RENAL DATA FROM THE ARAB WORLD
|Year : 2008 | Volume
| Issue : 5 | Page : 831-837
|Living Related Donor Kidney Transplantation in Libya: A Single Center Experience
Ahmed Elusta1, Taib Shawish1, Anuj Mishra2, Husni Ajaj3, Nagib Milud3, Abdulhafidh Shebani4, Tamer S Abdulmola1, Osama Altajori1, Ehtuish F Ethuish1
1 Department of Surgery, National Organ Transplant Program, Tripoli Central Hospital, Tripoli, Libyan Arab Jamahiriya, Libya
2 Department of Radiology, National Organ Transplant Program, Tripoli Central Hospital, Tripoli, Libyan Arab Jamahiriya, Libya
3 Department of Anesthesia, National Organ Transplant Program, Tripoli Central Hospital, Tripoli, Libyan Arab Jamahiriya, Libya
4 Department of Nephrology, National Organ Transplant Program, Tripoli Central Hospital, Tripoli, Libyan Arab Jamahiriya, Libya
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| Abstract|| |
The aim of this study is to report the experience from a single center in Libya, on the prevailing live-related kidney transplantation program. The results of three years work on kidney transplantation at the Tripoli Central Hospital (National Organ Transplant Program) in Libya were evaluated. The transplant program was launched on 17 th August, 2004 and 135 patients have been transplanted since then till 17 th August, 2007. All donors and recipients were screened thoroughly prior to transplant and monitored closely in the post-transplant period. Our immunosuppressive protocol was cyclosporine-based. Among the 135 accepted pairs, donors and recipients were genetically-related in 133 cases (98.5%) and emotionally-related in two others. The mean donor age was 37 ± 9.5 years (range 18-56 years) and recipient age 37 ± 13.6 years (range 7-67 years). There were 95 males (70.4%) and 40 females (29.6%) among the recipients while among the donors, there were 102 males (75.6%) and 33 females (24.4%). Delayed graft function was seen in three patients (2.2%), acute rejection in six (4.4%), post-transplant urinary tract infection in six (4.4%), pneumonia in three (2.2%), ureteric kink in two (1.5%) and urine leak in four (3.0%). Graft survival at 36 months was 93.3% while patient survival at the same period was 96.3%. This report indicates that the results of our transplant program are good and comparable with other international programs.
Keywords: Living-related, Kidney transplantation, Immunosuppression
|How to cite this article:|
Elusta A, Shawish T, Mishra A, Ajaj H, Milud N, Shebani A, Abdulmola TS, Altajori O, Ethuish EF. Living Related Donor Kidney Transplantation in Libya: A Single Center Experience. Saudi J Kidney Dis Transpl 2008;19:831-7
|How to cite this URL:|
Elusta A, Shawish T, Mishra A, Ajaj H, Milud N, Shebani A, Abdulmola TS, Altajori O, Ethuish EF. Living Related Donor Kidney Transplantation in Libya: A Single Center Experience. Saudi J Kidney Dis Transpl [serial online] 2008 [cited 2019 Nov 14];19:831-7. Available from: http://www.sjkdt.org/text.asp?2008/19/5/831/42474
| Introduction|| |
Kidney transplantation remains the optimal therapy for patients with end-stage renal disease (ESRD) and is not only associated with an improved quality of life but also offers a significantly extended life span. Realistically, only living donor transplantation offers the option of sparing the recipient a long waiting period on dialysis. Kidney transplantation and the immunosuppressive therapy used are associated with an increased risk for certain types of infection, an increased tumor risk and an increased risk for cardiovascular complications. To address these problems, specific recommendations for patient surveillance have been provided by different transplantation societies. The reported incidence of ESRD in Libya is 80–100 per million per year. There are approximately 2100 patients on dialysis in Libya presently. The Libyan National Organ Transplantation Program has completed its third year since inception in August 2004, during which time a total of 135 patients have been transplanted, all from live-related donors. The immunosuppressive protocols adapted have been cyclosporine-based with steroids used only in the first post-transplant month. Although we have succeeded in getting the regulation regarding promoting deceased organ donation act passed and have also commenced a good organ donation education program for the society, deceased donation still seems a far cry. We herein present our experience on living donor transplantation in Libya.
| Subjects and Methods|| |
Potential donors and recipients were first informed by the medical team, without any pressure or obligation, about the risks and advantages of the procedure for living donor transplantation. Pre-requisites for further evaluation were blood group compatibility and a negative cross-match. Subsequently, potential donors were subject to extensive medical evaluation. Kidney function was measured by means of serum creatinine, 24–hour urine collection for creatinine clearance and protein excretion and urinalysis. When proteinuria and/or microscopic hematuria were present, the donor was rejected. All donors and recipients underwent screening for hepatitis B and C viruses. The potential donors also underwent a routine ultrasound examination to exclude congenital renal anomalies. Computed tomography angiography was performed as one of the last examinations to determine the vascular and ureteric anatomy.
Donors, in whom the renal angiogram did not show any vessel abnormality and/or kidney malfunction, underwent left nephrectomy. In those with vascular anomalies/complex anatomy, right nephrectomy was performed. Leftto-right or right-to-left transplant was performed routinely. Right-to-right or left-to-left were performed in some surgical necessities. At our center, donor nephrectomy and transplantation are performed exclusively by a very experienced surgeon.
The donor and recipient were prepared in parallel localized operating theaters. Usually, the incision for transplantation was not started until the kidney was dissected and ready to be removed. Warm and cold ischemia times were recorded. The anastomosis of the donor renal artery was performed end-to-end with the recipient internal iliac artery or end-to-side with the external iliac artery. The renal vein was anastomosed end-to-side with the external iliac vein. A neo-ureterocystostomy was performed.
Post nephrectomy donor follow-up
All donors were monitored closely after transplantation for four to six days and were thereafter discharged. Thereafter, they were followed-up regularly according to a set protocol.
Recipient management and outcome
Immunosuppression consisted of triple therapy in recipients having good match with the donor (steroids, cyclosporine, mycophenolate mofetil (MMF)/Myfortic) and quadruple therapy including induction immunosuppression with Simulect, (Novartis Pharma, Nurnberg, Germany) in recipients without good match.
Prophylaxis against the cytomegalovirus (CMV) was given to all patients who tested positive for IgG or if the donor tested positive for IgG; all patients were regularly screened for CMV IgM and IgG antibodies during follow-up.
At the occurrence of clinical signs of rejection, allograft biopsy was performed; initial treatment was with solumedrol 500 mg daily, given for three days. In cases of steroid-resistant rejection, anti-thymocyte globulin (ATG) (Fresenius S, Fresenius Hemocare, Graefling, Germany) was given for two weeks.
Delayed graft function (DGF) was defined as requirement of dialysis post-transplantation, even in patients in whom only one dialysis was necessary.
The cyclosporine level was monitored and kept in the range of 150–250 ng/ml (C0).
The results were statistically analyzed and statistical significance was fixed at p< 0.05. Values are expressed as mean values ± standard deviation. The Student's t test was used to compare donor and recipient characteristics before and after transplantation.
| Results|| |
A total of 135 living related kidney transplants were performed between 17 th August 2004 and 17 th August 2007. There was some decline in the transplant numbers in the second year of study. We have observed monthly fluctuation in the number of patients transplanted according to the availability of willing and surgically fit donors.
Out of 140 pairs who presented for living donor transplantation, five (3%) were not accepted, the reasons being medical problems in the donor (n= 4) and extensive atherosclerosis of the iliac vessels in the recipient (n= 1).
Among the 135 accepted pairs, the donors and recipients were genetically related (living related) in 133 cases (98.5%) and emotionally related in two others (1.5%). The mean donor age was 37 ± 9.5 years (range 18–56 years) and recipient age was 37 ± 13.6 years (range 7–67 years). Out of the total 135 recipients, 95 (70.4%) were males and 40 (29.6%) were females and of the 135 donors, 102 (75.6%) were males and 33 (24.4%) were females.
The patients came from all parts of Libya with the majority being the two largest cities of Tripoli and Benghazi. The most common donor-recipient relationship was siblings followed by son-to-parent. The most common blood groups in both donors and recipients were either O or A. The HLA matching was either identical or one haplotype. The important causes of ESRD were glomerulonephritis and hypertension, seen in 70% of the patients. Out of the 135 patients studied, 81% were negative for hepatitis screening.
There was no early or late surgical mortality. There were no early complications after nephrectomy in any of the donors. Operative site collection was seen in seven donors (5%), which were treated with antibiotics and drainage. None of the donors had an increase in serum creatinine or blood pressure after nephrectomy.
Recipient management and outcome
The immunosuppression protocol at our center varied according to the immunological risk status and HLA matching. HLA identical recipients were not given any induction therapy while non-HLA identical recipients were given induction therapy with Basiliximab (Simulect) 20 mg, given on days zero and four. Early withdrawal of steroids was applied to all patients except three (2.2%) of whom one had the Good Pasture's syndrome and two had systemic lupus erythematosus; these patients were maintained on small dose of steroids. Three patients with severe hypertension underwent simultaneous unilateral native kidney nephrectomy; all three have functioning grafts with normal blood pressure. There were three pediatric patients (aged 7, 8 and 9 years each) who received the allografts from their parent and all have excellent renal function and are attending school.
The immunosuppression regimen followed at our center is as follows:
- Methylprednisolone (MP) given in a dose of 500 mg intravenous (IV) intra-operatively, followed by a dose of 250 mg IV on the first post-transplant day; 125 mg on the second post-transplant day and 80 mg IV on the third post-transplant day. Oral prednisolone replaced MP from day four onwards in a tapering dose to reach 10 mg on day 11; steroids are stopped on day 29.
- MMF was administered in a dose of 1 gram twice daily. Recently, we started using mycophenolate sodium in a dose of 720 mg twice daily.
- Cyclosporine was generally withheld until the serum creatinine dropped to < 2.5 mg/dL after which the drug was introduced (usually on the 1st to 3 rd day post transplant) in a dose of 6–8 mg/kg/day.
The regimen for maintenance therapy was:
- Cyclosporine in a dose 3–5 mg/kg/day adjusted to maintain the drug level recommended by the protocol. (150–250 ng/ml)
- MMF in a dose of 1 gram twice daily, or mycophenolate sodium 720 mg twice daily.
Delayed graft function was seen in three patients (2.2%). These patients required dialysis for a period of 2–3 weeks post-transplant. They all recovered completely with normal graft function.
Acute rejection (AR) was seen in six patients (4.4%) and was confirmed by biopsy. They were treated with methylprednisolone. In steroid-resistant cases, ATG was used. Complete recovery of graft function occurred in four patients while partial recovery and graft loss occurred in one patient each.
Post-transplant urinary tract infection was seen in six patients (4.4%) and pneumonia in three patients (2.2%). All patients recovered completely after treatment with appropriate antibiotics.
Post-transplant surgical complications included ureteric kink, seen in two patients (1.5%), which needed surgical intervention in both. Anastomotic urine leak was seen in four patients of whom, two (1.5%) needed surgical intervention and in two others, there was spontaneous resolution. Vascular thrombo-embolic disease with loss of graft and, acute tubular necrosis were seen in one patient each (74%). One patient died during surgical intervention for post-transplant external iliac artery "pseudoaneurysm". Superadded graft site infection leading to death of the patient was seen in one (74%) while one other patient lost his allograft due to this complication. By August 2007, two patients (1.5%) had died with a functioning graft after a major stroke.
Overall, the graft survival rate at 36 months was 93.3% while patient survival at the same period was 96.3%.
The duration of hospital stay for the donors was four to six days with a mean stay of 4.5 days and for recipients, it was eight to 24 days with a mean stay of 14 days. Kidney function at the time of discharge was acceptable with serum creatinine values of 1.1 ± 0.5 mg/dL. At last follow-up, all donors were in excellent health and back to their normal life.
| Discussion|| |
The first successful kidney transplantation in humans was performed from identical twin donor. , With the advent of immunosuppressive drugs such as prednisone and azathioprine, the use of transplantation became wide spread. , Considerable controversy soon followed as to whether it was ethical to use living donors for kidney transplantation. ,,, Proponents of the use of living donors noted that the short- and longterm patient and graft survival rates were better after living (vs. cadaver) donor transplants. Opponents expressed worry that living donor nephrectomy was a major operation with potential risk to the donor; they believed that these risks did not justify the benefits to the recipient. More recently, living unrelated donors have been utilized at several centers in an attempt to provide renal transplantation to more patients which has sparked off even more controversy and "commercialization". Our program has always advocated the use of living donors. We recognized the risks to the donor but decided that a fully informed donor could choose whether or not to accept these risks. In fact, some studies have confirmed that donors do live longer due to the close follow-up program with early detection of disease and prompt treatment. 
Kidney transplantation in Libya was first started in 1989 at the Al Zahra Hospital in Tripoli, Libya. The transplant program was not very successful with only 63 transplants being performed during the next eight years. Therefore, the transplant program was completely suspended in 1997.
The National Organ Transplant Program in Libya was conceived in August 2004 and the recent diagnostic and immunosuppressive protocols were adopted. The first kidney transplant under this program was performed on 17 th August 2004 and till August 2007, 135 kidney transplants have been successfully performed, all from living-related donors.
During the last three years in Libya, the general attitude towards kidney transplantation from living donors has seen a considerable change with more families willingly coming forward for organ donation. Despite a slump in the total number of patients transplanted in the year 2005–2006, there has been a steady increase in the number of patients in 20062007 and shows signs of further increase in the following year.
The incidence of acute rejection in our study patients was low (3.7%) which can be attributed to our immunosuppressive regimen of cyclosporine, MMF/Myfortic and prednisolone. Kim et al  in 1999 reported the clear benefit of MMF-based triple-therapy in reducing the incidence of acute rejection after living donor renal transplantation. The prevalence of delayed graft function and vascular complications at our centre was also low, probably due to improved surgical techniques.
Excellent patient and graft survival rates were observed in our transplant recipients. When comparing results, the differences in immunosuppressive therapies employed must be taken into consideration. The reported one-year graft survival among groups receiving similar immunosuppressive protocols to ours is as high as 92–100%. 
In our series, there was a higher incidence of males as compared to females, who were willing for donation. Majority of the patients came from the two major cities in Libya, Tripoli and Benghazi. This could be attributed to the higher density of population in these two cities in comparison with the other towns and villages in the country.
The biggest challenge in transplantation today is increasing the number of available donor organs. Many patients with ESRD do not have a willing or suitable genetically related donor. Instead, some of them have the opportunity to receive a kidney from an unrelated donor who has clear emotional bonds with the patient and has strong motivation. Binet et al  in 1997 reported 46 emotionally related living kidney donor transplantations and concluded that it was a viable option. The donors, mostly spouses, showed high motivation and their donation were based on love and altruism. Karakayali et al  reported on 81 living unrelated kidney transplantations from spouse donors and concluded that such transplantations are an important option offering good clinical results, and also enabling a husband and wife to receive the "gift of life" from each other. Roozbeh et al  in 2006 attributed the high survival rate of spousal donor trans-plants to their strong emotional support. The excellent graft and patient survival rates are comparable to other transplantation programs in the major centers of the world.  Celik et al  in 2007 reported a case of successful reuse of kidney graft with a threeyear follow-up.
Various immunological, metabolic and technical factors render pediatric recipients with ESRD unique from their adult counterparts. In our series, we had transplanted two children with excellent results. Sipzen et al  in 2006 reported renal transplantations in 83 pediatric patients and concluded that better outcomes may be obtained by strict adherence to precise surgical techniques, better immunosuppressive management and early diagnosis and effective management of complications. Our results of living related transplantation are better than some reported series in the literature. ,
In three patients with malignant hypertension, we had to perform unilateral nephrectomy and one patient with polycystic kidney disease underwent bilateral nephrectomy. Wagner et al  in 2007 developed an algorithm for performing bilateral nephrectomies for specific indications before or during renal transplantation, in patients with polycystic kidney disease, and concluded that concurrent bilateral nephrectomy is safe and does not compromise patient or graft outcomes.
Besides undertaking living unrelated kidney transplantation to increase the donor pool, different other strategies have also been prescribed. Barry et al  concluded that the use of organs from genetically unrelated donors, ABO-incompatible donors and cross-match positive donors as well as the introduction of hand-assisted laparoscopic donor nephrectomy, has increased the number of living renal donor transplants without compromising short-term kidney transplant survival rates. We, in our center, also plan to introduce laparoscopic donor nephrectomy in the near future. Interestingly, according to the UNOS Renal Transplant Registry report published in 2005,  the number of non-spouse unrelated living donor transplants has increased 10-fold over the last 10 years and does not appear to be slowing. However, most of the authors agree that transplantation from living donors definitely is a complementary, not substitutive, program to that from cadaveric donors, which should always be encouraged with awareness campaigns among the general population as well as health-care personnel. 
The reluctance to use organs from marginal living donors (e.g. elderly donors) is declining all over the world. At our center too, we have started accepting elderly donors above 50 years age in order to increase our donor pool. Baid-Agrawal et al  in 2007 have indicated that increase donor age should not be a hinderant to transplantation. However, thorough evaluation and careful screening for pre-morbid conditions in both elderly donors and elderly recipients is essential.
In our series, none of the donors developed any renal disease post-nehrectomy. Few reports in the literature report a small incidence (0.5%) of this complication.  We are following-up all our donors with routine 6-monthly serum creatinine and urine analysis.
In conclusion, the National Organ Transplant Program in Libya has based its clinical program on the most recent achievements of transplant medicine, in order to optimize the outcome of kidney grafts and improve the quality of life of kidney transplant recipients. Despite all efforts, the available supply of donor organs continues to fall short of the need. This observation prompted us to focus on the expansion of the available pool of deceased donor organs, besides the emotio nally-related living donors.
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Ehtuish F Ethuish
Tripoli Central Hospital,Tripoli, Libyan Arab Jamahiriya, P.O. Box 84536, Tripoli
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