, 10, 15, and 20 years were 96%, 89.3%, 79.5%, 71.1%, and 65.4%. Graft survival rates were 95%, 86.5%, 76.2%, 66.3%, and 57.2%. The annual graft loss was 2.9%, with a mortality rate of 2.4% and without significant differences between patients receiving deceased-donor and living-donor organs.
Conclusions: Kidney transplant activity remains suboptimal in our country. The reduction in deceased-donor organs could be related to the political transformations facing our country with their resulting social and economic consequences. Efforts should be made to increase governmental resources and to improve both public awareness of organ donation and the motivation of transplant teams.
Key words : Complications, Kidney transplantation, Socioeconomic factors, Survival rate
Tunisia is a country located in Northern Africa that encompasses 163 610 square kilometers and has a population of 11.3 million people.1 In 2014, the Tunisian health expenditure was estimated to be 7% of the gross national product.2 A dialysis program for patients with end-stage renal disease (ESRD) was launched in 1976 but was limited for many years to the capital city of Tunis and 3 other major cities.3 The treatment is provided at no cost to the patient by the Ministry of Health or through social security funds without any restrictive policy.3,4 The program has expanded and, currently, there is a large network of dialysis centers throughout the country serving about 10 000 patients.
The Tunisian kidney transplant activity started in June 1986, at Charles Nicolle Hospital in the capital city of Tunis.5,6 Between June 1986 and December 2015, there had been 1686 kidney transplants performed in the 6 transplant centers currently active in Tunisia.
The aim of this study was to report the results of 30 years of experience at Charles Nicolle Hospital, the first kidney transplant center in Tunisia, at which 42% of all kidney transplants performed in our country have taken place.
Materials and Methods
The study period was the 30 years from June 4, 1986, the date of the first kidney transplant performed in Tunisia, to June 3, 2016, and included all kidney transplants performed at Charles Nicolle Hospital. The study period was divided into 3 decades as follows: 1986-1996, 1996-2006, and 2006-2016.
Recipient and donor data were obtained from a local database. Follow-up information was compiled from data that were found in patient medical records and that were recorded during regular medical visits. Follow-up duration was calculated from the date of transplant to the date of death or graft loss or to the date of September 3, 2016.
The incidences of mortality and graft loss were calculated by dividing the number of such events by the total duration of the follow-up and were expressed in 100 patient-years. Comparative analyses were performed using the t test for continuous variables and the χ2 test for quantitative variables. Patient and graft survival rates were calculated according to the actuarial method, and survival curves were compared according to the log-rank test using Statview 5.0 software. The level of statistical significance was set at 5%.
A total of 702 kidney transplants were performed during the study period. Deceased-donor organs were used in 21.4% of the transplants. About one-half of the transplants were performed during the last decade (2006-2016) of the study (P < .0001). Most of these patients (98%) were Tunisian; the remaining patients (n = 16) were from North African and sub-Saharan African countries. The 16 foreign patients—7 Ivorian, 2 Senegalese, 1 Nigerien, 2 Moroccan, 2 Libyan, and 2 Mauritanian—received kidneys from living-related donors. The mean age of recipients was 32.7 years (range, 6-65 y); however, the mean age increased from 28.8 years to 35.7 years between the first and last decade of the study (P < .0001). At the time of transplant, 80% of our patients were between 20 and 50 years of age, 6 patients were at least 60 years old, and 30 patients were younger than 15 years. There was a male predominance among recipients of living-donor transplants, with a gender ratio of 2.7 contrasting with that of 1.1 in recipients transplanted with deceased-donor kidneys (P < .0001).
Causes of ESRD remained undetermined in 52.7% of patients; this proportion decreased from 67.7% to 43.5% during the last decade of the study (P < .001). Diabetic nephropathy was determined to be the cause of ESRD in 14 of our patients; none of these patients received a transplant during the first decade of the study.
Hemodialysis was the more common dialysis modality used in our patients; only 20.3% of patients were receiving peritoneal dialysis. Only 12 patients received a transplant preemptively. The wait times to transplant varied from 2 months to 20 years, with a median of 27.5 months that increased from 23 months to 27 months and 34 months during the 3 decades of the study (P < .003).
The mean age of donors was 40.2 years. In deceased donors, the mean age was 33.9 years, and in living donors it was 42 years (P < .0002). A difference in ages between living and deceased donors was found in all 3 decades of the study (P < .02). There was a male predominance among deceased donors versus a female predominance among living donors (P < .0002). Furthermore, 14% of recipients received a kidney from a fully human leukocyte antigen (HLA)-matched donor and 4.8% received a kidney from an HLA-mismatched donor.
Table 1 shows the characteristics of both the recipients and donors in our study. Table 2 contains the list of drugs available for induction and maintenance therapy. Table 3 shows that surgical complications remained frequent during the early part of the study period and that infections were the leading cause of morbidity and hospitalization throughout follow-up.
During an accumulated follow-up of 5466 years, a total of 131 patients (18.7%) died and 158 patients (22.5%) lost their kidney graft. There was no significant difference between patients who received a deceased-donor kidney and those who received a living-donor kidney during the 30-year study period. Graft dysfunction was mostly related to chronic allograft nephropathy, which accounted for 60% of graft loss. Infections represented the leading cause of death in these patients during the study period (Table 3).
Actuarial patient survival rates at 1, 5, 10, 15, and 20 years were 96%, 89.3%, 79.5%, 71.1%, and 65.4%. Graft survival rates were 95%, 86.5%, 76.2%, 66.3%, and 57.2% (Figure 1). The yearly rate of graft loss was of 2.9%, and the mortality rate was 2.4%.There was no significant difference in these rates between deceased-donor and living-donor recipients.
Before June 1986, about 120 Tunisians with ESRD received a kidney transplant abroad. The Tunisian government and social funds covered the costs of these transplants and all related expenses.7 The initiation of the kidney transplant program at our hospital was a collaborative initiative of different medical teams at our facility without a suitable legal statute enabling such a therapeutic procedure. This initiative was followed by many government measures, including the establishment, since 1991, of a legislative framework that sets rules and standards concerning brain death and human organ transplant, and the creation, in 1995, of a national organizational system to oversee and promote organ donation and transplant.6,8
With this national system and a legislative framework within which to work, the official Tunisian Islamic authority now supports organ donation and transplant, public hospitals are exclusively authorized to perform transplants, financial compensation for organ donation is strictly prohibited, and organ transplant and immunosuppressive therapy are provided at no cost to the patient by the government and social funds.
These organizational and legislative approaches, along with the participation of different medical teams, have resulted in an increase in the number of kidney transplants, especially with the attempted expansion of living donor pools, as discussed below. Unfortunately, given the high prevalence of ESRD, the number of transplants, currently being performed, fails to respond to the growing need. Indeed, Tunisia is ranked among the countries with the lowest numbers of kidney transplants being performed with either living-donor or deceased-donor organs.8,9 Whereas more than one-third of patients receiving dialysis could receive a transplant, only 10% of these patients are on wait lists to receive a kidney from a deceased donor. This opportunity did not exceed the rate of 2% yearly knowing that the annual mortality rate is estimated at 1% in patients who remain on wait lists.
Many factors could limit access of such patients to kidney transplant, including the political transformations currently facing our country with the resulting social and economic consequences; the under-declaration of brain death related to the fact that a large proportion of physicians are indifferent to organ donation; and the high proportion of family refusals of organ donation, leading to the loss of more than 75% of potential donors and that could raise our transplant activity by 60%.
Current strategies to increase living-donor pools include paired exchange programs, altruistic donations, and the acceptance of kidneys from marginal and ABO-incompatible donors.10-13 To ensure their success, such strategies should accommodate international recommendations14-16 and local resources and also take into account cultural issues.11,13 In our experience, the acceptance of kidney donations between spouses and among extended family members has resulted in an increase in the numbers of living donors during the last decade of this study.
Tunisia is considered to be among the pioneer Arab and Muslim countries in kidney transplant using deceased donors, having had this option available since July 1986, just a few weeks after the first living-related donor kidney transplant.6,8 The current legislation sets rigorous and detailed rules and standards concerning brain death, as well as the removal, storage, allocation, and transplant of human tissue and organs.16 In addition, the official Tunisian Islamic authority supports organ donation and transplant. This position is based on the Quran verses and prophet sayings and the position of other prestigious academies or personalities in the Muslim world.6,8,17 About 20% of our patients have received kidneys from deceased donors. This rate has increased significantly from 9.1% during the first decade of our study to 30.3% during the second decade of the study and 22% during the last decade of the study.
There is a gender imbalance in living-donor transplant, with male predominance among recipients contrasting with female prevalence among donors. Such disparity is attenuated when we considered transplant using deceased donors, with the gender ratio reaching 4.25 in contrast to that of 1.1 in recipients. This gender imbalance in living donors has been reported even in developed countries and was not explained by the higher proportion of wife-to-husband donation.18-20
It is well established that HLA matching remains one of the most important modifiable factors for improving kidney graft survival.21 In our study, more than 80% of recipients received a kidney from donors with less than 3 HLA mismatches. This could be related to our policy concerning kidney allocation from deceased donors based on HLA matching and the dominance of living-related donors. In addition to our HLA matching policy, the fact that most of our patients are young, are without comorbidities, and are receiving kidneys from young living-related donors have contributed to the satisfactory early and late patient and graft survival rates observed in our study.22
We can also speculate that providing immunosuppressive therapy free of cost helps to limit the graft loss that can result from poor medication adherence related to limited financial resources.23 Unfortunately, some of our patients have lost their kidney grafts after an abrupt withdrawal of immunosuppressive therapy. Graft loss was observed mainly in young recipients who were faced with psychosocial conflicts.23,24 The long follow-up duration and successive changes in our immunosuppressive regimens did not allow us to determine the effects of both induction and maintenance immunosuppressive therapy on graft and patient survival rates and the occurrence of posttransplant complications. Because of restrictive government policy, we have used generic formulations of mycophenolate mofetil and tacrolimus exclusively during the past years; both are locally manufactured. The use of generic immunosuppressive drugs is pervasive worldwide, although evidence of their efficacy and safety remains inconclusive.25-27
Early graft loss was mostly related to vascular thrombosis, which was considered to be related to technical problems.28 Transplant physicians should have theoretical and practice expertise in Doppler ultrasonography for early detection of such complications.29 It has been reported that prompt revascularization could allow for graft salvage.30
In our study, infections were the leading cause of morbidity and mortality throughout follow-up. Infectious complications remained frequent after transplant, most of which were urinary tract infections that were observed in 29% to 47% of cases.31 In our study, urinary tract infections were often nosocomial and recurrent, leading to multiple prolonged hospitalizations. Other infections were described in our patients, including tuberculosis, which was observed with an overall annual incidence of 0.42% in our kidney transplant recipients32 versus 0.033% in the general Tunisian population.33
Malignancies that occurred in our patients corresponded to postkidney transplant lymphoproliferative disorders and to Kaposi sarcoma. We have already reported that the annual incidences of postkidney transplant lymphoproliferative disorders and Kaposi sarcoma were 0.32% and 0.27%.34,35
Although there are the necessary legal texts that regulate organ transplant in Tunisia according to international recommendations, the number of kidney transplants being performed in our country remains suboptimal. Therefore, both the medical community and government authorities should improve on the acquired gains of our experience and meet the remaining challenges. We must make efforts to reduce the rate of preventable causes of graft loss, reduce the rate of infectious complications, have adequate governmental resources to improve motivation of transplant teams, and change public and professional attitudes toward brain death and organ donation.
Volume : 15
Issue : 1
Pages : 84 - 89
DOI : 10.6002/ect.mesot2016.O66
From the 1Department of Nephrology and Internal Medicine, 2Department of
Pediatrics, 3Laboratory of Immunology, 4Department of Urology,
Laboratory (LR03SP01), 6Faculty of Medicine, University Tunis El Manar, Charles
Nicolle Hospital, Tunis, Tunisia
Acknowledgements: The authors declare that there is no conflict of interest regarding the publication of this article. The authors thank all colleagues who contributed to this work by providing information concerning the follow-up of their patients. Special thanks to Yosr Gorgi, Amine Derouiche, Fethi El Younsi, Fethi Ben Hamida, Rim Goucha, Hayet Kaaroud, Samia Barbouch, Imed Helal, Amel Harzallah, Imen Gorsane, Soumaya Chargui, Abdellatif Achour, Habib Skhiri, and Jamil Hachicha.
Corresponding author: Ezzedine Abderrahim, Department of Nephrology and Internal Medicine, Charles Nicolle Hospital, Boulevard du 9 Avril, 1006 BS, Tunis, Tunisia
Phone: +216 71 578 146
Table 1. Kidney Transplant Recipient and Donor Characteristics by Study Period
Table 2. Immunosuppressive Drugs Used for Prevention and Treatment of Kidney Graft Rejection
Table 3. Complications After Kidney Transplant
Figure 1. Patient and Graft Survival