Study of graft survival rates of renal transplants in Cairo University Hospitals

Background Many factors and events can complicate the outcome of renal transplantation and can eventually lead to progressive renal dysfunction and graft failure. We aimed in this study to identify the risk factors for the entire course after transplantation, and then to analyze the relative impact of these risk factors on short-term and long-term graft survival in our patients. Patients and methods This analytical retrospective study was conducted at the King Fahd Unit, the Faculty of Medicine, Cairo University, on 104 patients for the study of 1-year graft survival, though 43 patients were followed-up for 3 years for the study of 3-year graft survival. Serum creatinine was used to evaluate the renal function; graft dysfunction was defined as serum creatinine more than 2.5 mg/dl. Survival analysis was carried out by using the Kaplan–Meier survival curve estimation. To predict the value of graft survival after 5 years, regression analysis was used. Results In our study, the overall graft survival rates were 88.6 and 76.7% at 1 and 3 years, respectively. The corresponding overall patient survival rates were 89.4 and 79.1% at the first and third years after transplant. Our study showed that among the long list of predictors for graft outcome variables, factors that had a significant impact on outcome by Kaplan–Meier analysis included donor’s age, primary immunosuppression, and serum creatinine 1 month after transplant. There was a greater rate of graft dysfunction with the presence of hypertension and hepatitis C virus but these results did not reach statistically significant values. Conclusion Old donor’s age, primary immunosuppression, and serum creatinine 1 month after transplant are the most effective factors on graft survival in kidney transplantation. Whatever the cause, graft dysfunction should be treated early and aggressively.


Introduction
Kidney transplantation is the most desired and costeffective modality of renal replacement therapy for patients with irreversible chronic kidney failure [1].
The quality of life of transplant patients with good biochemical control was clearly better than that of chronic dialysis patients [2].
Epidemiologic studies have shown that renal allograft survival is associated with a large number of risk factors, such as donor or recipient age, sex, and race, or comorbid conditions, type of donor (living vs. cadaver), and the presence of delayed graft function or acute rejection. Moreover, renal function is also a major determinant of patientsurvival.Thus,ithasbeensuggestedthatstrategies to improve renal function after transplantation may contribute to increased patient and allograft survival [3].
We aimed to identify the risk factors for the entire course of renal transplantation, and then analyzed the relative impact of these risk factors on the probability of graft loss.

Patients and methods
This retrospective study was conducted at the King Fahd Unit, Faculty of Medicine, Cairo University. This protocol was approved by local ethical committee.
For evaluating 1-year graft survival rates we studied 104 patients and for evaluating 3-year graft survival rates we studied 43 patients.
In our study, serum creatinine was used to evaluate the renal function; graft dysfunction was defined as serum creatinine more than 2.5 mg/dl.
The following variables were recorded for each patient.
(2) History taking and clinical examination.
(3) Immunosuppressive medications. (4) Assessment of renal graft functions by serial measurement of serum creatinine during the follow-up period.

Statistical analysis
Statistical package for social science, version 9.0 was used for data analysis. Data were summarized as mean, SD, and percentage. Nonparametric test (Mann-Whitney U) was used for the analysis of two independent variables as data was not symmetrically distributed. The χ 2 -test was used for the analysis of qualitative data. Survival analysis was carried out by using the Kaplan-Meier survival curve estimation. Statistical significance was judged at the two-sided 0.05 levels. To predict the value of graft survival after 5 years, the regression analysis was used.
All the parameters are significant at 5% significance level. R 2 is an indicator of the goodness of fit for the line.

Results
The 1-year graft survival rate was 88.6% in 104 patients and the 3-year graft survival rate was 76.7% in 43 patients (Table 1).
To predict the value of projected graft survival after 5 years in those patients, the regression analysis was used; this means that the graft survival after 5 years will be 60.5% (Fig. 1).

Figure 1
Graft survival in King Fahd Unit at 1, 3, and 5 years. As shown in Tables 5 and 6, male recipients had an inferior 1-year graft survival rates compared with female recipients. Whereas female recipients had an inferior 3-year graft survival rates compared with male recipients. Yet, these results did not reach statistical significance.
As regards donor's sex, male donors had an inferior 1-and 3-year graft survival rates compared with female donors. Yet, this result did not reach statistical significance (Tables 7 and 8).
As shown in Tables 9 and 10, an increasing number of HLA and DR loci mismatches did not significantly lower graft survival rates in kidney transplantation. Yet, these results did not reach statistical significance.
There was no statistically significant difference regarding consanguinity, as unrelated donor transplants exhibited a high graft survival rate similar to the outcome of related donor transplants (Fig. 3).

Figure 2
Graft survival in relation to donor's age.

Figure 3
Graft survival in relation to consanguinity.

Figure 4
Graft survival in relation to HTN before transplantation. HTN, hypertension.

Figure 5
Graft survival in relation to HTN after transplantation. HTN, hypertension.
The results show that hepatitis C virus (HCV)positive patients can be transplanted with the success close to that of HCV-negative patients, although there is a tendency to better outcome in HCV-negative patients. Yet, this result did not reach statistical significance. Graft survival rates in HCVpositive and HCV-negative patients of living kidney were 66.7 and 80% at 1-year after transplant, respectively (Table 11).
As shown in Fig. 6, preemptive patients had a tendency to have better outcome. Yet, this result did not reach statistical significance. Graft survival rates in preemptive transplants and transplants performed after initiation of dialysis of living kidney donors were 88.9 and 86.3% at 1 year, and 80 and 78.9% at 3 years after transplant, respectively.
There was a statistically significant relation (P=0.0001) between graft survival and serum creatinine 1 month after transplant. Graft survival rate when serum creatinine is less than 1.5 mg was 95.9%, 45.5% when serum creatinine ranged between 1.5 and 3 mg, and 12.5% when serum creatinine was more than 3 mg (Fig. 7).
As shown in Tables 12 and 13, there was a statistically significant relation (P=0.0003) between graft survival and maintenance immunosuppressive treatment protocol. The 1-year graft survival rate was 92.2% when cyclosporine, prednisolone, and mycophenolate mofetil (MMF) were used, and 78.6% when azathioprine was used instead of MMF. The 3-year graft survival rate was 93.1% for cyclosporine, prednisolone, and MMF and 78.6% when azathioprine was used instead of MMF.

Discussion
Renal transplantation has been the main treatment option for end-stage renal disease patients. Life satisfaction, physical, emotional wellbeing, and the

Figure 7
Graft survival in relation to serum creatinine at 1 month after transplant.   Graft survival in relation to dialysis.
ability to return to work are all significantly better among transplant recipients than among dialysis patients. Yet, despite the continuous progress in immunosuppressive and supportive therapy, a number of factors still interfere with the complete success of renal transplantation.
Some factors present at the time of transplantation, which concern the donor as well as the recipient, whereas other complications originate after transplantation. In our study, particular attention was paid to the main factors and events that impair graft function in the short-term and long-term. Although the quality of life and survival rates following organ transplantation have greatly improved due to advances in surgical technique, immunosuppressive therapy, and medical management, allograft rejection and infection remain the major causes of morbidity and mortality [4].
In our study, we retrospectively analyzed renal transplants in King Fahd Unit: we aimed to identify the risk factors for the entire course, and then to analyze the relative impact of these risk factors on short-term and long-term graft survival in the patients.
The gold standard to measure renal function is the glomerular filtration rate, evaluated according to the insulin clearance or an isotopic method. Because these procedures cannot be applied in the clinical setting because of their cost and complexity, serum creatinine was used to evaluate the renal function; graft dysfunction was defined as serum creatinine more than 2.5 mg/dl.
In our study, the overall graft survival rates were 88.6 and 76.7% at 1 and 3 years, respectively. The corresponding overall patient survival rates were 89.4 and 79.1% at the first and third posttransplant years. The projected graft survival rate after 5 years in those patients at King Fahd Unit was predicted to be 60.5%.
This comes with the fact that we accept some marginal living donors. Another explanation might be the fact that we do not use induction therapy routinely in all cases; only anti-Thymocyte Globulins (ATG) was used in few cases before transplantation. Furthermore, 43.3% of our patients received azathioprine-based de-novo immunosuppresion.
In the Mansoura experience, the overall graft survival rate was 76.1 and 49.5% at 5 and 10 years, respectively. The corresponding patient survival rate was 87.1 and 71.5%, respectively.
In our study, as regards the relation between graft survival rate and age of both recipients and donors, the 1-year graft survival rates for various age groups (<10, 10-18, 19-30, 31-40, and 41-50 years) were 100, 77.3, 80, 73.4, and 85.7%, respectively, whereas the 3-year graft survival rates for various age groups (<10, 10-18, 19-30, 31-40, and 41-50 years) were 100, 82.4, 70, 55.6, and 100%, respectively. However, this difference did not reach statistical significance. Graft survival rates were especially low in the second decade of life. This may be attributed to the fact that in this age group patients are less complaint to treatment. In addition, low graft survival rates in the fourth decade can be explained by the fact that patients in this age group are not complaint to treatment because of financial reasons.
Regarding donor age we found that graft survival rate had a tendency to be lower in older age groups and there was a statistically significant difference regarding donor age at the 3-year graft survival; the grafts did not survive in the old donor group (>50 years old).
The UNOS registry documented that the higher the age of the donor, the worse the long-term outcome of the graft [5].
Some investigators feel that the poorer results of grafts of elderly donors are mainly caused by the agedependent progressive reduction of glomerular filtration rate and renal reserve [6].
Regarding the relation to the sex of recipients, male recipients had an inferior 1-year graft survival rate compared with female recipients, whereas female recipients had an inferior 3-year graft survival rate compared with male recipients. Regarding the relation to the sex of donors, male donors had an inferior 1-and 3-year graft survival rates compared with female donors; however, these findings did not reach statistical significance.
In a study that included 85 135 patients from the Organ Procurement and Transplantation Network/ United Network for Organ Sharing, it was found that older donor age, younger recipient age, male recipient sex, and the presence of acute rejection were associated with elevated serum creatinine at 1-year, graft survival, and death-censored graft survival [7].
As regarding HLA and DR matching between recipients and donors and their relation to graft survival in our study, increasing number of HLA and DR loci mismatches did not significantly lower the graft survival rates in kidney transplantation. This might be attributed to the fact that these mismatches were in class I and not in class II.
Our results were in agreement with a study by Gjertson and Cecka [9] that reported that increasing numbers of HLA-A, HLA-B, and HLA-DR loci mismatches did not significantly (P=0.50) lower graft survival rates among living unrelated donor kidney transplant recipients.
Regarding the relation between graft survival and HTN in our study, there was a greater rate of graft dysfunction with the presence of HTN but this result does not reach statistical significance.
In a study on 196 patients by Raiss Jalali and colleagues, a slow but significant increase in mean creatinine levels was observed in the HTN group during 3 years of follow-up, whereas in the non-HTN group, graft function remained stable. Cardiovascular events were observed only in HTN patients. They concluded that HTN accelerates the deterioration of transplanted kidney function [10].
As regards HCV infection of our patients and its relation to graft survival, the results indicated that HCV-positive patients can be transplanted with the success close to that of HCV-negative patients, although there was a tendency to get better outcomes in HCV-negative patients. The followup of these HCV-positive patients revealed no elevation in their liver enzymes with acceptable serum creatinine.
These results are in agreement with Arangoa et al. [11] who found that patient survival was not significantly different in 39 HCV-positive and 96 HCV-negative patients transplanted with living-related donors (71 and 77% at 5 years, respectively).
Regarding relation of graft survival to serum creatinine of the recipients at 1 month after transplant, there was a statistically significant relation (P=0.0001) between graft survival and serum creatinine 1 month after transplant. Graft survival rate when serum creatinine was less than 1.5 mg was 95.9%, 45.5% when serum creatinine ranged between 1.5 and 3 mg, and 12.5% when serum creatinine was more than 3 mg; and regarding the relation of graft survival to maintenance immunosupression post-transplant, there was a statistically significant relation (P=0.0003) between graft survival and maintenance immunosuppressive treatment protocol.
One-year graft survival rates was 92.2% for cyclosporine, prednisolone, and MMF and 78.6% when azathioprine was used instead of MMF. On the other hand, 3-year graft survival rates was 93.1% for cyclosporine, prednisolone, and MMF and 78.6% when azathioprine was used instead of MMF.
The introduction of calcineurin inhibitors − cyclosporine and tacrolimus − in the last two decades has resulted in a significant decrease in acute rejection and an improvement in short-term graft survival [12].

Conclusion
Despite the continuous advancement in immunosuppressive and supportive therapy, a number of factors still interfere with the complete success of renal transplantation.
Among the long list of predictors for graft outcome variables, factors that had a significant impact on outcome by the Kaplan-Meier analysis included donor's age, serum creatinine at 1 month after transplant, and primary immunosuppression.

Financial support and sponsorship
Nil.

Conflicts of interest
There are no conflicts of interest.