| Abstract|| |
Chronic kidney disease is one of the main public health concerns in Sri Lanka. In comparison with dialysis, successful kidney transplantation improves both patient survival and quality of life, relieves the burden of dialysis in patients suffering from end-stage renal disease and decreases the cost of healthcare to the society and government. The objective of this retrospective cohort study was to evaluate graft and patient survival rates in patients who were transplanted from living donors at the Nephrology Unit of the National Hospital of Sri Lanka from January 2005 to January 2011. Data were collected using an interviewer-administered questionnaire and through a review of past medical records. The Kaplan-Meier method was used to determine the survival rate, the log rank test was used to compare survival curves and the Cox proportional hazard model was used for multivariate analysis. Mean follow-up was 26.44 ± 16.6 months. The five-year death-censored graft survival of kidney transplant recipients from living donors in our center was 93.5% and the five-year patient survival was 82.2%, which is comparable with other transplant programs around the world. The number of acute rejection episodes was an independent risk factor for graft survival. Delayed graft function, younger recipient age and unknown cause of end-stage renal disease were found to be risk factors for graft failure but after adjusting for confounding factors, and the difference was not apparent.
|How to cite this article:|
Galabada DP, Nazar AL, Ariyaratne P. Survival of living donor renal transplant recipients in Sri Lanka: A single-center study. Saudi J Kidney Dis Transpl 2014;25:1334-40
|How to cite this URL:|
Galabada DP, Nazar AL, Ariyaratne P. Survival of living donor renal transplant recipients in Sri Lanka: A single-center study. Saudi J Kidney Dis Transpl [serial online] 2014 [cited 2020 Jun 2];25:1334-40. Available from: http://www.sjkdt.org/text.asp?2014/25/6/1334/144317
| Introduction|| |
Kidney transplantation is the best treatment for patients with end-stage renal disease (ESRD).  In comparison with dialysis, successful kidney transplantation improves both patient survival and quality of life, and relieves the burden of dialysis in patients suffering from ESRD.  In addition, transplantation is also associated with markedly decreased cost of healthcare to the society and government.
The number of patients with chronic kidney disease (CKD) worldwide is rising markedly. In the United Kingdom, the annual incidence of ESRD was around 100 per 1,000,000 population in 2004.  The rise in ESRD worldwide most probably reflects the global epidemic of type 2 diabetes mellitus, obesity and the ageing of the populations in developed countries, with a higher incidence in elderly people.  The number of people with diabetes worldwide is set to double within the next 20 years, and the increase will be most notable in the developing world. 
The exact incidence and prevalence of CKD and ESRD in Sri Lanka are not known. The reported annual incidence from developing countries varies from 34 to 240 per million population (pmp), which is in contrast to an incidence between 98 and 198 pmp per year reported from the developed countries.  It has been recognized that the burden of CKD and ESRD requiring renal replacement therapy in Sri Lanka is significantly on the rise. With the recognition of CKD of unknown cause prevalent in the north and north central province and the epidemic of diabetes in Sri Lanka, it has become a public health problem.  Successful renal transplantation, therefore, provides the best hope for most patients with ESRD in this region.
The nephrology unit in the National Hospital of Sri Lanka (NHSL) has a well-established renal transplant program that has been functioning for the last six years. A significant number of patients have undergone renal transplantation up to now. Living donor transplantation is strictly regulated in order to prevent organ trafficking, transplant commercialism and transplant tourism. All the donors are evaluated for suitability on medical and surgical grounds by the transplant team. Ethical aspects of living donation are independently assessed by the consultant nephrologists and the transplant surgeons. All the unrelated living donors are finally evaluated by the ethical review committee of the NHSL with the aim of preventing commercial donation and other unethical practices and adhering to the principles of the Declaration of Istanbul. The final decision of the ethical committee is considered as the ultimate decision.
In view of the increasing incidence of CKD in Sri Lanka and the growing demand for transplantation, it is important to evaluate the outcome of the current transplant program. This study was designed to determine the one, three and five-year patient and allograft survival rates in patients who have undergone living donor renal transplantation in the nephrology unit at the NHSL.
| Materials and Methods|| |
This study is a retrospective cohort study with a survival rate analysis. All patients transplanted between January 2005 and January 2011 were included in this study. This center performed 110 living donor kidney transplantations during this time. Transplants were performed by the same medical team (one nephrologist and two transplant surgeons).
Data were collected using a pre-tested interviewer-administered questionnaire and through a review of past medical records (clinic book, bed head ticket). Information was entered into a computer database. Statistical analyses were performed using SPSS ® v15 statistical package.
The exact time of transplantation was considered to be the "initial event," and irreversible loss of renal allograft (when the patient needs regular dialysis again) was defined as end-point event when estimating the graft survival. Cases who did not achieve the end-point event because of death from any cause or those who were lost to follow-up were censored for estimation of graft survival. Death with or without functioning graft was the end-point for the calculation of patient survival.
The Kaplan-Meier method was used to determine the survival rate, the log rank test was used to compare survival curves and the Cox proportional hazard model was used for multi-variate analysis.
| Results|| |
A total of 64.9% of donors and 69.7% of recipients were male. About 58% of donors were living related, 47% of whom were genetically related and 35% were genetically closely related. Blood group O made up 56.1% and 44% of donors' and recipients' blood group, respectively. 86.9% of the donors and recipients were of the same blood group. Diabetes was the cause of ESRD in 33.3% of the patients who underwent transplantation, and the cause was unknown in 47% of the patients. Six percent had obstructive uropathy. The demographic details of the donors and recipients are given in [Table 1].
|Table 1: Distribution of demographic and transplant characteristics of recipients and donors.|
Click here to view
The mean age of the donors and recipients was 39.2 ± 10.9 and 42.5 ± 11.4 years, respectively. The duration on dialysis before transplant was 9.7 ± 6 months, duration of hospitalization after transplantation was 10.1 ± 4.5 days and serum creatinine at one week and one month were 1.9 ± 1.6 mg/dL and 1.2 ± 0.3, respectively. The mean value of cyclosporine A trough level on Day 4 after transplantation was 220.73 ± 68.7 ng/mL.
As shown in [Figure 1], the allograft survival rates at one, three, and five years after kidney transplantation were 97.8%, 94.4% and 93.5%, respectively. Univariate analysis showed that there was no significant difference in graft survival rate in our series in terms of the following factors: Donors' age, sex of the donors and recipients, blood group of donors and recipients, similarity of blood group, type of maintenance immunosuppressive regimen, cause of ESRD, type of donor (related or unrelated), cold ischemia time, duration on dialysis before transplantation, duration of hospitalization after surgery and serum creatinine level at one week and one month.
|Figure 1: Graft survival rates of living donor renal transplant patients.|
Click here to view
The presence of delayed graft function, number of acute rejections, unknown cause of chronic renal failure and recipient age less than 40 years were shown to be significantly associated with graft survival on univariate analysis.
For modeling, those variables with P-values less than 0.25 on univariate analysis were entered into the Cox proportional hazard model in a forward stepwise manner. After adjustment for the factors found to influence graft survival by multivariate analysis using the Cox proportional hazard model, the number of acute rejections were shown to be independently associated with graft survival and other differences were no longer apparent.
Patient survival rates at one, three, and five years after kidney transplantation were 87%, 83% and 82.2%, respectively [Figure 2]. Because of the lack of complete data in relation to patients who died, we could not analyze the risk factors associated with patient survival.
|Figure 2: Patient survival rates of living donor renal transplant recipients.|
Click here to view
Close to 50% of the deaths were due to infections, and cardiovascular causes contributed to 18% of deaths. Severe pneumonia due to bacteria, Cytomegalovirus and Pneumocystis carinii were the main infections that led to death of the patients (62.0%) [Table 2] and [Table 3].
| Discussion|| |
Since the first report on living kidney transplantation in 1954, the overall graft and patient survival after kidney transplantation has improved progressively, particularly because of the availability of better immunosuppressive drugs during the last two decades. Kidney transplant centers around the world have regularly analyzed the survival rates and factors affecting them in order to improve the outcome of kidney transplantation.
Analyzing the five-year results of our transplant program, we found a 93.5% five-year graft survival (excluding patient death with functioning graft). The five-year patient survival was 82.2%. Our results are comparable to the latest patient and graft survival figures from around the world.
Graft failure during the first year after transplantation is due to acute rejection, primary non-function, graft thrombosis and recurrent kidney disease, excluding death of patient with a functioning graft. The most common cause of graft failure after one year of transplantation is chronic rejection. In our study, one patient had primary non-function, another had graft thrombosis and two transplant recipients had irreversible chronic rejection.
Triple immunosuppression therapy was adopted after transplantation. Three different regimes have been used for the transplant recipients:
- Oral prednisolone, azathioprine and cyclosporine (CsA)
- Oral prednisolone, mycophenolate mofetil (MMF) and cyclosporine
- Oral prednisolone, mycophenolate mofetil and tacrolimus.
Most patients were on the second regime as these medicines are available in the government hospitals in continuous supply. In this study, tacrolimus was used in a very limited number of patients who developed cyclosporine-induced hypertrichosis and could afford tacrolimus therapy. Patients intolerant to MMF, mainly due to gastrointestinal side-effects, were given azathioprine. CsA was administered at an initial dose of 6.0-6.5 mg/kg/day, and the dosage was subsequently adjusted on the basis of the clinical status and plasma concentration; azathioprine or MMF were administered at a dose of 2-3 mg/kg/d and 2 g/d, respectively; prednisone was started three days post-operatively at an initial dose of 30 mg/d, with a gradual reduction of the dose over three to four months and a maintenance dose of 5-10 mg/d. Antibody induction therapy was administered for most of the patients (91.6%). Fifty-nine transplant recipients (64.8%) were administered basiliximab and 18 received daclizumab as the antibody induction therapy. Among the patients who were given basiliximab, 51 recipients who had a low risk of acute rejection received only one dose and eight recipients with a higher risk of acute rejection were given two doses. The risk of rejection was determined by HLA mismatch, number of blood transfusions, presence of delayed graft rejection, duration of cold ischemia and presence of panel-reactive antibodies. There was no significant difference in the graft survival rates among patients who received one dose or two doses of basiliximab in our series.
In this study, younger recipient age was associated with increased risk of graft failure on univariate analysis, but after adjusting for the confounding factors, this difference was not apparent. A number of studies have shown that there is no significant relationship between recipient age and graft survival rate. , However, Gjertson reported that young adult recipients have poorer graft survival compared with older recipients. 
According to our study, donor age and sex had no effect on the graft survival. Twenty-one percent of the donors were >50 years and only one donor was aged more than 60 years. There are numerous studies showing that advanced donor age and female sex result in poorer graft outcome, reflecting decreased functional renal mass. ,,
Univariate and multivariate analyses of our data showed that the number of acute rejection episodes was an independent risk factor for poor graft survival, which is corroborated by many other studies. ,, Patients who experience recurrent or refractory acute rejection episodes are more likely to develop chronic rejection and subsequent graft failure. Even if a patient experienced acute rejection only once, the data suggest that they were prone to experience chronic rejection and renal graft loss. However, there are reports suggesting that if the acute rejection episode is completely reversible, it may not have a significant impact on graft survival. 
Boom et al reported, after analyzing 734 cadaveric kidney transplantations, that delayed graft function (DGF) influenced kidney function but not the survival.  Similarly, DGF was not associated with poor graft survival in our study after multivariate analysis, although univariate analysis showed a statistically significant difference. However, there is evidence that long-term graft survival is affected by the presence of DGF, although it is still controversial. ,,
According to our findings, there was no significant difference in graft survival between genetically related donors and unrelated donors with the use of modern immunosuppressive drugs. There are plenty of studies that support this finding, and that the short-term and long-term outcomes of the allograft from genetically unrelated donors were comparable with that from related donors. ,,
Several studies , have reported that prolonged cold ischemia time affects transplant survival rate significantly. Because the cold ischemia time was accurately known in only 46% of the patients, we could not reach any valid conclusions with regard to its effect on graft survival in our study.
Courtney et al  have shown that the underlying cause of ESRD may affect the renal transplantation survival rate; some other studies do not report such a relationship. , Our study did not show a significant association between graft survival rate and primary renal disease, but it has to be noted that the underlying primary renal disease was not known in 47% of the transplant recipients, because most of them presented with ESRD with small non-functioning kidneys, and diagnosing the cause in this group was not possible. Univariate analysis revealed that transplant recipients with unknown underlying cause had significantly poorer graft survival but again multivariate analysis failed to show a significant difference.
In our study, duration on dialysis prior to renal transplantation had no significant relationship with survival rate, while some other studies , revealed that longer time on dialysis prior to transplantation is an independent predictor of worse graft survival rate.
When considering deaths after renal transplantation, post-transplant infections were the most common cause (47%), which is a similar finding in most developing countries. However, cardiovascular disease has become the leading cause of death after renal transplantation in most developed countries, and there is dramatic decline of infections as a cause of mortality. Poor economic status along with lack of clean water, food and sanitary facilities, low educational status and lack of proper health-care facilities probably contribute to high post-transplant infection rate in developing countries.
This study had some limitations as it is a retrospective study, with significant differences in the length of follow-up ranging from seven months to 70 weeks. As some of the data were not complete, we could not assess the effect of some variables on graft outcome such as cold ischemia time and HLA mismatch. Similarly, although the patient survival of our transplant population was analyzed, risk factors affecting patient survival were not analyzed due to the incompleteness of the pre- and post-transplant data of these patients.
| Conclusions|| |
The five-year death-censored graft survival of kidney transplantation from living donors in our center was 93.5% and the five-year patient survival was 82.2%, which is comparable with other transplant programs around the world. The number of acute rejections was an independent risk factor for graft survival. Delayed graft function, younger recipient age and unknown cause of ESRD were found to be risk factors for graft failure, but, after adjusting for confounding factors, the difference was not apparent. Post-transplant infections constituted the most common cause of death.
| References|| |
Ojo AO, Hanson JA, Wolfe RA, Leichtman AB, Agodoa LY, Port FK. Long-term survival in renal transplant recipients with graft function. Kidney Int 2000;57:307-13.
Wolfe RA, Ashby VB, Milford EL, et al. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med 1999;341:1725-30.
Zoccali C, Kramer A, Jager KJ. Chronic kidney disease and end-stage renal disease - a review produced to contribute to the report 'the status of health in the European union: Towards a healthier Europe'. NDT Plus 2010;3:213-24.
Arýkan H, Tu lular S. The growýng global burden of end stage renal dýsease (ESRD) Marmara Med J 2005; 18;143-50.
King H, Aubert RE, Herman WH. Global burden of diabetes, 1995-2025: prevalence, numerical estimates, and projections. Diabetes Care 1998;21:1414-31.
Chugh KS, Jha V, Chugh S. Economics of dialysis and renal transplantation in the developing world. Transplant Proc 1999;31:3275-7.
Wanigasuriya KP, Peiris-John RJ, Wickremasinghe R. Chronic kidney disease of unknown aetiology in Sri Lanka: Is cadmium a likely cause? BMC Nephrol 2011 ;12:32.
Fuggle SV, Allen JE, Johnson RJ, et al. Factors affecting graft and patient survival after live donor kidney transplantation in the UK. Transplantation 2010;89:694-701.
Kwon OJ, Kwak JY, Kang CM. The impact of gender and age matching for long-term graft survival in living donor renal transplantation. Transplant Proc 2005;37:726-8.
Gjertson DW. Center and other factor effects in recipients of living-donor kidney transplants. Clin Transpl 2001:209-21.
Hassanzadeh J. Hashiani AA, Rajaeefard A, et al. Long-term survival of living donor renal transplants: A single center study. Indian J Nephrol 2010;20:179-84.
Emiro lu R, Yagmurdur MC, Karakayali F, et al. Role of donor age and acute rejection episodes on long-term graft survival in cadaveric kidney transplantations. Transplant Proc 2005;37:2954-6.
Park YH, Min SK, Lee JN, et al. Risk factors on graft survival of living donor kidney transplantation. Transplant Proc 2004;36:2023-5.
Wu JY, Chen JH, Wang YM, et al. Impact of acute rejection episodes on long-term renal allograft survival. Chin Med J 2003;116:1741-5.
Boom H, Mallat MJ, De Fijter JW, Zwinderman AH, Paul LC. Delayed graft function influences renal function but not survival. Transplant Proc 2001;33:1291.
Pieringer H, Biesenbach G. Risk factors for delayed kidney function and impact of delayed function on patient and graft survival in adult graft recipients. Clin Transplant 2005;19:391-8.
Shoskes DA, Cecka JM. Effect of delayed graft function on short and long-term kidney graft survival. Clin Transpl 1997:297-303.
Senel FM, Karakayali H, Moray G, Haberal M. Delayed graft function: Predictive factors and impact on outcome in living-related kidney transplantations. Ren Fail 1998;20:589-95.
Foss A, Leivestad T, Brekke IB, et al. Unrelated living donors in 141 kidney transplantations: A one-center study. Transplantation 1998;66:49-52.
Simforoosh N, Basiri A, Fattahi MR, et al. Living unrelated versus living related kidney transplantation: 20 years' experience with 2155 cases. Transplant Proc 2006;38:422-5.
Lowell JA, Brennan DC, Shenoy S, et al. Living-unrelated renal transplantation provides comparable results to living-related renal transplantation: A 12-year single-center experience. Surgery 1996;119:538-43.
Kaplan B, Schold JD, Meier-Kriesche HU. Long term graft survival with neoral and tacrolimus: A paired kidney analysis. J Am Soc Nephrol 2003;14:2980-4.
Quiroga I, McShane P, Koo DD, et al. Major effects of delayed graft function and cold ischaemia time on renal allograft survival. Nephrol Dial Transplant 2006;21:1689-96.
Courtney AE, Mcnamee PT, Maxwell AP. The evolution of renal transplantation in clinical practice: For better, for worse? Q J Med 2008; 101:967-78.
Briganti EM, Wolfe R, Russ GR, Eris JM, Walker RG, McNeil JJ. Graft loss following renal transplantation in Australia: Is there a center effect? Nephrol Dial Transplant 2002;17: 1099-104.
El-Husseini AA, Foda MA, Shokeir AA, Shehab El-Din AB, Sobh MA, Ghoneim MA. Determinants of graft survival in pediatric and adolescent live donor kidney transplant recipients: A single center experience. Pediatr Transplant 2005;9:763-9.
Kevin CM, Marshall MJ, Harold IF. Effect of the use or nonuse of long term dialysis on the subsequent survival of renal transplantation from living donor. N Engl J Med 2001;344:726-31.
Dr. Abdul L. M. Nazar
Nephrology and Transplant Unit, National Hospital of Sri Lanka, Colombo
[Table 1], [Table 2], [Table 3], [Figure 2]