|Year : 2022 | Volume
| Issue : 3 | Page : 267-273
A comparative study of recipients' outcomes receiving a kidney from the same deceased donor: An observational study
A Ayyappa1, Manisha Sahay2, Kiran Mai Ismal3, P Sharmas Vali4, Samuel Raju Palli5, Swarnalata G6
1 Department of Nephrology, Alluri Sitarama Raju Academy of Medical Sciences, Andhra Pradesh, India
2 Department of Nephrology, Osmania Medical College and Hospital, Hyderabad, Telangana, India
3 Department of Nephrology, Osmania General Hospital, Hyderabad, Telangana, India
4 Department of Nephrology, Asian Institute of Nephrology and Urology, Hyderabad, Telangana, India
5 Department of Nephrology, Al Sharq Hospital, Fujairah, UAE
6 Nizam Institute of Medical Sciences, Hyderabad, Telangana, India
|Date of Submission||12-Jan-2022|
|Date of Acceptance||19-Sep-2022|
|Date of Web Publication||30-Sep-2022|
Dr. Manisha Sahay
Osmania Medical College, Hyderabad, Telangana
Source of Support: None, Conflict of Interest: None
Introduction: Kidney transplantation is the renal replacement therapy (RRT) of choice for patients with end-stage renal disease. Although outcomes of deceased-donor kidney transplantation are inferior when compared to live donor kidney transplantation, they are still significantly better than being on chronic dialysis. There are very few studies comparing transplant outcomes between two kidneys obtained from the same donor. Aims: The aim of this study is to compare the graft and patient outcome of the kidneys of the same deceased donor transplanted into two different recipients. Materials and Methods: This is a prospective observational study done at the tertiary care center in South India over 2 years. A total of 29 pairs of deceased-donor transplants were followed up with one-half performed at donor institute (Group 1) and the same number performed at another network hospital (Group 2). Outcomes between the recipients of the two kidneys were compared. Data were statistically analyzed. Results: The majority of donors were relatively young (with a mean age of 37 years) and did not have multiple comorbidities. 1st kidney went to the donor hospital, whereas 2nd kidney was sent to other hospitals in the network. Cold ischemia times were higher (10.3 h vs. 6.5 h) for the 2nd kidneys. The majority of Group 1 patients did not receive induction, whereas 100% of Group 2 patients received basiliximab induction. The incidence of acute rejection (antibody plus cellular rejection) was numerically less in Group 2 compared to Group 1 but was not found to be statistically significant (P = 0.227). The incidence of acute cellular rejection in Group 1 was more compared to Group 2, and was found to be statistically significant (P = −0.038). Graft survival was similar in both groups (95.7 in Group 1 vs. 95.8 in Group 2). Patient survival was similar in both groups (P = −0.555) with a mean follow-up 25.9 months in Group 1 versus 24.6 months in Group 2. The choice of induction agent did not affect the graft or patient survival. In addition, there was no significant difference in the incidence of infections or mortality rate. Conclusion: Overall, the outcomes in the paired kidneys from the same donor transplanted to different recipients at different institutes had similar outcomes. The choice of induction agent did not have any influence on the overall graft and patient survival.
Keywords: Allograft recipients, basiliximab, cold ischemia time, deceased-donor transplant, induction, outcome
|How to cite this article:|
Ayyappa A, Sahay M, Ismal KM, Vali P S, Palli SR, Swarnalata G. A comparative study of recipients' outcomes receiving a kidney from the same deceased donor: An observational study. Indian J Transplant 2022;16:267-73
|How to cite this URL:|
Ayyappa A, Sahay M, Ismal KM, Vali P S, Palli SR, Swarnalata G. A comparative study of recipients' outcomes receiving a kidney from the same deceased donor: An observational study. Indian J Transplant [serial online] 2022 [cited 2022 Dec 4];16:267-73. Available from: https://www.ijtonline.in/text.asp?2022/16/3/267/357616
| Introduction|| |
Kidney transplantation is the treatment of choice for patients with end-stage renal disease (ESRD), as a successful kidney transplant improves the quality of life and reduces the mortality risk for most patients when compared with maintenance dialysis. In India, there are a large number of ESRD patients waiting for renal transplants. The two sources of kidneys for clinical transplantation are living-related donors (LRDs) and deceased-donor organ donation after brain death, i.e. donation after brain death. In the context of renal transplantation, allografts from LRDs have superior graft function and survival compared with deceased-donor allografts. Graft and patient survival after kidney transplantation have improved over the past decade. Death-censored graft survival has increased steadily over the past decade in both adults and pediatric recipients. Patient and graft survival after renal transplantation varies based on the source of the allograft, patient age, and the presence and degree of the severity of comorbid conditions. Increased time on dialysis before renal transplantation is associated with decreased survival of transplant recipients. Rejections are an important cause of poor graft outcomes. Acute rejection episodes are considered a risk factor in the development of chronic rejection. Induction therapy is recommended for deceased-donor transplants; however, the cost of induction therapy is high. There is a paucity of data regarding the outcomes of transplant recipients receiving kidneys from the same deceased donor.
| Materials and Methods|| |
This is a prospective observational study of 58 consecutive deceased-donor renal transplants performed at a tertiary care hospital, to determine the factors that affect the graft and patient outcomes. Data were collected from the patients with ESRD who underwent deceased-donor renal transplantation at a tertiary care government hospital, for 2 years.
Of the 58 transplant recipients, 29 transplants which comprised Group 1 were performed at the donor hospital (in-center) from deceased donors, and the other 29 transplants which comprised Group 2 were performed at the network hospital from the same cadaveric donors. That is, from a single deceased donor. One kidney was received by donor hospital (in-center) and the other kidney was given to another tertiary care hospital meaning that donor characteristics were similar in both groups. Human leukocyte antigen matching and panel reactive antibodies could not be done due to logistic reasons. Crossmatch test was carried out by a complement-dependent lymphocytotoxicity test. The occurrence of acute graft rejection was confirmed histologically by core-needle biopsy during the first 12 months following transplant, episodes of infectious and noninfectious complications, and 12-month graft function, and patient/graft survival was compared between the two recipients of donor's kidneys.
All consecutive patients who underwent deceased-donor renal transplantation during the study period were included in the study.
ABO-incompatible transplants, recipients of living-related renal transplants, and those who were not willing to provide informed consent were excluded from the study.
Donor characteristics were noted. Cold ischemia times were recorded. Transplant details were recorded. All the recipients (n = 58), i.e. 29 in Group 1 and 29 in Group 2 were on triple immunosuppression with tacrolimus, mycophenolate, and prednisolone. In Group 1, induction therapy with rabbit anti thymocyte globulin (ATG) at a dose of 3 mg/kg body weight was given in six patients and the remaining 23 patients did not receive induction therapy in view of financial constraints. In Group 2, induction therapy with basiliximab, (20 mg, two doses at 0 and 4th day) was given to all 29 patients.
Following transplantation, all patients were kept on trimethoprim–sulfamethoxazole prophylaxis, one single strength tablet once a day for 1 year; Valganciclovir prophylaxis was given for 6 months in patients with the highest risk for cytomegalovirus (CMV) infection and disease, i.e. D+/R− patients and for 3 months in patients with high risk for CMV infection and disease, i.e. D−/R+ and prophylaxis with acyclovir 200 mg twice daily for 3 months in patients with very low risk for CMV infection, i.e. D−/R− patients.
All the patients received appropriate follow-up care as per the institute transplant protocol during the entire period of follow-up. Episodes of renal allograft dysfunction were defined either by an increase in serum creatinine concentration of 0.3 mg/dL or greater or rise in serum creatinine concentration >25% from the baseline or onset of oliguria and evidence of proteinuria of >1 g/day. For patients who presented with renal allograft dysfunction, the following investigations were done: ultrasound abdomen with Doppler to renal artery stenosis or thrombosis, perigraft collections and ureteric obstruction, blood and urine cultures, CMV, Ebstein Barr virus, BK virus DNA PCR, and tacrolimus trough levels to determine the blood tacrolimus concentration and to rule out calcineurin inhibitor (CNI) toxicity. Renal allograft biopsy to determine the cause of graft dysfunction.
Renal allograft biopsy samples were subjected to histopathological examination with light microscopy, immunofluorescence, and electron microscopy as needed. Immunohistochemistry for SV40 antigen, for the detection of BK virus nephropathy, was performed when clinically indicated. The acute cellular rejection (ACR) was treated with three doses of intravenous methylprednisolone (500 mg each), and antibody-mediated rejection was treated with plasmapheresis (one plasma volume removal per session over 5–8 sessions) and intravenous immunoglobulin (100 mg/kg/day over 5–10 doses). During each follow-up visit, the patient was assessed by history, physical examination, and routine laboratories including renal function tests, urine spot protein creatinine ratio, and complete blood picture. Other investigations such as chest X-ray, computed tomography scan, cultures, liver function tests, and bone marrow examination as and when required were performed depending on the clinical features. For all the patients, estimation of serum creatinine was done by enzymatic method, i.e. Jaffe kinase method. All patients had a minimum 12-month posttransplant follow-up. Immediate graft function was defined as nonrequirement of dialysis after transplantation; delayed graft function (DGF) as the need for dialytic support within a week of transplant.
Patient data were entered on an Excel spreadsheet and analyses were performed. The proportion of patients among Group 1 and Group 2 experiencing biopsy-proven acute rejection, infectious complication, and 1-year graft function, and patient/graft survival was analyzed using the Chi-square test. Continuous baseline variables, such as patient's and donor's age, and cold ischemia time were compared between the treatment groups using unpaired Student's t-tests. Results were reported as mean ± standard deviation when indicated and P < 0.05 was used for statistical significance.
Declaration of patient consent
The authors certify that patient consent has been taken for participation in the study and for publication of clinical details and images. Patients understand that their names and initials would not be published, and all standard protocols will be followed to conceal their identity.
The study was approved by the Institutional Ethics Committee (ECR 300/Inst/AP/2013/RR-19). Guidelines as per the Declaration of Helsinki were followed.
| Results|| |
The mean age of the donors was 37 ± 8.43 years. Head injury due to road traffic accidents was the most common cause of death and accounted for 93.1% (n = 27) cases; Stroke was the cause of death in 6.9% (n = 2) cases.
Inotropic support was given to most of the donors, 96.5% (n = 28) of cases. In 19 cases, dual vasopressor support was required and three cases required triple vasopressor support.
31.3% (n = 9) of donors experienced episodes of hypotension. The mean duration of intensive care unit stay was 1.2 days. Thus, donors were relatively young and did not have multiple comorbidities.
The baseline recipient characteristics were comparable in both groups [Table 1]. There was a significant difference in cold ischemia time (CIT) between the in-center and outbound kidneys. All recipients had a negative lymphocyte crossmatch and none were retransplanted.
The most common organism isolated was E. coli, followed by pseudomonas sps. All patients responded to treatment with antibiotics. Fungal infections were not different in the two groups, even in those with or without induction therapy. Incidence of CMV and response to treatment was comparable in the two groups and also in those with or without induction [Table 2].
The incidence of acute CNI toxicity in graft renal biopsy in Groups 1 and 2 were seen in 6.9% and 3.44% (n = 2), respectively, and it responded to optimization of tacrolimus dosage, there was no difference in dose of CNI in groups with and without induction. The incidence of chronic acute antibody-mediated rejection (ABMR) was 3.44% (n = 1). The incidence of chronic allograft nephropathy in Group 1 was 10.3% and in Group 2 was 3.44%, the cause of which was chronic ABMR in one case and unexplained in the remaining two cases. Chronic allograft dysfunction was higher in Group 1 (P = 0.300).
New-onset diabetes after transplantation (NODAT) was comparable in both groups.
Incidence of NODAT in Group 1 was 27.5% (n = 8), and in Group 2, it was 20.7% (n = 6).
The incidence of immediate posttransplant vascular complications was 6.9% (n = 2, of which one patient had graft renal arterial thrombosis and the other had graft renal vein thrombosis. Graft loss was seen in both cases. Clinically symptomatic perigraft collections in Groups 1 and 2 were similar and were seen in 6.9% (n = 2) of patients and were treated with percutaneous drainage, with betadine sclerosing done in one patient. One patient had urinoma and the other patient had lymphocele [Table 2].
Incidence of DGF in Group 1 and Group 2 patients was 27.5% (n = 8) and 31% (n = 9), respectively. The incidence of acute rejection overall in Group 1 was 17.2% (n = 5), among which ACR was seen in four cases and ABMR was present in one case. The incidence of acute rejection was less in Group 2 compared to Group 1 but was not found to be statistically significant (P = −0.227). However, the incidence of ACR in Group 1 was more compared to Group 2 and was found to be statistically significant (P = −0.038) [Table 3].
|Table 3: Incidence of delayed graft function and acute rejection in Group 1 and Group 2|
Click here to view
There was no difference between surgical or vascular complications in the two groups [Table 4].
Death-censored graft survival at 1 year in Group 1 without (n = 23) and with ATG induction (n = 6) was 94.7% (n = 18) and 100% (n = 4) respectively and in Group 2 it was 95.8% (n = 23). Overall death-censored graft survival at 1 year in Group 1 was 95.6%. Graft survival was similar in both groups (P = 0.753).
Patient survival at 1 year in Group 1 without ATG induction (n = 23) and with ATG induction (n = 6) was 82.6% (n = 19) and 83.3% (n = 4), respectively, the most common cause of death was sepsis, which was seen in five cases and sudden cardiac arrest in one case. Patient survival was similar in both groups (P = −0.555) [Table 5].
In summary, transplantation in-center versus network hospital kidneys did not affect graft or patient survival.
| Discussion|| |
This study was designed to compare the graft and patient outcomes of in-center (Group 1) versus other center (Group 2) allograft recipients of paired kidneys from the same deceased donor.
Fifty-eight patients were involved in the study, Group 1 with 29 patients (of which six patients received induction with ATG and in the remaining 23 patients induction was not given) and Group 2 which included 29 patients, all of them received induction with basiliximab. There were no significant differences in patient demographic characteristics between the two groups with respect to age, dialysis vintage, diabetes, hypertension, mode of dialysis, cause of ESRD and CMV seropositivity status. No patients were positive for hepatitis C and hepatitis B virus infection.
In our study, the mean CIT in in-center patients was lower than in patients from other network hospitals (6.5 h vs. 10.3 h). A similar study done by Giessing et al. compared transplant recipients of 1st retrieved kidney versus 2nd retrieved kidney with a higher CIT in kidneys retrieved 2nd (8.3 h vs. 14.3 h). The mean CIT in Ahsan et al.'s study was 8.0 h and in Gopalakrishnan et al.'s study, it was 4.1 h. The mean CIT in our study was lower compared to Debout et al. (20.6 h). The maximum CIT in Debout et al.'s study in 2014 was 42 h and the risk of graft failure was 4% at 1 year for CIT <16 h, versus 5%, respectively, for CIT between 16 and 36 h. The risk of graft failure was higher when CIT was longer than 36 h, i.e. 8% at 1 year. Hence, the deceased-donor transplant program allocation system should focus on attaining low CIT and kidneys should be transported to far-off places only if mandatory. In our study, although CIT in outbound kidneys was more versus in-center kidneys, it was in the acceptable range, i.e. <16 h.
Chronic allograft dysfunction was found in 13% (n = 3) of recipients in Group 1 without induction and in 3.44% (n = 1) of recipients in Group 2, respectively. The mean follow-up of recipients in both these groups was similar (25.9 months vs. 24.6 months) and the difference in chronic allograft dysfunction incidence could be probably due to the lower incidence of acute rejection in Group 2 patients. Chronic allograft dysfunction was not found in Group 1 patients who have received induction. In Giessing et al.'s study, there was no difference in 1st or 2nd kidneys in the incidence of chronic graft dysfunction.
The incidence of DGF in Group 1 and Group 2 was similar although CIT was more in Group 2. Thus, CIT up to 16 h does not impact DGF. Similar results were reported by Giessing et al. DGF in patients without induction was 27.6% in our study, which was higher compared to 20% in Ahsan et al.'s study and 10.3% of cases in Willoughby et al.'s study. A similar incidence of DGF was also reported by Gopalakrishnan et al., with 24.2%. The incidence of DGF in patients with induction was 31% in our study which was lower compared to the study by Gopalakrishnan et al. (67.6%) and was higher compared to 24% of cases in Ahsan et al.'s study and 12.2% of cases in the Willoughby et al.'s study. The mean cold ischemic time and mean donor age were comparable with other studies, but the incidence of expanded criteria donors was higher in our study compared to Ahsan et al. and Willoughby et al. The higher percentage of expanded criteria donors could be the reason for the higher incidence of DGF in our study.
The rejection was more in Group 1 in those without induction while Group 1 with induction and Group 2 had comparable rejection rates. In patients without induction therapy, the incidence of acute rejection was found in 21.7% of patients in our study, which was slightly higher compared to acute rejection episodes in Ahsan et al.'s study group (16% in those without induction) and Gopalakrishnan et al. with 15.2%. Acute rejection was significantly higher compared to acute rejection episodes in Willoughby et al.'s, and Tanriover et al.'s studies with i.e., 13%, and 12.4%, respectively., One possible reason for the higher incidence of acute rejection episodes in our study might be due to the higher incidence of DGF in our study compared to other studies and also the study population is small compared to Willoughby et al., and Tanriover et al. Patient survival at 1 year was found to be 82.6% in our study, which was lower compared to patient survival rates with other studies. Patient survival rates at 1 year in Ahsan et al.'s, Willoughby et al.'s, and Tanriover et al.'s studies were 98%, 97.5%, and 98%, respectively. Death-censored graft survival at 1 year in Group 1 without induction was 94.7% which was comparable with other studies. Graft survival rates at 1 year in Ahsan et al.'s, Willoughby et al.'s, and Tanriover et al.'s studies were 94%, 95%, and 96%, respectively.,
In patients with basiliximab induction, the incidence of acute rejection was found in 6.9% of patients in our study, which was comparable to acute rejection episodes in the Ahsan et al.'s study group; and was lower compared to acute rejection episodes in Willoughby et al.'s, and Tanriover et al.'s studies with 11%, and 11.7%, respectively.
Patient and graft survival were comparable between Group 1 and Group 2. In recipients who were given induction with basiliximab, patient survival at 1 year was found to be 82.8% in our study, which was lower compared to patient survival rates with other studies. Patient survival rates at 1 year in Ahsan et al.'s, Willoughby et al.'s, and Tanriover et al.'s studies were 100%, 98%, and 98%, respectively. Death-censored graft survival at 1 year was found to be 95.8% in our study, which was comparable with other studies. Graft survival rates at 1 year in Ahsan et al.'s, Willoughby et al.'s, and Tanriover et al.'s studies were 100%, 94%, and 95%, respectively.,
In patients with ATG induction, the incidence of acute rejection was found in 6.9% of patients in our study, which was comparable to acute rejection episodes in the Ahsan et al.'s study group and was lower compared to acute rejection episodes in Willoughby et al.'s, and Tanriover et al.'s studies with 11.6%, and 11.7%, respectively.
Patient and graft survival were comparable irrespective of the difference in CIT in Group 1 and Group 2. In recipients who have given induction with ATG, patient survival at 1 year was found to be 83.3% in our study, which was lower compared to patient survival rates with other studies. 97% in the Willoughby et al.'s study and 98% in the Tanriover et al.'s study.
Patient survival rates at 1 year were higher compared to Mani with 72% survival [Table 6]. Patient survival rates at 1 year in our study were comparable to other studies of Indian origin.,,,,
Death-censored graft survival at 1 year was found to be 95.7% in our study, which was comparable with other studies. Graft survival rates at 1 year in Willoughby et al.'s and Tanriover et al.'s studies were 95% and 95%, respectively. Thus, most of the graft loss was due to patient death with functioning grafts due to infection. Death-censored graft survival rates at 1 year in our study were higher compared to Mani (72%) and Prabhakar et al. (73%). Patient and graft survival in patients with ATG and IL-2R antagonists in our study was similar to Kim et al.'s study. Patient and graft survival rates in ABO-incompatible transplantation are 96.8% and 94.1%, respectively.
Bacterial, fungal, and viral infections were comparable in Group 1 and Group 2 in our study. Thus, the difference in CIT does not impact infections. Overall bacterial infections were comparable to Gopalakrishnan et al.'s study. CMV infection in the induction group was comparable to that in Ahsan et al.'s study in the induction group, whereas fungal infections in our study were higher compared to Ahsan et al.'s study. Fungal infections in the noninduction group were comparable to Gopalakrishnan et al. However, fungal infections in the induction group were higher compared to Gopalakrishnan et al.
The incidence of CMV infection in Group 1 was 18.7% (n = 3), and all three cases were seen in patients who have not received valganciclovir prophylaxis.
One drawback of our study is the relatively small cohort size. A higher number of patients are needed to make firm conclusions. Furthermore, individual surgical skills of different surgeons, immunosuppressive therapy strategies, and changes in peri- and postoperative management may influence the outcome.
| Conclusion|| |
In summary, the patient and allograft survival is comparable between paired kidneys from the same deceased donor irrespective of where the transplant was performed and slightly longer CIT. Secondary outcomes such as rates of infection, fungal infection, CMV reactivation, and NODAT were similar as well. There was a numerically lower incidence of immunological complications in the network hospital where basiliximab was used compared to our institute where the majority of patients did not receive any induction. The results of this study prove transplant outcomes are comparable between in-center versus other hospital transplant recipients from the same deceased donors provided CIT is reasonable.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]