Long term graft and recipient outcome of deceased donor renal transplantation at the National Kidney and Transplant Institute

Background: The number of patients with end-stage renal disease (ESRD) is increasing and the gap between the demand for kidney transplantation (KT) and available donors is widening. Thus, deceased donation is very important to the donor pool for ESRD. Objectives: This study aims to determine the long-term graft and recipient outcome of deceased donor renal transplantation at the NKTI from 2002-2007 and to determine the donor and recipient factors that affect graft and recipient survival. Materials and methods: This is a retrospective cohort of deceased donor KT from January 2002 to December 2007. Data were reviewed and collected from NKTI medical records and the Philippine Renal Disease Registry (PRDR). Recipient and donor demographic profile were expressed as frequency counts, percentages and means with standard deviation. Kaplan Meier was used to determine graft and patient survival and logistic regression to establish correlation between certain factors and survival Results: Among 1,598 KT, 1488 were from living donors and 110 from deceased donors. 91 patients were included in this study. The mean recipient age was 40.40 ± 11.8 years and 65.9% were males. The primary renal diseases were chronic glomerulonephritis (63.7%), diabetic nephropathy (18.7%) and hypertensive nephrosclerosis (6.6%). Around 39.6% had 3 HLA mismatches and 61.5% had at least 1 DR match. Majority received induction therapy (90.1%) and 64.8% had tacrolimus-based immunosuppressive regimen. The patient survival rate at 1, 3, 5 and 7 years was 91, 89, 86 and 86 percent while graft survival was 89, 79, 73 and 68 percent respectively. Infection was the leading cause of death. Cold Ischemia Time was significantly associated with patient survival (P = 0.033) while patients with male donors had significantly better graft survival (P= 0.001) Conclusion: There was an acceptable outcome of KT from deceased donors up to 7 years post KT. Correspondence to: Romina A. Danguilan, Chair of the Department of Adult Nephrology, National Kidney and Transplant Institute, East Avenue, Diliman, 1101 Quezon City, Philippines, Tel: 6329810300, Fax: 6329810368, E-mail: dr.radanguilan@gmail.com


Introduction
Kidney transplantation (KT) is the preferred treatment for end stage renal disease (ESRD). A successful transplant triples the life expectancy of a renal failure patient. The projected life expectancy with a transplant was 17.19 years compared with only 5.84 years on dialysis [1]. Hence, despite an initial higher risk of death, long-term survival for patients who underwent transplantation is significantly better compared with patients who remain on dialysis.
In addition, KT is more cost effective and improves quality of life. A study showed that the costs of patient therapy by hemodialysis is far greater than transplantation and its maintenance three and a half times costlier [2]. The difference in quality of life between dialysis and transplant patients is statistically significant with 18.12% greater in transplant patients. Another study showed that KT provides greater survival benefits to patients with end-stage renal disease, at less cost [3].
There is an increasing prevalence of ESRD and the demand for KT is increasing. Majority comprise living donation and unfortunately decease donation has not increased at an equivalent rate to meet the demand for KT [4]. In the Philippines, there are 10,000-12,000 new cases of ESRD annually [5]. 50-60% will need KT but only 10% is done. Of those being transplanted, 90% from living donors and only 10% from deceased organ donation.
Various studies has been done in the Philippines regarding outcomes of deceased donor KT as shown in Table 1 [6][7][8][9]. These studies showed a remarkable improvement in the outcome of deceased donor KT.

Study population
All patients ≥18 years of age who underwent primary deceased donor KT from January 2002 to December 2007 at the National Kidney and Transplant Institute were included in this study. Excluded were pediatric patients, foreigners and those who were lost to follow up for at least 12 months post KT.

Materials and methods
The following data were reviewed and collected from medical records and PRDR: a) recipients' demographic characteristics such as age, gender, cause of kidney disease, presence of diabetes mellitus, immunosuppressive regimen, induction therapy and immunologic status (Panel reactive antibody (PRA), number of HLA-ABDR mismatches and HLA-DR mismatches); b) donor factors such as age, gender and cold ischemia time (CIT) Patients were followed up to 7 years post-KT to determine graft and patient survival.

Definition of terms
 Patient survival is the survival from the date of transplant until the date of death.
 Graft survival is the presence of renal function adequate to prevent the patient from resuming maintenance dialysis.
 Graft loss is patient's permanent return to dialysis.

Statistical analysis
The demographic profile of recipients and donors were expressed as frequency count, percentage and mean with standard deviation. Kaplan meier was used to determine graft and patient's survival rate. To establish correlation between certain factors and survival, logistic regression analysis was utilized.

Ethical consideration
Confidentiality of the subjects were maintained. Anonymity were ensured and each patient was assigned a case number.

Results
From January 2002 to December 2007, a total of 1,598 KT were performed at the NKTI, 1488 (93.1%) were from living donors and 110 (6.9%) were from deceased donors. Among the 110 recipients of deceased grafts, 91 (82.7%) patients were included in this study and 19 (17.3%) patients were excluded due to the following reasons: 3 subjects were foreigners; 10 pediatric patients and 6 subjects had incomplete data.

Graft and patient outcome
The survival rate at 1, 3, 5 and 7 years for patients was 91, 89, 86 and 86 percent while graft survival was 89, 79, 73 and 68 percent respectively ( Figure 1 and Figure 2). The leading cause of death was infection (76%) followed by cardiovascular disease (14%). Most of the death occurred less than 5 years post-KT (Table 3).

Factors associated with graft and patient survival at 7 years postkidney transplant
There were no recipient factors that was significantly associated with graft and patient survival at 7 years post-KT (Table 4 and Table 5).
Cold ischemia time was significantly associated with patient survival rate among the donor factors while the gender of the donor was significantly associated with graft survival rate. The patient survival rate among patients was significantly different when grouped according to cold ischemia time. (Log Rank = 6.81, p=0.033). The cold ischemia time (CIT) with less than 12 had highest estimated mean survival rate (6.83 years), followed by 12-24 CIT (6.46 years). Patients with CIT greater than 24 had the lowest estimated survival rate (5.52 years) ( Table 6). Graft survival of patients was significantly different when grouped according to donor's gender (Log Rank = 11.055, p=0.001). Patients who had male donors had significantly higher estimated survival rate (6.06 years) than patients with female donors (3.69 years) ( Table 7).
Our study showed an improvement in graft survival when compared to studies done from 1983 to 2001 probably due to the improved immunosuppressive regimen, use of induction therapy and shorter CIT. When compared with the United States Renal Data System (USRDS) of 2013, our study was comparable in which their 1, 3 and 5 year patient survival rate were 94%, 86.6% and 75.5% while graft survival rates were 91.8%, 82.6% and 70.5% respectively [10].      Infection (76.9%) was the most common cause of death in our study followed by cardiovascular disease (15.4%). Compared to the United States Renal Data System (USRDS) wherein the most common cause of death is cardiovascular disease (31%) followed by infection (19%) and malignancies (10%) [10]. However, in a study in India of 160 deceased donor KT between 2006-2009, the most common cause of death was infection which was comparable to our study [11]. Factors for the high incidence of infections were unhygienic conditions, late presentation and diagnosis, high cost of life-saving antimicrobial agents and lack of sensitive and specific diagnostic tools that were either not available or were too expensive [11,12].
Among the recipient and donor factors studied, the donor's gender was noted to affect the 7-year graft survival in which male donor had better outcome than female (p value = 0.001). This was similar to the study involving 464 renal transplant centers in Europe in which both patient and graft survival were worse with a female donor. Graft survival in female recipients of male donors was 48.4 ± 0.4 year vs. 46.9 ± 0.6 year for female donors (p value 0.0020). In male recipients, actuarial survival was 46.5 ± 0.3 year for male donors vs. 42.1 ± 0.5 year for female donors (p value < 0.0001). The assumption about the relative benefit of a male donor is that male kidneys have greater nephron number [13].
Patients with CIT of 12 hours had a significant patient survival. This is explained because there was less rejection with shorter CIT hence no need to give solumedrol pulsing hence no infection which is the main cause of patient mortality. The acute rejection with prolonged ischemia time could be reversed with solumedrol pulsing but could cause severe infection which may lead to death. United Network for Organ Sharing (UNOS) data noted a reduction in CIT during the 10year period (1990-2000) with an overall reduction of 4.8 hour and noted improvement in 3-year graft survival (80% in 1996-2000 vs. 72% in 1990-1995 (p < 0.001) [14] Another study showed that CIT had a significant effect on the 6-year graft survival , a 10-hour increase in CIT was associated with a hazard risk ratio (HRR) of 1.20 for graft failure (p < 0.001) [15]. In our study, CIT <12 hours showed better 7-year graft survival compared to CIT 12-24 hours and >24 hours however it did not achieved statistical significance. In contrast, CIT influence on patient survival achieved statistical significance (P value 0.033). CIT with less than 12 hours had highest estimated mean survival rate (6.83 years), followed by 12-24 hours CIT (6.46 years) and >24 hours CIT had the lowest estimated survival rate (5.52 years).

Conclusion
There was an acceptable outcome of KT from deceased donors up to 7 years post KT. The most common cause of death was infection followed by cardiovascular disease. Among the recipient and donor factors, the donor's gender had effect on the 7-year graft survival in which male deceased donor KT had better graft survival compared to females and CIT was significantly associated with patient survival rate with CIT of less than 12 hours having better survival compared to CIT 12-24 hours and > 24 hours.