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Long-Term Results of Renal Transplantation: A Single-Center Analysis of 1200 Transplants S. Malek-Hosseini, A. Razmkon, A. Mehdizadeh, H. Salahi, A. Bahador, G.H. Raiss-Jalali, J. Roozbeh, S. Behzadi, M. Salehipour, M. Khosravi, and M.H. Anbardar ABSTRACT The present study is a report of long-term results of the first 1200 operations from December 1988 to December 2003. Graft and patient survival rates in eligible cases were computed with Kaplan-Meier analysis. Recipients were 808 men, 392 women of mean age 33.6 ⫾ 12.5 years. Eighty six percent of cases used organs from living donors (40% related, 41% unrelated, and 5% spouses) and 14% from cadaveric source. The most common causes of end-stage renal disease were chronic glomerulonephritis (18.2%); reflux nephropathy (13.4%); and diabetic nephropathy (10.1%). Among 215 (17.9%) patients, 156 patients (13%) died in the posttransplant period. Most common causes of death were cardiovascular (28.3%), graft loss (20.7%), and infections (19.6%). The 1- and 3-year patient survival rates were 94% and 91.5%, and graft survival rates were 88% and 84%. Although the success rate of operations was not satisfactory at the beginning, the current data reflect a ⬎90% survival rate comparable to the major centers in the world.

R

ENAL TRANSPLANTATION is now considered the best therapeutic option for chronic renal failure. It was performed for the first time ever in Iran in 1963, in the southern city of Shiraz at Nemazee Hospital. The process accelerated after establishment of Shiraz (Southern Iran) Organ Transplant Center in 1988 as a leading center for organ transplantation and the only center for liver transplantation in Iran. The present study is a report of longterm results of the first 1200 operations performed in this center. PATIENTS AND METHODS This retrospective study included all kidney transplant patients who were operated from December 1988 to December 2003. In addition to the Persian Network for Organ Transplant (PNOT), patient files were used as data sources. The immunosuppressive protocol and general procedures used in our transplant unit consisted of cyclosporine (CsA), methylprednisolone, Imuran, Cellcept, and Prednisolone. Patients were divided into three groups depending on their donors: related, unrelated, and cadaveric. Cellcept was first used in October 29, 2001. Among CsA patients were those with Cr ⬎ 3 and others with Cr ⬍ 3. The methylprednisolone was used for 3 days; thereafter from the fourth day prednisolone was used. Imuran was not used in cadaveric patients.1 Regular indefinite follow-up was considered uniformly for all patients. Graft loss was defined as nephrectomy, return to dialysis, or death with a functioning graft. The diagnosis of acute rejection was made by clinical rising of serum blood urea nitrogen and creatinine 0041-1345/06/$–see front matter doi:10.1016/j.transproceed.2006.01.020 454

as well as confirmed by biopsy. Graft and patient survival rates in eligible cases were computed with the Kaplan-Meier analysis.

RESULTS

Among 1200 patients the male/female ratio was 2.1 (808 men, 392 women). The mean age was 33.6 ⫾ 12.5 years (4.5 to 68). Among donors, the male/female ratio was 1.4. The mean age was 32.2 ⫾ 10.7 years (5 to 70). Of the recipients, 56.5% were between 18 and 40 years of age. Eighty six percent of cases used organs from living donors (40% related, 41% unrelated, and 5% spouses) and 14% from cadaveric sources. Cadaveric organs constituted just 3.5% of cases before 2000. There has been no significant difference in number of living related and unrelated cases over different time periods. Common causes of end-stage renal disease were chronic glomerulonephritis (18.2%), reflux nephropathy From the Shiraz Transplant Research Center (H.S.), Shiraz University of Medical Sciences; and the Shiraz Transplant Center (S.M.-H., A.R., A.B., G.H.R.-J., J.R., S.B., M.S., M.K., M.H.A.), Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran. Address reprint requests to A. Razmkon, MD, Shiraz Transplant Scientific Pole, Shiraz University of Medical Sciences (SUMS), P.O. Box 71455-166, Shiraz, Iran. E-mail: [email protected] © 2006 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 38, 454 – 456 (2006)

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Fig 1. Patient survival among different donor groups.

(13.4%), diabetic nephropathy (10.1%), hypertension (9.3%), autosomal-dominant polycystic kidney disease (6.3%), chronic pyelonephritis (4.3%), and 38.4% unknown cause. The most common blood groups were O (40%) and A (30.5%). The mean duration of hospitalization after transplant surgery was 18.9 ⫾ 10.5 days. Mean follow-up duration was 68.1 ⫾ 29.2 (range: 12 to 200) months. Rejection occurred in 215 (17.9%) patients, 15% of which led to patient death. One hundred fifty six patients (13%) died in the posttransplant period. Patient death has been more prominent in first years of the study. From 1988 to 1998 there were 600 transplantations. Nineteen percent (n ⫽ 114) patients died but the mortality rate of patients who were transplanted between 1998 to 2003, which included 600 patients, was 7% (42 patients). Most common

causes of death were cardiovascular (28.3%), graft loss (20.7%), and infections (19.6%). We analyzed the deaths within 60 days after loss of graft function separately rather than those attributed to the transplantation period. In this analysis, there was no excess risk of mortality during the period of graft function (for first 3 months posttransplantation, hazards ratio 1.0 [0.73 to 1.5], P ⫽ .8). However, there was a substantial increase in mortality risk in the 60 days after graft failure. This difference was more pronounced where the duration of graft function had been short. The 1- and 3-year patient survival rates were 94% and 91.5% in 1200 patients transplanted in our center. The corresponding rates were 96% and 92% in 480 living unrelated donor transplants, 93% and 91% in 491 living related donor transplants, 93% and 90.5% in 168 cadaveric transplants, 97% and 93% in 61 spousal transplants, 95%

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and 93% in 137 parental transplants, and 97% and 92.5% in 37 offspring transplants (Fig 1). Graft survival rates in 1200 recipients in our center were 88% and 84%. The grafts from spouses, offspring, and living related showed the highest survival rates. The survival rate of cadaveric grafts at 3 years is slightly lower than that of grafts from related and spousal donors. Statistical analysis of survival rates showed no significant difference between patient and graft survival in various donor groups (P ⫽ .643). Since the living unrelated donors were older than the typical cadaveric donors, we compared the rate of graft survival according to donor age. The survival rates of grafts from living donors were higher than those of cadaveric grafts within each age category, which was not significant (P ⫽ .06). DISCUSSION

A significant difference (P ⬍ .05) was seen between recipient sexes, which was due to greater number of male endstage renal disease (ESRD) patients. Mean recipient age and also the largest age group reflected a young age, which can be due to a long waiting list and the priority in this age group. Common causes of ESRD included glomerulonephritis and reflux, which was different from worldwide reports in which diabetic and hypertensive nephropathy were the most common etiologies. However, the number of hypertensive and diabetic cases has increased steadily in recent years, eventually making these two entities the most common. Currently there is a shift to living unrelated donation in countries with more stringent ethical laws: United States Renal Data records show that transplant centers have reported a 10-fold increase in living unrelated donation compared to a 16% and a 68% increase in cadaveric and living related donors, respectively.2 In our center, the major source of organs has been from living unrelated donors even in the first years, which can be attributed to the Iran model of donation. In our center, all renal transplant candidates are told of the advantages of living related donors compared with living unrelated donors. If the patient has no living related donor, he or she is placed on the waiting list for cadaveric kidneys for 6 months, after which referral is made to the Dialysis and Transplant Patients Association to find a suitable living unrelated donor. Although the success rate of operations has not been satisfactory at the beginning, the current data reflecting a

MALEK-HOSSEINI, RAZMKON, MEHDIZADEH ET AL

⬎90% survival rate is comparable to major centers throughout the world.3–5 Patient death was more prominent in the first years of the study; our data showed that the outcome rate for transplant treatment is changing. There have been considerable changes in immunosuppressive therapy, especially over the past 5 years with the availability of tacrolimus, mycophenolate, and sirolimus. While these agents may affect rejection rates and graft function, they have had an effect on patient mortality. Among causes of death, the high incidence of myocardial infarction (28.3% in this study) warrants consideration. According to Briggs,6 cardiac causes of death in all renal transplant recipients account for 18% to 37%; the higher the patient age, the greater the mortality rate. The etiology of the excess risk immediately after loss of graft function is clearly related to the transplantation process. Whether both the loss of graft function and subsequent deaths arose from the same circumstances or whether the loss of graft function itself caused the increased risk was not examined herein. Studies with longer follow-up of this cohort, which include both a greater number of people returning to dialysis treatment and also increased length of graft function (and associated immunosuppression), may alter the mortality pattern seen when transplant function is lost. The high prevalence of infection can be reduced with better attention to early diagnosis, use of proper antibiotic therapy, and avoidance of excessive immunosuppression.7 REFERENCES 1. Ahmad E, Malek-hosseini SA, Salahi H, et al: Experience with 300 renal transplants in Shiraz, Iran. Transplant Proc 27:2767, 1995 2. United States Renal Data System: 1998 Annual Data Report. Am J Kidney Dis 32(suppl 1):S91, 1998 3. Haberal M, Gulay H, Tokyay R, et al: Living unrelated donor kidney transplantation between spouses. World J Surg 16:1183, 1992 4. Rashed A, Aboud O: Renal transplantation: seventeen years of follow-up in Qatar. Transplant Proc 36:1835, 2004 5. Poblete H, Toro J, Nicovani V, et al: Survival of grafts in the first 100 renal transplants at the Carols van Buren Hospital. Rev Med Chil 129:763, 2001 6. Briggs JD: Causes of death after renal transplantation. Nephrol Dial Transplant 16:1545, 2001 7. Rubin RH: Infectious disease complications of renal transplantation. Kidney Int 44:221, 1993