|Year : 2019 | Volume
| Issue : 3 | Page : 179-183
Graft function and outcomes of deceased donor kidney transplant patients in a tertiary care center
Sujit Surendran, M Edwin Fernando, S Thirumavalavan, S A. K Noor Mohamed, P Senthil Kumar
Department of Nephrology, Stanley Medical College, Chennai, Tamil Nadu, India
|Date of Submission||24-Oct-2018|
|Date of Decision||10-Jan-2019|
|Date of Acceptance||01-Feb-2019|
|Date of Web Publication||17-Sep-2019|
Dr. M Edwin Fernando
Plot 1623, 9th Main Road, Ram Nagar South Extension, Madipakkam, Chennai - 600 091, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Introduction: In India, deceased donor kidney transplantation accounts for less than 1% of total kidney transplants that are performed each year. Objectives: To assess the outcomes of deceased donor kidney transplantation. Methodology: We retrospectively reviewed deceased donor kidney transplantation in our centre from January 1996 to March 2016. All recipients were followed to the point of graft loss or death. Results were analysed in terms of age of donor and recipient, graft ischemia time, graft function,discharge serum creatinine, any rise in serum creatinine during follow up, post transplant complications, graft and recipient survival. Results: A total of 105 kidney transplant recipients including 81 men (77.14%) and 24 women (22.85%) were included in our analysis. The one year recipient survival rate was 75.8% and one year graft survival was 89.58%. The graft rejection rates were 18% in our centre and the mortality rate was 27.6%. Conclusions: By minimizing ischemia times, using better perfusion techniques and optimized immuno suppresion deceased donor transplant outcomes can be improved.
Keywords: Deceased donor, graft function, kidney transplant, outcomes
|How to cite this article:|
Surendran S, Fernando M E, Thirumavalavan S, Mohamed S A, Kumar P S. Graft function and outcomes of deceased donor kidney transplant patients in a tertiary care center. Indian J Transplant 2019;13:179-83
|How to cite this URL:|
Surendran S, Fernando M E, Thirumavalavan S, Mohamed S A, Kumar P S. Graft function and outcomes of deceased donor kidney transplant patients in a tertiary care center. Indian J Transplant [serial online] 2019 [cited 2019 Oct 19];13:179-83. Available from: http://www.ijtonline.in/text.asp?2019/13/3/179/266954
| Introduction|| |
Background and rationale
In India, more than 175,000 individuals are diagnosed with end-stage kidney disease every year. Among them, only 2.4% receive kidney transplantation. One of the main reasons for the huge gap between demand and supply is the limited availability of live donors. Deceased donor kidney transplantation may thereby prove to be a potential solution for this problem. Deceased donor organ donation has been accepted legally by “The Transplantation of Human Organs Act” in 1994. In India, deceased donor kidney transplantation accounts for <1% of total kidney transplants that are performed each year.
The objective was to assess the outcomes of deceased donor kidney transplantation.
We conducted a retrospective analysis of kidney transplant patients (n = 105) who underwent deceased donor kidney transplantation between January 1996 and March 2016 in our center. All donors and recipients were ABO compatible, and all recipients had a negative donor T-cell crossmatch. The organs were harvested on the availability and preserved with cold histidine-tryptophan-ketoglutarate solution. Transplantation was carried out as per standard techniques. All patients were followed to the point of graft loss or death. Results were analyzed in terms of age of donor and recipient, terminal serum creatinine, graft ischemia time, graft function, posttransplant complications, and graft and patient survival. Patient survival was defined as the time from transplantation to death. Graft survival was defined as the time from transplant to requirement for hemodialysis.
We collected demographic data, medical history, native kidney disease, comorbidities, type of induction treatment, immunosuppression regimen, posttransplant complications, graft rejection or graft loss, and patient survival.
As per our protocol, these patients were followed with routine laboratory investigations at weekly intervals for the first 3 months, fortnightly for the next 3 months, monthly for the next 6 months, and three monthly intervals thereafter. During each visit, kidney and liver function statuses were monitored; complete blood counts, ultrasound, and Doppler studies were performed. Kidney biopsy was done when there was a persistent rise in serum creatinine and proteinuria either new onset or ≥3 g/day. During infections, apart from blood cultures and urine cultures, appropriate investigations for diagnosing suspected infective agents were done.
All patients were followed up to the point of graft loss or death.
Statistical analysis was performed using R Software, foundation (Ross Ihaka and Robert Gentleman at the University of Auckland, New Zealand). Demographic characteristics were summarized with descriptive statistics (mean and standard deviation for continuous variables and frequency and percentages for categorical variables). The Friedman test, a nonparametric alternative to the one-way ANOVA with repeated measures, was performed to compare the serum creatinine on various time points. P < 0.05 was considered statistically significant.
| Results|| |
A total of 105 kidney transplant recipients including 81 men (77.14%) and 24 women (22.85%) were included in the analysis. The cause of deaths were road traffic accidents- 77grafts(73.35%), fall from height -18 grafts(17.14%), fall at home -2 grafts(1.9%), aneurysmal bleed -5 grafts (4.75%) and traumatic asphyxia -1 graft (0.9%). Three were expanded criteria deceased donors. Most of the grafts (56%) were from the right side. The mean duration of dialysis in our recipient group was 20.1 months with minimum of 1 month and maximum of 60 months on dialysis. Our center was the source of kidney in 41 deceased donor transplantations (39.04%).
Baseline demographics and clinical characteristics of the patients have been given in [Table 1] (n = 91).
Cold ischemic times
In our series, the mean cold ischemic time (CIT) was 8.01 (±2.73) h in deceased donor kidney transplantation. When graft was harvested from our center, the CIT was 3 h, and when the graft was harvested from other centers, CIT was 15 h. It was noted that there was no difference in graft function among groups with CIT <8 h and with CIT beyond 12 h.
Our transplantation protocol
We started using basiliximab from October 2010 and anti-thymocyte globulin rabbit origin (rATG) from October 2012 as induction agents. A single dose of 1.5 mg/kg of rATG was given as intravenous infusion in the preoperative and intraoperative period. Valganciclovir 450 mg twice daily is given for 3 months for cytomegalovirus prophylaxis if ATG is used. We also used interleukin -2 receptor blockers (basiliximab), given as two doses of 20 mg each. The first dose was given just before surgery followed by the second dose 4 days later.
The immunosuppression regimen mainly included cyclosporine/tacrolimus, mycophenolate mofetil/azathioprine, and prednisolone [Table 2].
Assessment of kidney function
The mean serum creatinine levels were 2.43 ± 2.07 mg/dL at the 1st week after transplant, 1.49 ± 1.05 mg/dL at the 1st month, and 1.24 ± 0.48 mg/dL at the 6th month after transplant [Figure 1]. Change in serum creatinine levels was statistically significant (P < 0.05).
|Figure 1: Mean serum creatinine levels at week 1, month 1, and month 6 after transplantation|
Click here to view
Graft function, rejection, and loss
Normal graft function was observed in 59 (56.19%) recipients followed by graft dysfunction in 17 recipients, out of which 9 became dialysis dependent. Delayed graft function (DGF) (requirement of hemodialysis within the 1st week of transplant) occurred in 16 (15.24%) recipients. Graft rejection was observed in 18 recipients (17.14%). Details of graft rejection have been shown in [Table 3].
One of the most common posttransplant medical complications was acute tubular necrosis (12.4%), followed by pneumonitis (5.71%), new-onset diabetes after transplant (5.71%), posttransplant erythrocytosis (4.8%), and sepsis (5.71%). The significant posttransplant complications and surgical complications have been summarized in [Table 4].
Kidney biopsy was done for 35 recipients (33.33%). The findings revealed early acute cellular rejection (ACR) – 8 (22%), late ACR – 4 (3.81%), ACR/acute humoral rejection – 2 (5.7%), antibody-mediated rejection (ABMR) − 2 (5.7%), ACR/chronic active ABMR – 2 (5.7%), acute tubular necrosis – 14 (40%), chronic allograft nephropathy/interstitial fibrosis and tubular atrophy – 5 (14.28%), calcineurin inhibitor toxicity – 2 (5.7%), hemolytic-uremic syndrome – 1 (2.8%), and cortical necrosis – 1 (2.85%).
Twenty-nine (27.6%) transplant recipients expired during follow-up. The median survival time after transplant was 23 months (n = 105). Since ours is a tertiary care center, patients were referred to us after long period of hemodialysis. The patients had lower standard of living accounting for increased incidence of sepsis which might have contributed to the low survival.
| Conclusions|| |
The survival rates of our 96 recipients who have completed minimum of 1 year of follow-up, shown in [Table 5] are as follows. The 1-year recipients' survival rate was 75% and 1-year graft survival rate was 89.58%.
Although the graft rejection rates (18%) were quite low in our center, the mortality rate was quite high (27.6%). The overall outcomes of deceased donor transplantation in our series are compared with other series, as shown in [Table 6] and [Table 7].
|Table 7: Comparison of graft outcomes with cold ischemic times in various series|
Click here to view
The occurrence of death in various time periods after transplant was <1 month: 5 patients (17.24%), 1 month–3 months: 7 patients (24.13%), 3 months–6 months: 6 patients (20.68%), 6 months–1 year: 6 patients (20.68%), and >1 year: 5 patients (17.24%). The majority of the deaths occurred within the early transplant period.
The cause of death of 29 recipients was sepsis in 22 recipients (75.86%), cardiovascular events in 5 recipients (17.24%), and graft artery thrombosis in 2 recipients (6.8%). Sepsis contributed to the majority of mortality. Since our patients were from lower socioeconomic status, they probably might not tolerated immunosuppresion. The use of induction agents could also have contributed to the increased incidence of sepsis leading to death.
| Discussion|| |
In a population cohort study from the Australia and New Zealand Dialysis and Transplant Registry, deceased donor transplantation was associated with an initial increase in mortality during the first 3 months posttransplantation was (hazard ratio [HR]: 2.0 [1.5–2.7], P = 0.001), which reduced below the dialysis group at 6 months (adjusted HR: 0.27 [0.16–0.47], P = 0.001). At 12 months, the reduction in mortality risk was nearly 80% (adjusted HR: 0.19 [0.15–0.24], P = 0.001). In a study involving 309 patients from a deceased donor kidney transplantation center of Mannheim, transplantation was associated with a lower HR (0.36, 95% confidence interval: 0.15–0.87) compared to the wait-listed group (1.00). The mortality rate was 0.026 per patient-year (0.032 on dialysis compared to 0.016 with functioning graft).
Few transplant centers in India have made significant contributions in the field of deceased donor kidney transplantation. In a retrospective analysis of 68 deceased donor kidney transplantation by Prabahar and Soundararajan, the 5-year patient and graft survival rates were 61.7% and 58.8%, respectively. In another retrospective study of 38 deceased donor kidney transplantation by Feroz et al., the graft survival rate was 85% and was associated with satisfactory patient and graft survival, despite the high incidence of DGF (68%).
Our series had comparable graft function with other series in India. Moyers et al. had reported a better graft outcome in spite of having higher CITs. This probably could be due to postoperative factors such as higher dose of immunosuppression given in western countries which our nephrologists here find it difficult to administer due to fear for infections. Most of these deaths in our series were caused by sepsis. It is possible that long duration of hemodialysis before transplant, extended criteria donor, increased DGF, triple immunosuppressive regimens with ATG induction, a delayed presentation leading to late diagnosis, tropical climate, and socioeconomic factors may have contributed to high infection rate leading to a higher 1-year posttransplantation mortality, with most of these deaths caused by sepsis.,,
As brought out by Samhan et al., the recipients of kidney allograft in developing countries may be more prone to infections, which are the most common cause of posttransplant mortality. It is necessary to take steps to minimize ischemia times and use of better perfusion techniques and optimize the dose of immunosuppressants as low as possible for better outcomes in deceased donor transplantation. Despite tremendous potential, a deceased donor kidney transplantation program has not been developed in many centers. We should also create more awareness and involve various community programs to increase the incidence of deceased donor transplantation.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Swami YK, Singh DV, Gupta SK, Pradhan AA, Rana YP, Harkar S, et al.
Deceased donor renal transplantation at army hospital research and referral: Our experience. Indian J Urol 2013;29:105-9.
] [Full text]
Feroz A, Dabhi M, Gumber M, Gupta S, Shah PR, Rizvi SJ, et al.
Cadaveric renal transplantation: Our experience at the institute of kidney diseases & research centre, institute of transplantation sciences, Ahmedabad. Transplant Proc 2007;39:721-2.
McDonald SP, Russ GR. Survival of recipients of deceased donor transplant kidney transplants compared with those receiving dialysis treatment in Australia and New Zealand, 1991-2001. Nephrol Dial Transpl 2002;17:2212-9.
Schnuelle P, Lorenz D, Trede M, Van Der Woude FJ. Impact of renal cadaveric transplantation on survival in end-stage renal failure: Evidence for reduced mortality risk compared with hemodialysis during long-term follow-up. J Am Soc Nephrol 1998;9:2135-41.
Prabahar MR, Soundararajan P. Cadaveric renal transplantation: The Chennai experience. Transplant Proc 2008;40:1104-7.
Tasaki M, Saito K, Nakagawa Y, Ikeda M, Imai N, Ito Y, et al
. 20-year analysis of kidney transplantation: A single center in Japan. Transplant Proc 2014;46:437-41.
Shroff S, Navin S, Abraham G, Rajan PS, Suresh S, Rao S, et al.
Cadaver organ donation and transplantation-an Indian perspective. Transplant Proc 2003;35:15-7.
Mani MK. Review article, development of cadaver kidney transplantation in India. Nephrology 2002;7:177-82.
Moers C, Smits JM, Maathuis MH, Treckmann J, van Gelder F, Napieralski BP, et al
. Machine perfusion or cold storage in deceased-donor kidney transplantation. N Engl J Med 2009;360:7-19.
Mehta TR, Shah VR, Butala BP, Parikh GP, Parikh BK, Vora KS, et al.
Intercity deceased donor renal transplantation: A single-center experience from a developing country. Saudi J Kidney Dis Transpl 2013;24:1280-4.
] [Full text]
Jha V, Chugh KS. Posttransplant infections in the tropical countries. Artif Organs 2002;26:770-7.
Jha V, Chugh S, Chugh KS. Infections in dialysis and transplant patients in tropical countries. Kidney Int 2000;57:S85-93.
Goldfarb-Rumyantzev A, Hurdle JF, Scandling J, Wang Z, Baird B, Barenbaum L, et al.
Duration of end-stage renal disease and kidney transplant outcome. Nephrol Dial Transplant 2005;20:167-75.
Samhan M, Al-Mousawi M, Hayati H, Dashti M, Mansour M, Johny KV, et al.
Results in 158 consecutive cadaveric renal transplantations. Transplant Proc 2005;37:2965-6.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]