| Abstract|| |
Renal transplantation is the treatment of choice for patients with end-stage renal disease. In Iraq, renal transplantation started in 1973 and has continued until now with live donor transplantation, since deceased donor transplant program is not approved as yet. Long-term transplant data are still scarce. The aim of our study is to present data on transplantation and medical follow-up at one year and, survival analysis at one, three and five years. A total of 250 renal transplantations were performed at the Nephrology and Renal Transplantation Center, Baghdad between January 2009 and January 2014. It is a living donor, blood group compatible donor program. All patients received triple immunosuppression (calcineurine inhibitor, mycophenolate mofetil or mycophenolic acid, and steroid). The Kaplan-Meier method was used to determine the survival rate. There were 92 live related donors, 143 unrelated donors, and 15 spouse donors. The mean age was 34.07 ± 12.2 years. The one-year graft survival for related and unrelated donor transplants was 98.9% and 91.8%, respectively. Graft survival was lower (82.9%) in recipients with acute rejection episodes. The patient survival at one-year was 94%. The three-year graft and patient survival was 91% and 90%, respectively, and five-year survival for grafts and patients was 87.1% and 88%, respectively. The outcome of the renal transplantation in Iraq is improving. Long-term patient follow-up needs more meticulous attention. The development of renal transplant registry is critical for future planning. Moreover, renal transplantation practice in Iraq needs more social, religious, and governmental support.
|How to cite this article:|
Ali AA, Al-Saedi AJ, Al-Mudhaffer AJ, Al-Taee KH. Five years renal transplantation data: Single-center experience from Iraq. Saudi J Kidney Dis Transpl 2016;27:341-7
|How to cite this URL:|
Ali AA, Al-Saedi AJ, Al-Mudhaffer AJ, Al-Taee KH. Five years renal transplantation data: Single-center experience from Iraq. Saudi J Kidney Dis Transpl [serial online] 2016 [cited 2019 Aug 19];27:341-7. Available from: http://www.sjkdt.org/text.asp?2016/27/2/341/178559
| Introduction|| |
Renal transplantation in Iraq started at the Al-Rasheed Military Hospital in 1973.  It has continued until now using blood group compatible, living related, and unrelated donor organs. Renal transplantation started in the medical city teaching hospital of Baghdad in 1985 and in the Nephrology and Renal Transplantation Center in 1990. The renal transplant recipients in our program were referred from different nephrology and dialysis units in Iraq. Herewith, we present the clinical and survival data from the Nephrology and Renal Transplantation Center for a period of five years (2009-2014).
| Materials and Methods|| |
Our program is a living, blood group compatible, donor program. From January 2009 to January 2014, 250 renal transplants were performed in our center. All transplants were from living donors with 92 living related (LRD), 143 live unrelated (LURD), and 15 spouse donors.
Unrelated donors were nonpaid donors according to the Iraqi law. This was ascertained by two committees, a local one in our center and a central one by the Iraqi Ministry of Health. This governmental team gives the final decision to proceed with transplantation after full assessment.
Data were collected through a review of medical records and computer-based registry data including preoperative information, hospital records, and transplantation clinic follow-up data. Statistical analyses were performed using the IBM SPSS ® statistical package. The Kaplan-Meier method was used to determine the survival rate. Spouse donors were included as LURD during survival analysis. Death with functioning graft and return to dialysis were defined as graft failure preceding death.
All transplant recipients had renal replacement therapy in the form of hemodialysis (HD) for <1 year prior to transplantation. They had been included consecutively in the study with no exclusion. [Table 1] shows the basic characteristics of the study group. All patients were transplanted for the first time. Open donor nephrectomy was the only procedure as laparoscopic donor nephrectomy is still unavailable in Iraq for logistic reasons. Delayed graft function (DGF) was defined as the need for dialysis during the 1 st week after transplantation. Acute rejection was defined as an acute deterioration in allograft function associated with specific pathologic changes in the graft. All acute rejection episodes were biopsy proven using the Banff 2007 criteria. 
Induction regimen included basiliximab (day-0 and day-4) in 95% of cases and anti-thymocyte globulin (ATG), 1.5 mg/kg single dose, administered intraoperatively. All patients received methyl prednisolone during induction. Cyclosporine in a dose of 8-10 mg/kg or tacrolimus in a dose of 0.05-0.1 mg/kg was used. Mycophenolate mofetil (2 g/day) or mycophenolic acid (1440 mg/day) was also used. Azathioprine was not used during the 1 st year of transplantation. Cyclosporine was the main calcineurin inhibitor to be used at six-and 12-month posttransplant. There is a little paradigm shift in the last two years with slightly increasing use of tacrolimus but its irregular availability prevented regular use. Oral prednisolone was started in a dose of 1 mg/kg and tapered to 10 mg/day at the end of the 1 st month posttransplant.
For acute rejection, three intravenous pulses of 500 mg/day of methyl prednisolone were used. Renal allograft biopsy was performed in nonresponders. Steroid-resistant acute cellular rejection was managed with ATG 1.5 mg/kg/ day for a maximum of 10 days. For antibody-mediated rejection, five therapeutic plasma exchanges were initiated in addition to five doses of intravenous immunoglobulin (0.2-0.4 mg/kg/day).
| Results|| |
The mean age of the study patients was 34.07 ± 12.2 years, and the median age was 32.5 years. The youngest recipient was nine-year-old and the eldest was 66-year-old. There were 155 males (62%) and 95 females (38%). About 62% of patients had three or less mismatches. Hypertension and/or diabetes mellitus constituted 55% of the primary cause of end-stage renal disease (ESRD).
Five grafts (2%) had DGF due to acute tubular necrosis secondary to blood loss. Forty-one patients were suspected to have acute rejection episodes (16.4%). The mean age of these patients was 33.5 ± 11 years, and included nine females. The mean duration after transplantation when acute rejection episodes occurred was 158.2 ± 12.4 days. Six episodes responded to three intravenous 500 mg/day of methyl prednisolone pulses. Thirty-five patients with suspected acute rejection underwent allograft biopsy. Thirty of these 35 patients (85%) had allograft histology suggestive of acute T-cell mediated rejection. There were 15 cases with Banff Type IA and IB while 15 others had Type IIA. The remaining five were proved to have acute antibody-mediated rejection (B-cell mediated).
The mean systolic blood pressure at one year was 124 ± 18.4 mm Hg, while the mean diastolic blood pressure was 89 ± 11.6 mm Hg. Fifty-six patients (22.4%) had blood pressure more than or equal to 140/90 mm Hg at one year.
The mean body mass index (BMI) at one year was 24.2. Forty patients (16%) developed newonset diabetes after transplantation (NODAT). Eighteen of them experienced acute rejection episodes.
The mean urinary protein excretion at one year was 152.5 mg. Ten patients (4%) had 0.5- 1 g of protein on 24 h urine collection.
Recurrent urinary tract infections (UTIs) were the most frequent type of infection seen in 97 patients (38.8%); Escherichia coli was isolated on urine culture in 92% of the patients. Fifty-four of these patients, (56.7%), responded to oral third generation cephalosporins or ciprofloxacin. The other 43 patients were managed with injectable 3 rd or 4 th generation cephalosporins or meropenem. Ten patients (4%) developed Cytomegalovirus (CMV) infection which was diagnosed clinically, serologically, and by tissue diagnosis. Only one patient (0.4%) was diagnosed with BK virus nephropathy by polymerase chain reaction (PCR) and allograft biopsy.
Hepatitis C virus (HCV) infection was diagnosed in six patients (2.4%) by real time PCR. All of them were HCV-negative prior to transplantation. Three patients had tuberculosis (TB, 1.2%). One of them had TB lymphadenitis.
At one year posttransplantation, one patient was diagnosed with breast cancer (0.4%). [Table 2] represents rejection and medical complications at one year in the study patients.
|Table 2: Allograft rejection episodes and medical complications in the 1st posttransplant year.|
Click here to view
The overall one-year graft survival was 94.4%. For LRD grafts, it was 98.9% and for LURD grafts, it was 91.8%. The one-year graft survival declined to 82.9% in patients who experienced acute rejection episodes. The mean serum creatinine at one year was 1.3 mg/dL, while it was 2.2 mg/dL for recipients with prior acute rejection. The mean estimated glomerular filtration rate at one year was 60.2 mL/min and 40.3 mL/min in LRD and LURD grafts, respectively. Patient survival at oneyear was 94%.
[Figure 1] and [Figure 2] depict the Kaplan-Meir analysis of graft and patient survival at one year.
The overall three-year graft and patient survival was 91% and 90%, respectively and fiveyear survival rates were 87.1% and 88%, respectively.
| Discussion|| |
Kidney transplantation is the treatment of choice for selected patients with ESRD. A successful kidney transplant improves the quality of life and reduces the mortality risk for most patients, when compared with maintenance dialysis. ,
It is fortunate that renal transplantation has one of the largest and most complete databases of any field of medicine.  However, renal transplantation data from Iraq are still scarce and sparse, especially the survival data. Two studies reported survival of patients in Baghdad for the periods from 1979 to 1999 (182 patients) in the first study and from 1979 to 2005 in the second study (512 patients). One recent single study presented survival at six months for 88 patients. In our study, the one-year graft survival was 94.4% compared to these three studies; 83.5%, 89%, and 88%, respectively. Patient survival at one year was 94% in our study compared to 82.9%, 91%, and 90%, respectively, in the previous three studies. ,,
In Saudi Arabia, the one-year survival of grafts in those who received LRD renal transplants was 96.9% and this is comparable with our data of LRD, which was 98.9%.  The one-year graft survival for LURD transplants in the Saudi study was 93% and again this is comparable with our data of 91.8%. 
Our data is also comparable to the US Scientific Registry of Transplant Recipients with graft and patient survival of 94.47% and 96.26%, respectively. 
The three and five-year graft and patient survival showed improvement from the previous Iraqi study by Al-Taee, et al for the period from 1979 to 1999 and they are comparable with data from the UK renal registry 2012 report for patients transplanted between 2002 and 2006. The 2012 US organ procurement and transplantation network data for patients transplanted in 2006 were also comparable to our three-and five-year survival data. ,
It is apparent that the practice and outcome of renal transplants have improved in Iraq in spite of all struggles. This is mostly attributed to the increased community awareness to the value of renal transplantation as the best opportunity for ESRD patients. It is also related to the steady increase of young qualified nephrologists managing transplant recipients. In addition, the availability of newer immunosuppressive medications has further contributed to better management and follow-up. The introduction of renal allograft biopsy and management of rejection with modern anti-rejection therapies has had a positive impact on transplantation practice and outcome. 
Despite the increasing age of ESRD patients, transplanting kidneys in the elderly is limited in our experience. This is mostly attributed to delayed referral to nephrologist, multiple comorbidities, and surgeons' fear to operate on such complicated patients.
Hypertension is common after transplantation and is present in 50-90% of renal transplant recipients. In our study, we used blood pressure of 140/90 mm Hg as the defining threshold according to the recently published Joint National Committee-8 recommendations. , NODAT occurs in 4-25% of renal transplant recipients.  Our data are consistent with these data. NODAT is mostly related to the higher steroid doses used and to the increasing BMI after the first three months of transplantation. This can lead to a change in the management policy by reducing the dose of steroids as early as possible in the posttransplant period.
Proteinuria has been reported in 9-40% of kidney transplant recipients with a functioning graft.  In our experience, all patients with stable graft function and urinary protein excretion of >0.5 were started on angiotensin converting enzyme inhibitors.
The high percentage of recurrent UTI in the 1 st year can be explained by the prolonged catheter and stent placement time (up to six weeks). All transplant recipients received six months prophylaxis of trimethoprim and sulfamethoxazole.
All patients received CMV prophylaxis with gancyclovir for high-risk and acyclovir or valcyclovir for low-risk recipients. Valgancyclovir is still not available in Iraq. 
In this era of modern immunosuppression, polyoma (BK) virus-related graft dysfunction is increasingly being recorded, despite which we did not implement monitoring schedule because of unavailability. The only case with proven BK virus nephropathy was diagnosed by PCR and biopsy outside Iraq. She was a female who received multiple courses of intensified immunosuppression for resistant rejection. 
The prevalence of HCV in patients with chronic kidney disease is higher than in the general population, particularly in patients on HD. During pretransplant assessment, all donors and recipients were evaluated for any evidence of positive viral hepatitis serology. Six patients were diagnosed with HCV. 
The prevalence of active TB among solid organ transplant recipients in developed countries has ranged from 1.2% to 6.4% but has been reported to be as high as 10-15% in solid organ recipients from endemic regions.  Iraq is an endemic country for TB and it is not surprising to have reactivation of TB posttransplantation. However, the policy of TB prophylaxis is not uniformly practiced by transplant physicians.
A previous Iraqi data reported that Kaposi's sarcoma was the most common malignancy encountered and there was no record of solid malignancy in the 1 st year posttransplant. In this series, only one solid malignancy and no skin malignancy was recorded. This may be due to nonuse of azathioprine, which is no longer the first line immunosuppressive drug. Previous reports from Europe and the US have shown that the risk of breast cancer is not significantly higher than in the general population. ,,
| Conclusion|| |
The apparent success of the transplant program in Iraq is a result of greater awareness of people and health personnel about organ donation and transplantation. The improved survival is related to the better adoption of modern transplantation practice and the implementation of evidence-based knowledge and technology in patient care. Long-term data are still lacking as also proper follow-up, particularly in remote areas. This may be improved by the recently approved renal transplant registry program. In addition, renal transplantation practice needs more social, religious, and governmental support.
| Acknowledgment|| |
We would like to acknowledge our sincere thanks to Miss Suhair Saeed for her hard work and faithful commitment in conducting this study.
| References|| |
Sh Al-Taee IK, Al-Shamaa I. Long term follow-up of renal transplant patients - A single center experience in Iraq. Saudi J Kidney Dis Transpl 2005;16:40-5.
Solez K, Colvin RB, Racusen LC, et al. Banff ′05 Meeting Report: differential diagnosis of chronic allograft injury and elimination of chronic allograft nephropathy (′CAN′). Am J Transplant 2007;7:518-26.
Suthanthiran M, Strom TB. Renal transplantation. N Engl J Med 1994;331:365-76.
Port FK, Wolfe RA, Mauger EA, Berling DP, Jiang K. Comparison of survival probabilities for dialysis patients vs cadaveric renal transplant recipients. JAMA 1993;270:1339-43.
Kaplan B, Schold J, Meier-Kriesche HU. Overview of large database analysis in renal transplantation. Am J Transplant 2003;3:1052-6.
Al-Jebory HM, Abd KH, Mahmood S, Jabur WL, Al Khyat QJ. Characteristics of kidney transplantation in baghdad: an epidemiological study. Saudi J Kidney Dis Transpl 2007;18: 432-8.
Al-Bazzaz PH. Kidney transplantation in Erbil, Iraq: a single-center experience. Saudi J Kidney Dis Transpl 2010;21:359-62.
Shaheen FA, Souqiyyeh MZ. Current status of renal transplantation in the Kingdom of Saudi Arabia. Transplant Proc 2004;36:125-7.
Al-Wakeel J, Mitwalli AH, Tarif N, et al. Living unrelated renal transplant: outcome and issues. Saudi J Kidney Dis Transpl 2000;11: 553-8.
Ali AA, Al-Mudhaffer AJ, Al-Taee Q, AlWindawi S. Allograft biopsy in kidney transplant recipients in the medical city of Baghdad. Saudi J Kidney Dis Transpl 2013;24: 1039-43.
Kasiske BL, Anjum S, Shah R, et al. Hypertension after kidney transplantation. Am J Kidney Dis 2004;43:1071-81.
James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA 2014;311:507-20.
Peev V, Reiser J, Alachkar N. Diabetes mellitus in the transplanted kidney. Front Endocrinol (Lausanne) 2014;5:141.
Pham PT, Pham PC, Danovitch GM. Cardiovascular disease posttransplant. Semin Nephrol 2007;27:430-44.
Kalil AC, Levitsky J, Lyden E, Stoner J, Freifeld AG. Meta-analysis: the efficacy of strategies to prevent organ disease by cytomegalovirus in solid organ transplant recipients. Ann Intern Med 2005;143:870-80.
Hirsch HH, Randhawa P; AST Infectious Diseases Community of Practice. BK virus in solid organ transplant recipients. Am J Transplant 2009;9 Suppl 4:S136-46.
Fabrizi F, Poordad FF, Martin P. Hepatitis C infection and the patient with end-stage renal disease. Hepatology 2002;36:3-10.
Subramanian A, Dorman S; AST Infectious Diseases Community of Practice. Mycobacterium tuberculosis in solid organ transplant recipients. Am J Transplant 2009;9 Suppl 4:S57-62.
Altaee IK, Jaleel NA, Aljubury HM, Alshamaa IA, Gazala S. Incidence and types of malignancies in renal transplant recipients in Iraq. Saudi J Kidney Dis Transpl 2006;17:408-14.
Sodemann U, Bistrup C, Marckmann P. Cancer rates after kidney transplantation. Dan Med Bull 2011;58:A4342.
Engels EA, Pfeiffer RM, Fraumeni JF Jr., et al. Spectrum of cancer risk among US solid organ transplant recipients. JAMA 2011;306:1891901.
Ala A Ali
Nephrology and Renal Transplantation Center, The Medical City Teaching Hospital, Baghdad
[Figure 1], [Figure 2]
[Table 1], [Table 2]