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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
ORIGINAL ARTICLE  
Year : 2012  |  Volume : 23  |  Issue : 4  |  Page : 707-714
Graft survival rate following renal transplantation in diabetic patients


1 Department of Epidemiology, School of Health and Nutrition, Shiraz, Iran
2 Department of Epidemiology, Arak University of Medical Sciences, Arak, Iran
3 Shiraz Organ Transplantation Center, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran

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Date of Web Publication9-Jul-2012
 

   Abstract 

Diabetic nephropathy is the most common cause of kidney failure needing dialysis in most countries of the world. Kidney disease occurs in one-third of diabetic patients, and signi­ficantly increases the mortality rates and treatment costs. The aim of the present study was to investigate the survival rate and to determine factors that influence survival among diabetic patients who underwent transplantation at the Shiraz Namazi Hospital Transplant Center during the years 1999 to 2009. This study is a historical cohort study, which examined the graft survival rate among 103 kidney transplant patients with diabetes. The Kaplan-Meier method was used to determine the survival rate and the log-rank test was used to compare survival curves; P-value of less than 0.05 was considered significant. The mean follow-up period of patients was 48.15 ± 31.05 months (range: 3.07-118.03 months), and the estimated nine-year graft survival rate was 84.2% (±0.045). Based on the results of the Cox regression model, age of the donor was a contributing factor to graft survival rate. In summary, the graft survival rate in our cohort is satisfactory and comparable with reports from other larger centers in the world.

How to cite this article:
Rajaeefard A R, Almasi-Hashiani A, Hassanzade J, Salahi H. Graft survival rate following renal transplantation in diabetic patients. Saudi J Kidney Dis Transpl 2012;23:707-14

How to cite this URL:
Rajaeefard A R, Almasi-Hashiani A, Hassanzade J, Salahi H. Graft survival rate following renal transplantation in diabetic patients. Saudi J Kidney Dis Transpl [serial online] 2012 [cited 2020 Apr 3];23:707-14. Available from: http://www.sjkdt.org/text.asp?2012/23/4/707/98143

   Introduction Top


Chronic kidney disease (CKD) is defined either as kidney damage, evidenced by struc­tural or functional abnormality for more than three months, or a persistent reduction of the glomerular filtration rate to less than 60 mL/min/1.73 m [2] for more than three months. [1] Early diagnosis and appropriate management of CKD play an important role in delaying progression to end-stage renal disease (ESRD). [2] According to data obtained from "Manage­ment Center for Transplantation and Special Diseases," the number of ESRD patients on renal replacement therapy in Iran was about 25,000 in 2006. Thus, expecting an annual in­crease of 12%, the number is expected to have reached 40,000 by 2011. The annual incidence and prevalence of ESRD have been reported to be about 57 and 357 persons per million popu­lation (pmp) per year, respectively. Globally, the need for using renal replacement therapy is increasing, and Iran is no exception. [3] The three methods for treatment of patients with ESRD are hemodialysis, peritoneal dialysis and renal transplantation. [4],[5],[6],[7] Renal transplantation is the appropriate therapeutic option and the most effective strategy for patients with ESRD. [8],[9],[10],[11],[12],[13],[14],[15] Through renal transplantation, patients with ESRD experience longer survival rate and bet­ter quality of life. [16],[17] Renal allograft transplan­tation began in 1954 using a living-related donor. In Iran, the first renal transplantation was performed in 1967 in Shiraz. [6],[18] Presently, the number of renal transplantations performed in Iran is around 24 cases pmp. [18] Blood pres­sure, diabetes and unknown reasons are the most important causes of ESRD. [19] Renal dis­ease afflicts one-third of diabetic patients and increases mortality rates and treatment costs greatly. Diabetic nephropathy is the most com­mon indication for renal transplantation and dialysis. In the USA and Germany, more than 40% of the patients afflicted with kidney fai­lure are diabetic, and the number of such pa­tients is increasing. Early diagnosis, assessment of the nature of progress of kidney damage and attempts at prevention of this progression are important in diabetic patients. [20] In Iran, the percentage of newly afflicted patients with ESRD due to diabetes has doubled from 1997 to 2006, and has increased from 16% to 31%. [21] On the other hand, according to the World Health Organization, the expected prevalence of diabetes mellitus in 2025 will be about 6.8%, which means that 5.1 million people will be suffering from diabetes mellitus. [22] Considering the observation that the inci­dence and prevalence of diabetes and related ESRD is growing and that the best therapeutic option for ESRD-afflicted patients is renal transplantation, this study was performed to determine the ten-year survival rate in diabetic renal transplant recipients at the Namazi Hos­pital Transplant Center, Shiraz, from 1999 to 2009. We also attempted to study the factors influencing graft survival.


   Subjects and Methods Top


Our study was a historical cohort study and included 103 diabetic patients who underwent renal transplantation between 1999 and 2009; the cause of ESRD in all was diabetic nephropathy. Patients with less than three months follow-up were excluded from the study. The time of transplantation was considered as the "initial event" and the time at which the renal allograft was diagnosed to be completely and irreversibly non-functioning, and the patient needed regular dialysis again, was defined as the "end-point event." Patients who did not en­counter end-point event due to death and those with failure of follow-up were considered as censored. All relevant data were collected through review of patients' hospital records. Organ survival and patient's need to undergo regular dialysis were assessed and determined by nephrologists and recorded in follow-up cli­nics and related institutions such as "Manage­ment Center for Transplantation and Special Diseases" and "Renal Patients Support Society." Intravenous methylprednisolone was used in all patients for induction of immunosuppression. Four different regimens were used on the recipients for maintenance immunosuppression:

  1. Oral prednisolone, azathioprine (Imuran® ) and cyclosporine (Neoral® ).
  2. Oral prednisolone, mycophenolate mofetil (Cellcept® ) and cyclosporine (Neoral® ).
  3. Oral prednisolone, azathioprine that was changed to mycophenolate mofetil (Cell-cept® ) after different time intervals and cyclosporine (Neoral® ).
  4. Oral prednisolone, mycophenolate mofetil (Cellcept® ) and tacrolimus (Prograf® ).
Survival rates were calculated by the Kaplan­Meier method. The Log-rank test was used to compare survival curves and Cox Regression Models, to define the hazard ratio (HR) and for modeling of factors influencing the sur­vival rate. For evaluating proportionality hazard assumption (as one of the Cox model assump­tions), graphic model (plotting curve of observed curve accompanied with predicted curve) and goodness of fit method were used.

Analysis of survival data was done by run­ning SPSS software, version 16 (SPSS Inc., Chicago, IL, USA). For evaluation of proportio­nality of HR assumption, Intercooled STATA 9 has been used. A P-value of less than 0.05 was considered to be statistically significant.


   Results Top


A total of 1356 kidney transplantations were performed at the Shiraz Transplant Center, Namazi Hospital, Shiraz, Iran, during a period between March 1999 and March 2009. Of them, 103 were diabetic. Of this group, 97 cases (94.2%) had attended regular follow-up. The mean age of the recipients was 47.69 ± 10.6 years while that of the donors was 31.6 ± 10.4 years. Thirteen of the 97 followed-up cases (13.4%) had irreversible allograft rejection re­sulting in return to dialysis or death. As shown in [Table 1], 74.5% of the recipients and 74.3% of the donors were male. In 61% of the cases, the donor and recipient were of the same gender. In most of the cases (85.4%), the blood group of the recipient and the donor was the same; in 86.4% of the cases, the donors were less than 40 years old and, among the recipients, 75.5% were over 40 years old. In 87% of the cases, the duration on dialysis before transplantation was longer than 18 months and in 68% of the patients, the du­ration of hospitalization after transplantation was more than 14 days. The weight of most of the donors and re­cipients was more than 75 kg; unrelated donor transplantation comprised 48.5% of the cases. As shown in [Table 1], the first immunosuppressive regimen, as mentioned above, was the most frequently used therapy, and was admi­nistered in 53.4% of the cases. The fourth regimen were used for patients with panel reactive antibody >20% or in patients under­going second transplantation due to immunologic rejection of their previous grafts. How­ever, the effects of third and fourth drug-re­gimens on graft survival were not assessed because of their infrequent administration.
Table 1: Distribution of demographic and medical variables in the study patients.

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In 96.7% of the cases, the cold ischemia time was less than 2 h and diuresis occurred imme­diately after release of the clamps; in 80% of the cases, there was a single donor renal artery for anastomosis. The mean follow-up period was 48.15 ± 31.05 months (range: 3.07- 118.03). The one-, three-, five- and nine-year graft survival rates along with their standard errors were 93.4% ± 0.025, 88.7% ± 0.034, 84.2% ± 0.045 and 84.2% ± 0.045, respec­tively [Figure 1]. The five- and nine-year sur­vival rates were similar, which suggests that allografts that are not rejected during the first five years post-transplant did not have graft loss until nine years after transplantation.
Figure 1: Allograft survival rate in diabetic renal transplant recipients.

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The log-rank test revealed that variables such as blood group (P = 0.09), gender of recipient (P = 0.74), similarity of gender in recipient and donor (P = 0.5), age of recipient (P = 0.49), weight of donor (P = 0.82), weight of recipient (P = 0.12), type of drug regimen used (P = 0.35), time to first diuresis (P = 0.57), cold ischemia time (P = 0.8) and number of donor arteries (P = 0.56) did not have any significant relation­ship with graft survival rate. On the other hand, cases with male donors (P = 0.03), male to male transplants (P = 0.004), donor under 40 years of age (P = 0.004) and living donor transplants (P = 0.03) showed significantly higher survival rates. For analyzing continuous variables, Cox model (univariate method) was used, which showed that duration on dialysis (HR = 1.03, 95% CI: 0.992-1.072, P = 0.12) and creatinine level at discharge (HR = 1.28, 95% CI: 0.987-1.66, P = 0.063) did not have a significant relationship with graft survival rate. However, the duration of hospitalization after transplantation showed a significant relation­ship with survival rate so that an increase of every single day of hospitalization resulted in an increase in HR 1.081-times (95% CI: 1.016-1.15, P = 0.014). For modeling, variables that had P-values less than 0.25 on univariate analysis and assumption of HR proportionality deemed rea­sonable were entered into the Cox model. Testing the assumption of HR proportionality by using goodness of fit method showed that this assumption was true for variables at issue.

Also, testing the HR proportionality by using graphic method has been done, and this me­thod has been shown only for variables of donor's gender as examples [Figure 2]. Based on the results of the Cox regression model, age of the donor was a contributory factor on transplant survival rate, and the HR was 4.99 (P = 0.037) for donors over 40 years old.
Figure 2: Assessment of proportionality of hazard ratio assumption using the method of predicted and observed values based on donor's gender.

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   Discussion Top


Thanks to the progress achieved in surgical techniques and immunosuppressive drugs, the survival rates of transplantation have risen stunningly compared with the past decade. In our study, the one-, three-, five- and nine-year survival rates of renal transplantation among diabetic patients in this center have been esti­mated to be 93.4%, 88.7%, 84.2% and 84.2%, respectively. In the same period, the graft sur­vival rates among non-diabetic patients in the same center were 93.7%, 94.5%, 89.6% and 86.2%, respectively, after one-, three-, five-and nine-years after transplantation; however, these differences were not significant (P = 0.241) [Figure 3].
Figure 3: Allograft survival rate in renal transplant recipients based on presence or absence of diabetes.

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As seen in our study, several other studies have shown that there is no significant rela­tionship between gender of recipient and donor and transplant survival rate. [23],[24],[25],[26] Also, while the relationship between blood group and graft survival rate is a contentious issue, we did not find any significant difference in graft survival in transplantation between donors and recipients with the same blood group or with com­patible groups, which is in accordance with the results of other studies. [27],[28] However, in a study conducted by Park et al, [29] better graft survival rates were seen in transplants between the same blood group in comparison with those with different blood groups. Duration on dia­lysis before renal transplantation has been one of the factors that has been shown to have an insignificant relationship with survival rate in our study, in contrast to some other studies. [24],[30] One reason for this lack of significant relation­ship could be that the number of patients in the group on dialysis for more than 18 months was very small (12/6%). In this study, variables such as donor source, duration of hospitalization or side of the kid­ney did not show a significant relationship with graft survival rate. Although there was no sig­nificant relationship between survival rate and type of donor, the prevalence of rejection was much higher in deceased-donor transplants (25.8%), whereas in living-related and living-unrelated transplants, the prevalence of rejection was 5% and 8.7%, respectively. The creatinine level at discharge is another variable, which, by applying the Cox model, revealed no significant relationship with allograft survi­val, in our study. Rayhill and colleagues found that the creatinine level at discharge has a significant relationship with allograft survival rate, and for each 1 mg/dL increase in creatinine above the mean, the HR of graft rejec­tion increased 1.8 units. [31] In recent decades, progress in immunosuppressive drug regimes has led to improvement in graft survival rate and longer survival of patients. Early studies on drugs have indicated that mycophenolate can reduce the acute graft rejection rate in comparison with azathioprine. [32],[33],[34],[35] However, more recent studies have not shown any diffe­rence between these two drugs in terms of acute graft rejection, graft survival rate and patient survival. [36] Also, numerous studies have shown that there is no significant relationship between type of immunosuppressive drugs administered and graft survival rate, [30],[37] some­thing that was not seen in our study. Mohamed et al [26] showed that age of the donor is one of the factors that influences allograft survival rate; this could be due to reduction of the number of functioning nephrons in older age. However, numerous other studies, [25],[38] inclu­ding our study, did not show any significant relationship between age of recipient or donor and survival rate. Bennett et al, in their study, [39] showed that there is no significant relationship between body mass index and allograft survi­val rate. In our study, due to non-availability of the height of donors and recipients, we used body weight as a variable; we did not find any relationship between weight of donor and/or recipient and graft survival rate, and the results between the two groups (<75 kg and ≥75 kg) were similar. The cold ischemia time, time to first diuresis and number of donor arteries also did not show any significant relationship with graft survival rate, a result which is similar to that of Mohamed et al. [26] Considering the fact that diabetes mellitus is one of the most prevailing diseases in the de­veloped and developing countries (including Iran), the best strategy against this problem is to reduce the incidence. Preventive programs, especially in early stages of the disease to decrease the complications, can play a great role in control of the disease. However, if renal involvement does occur, early detection and appropriate management can reduce the finan cial burden greatly. According to the findings of this study, there is no difference between allograft survival rates in diabetic and non-diabetic patients and, thus, renal transplan­tation can be a promising therapeutic option for patients with diabetic nephropathy.

 
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Correspondence Address:
A Almasi-Hashiani
Department of Epidemiology, School of Health, Arak University of Medical Sciences, Arak
Iran
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DOI: 10.4103/1319-2442.98143

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