Year : 2009 | Volume
: 20 | Issue : 3 | Page : 370--374
Acute rejection episodes after kidney transplantation
Fethi Ben Hamida1, Samia Barbouch1, Rafika Bardi2, Imed Helal1, Hayet Kaaroud1, Lilia Ben Fatma1, Hafedh Hedri1, Ezzeddine Abderrahim1, Taieb Ben Abdallah2, Khaled Ayed2, Hedi Ben Maiz3, Adel Kheder1,
1 Department of Nephrology, Charles Nicolle Hospital, Tunis, Tunisia
2 Laboratory of Immunology: LITRI LR 03SP01, Tunisia
3 Laboratory of Renal Pathology: LR 00SP01, Tunisia
Fethi Ben Hamida
Department of Nephrology, Charles Nicolle Hospital, Tunis
Acute rejection episodes (AREs) are a major determinant of renal allograft survival. The incorporation of new immunosuppressive agents explains, at least partially, the improvement seen in the results of transplantation in recent years. The objectives of this study are to analyze the incidence and severity of AREs, their risk factors and their influence on graft and patient survival. We retrospectively studied 280 kidney transplants performed in adults at the Charles Nicolle Hospital, Tunis, between 1986 and 2004. The diagnosis of ARE was based on clinical data and response to treatment. Allograft biopsies were performed in ten cases. The treatment of AREs consisted of pulse methylprednisolone and antithymocyte globulin. There were 186 males (66.4%) and 94 females (33.6%), and their mean age was 31 ± 8.9 years. Overall, the 280 study patients experienced a total of 113 AREs. Of them, 85 had only one ARE, 28 had two to three and none had more than three AREs. A total of 68 AREs were completely reversible, 42 were partially reversible while three could not be reversed with treatment. The mean incidence of AREs was 40.4%. The incidence was > 45% between 1986 and 1997, decreased to 20.5% between 1998 and 2000 and to 9% between 2001 and 2004. Graft survival rates in patients with and without AREs were respectively 91% and 93% at three years, 82% and 90% at five years and 73% and 83% at 10 years. We found a decrease in the incidence of AREs in recent years in our study patients, and this was related to the introduction of sensitized cross-match and the newer immunosuppressive agents, particularly MMF. Additionally, AREs had a deleterious impact on late graft survival in our study population.
|How to cite this article:|
Hamida FB, Barbouch S, Bardi R, Helal I, Kaaroud H, Fatma LB, Hedri H, Abderrahim E, Abdallah TB, Ayed K, Maiz HB, Kheder A. Acute rejection episodes after kidney transplantation.Saudi J Kidney Dis Transpl 2009;20:370-374
|How to cite this URL:|
Hamida FB, Barbouch S, Bardi R, Helal I, Kaaroud H, Fatma LB, Hedri H, Abderrahim E, Abdallah TB, Ayed K, Maiz HB, Kheder A. Acute rejection episodes after kidney transplantation. Saudi J Kidney Dis Transpl [serial online] 2009 [cited 2021 Sep 22 ];20:370-374
Available from: https://www.sjkdt.org/text.asp?2009/20/3/370/50758
Many risk factors are known to influence graft survival such as age of the recipient, race, presence of diabetes, delayed graft function and human leukocyte antigen (HLA) mismatch. , Additionally, acute rejection episodes (AREs) have consistently been reported to be the most important risk factor leading to chronic allograft failure. ,,
The introduction of new immunosuppressive agents such as cyclosporine, tacrolimus, sirolimus and mycophenolate mofetil (MMF) explains, at least partially, the improvement seen in the results of transplantation in recent years. , However, in spite of the progressive decrease in the incidence of AREs, chronic allograft nephropathy remains the most common cause of graft loss after kidney transplantation. ,,
The objectives of this study are to analyze the incidence and severity of AREs, the associated risk factors and their influence on graft and patient survival.
Patients and Methods
We retrospectively analyzed data of 280 kidney transplants performed in adults between 1986 and 2004. The recipients included 186 males (66.4%) and 94 females (33.6%) with a mean age of 31 ± 8.9 years (16 to 61 years). There were 136 patients (48.6%) in the age-group 16 to 29 years, 133 (47.5%) in the age-group 30 to 49 years and 11 patients (3.9%) >_ 50 years of age. The donor source was cadaveric in 46 cases (16.4%), living related in 231 cases (82.53%) and living unrelated in three (1.7%). The mean age of the donors was 35.8 ± 12.9 years (16 to 65 years). Sensitized cross-match was introduced in our center in 1997. The immunosuppressive therapy comprised of corticosteroids in all cases, azathioprine in 199 patients (71%), MMF in 114 patients (59.3%) (First introduced in our center in 1999), cylosporine in 182 cases (65%), tacrolimus in 24 cases (8.6%) and anti-thymocyte globulin (ATG) in 170 cases (60.7%). ATG was not used in HLA identical living related recipients.
The diagnosis of ARE was based on clinical and analytical data as well as response to treatment. Allograft biopsies were performed in 10 cases. The treatment of AREs consisted of pulse methylprednisolone and/or ATG.
The data are presented as mean ± SD. Comparative analysis was performed using T-test for continuous variables and Chi square test for quantitative variables. Cumulative survival rates were calculated according to the actuarial method and comparison was performed using Log rank test. The level of statistical significance was set at P= 0.05%.
Overall, the 280 study patients experienced a total of 113 AREs. Of them, 85 had only one ARE, 28 had two to three and none had more than three ARE. Of the 113 AREs, 68 were completely reversible, 42 were partially reversible while three could not be reversed with treatment. The mean incidence of AREs in our study patients was 40.4%. The incidence was more than 45% between 1986 and 1997, decreased to 20.5% between 1998 and 2000 and to 9% between 2001 and 2004. The incidence of AREs was not significantly related to: (a) type of donors: 30.4% in cadaveric donor transplants and 42.3% in living donor transplants: (b) mode of renal replacement therapy before transplantation: 35.7% in peritoneal dialysis and 41.2% in hemodialysis and (c) number of HLA mismatches (MM): 29.7% in zero MM, 43.4% in one or two MM and 43.6% if there was > two MM.
The proportion of patients experiencing an episode of ARE was significantly lower when sensitized cross-match was performed (15.2% vs 57.2%, P (22.1% vs 19.5%).
The serum creatinine level was significantly higher in patients who had AREs when compared with those who did not have an episode of ARE, both at discharge from the hospital (117 µmol/L vs 107.7 µmol/L, P  Although this reduction has not been associated with a better graft survival in the shortterm, longer duration of follow-up has shown that MMF improves allograft survival. , This was also observed in our study, as a reduction noted in the incidence of AREs in 1998, coincided with the introduction of MMF in the immunosuppressive protocol in our country that year.
Contrary to one large analysis,  we observed no influence of the number of HLA-mismatches on the incidence of AREs. In our study, we did not find a significant difference between patients with or without AREs, regarding the occurrence of infection during the first three months, the number of hospitalizations during the first year as well as the onset of post-transplantation diabetes mellitus.
Patients with AREs showed higher serum creatinine levels at discharge from the hospital and at 12 months after transplantation. Leggat et al,  in a review of 31,600 first cadaveric transplants from the US Renal Data System, showed a significantly lower four year graft survival of 54% in patients with AREs in contrast to 78% graft survival in those who had no rejection. In our study, the lower graft survival in patients with AREs was not statistically significant. However, this difference became significant when late graft loss was analyzed, confirming the findings of other investigators. ,,,
We found a decrease in the incidence of AREs in the last decade in adult renal transplants. This is probably related to the introduction of sensitized cross-match and newer immunosuppressive agents, particularly MMF. As well documented, ARE had a deleterious impact in late graft survival in our population. These findings stress the importance of effectively preventing acute rejection, which still remains a major determinant in the development of chronic allograft nephropathy. Although our study throws good insight into the incidence and after effects of AREs, one major drawback is that we performed only ten allograft biopsies to confirm the diagnosis of ARE. Thus, a similar study with histological evidence of ARE will throw more light on this entity.
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