| Abstract|| |
Between March 1976 and December 2004, 1690 consecutive allogenic living donor renal transplants were carried out at Mansoura, Egypt. We herewith report on 1600 transplants that had a minimum follow-up period of one year. The overall graft survival rates were 76% and 52% at five and 10-years respectively. The corresponding patient survival rates were respectively 86% and 71%. The projected half-life was 10.7 years for grafts and 18.2 years for patients. Predictors for graft outcome were classified as pre-transplant variables, technical factors or post-transplant predictors. Among the long list of these variables, factors that had a significant impact on outcome by univariate analysis included donor's and recipient's age, donor-recipient consanguinity, HLA-A, cytomegalovirus (CMV) and hepatitis C virus (HCV) markers, ischemia time, primary immunosuppression, ad juvant therapy, total steroid dose within the first three months, number of acute rejection episodes, time to onset of diuresis, hypertension post-transplant, serum creatinine at one year and at last follow-up besides chronic rejection. Only five factors sustained their significance by multivariate analysis: they included recipient's age, primary immunosuppression, post-transplant hypertension and serum creatinine at one year and last follow-up. Some specific complications encountered among the recipients such as hemolytic anemia, post-transplant diabetes mellitus, bone complications, malignancy, erectile dysfunction and surgical complications are discussed. In conclusion, we hope to start the cadaveric donor transplant program soon in our unit. Also, the ambition concerning the transplantation field in the new millennium is to overcome xenotransplantation barriers and to induce immunologic tolerance with neither rejection nor immunosuppression.
Keywords: Living donor, Kidney Transplantation, Outcome predictors.
|How to cite this article:|
Bakr MA, Ghoneim MA. Living Donor Renal Transplantation, 1976 - 2003: The Mansoura Experience. Saudi J Kidney Dis Transpl 2005;16:573-83
|How to cite this URL:|
Bakr MA, Ghoneim MA. Living Donor Renal Transplantation, 1976 - 2003: The Mansoura Experience. Saudi J Kidney Dis Transpl [serial online] 2005 [cited 2022 Aug 9];16:573-83. Available from: https://www.sjkdt.org/text.asp?2005/16/4/573/34967
| Introduction|| |
The idea of transplantation attracted the attention of ancient Egyptians. The Great Sphinx standing for 50 centuries was a symbol where a human's head was transplanted to a lion's body. The Egyptians never gave up the dream till the transplantation practice became a reality.
| Historical Review|| |
The first two cases of renal transplantation carried out in Egypt were in March and May 1976 at Mansoura. Before the end of that year, the Mansoura transplant team successfully transplanted another six cases. 
Following a very slow start, the number of transplants gradually increased reaching an annual rate of 90-100 transplants. The total number is approaching 1700 transplants, which account for 24% of adult patients and 60% of children transplanted in Egypt. 
Presently, there are 20 centers that perform renal transplantation in Egypt, with the overall experience exceeding 7000 living donor transplants; the ratio of related versus unrelated donors varies from one center to another. 
| Policy|| |
In absence of cadaveric program, our main domain is to perform living related renal transplantation, which constitutes 83% of our cases. Spousal and unrelated donation represents six and 11% respectively. Beside our own strict criteria to accept an unrelated donor, the Egyptian Society of Nephrology and the Medical Syndicate has established a joint ethical committee that considers the medical and social circumstances of each case.
| Results|| |
The Mansoura Experience will be presented as follows:
I. Results in general.
II. Prognostic factors affecting graft outcome.
Results in General
In this report, we present the results of 1600 cases with a minimum of one-year follow-up. The majority of the recipients were males in their second and third decades of life. Sibling donation represented half of the cases. Fifty percent HLA A and B, and DR matching was seen in about 54 and 89% of the cases respectively while 41% of patients received no blood transfusion prior to transplantation. Post-operative mortality occurred in 1.7% of the study cases. A total of 53% of the cases did not experience any episode of acute rejection. Condition at last follow-up revealed that 61% are living and enjoying normal graft function. Pre-emptive transplantation was carried out in 82 patients, while another 54 received their second grafts. The overall graft survival was 76.1% and 49.5% at five and 10-years respectively. The corresponding patient survival was respectively 87.1% and 71.5%
[Figure - 1].
We classified factors that can affect graft survival into three main predictors. They included pre-transplant variables such as demographic data [Table 1 in PDF]A, hematological [Table 1 in PDF]B, immunological [Table 1 in PDF]C and current and past medical disorders [Table 1 in PDF]D. The transplant (technical) variables are tabulated in
[Table - 2] while the post-transplantation factors are presented in
[Table - 3].
The impact of these factors on 5-year graft survival was initially tested by univariate analysis (Log Rank test). Factors that had significant influence were further analyzed by multivariate model (Cox's proportion hazard model,
[Table 4]). 
| Specific Aspects|| |
Our immunosuppressive protocols consisted of 10 different strategies, with each strategy represented in an earlier specific study. The earliest study from our center demonstrated that cyclosporine (CsA) could reverse ongoing rejection as a rescue therapy in 15% of conventionally treated recipients.  Triple therapy subsequently emerged to reduce CsA toxicity as well as achieve better survival.  Also, coadministration of ketoconazole to calcineurin inhibitors was shown to reduce not only the treatment costs but also the incidence of both nephrotoxicity and fungal infections.  The era of CsA microemulsion was associated with reduction of 16% and 10% among renal transplant recipients with and without hepatic involvement respectively.  In a further study at Mansoura, ATG was shown to be effective in treating steroid resistant rejection with recovery in 90%.  Rescue therapy utilizing mycophenolate mofetil (MMF) is valuable for patients suffering from slowly rising serum creatinine levels and was also associated with improved liver function in those suffered from hepatic dysfunction. Salvage therapy with tacrolimus showed that predictors of success were early conversion and lower serum creatinine at conversion.  Induction with basiliximab reduced the incidence and severity of acute rejection episodes.  Recently, excellent outcome could be achieved with calcineurin inhibitor free regimen (sirolimus, MMF and steroids) with trends for better graft function, lower incidence of acute rejection episodes and encouraging histological findings. 
This is a major health problem and is endemic in Egypt. Hence, special care was given in preparation for renal transplantation. Recipients and donors were investigated for urinary schistosomiasis by examining tissue obtained intra-operatively from donor's ureter and recipient's bladder. The incidence of urological complications was 15% and 6% for schistosomal and control groups respectively which was statistically significant. No deaths or graft losses were attributed to either these complications or their surgical correction.  Moreover, in a long-term study extended for ten years, we found no significant difference of acute and chronic rejection between the two groups. However, larger cyclosporine doses were utilized for the infected group with subsequent higher incidence of both acute and chronic CsA nephrotoxicity. We concluded that schistosomal infection is not a major risk factor for renal transplantation and infected recipients were considered as suitable candidates if they have been treated properly before transplantation. The patient and graft survival rates were comparable between both groups. 
Pregnancy and Sexual Maturation
Forty-nine pregnancies occurred in 29 recipients. The mean gravid and para rates were 2.5 ± 1.3 and 0.8 ± 0.9 respectively; 14 cases were infertile before transplantation. Nearly half of the pregnant recipients had normal delivery. It can be concluded that successful pregnancy was possible after transplantation with acceptable maternal and fetal risks. The main risk factors were hypertension and urinary tract infection. This study highlighted the importance of pre-conception counseling. 
Sexual maturation of girls after transplantation was assessed. Delayed onset of menarche, and sexual maturation with poor linear growth was evident among transplanted girls when compared with the control subjects. These problems could be attributed to prolonged steroid therapy and graft dysfunction. The use of steroid-free regimen could allow such girls to achieve maturation. 
Hepatitis C Virus (HCV)
HCV is the main cause of post-transplant liver disease. The impact of HCV on renal graft and patient survival remains a debatable subject. In a comparative analysis of HCV-positive and negative recipients, it was reported that HCV-positive patients had longer duration on dialysis, had received more blood transfusions, had frequent pre-transplant liver diseases and 41% had received anti-schistosomal treatment. It was found that HCV infection had no adverse effects on patient or graft survival. However, HCV-positive recipients with abnormal liver function had poorer survival rates, greater incidence of proteinuria and chronic allograft nephropathy when compared with those with normal liver function. 
Our experience included 164 transplanted children with mean age 13.1 years. The common causes of end-stage renal failure in this agegroup were renal dysplasia, nephrotic syndrome, hereditary nephritis and obstructive uropathy. Parental donation constituted 81%. Triple immunosuppression (prednisone, cyclosporine, azathioprine) was utilized in 70.8% of transplants. The graft survival rates at 1- and 5year were 92.5% and 71% respectively, while the corresponding patient survival rates were 96% and 83.7%. Factors that had a significant impact on graft outcome by univariate analysis were HLA mismatches, time to onset of diuresis after release of clamp, acute tubular necrosis post-transplant, acute rejection episodes and post-transplant hypertension. The last two factors sustained their influence in multivariate analysis. 
TB is an important infection encountered after transplantation especially in developing countries. In our series, 45 patients developed TB 86.7% of whom were diagnosed in the first year post-transplantation. Urinary TB was more prevalent (53%). Triple anti-TB therapy (rifampicin, ethambutol and INH) was utilized with favorable response. More than 55% of cases developed chronic rejection, most of whom were on CsA, while 35% of TB patients lost their grafts. Recommendation for INH prophylaxis post-transplantation was highlighted with careful monitoring of CsA level and appropriate dose adjustment. 
| Complications Encountered After Transplantation|| |
ABO mismatched transplants are being performed these days. Acquired hemolytic anemia has been reported after transplantation in such cases. Among the 214 ABO mis-matched living-donor kidney transplants performed at our center, 10 patients who were maintained on cyclosporine-based therapy developed hemolysis.
The hemolysis was more frequent among blood group A recipients and more severe among blood group B recipients. Univariate analysis demonstrated significant impact of recipients' age, donor's sex, number of pretransplant blood transfusions, immunosuppressive drugs used, time to onset of diuresis as well as recipient and donor blood group. The last three variables sustained their effect in multivariate analysis.  The therapeutic modalities included temporary withdrawal of CsA, washed O cells transfusion, and plasmapharesis. Excellent prognosis was achieved in 90% of cases with one patient dying due to severe hemolysis. We concluded then that ABO mismatched kidney transplantation had no impact on patient survival; also, there seems to be a trend towards better graft survival among ABO mis-matched transplants when compared to blood group compatible couples.
Post-Transplant Diabetes Mellitus (PTDM)
PTDM is one of the most important risk factors for graft and patient survival after kidney transplantation. PTDM was diagnosed in 18% of our cases most of whom developed PTDM within the first six months post-transplantation. The significant risk factors by multivariate analysis for development of PTDM were older recipient age, positive family history, increased body mass index, cumulative steroid dose in the first three months, calcineurin inhibitors and HCV infection. Graft survival was comparable in PTDM group and their controls, while patient survival was markedly inferior among the PTDM group and cardiovascular events were the leading cause of mortality. 
Osteoporosis remains a frequent and serious complication affecting transplant recipients. The risk factors for bone loss among transplanted patients included pre-treatment renal osteodystrophy, persistent hyperparathyroidism and the use of immunosuppressive drugs. Our study showed that early bone loss occurring during the first 12 months after transplantation could be prevented by the use of alfacalcidol, calcitonin or alendronate. 
Avascular bone necrosis (AVN) of femoral head in renal allograft recipients is a disabling problem. The presentation of early AVN is with hip pain, normal X-ray and positive MRI and can be treated by core decompression, while advanced AVN required total hip replacement.
Malignancy is a growing problem after transplantation with marked increased risk in comparison to general population. We reported on 52 malignancies in 50 patients. The commonly encountered malignancies in our recipients included Kaposi's sarcoma (48%), lymphoma (11%), breast cancer (11%) and bladder cancer (8%). The incidence of malignancy is higher among CsA treated recipients in comparison to the azathioprine based therapy group.  Moreover, Kaposi's sarcoma presented earlier than other malignancies. The malignant group suffered from high incidence of both acute and chronic rejection episodes. Tailored reduction of immunosuppression was initially tried in all patients. However, some patients needed further specific treatment (surgery, chemotherapy, radiotherapy). The outcome was favorable in Kaposi's sarcoma. Early diagnosis and modification of immunosuppression may help to control post-transplant malignancy. 
Erectile Dysfunction (ED)
ED is highly prevalent among renal transplant recipients and its pathogenesis is multifactorial. The prevalence of ED was 35.8% in our study group. Erectile function, as compared to the pre-transplant status, improved, deteriorated or remained the same in 44, 12.5 and 43.5% of cases respectively. After logistic regression analysis, hemoglobin level and presence of diabetes mellitus and/or peripheral neuropathy had a significant and independent negative impact on erectile function. Thus, renal transplantation had a varying effect on erectile function. 
The use of multiple arteries in renal allografts does not adversely affect patient or graft survival. It is not associated with an increased rate of complications except for significantly higher mean serum creatinine levels at one year. Extracorporeal bench surgery was as effective as intracorporeal one for the anastomosis of multiple renal arteries with increased incidence of relevant complications.  Vascular complications after transplantation were seen in 2.8% of our study patients. They included graft venous thrombosis (1%) arterial stenosis and thrombosis (0.9%). Hemorrhagic complications were encountered in 1.9% of the cases. Stenosis and thrombosis as well as hemorrhagic complications were significantly associated with subsequent biopsy proven acute tubular necrosis leading to inferior patient and graft survival. 
| Conclusion|| |
In conclusion, our hope is to start a cadaveric donor program soon while the ambition in the new millennium concerning the transplantation field is to overcome xenotransplantation barriers and induce immunologic tolerance.
| Acknowledgement|| |
I would like to thank Miss Rasha El-Emam for her skill and patience during the preparation of this manuscript.
| References|| |
|1.||Bakr MA. Renal transplantation in Egypt. Organs-Tissues 2000;1:39-44. |
|2.||Ghoneim MA, Bakr MA, Hassan N, et al. Live-donor renal transplantation at the Urology and Nephrology Center of Mansoura: 1976-1998. In Cecka JM and Terasaki PI edts. 17 th edition. Clinical Transplants. UCLA Immunogenetics Center, Los Angles, California, 2001;167-78. |
|3.||Barsoum R and Bakr MA. The Egyptian renal transplant experience. In Cecka JM and Terasaki PI editors. 16 th edition. Clinical Transplants. ULCA Immunogenetics Center. Los Angelos, California, 2000;359-60. |
|4.||Bakr M. Living-donor renal transplantation: 25 years Mansoura experience. Transplant Proc 2002;34:2070-2. |
|5.||Ghoneim MA, Sobh MA, Shokeir AA, Bakr MA, el-Sherif AK, Fouda MA. Prospective randomized study of azathioprine versus cyclosporine in live donor kidney transplantation. Am J Nephrol 1993;13: 437-41. |
|6.||Bakr MA, Sally S, Foda MA, et al. Different trends in immunosuppression: 10 year experience with cyclosporine after living related donor renal transplantation. Transplant Proc 1994;26:3163-6. |
|7.||Sobh MA, Hamdy AF, El-Agroudy AE, et al. Coadministration of ketoconazole and cyclosporine for kidney transplant recipients: long term follow up and study of metabolic consequences. Am J Kidney Dis 2001;37 (3):510-7. |
|8.||Bakr MA, Refaie A, Mekresh M, et al. Cyclosporine neoral in renal transplant recipients: Impact on hepatic dysfunction. Transplant Proc 1997;29:2939-40. |
|9.||Bakr MA, Foda MA, Sally S, Sobh MA, Ghoneim MA. ATG in steroid resistant acute rejection in living related kidney transplantation: long term evaluation. Transplant Proc 1994;26:3161-2. |
|10.||M.A. Bakr, A. Refaie, N. Hassan et al. Rescue therapy with Tacrolimus and MMF after Live-Donor kidney transplantation. Afr J Nephrol. (In press). |
|11.||Sheashaa H, Bakr MA, Ismail AM, Sobh MA, Ghoneim MA. Basiliximab reduces the incidence of acute cellular rejection in live related donor kidney transplantation: a three year prospective randomized trial. J Nephrol 2003;16:393-8. |
|12.||Hamdy A, El-Agroudy A, Bakr MA, et al. Comparison of sirolimus with low dose tacrolimus regimen versus sirolimus based calcineurin inhibitor free regimen in live donor renal transplantation. Am J Transplant. (In press). |
|13.||Shokeir AA, Bakr MA, El-Diasty TA, et al. Urological complications following live donor kidney transplantation: effect of urinary schistosomiasis. Br J Urol 1992;70:247-51. |
|14.||Mahmoud KM, Sobh M.A, El-Agroudy AE, et al. Impact of schistosomiasis on patient and graft outcome after renal transplantation: 10-years follow up. Nephrol Dial Transplant 2001;16:2214-21. |
|15.||Bakr MA, El-Said Ghaneim M, Fouda MA, et al. Clinical course and outcome of pregnancies in recipient of renal allografts. Transplant Proc 1997;29:2787-9. |
|16.||El-Said M, Bogdady L, Bakr MA, et al. Sexual maturation of girls after renal transplantation. Afr J Nephrol 1999;25: 2297-8. |
|17.||Mahmoud IM, Elhabashi AF, Elsawy E, et al. The impact of hepatitis C virus viremia on renal graft and patient survival: a 9-year prospective study. Am J Kidney Dis 2004; 43:131-9. |
|18.||Fouda MA, El Hussini A, Bakr M et al. Living related kidney transplantation in children: A single center experience. Pediatr Nephrol. (In press). |
|19.||El-Agroudy A, Refaie A, Mousa O, Ghoneim MA. Tuberculosis in Egyptian kidney transplant recipients: study of clinical course and outcome. J Nephrol 2003;16:404-11. |
|20.||Bakr MA, Foda MA, Shokeir AA, et al. Haemolytic anemia after ABO-mismatched living donor kidney transplant. Transplant Proc 1993;25:2297-8. |
|21.||Sally S, Sobh M, Bakr MA, et al. Risk factors for post transplant diabetes mellitus (PTDM) and its impact on graft outcome. Afr J Nephrol 1999;3:30-3. |
|22.||El-Husseini AA, El-Agroudy AE, El-Sayed M, Sobh MA, Ghoneim MA. A prospective randomized study for the treatment of bone loss with vitamin D during kidney transplantation in children and adolescents. Am J Transplant 2004;4:2052-7. |
|23.||Bakr MA, El-Agroudy AE, Ali-El-Dein B, et al. Malignancy in Egyptian living donor kidney transplant recipients. Afr J Nephrol 2003;7:52-9. |
|24.||El-Agroudy AE, El-Baz MA, Ismail AM, et al. Clinical features and course of Kaposi's sarcoma in Egyptian kidney transplant recipients. Am J Transplant 2003;3:1595-9. |
|25.||El-Bahnasawy MS, Al-Assmy A, El-Sawy E, et al. Critical evaluation of the factors influencing erectile function after renal transplantation. Int J Impot Res 2004;16:521-6. |
|26.||Ali-El-Din B, Osman Y, Shokeir AA, et al. Multiple arteries in live donor renal transplantation: surgical aspects and outcomes. J Urol 2003;169:2013-7. |
|27.||Osman Y, Shokeir A, Ali-El-Din B, et al. Vascular complications after live donor renal transplantation: study of risk factors and effects on graft and patient survival. J Urol 2003;169:859-62. |
Mohamed Adel Bakr
Senior Consultant of Nephrology, Urology and Nephrology Center, Mansoura
Source of Support: None, Conflict of Interest: None
[Figure - 1]