|Year : 2021 | Volume
| Issue : 3 | Page : 130-137
Long-term outcome of kidney retransplants with different donor sources
Osama A Gheith1, Ayman Maher Nagib1, Medhat A Halim2, Suzann Rida2, Tarek Mahmoud2, Prasad Nair2, Torki Alotaibi2
1 Nephrology Department, Hamed Al-Essa Organ Transplant Center, Ibn Sina Hospital, Sabah Area; Department of Dialysis and Transplantation, The Urology and Nephrology Center, Mansoura University, Egypt, Kuwait
2 Nephrology Department, Hamed Al-Essa Organ Transplant Center, Ibn Sina Hospital, Sabah Area, Kuwait
|Date of Submission||06-Feb-2021|
|Date of Acceptance||15-May-2021|
|Date of Web Publication||09-Aug-2021|
Dr. Osama A Gheith
Department of Dialysis and Transplantation, The Urology and Nephrology Center, Mansoura University, Egypt; Working in Hamed Al-Essa Organ Transplant Center, Kuwait; P. O. Box 25427, Safat (13115)
Source of Support: None, Conflict of Interest: None
Background It has been reported that the long-term survival of second transplants may be similar to that of primary transplants. Reports of retransplantation outcomes are scarce, especially in the middle east region. We aimed to present our experience with second renal transplant in Kuwait and compare the donor source among our retransplant recipients.
Patients and methods Data of kidney retransplants, under follow-up at the Hamed Al-essa Organ Transplant Center of Kuwait, between 1980 and 2019 were retrospectively analyzed. Out of 3038 kidney transplants, 198 (6.51%) were kidney retransplants. The number of kidney transplants from living donors was 150; from deceased donors, 48 and third transplants represented 15 cases. We compared living donor group 1 with deceased donor group 2 in terms of demographics, posttransplant complications and outcome.
Results We observed that episodes of acute antibody-mediated rejection (nine cases, 18.7%, in group 1 vs. eight cases, 16.6%, in group 2, respectively) and T-cell-mediated rejection (14 cases, 9.33%, in group 1 vs.15 cases, 10%, in group 2, respectively) were more frequent among patients in group 2, but this did not reach statistical significance. In terms of the second graft outcome, we observed that the percentage of patients with failed grafts was higher among group 2 patients, but this did not reach statistical significance during their last follow-up, while the two groups were comparable in terms of patient outcome.
Conclusion Both living donor and cadaveric renal allotransplants carry the same risk for graft rejection, either AMR or ACR. Meanwhile retransplants who received their kidneys from either living or deceased donors had experienced similar graft and patients’ outcomes. Therefore, retransplant either from living or deceased donor is considered a good option after first renal allograft loss.
Keywords: kidney donors, kidney re-transplants, outcome
|How to cite this article:|
Gheith OA, Nagib AM, Halim MA, Rida S, Mahmoud T, Nair P, Alotaibi T. Long-term outcome of kidney retransplants with different donor sources. J Egypt Soc Nephrol Transplant 2021;21:130-7
|How to cite this URL:|
Gheith OA, Nagib AM, Halim MA, Rida S, Mahmoud T, Nair P, Alotaibi T. Long-term outcome of kidney retransplants with different donor sources. J Egypt Soc Nephrol Transplant [serial online] 2021 [cited 2021 Oct 17];21:130-7. Available from: http://www.jesnt.eg.net/text.asp?2021/21/3/130/323529
| Introduction|| |
Despite improving graft outcomes over the years, patients with kidney graft loss have a chance of retransplantation, which often provides the best chance for survival, better quality of life, and good health . Up to 24% of the kidney transplants are lost because of chronic rejection during the first 5 years posttransplant . Therefore, renal allograft failure has become one of the most common causes of end-stage kidney disease (ESKD), representing 25–30% of patients waiting for renal transplantation . The rate of renal retransplant has increased from 7.1% for living donors and from 9.7% in deceased donors in 2007 up to 11.8% in 2011, to 14.5% in 2014, and to 15% in 2015, with greater immunologic risk than first-time kidney recipients. The outcomes of retransplant are strongly dependent on many factors, especially the source of donor (living vs. deceased donor).
Kidney retransplant is commonly associated with higher immunological risk than first kidney transplant . The United Nations Organ Sharing (UNOS) registry reported 1- and 5-year survival rates of 91 and 70%, respectively, for first kidney transplants versus 88 and 65% for repeated kidney transplants . However, graft survival rates of kidney retransplants have improved considerably ,. Moreover, it has been reported that the long-term survival of second transplants may be similar to that of primary transplants . Also, the cost-effectiveness of transplantation for ESKD patients showed benefits over dialysis even for second transplant patients ,. The improvement in patient care and immunosuppressant medications has resulted in an improvement in graft survival in the early posttransplant period; however, there is a marked graft loss afterward . Not surprisingly, nearly 40% of all patients lose their grafts within 10 years , and the number of patients returning to dialysis with a failed allograft has increased every year. In the United States, more than 5500 patients returned to dialysis after transplant failure in 2010 .
To our knowledge, no controlled trial has been conducted as yet to study the outcome of patients suffering graft failure. Most of the scarce reports on this issue were retrospective, single-center reviews; therefore, registry reports are of major importance . Gill et al.  analyzed the United States Renal Data System (USRDS) data in patients who were started on dialysis from 1995 to 2003 and were subsequently placed on kidney transplant waitlists. The authors studied death rates in diabetic and nondiabetic patients during waiting time on transplant waitlists (89 000 patients), during the time after transplant (stable phase; 47 433 patients) and during the second dialysis period after graft failure (5461 patients) over a 3-year period. Death rates were determined at 3-month intervals during the stable phase and over 2-week intervals during transitions for a period of 3 months. When the three study periods were compared, the lowest death rate was found during transplant function, whereas the highest mortality was noted during the second dialysis period after allograft failure .
Reports of retransplantation outcomes are also scarce, especially in the middle east (MENA) region.
| Aim|| |
We aimed to assess the outcome of the renal retransplants in Kuwait with different donor sources.
| Patients and methods|| |
Data of kidney retransplant recipients, who were followed up at the Hamed Al-Essa Organ Transplant Center of Kuwait, at our hospital between 1980 and 2019 were retrospectively analyzed. Of 3038 kidney transplant, 198 (6.51%) were retransplants. Hundred and fifty were from living (50% related and 50% unrelated) donors, while 48 were from deceased donors, and 15 cases represented third transplants. Emotionally unrelated donors were accepted only after the exclusion of first-degree related donors due to medical causes. All the unrelated donors were evaluated by repeated interviews through the ethical committee of the ministry of health in Kuwait to be sure they were economically stable and be sure that altruistic factors are not there.
According to the donor source, we categorized this cohort into two groups of patients: those with living donors represented group 1 and those from deceased donors represented group 2. Most of the recipients from unrelated donors received their grafts outside Kuwait (48 cases out of 75).
The following recipient variables were assessed: recipient age at transplant, sex, cause of ESKD, and number of human leukocyte antigen (HLA) mismatches. Donor variables included donor age at donation and sex. Transplantation variables included type of induction therapy, immediate posttransplant graft function, and initial immunosuppressive regimen. Also, pretransplant comorbidities were assessed. Graft loss was defined as a return to dialysis or graft removal. Baseline characteristics were described as mean value±SD. Posttransplant complications were reported, with a special focus on immunological aspects (acute rejection episodes) and nonimmunological complications such as posttransplant diabetes, viral infections, and infections necessitating hospitalization. Patient survival and graft survival rates at 1, 5, and 10 years were evaluated using the Kaplan–Meier method.
Our immunosuppression protocol consisted of five doses of antithymocyte globulin (Sanofi US, Bridgewater, New Jersey, USA) for high-risk patients (patients with retransplants, previous pregnancies, blood transfusion, HLA-antibody positive, and/or more than four HLA mismatches) or two doses of interleukin-2 receptor blocker (basiliximab; Novartis Inc., Basel, Switzerland) for thymoglobulin allergic patients. Maintenance therapy consisted of prednisolone, mycophenolate mofetil (MMF), and a calcineurin inhibitor. The dose of calcineurin inhibitor was gradually decreased until the lowest dose by the end of year 1 was guided by the 12-h trough level. We maintained the cyclosporine levels between 200 and 250 ng/ml during month 1, then between 150 and 200 ng/ml for 6 months, and then from 75 to 125 ng/ml until the end of year 1. Similarly, we maintained tacrolimus trough levels between 8 and 10 ng/ml during the first 3 months and then from 5 to 8 ng/ml thereafter. Maintenance immunosuppression with a sirolimus-based regimen was used for rejection-free patients with low immunologic risk 3 months after transplant. All patients were administered cytomegalovirus (CMV) and pulmonary pneumocystis jiroveci (PCP) prophylaxis for 6 months at an adjusted dose according to estimated glomerular filtration rate.
All patients were followed twice per week during the first month, weekly for another month, every 2 weeks for the third month and then gradual spacing till it become monthly after the sixth month till the end of the first year posttransplant. On every visit, complete blood counts, fasting blood sugar, and renal and liver function tests were routinely monitored and other tests like ECG and ultrasound Doppler studies were performed when required.
Diagnosis and treatment of rejection
T-cell-mediated rejection was treated with intravenous methylprednisolone sodium succinate (1 g/d for 3 days) and/or thymoglobulin (1 mg/kg for 7–10 days) for steroid-resistant rejection. Acute antibody-mediated rejection was treated with plasma exchange (10 sessions), intravenous immunoglobulin G (2 g/kg), and a single dose of rituximab (375 mg/m2). All rejection episodes were biopsy proven according to Banff criteria 2018. Patients who received thymoglobulin as antirejection were treated with a secondary prophylaxis against CMV and PCP for 1 month, whereas those who developed viremia during this period were administered a therapeutic dose for 3 weeks, followed by prophylaxis for 3 months.
Ethics approval and consent to participate: this study was approved by the Research Ethics Committee of the Ministry of Health of Kuwait on 30.3.2021; reference number of approval: 1655/2021. All patients included in this research provided written informed consent to publish the data of this study.
Availability of data and materials: the datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Statistical analyses were carried out using SPSS software (SPSS: an IBM Company, version 25.0; IBM Corporation, Armonk, New York, USA). Variables and means were compared using an independent-sample t test, χ2 test, Fisher exact test, and analyses of variance as appropriate. Results are expressed as means±SD, and differences were considered significant at P value less than or equal to 0.05. Graft and patient survival rates were summarized using Kaplan–Meier curves and tested for significance using the two-sided log-rank test.
| Results|| |
Of the 3038 kidney transplant patients who were followed in our center, 198 (6.51%) renal transplants were second transplants. Of the 198 recipients, 103 were males and 95 were females, with a significantly higher mean age in group 1 (37.5±13.3 vs. 31.8±14.7, [Table 1], P=0.019).
The main identified original kidney disease in the two groups was chronic glomerulonephritis (20.7% in group 1 vs. 18.8% in group 2). Other causes were comparable in the two groups ([Table 1], P>0.05). The percentage of Kuwaiti patients in group 2 was significantly higher, while the percentage of non-Kuwaiti patients in group 1 was significantly higher (P=0.005). The mean HLA (HLA-A, B, DR) mismatches were significantly higher in group 2 compared with group 1 (1.4±0.61, 1.45±0.65, and 1.28±0.68 in group 2 vs. 0.92±0.72, 1.06±0.71, and 0.84±0.64 in group 1, respectively, P<0.05). Posttransplant graft function was evaluated and we observed that the percentage of patients with immediate graft function was significantly more prevalent in group 1, while the percentage of patients with delayed graft function (DGF) was significantly more prevalent in group 2 ([Table 1], P<0.001).
As for induction therapy, we observed that the percentage of patients who received lymphocyte-depleting agents was significantly higher in group 2 (P=0.006), but there were no significant differences between the two groups in the use of less potent induction therapy or the type of maintenance immunosuppression ([Table 1], P>0.05).
Although the percentage of patients who developed posttransplant diabetes was higher in group 1 (38 cases, 25.7% vs. seven cases, 15.9% in group 2), this did not reach statistical significance (P=0.18). Patients who had BK viremia, BK virus (BKV) nephropathy or recurrent urinary tract infection were comparable in both groups ([Table 2], P>0.05). However, we found that the percentage of patients who had CMV viremia was significantly higher among the cadaver donor group (21.3% in group 1 vs. 38.8% in group 2, [Table 2], P=0.049).
|Table 2 Posttransplant complications and outcome of the studied patients|
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In terms of the prevalence of rejection episodes ([Table 2]), we observed that episodes of acute antibody-mediated rejection (nine cases, 18.7%, in group 1 vs. eight cases, 16.6%, in group 2) and T-cell mediated rejection (14 cases, 9.33%, in group 1 vs. 15 cases, 10%, in group 2) were more frequent among patients in group 2, but this did not reach significance.
In terms of the second graft outcome, we observed that the percentage of patients with failed grafts was higher in group 2, but this did not reach statistical significance during their last follow-up, while the two groups were comparable in terms of patient outcomes ([Table 2] and [Figure 1] and [Figure 2]).
| Discussion|| |
Kidney retransplant is a high-risk procedure that is increasingly being performed because of previous graft failure. Developments in immunosuppressive protocols and in the medical care of transplant recipients have improved the early outcomes of kidney transplantation . However, long-term survival has not shown significant improvement, and grafts continue to fail ,. Upon transplant loss, the patients return to the dialysis program and some are relisted for second transplant.
Because of the organ donor shortage, retransplant outcomes provide useful information for allocation policies. It is important to show that the procedure is beneficial. Most reports on retransplantation are from transplant centers in Europe and the United States, which may not represent retransplant outcomes in our communities in the MENA region. We aimed to present our experience with renal retransplants in Kuwait.
The prevalence of retransplants in our cohort (198, 6.51%) was lower than that reported from the Organ Procurement and Transplantation Network, which accounted for 15.3% of the overall waiting list . However, our record was higher than that reported from Thailand  or from India ; only 3.03 and 3.5%, respectively, of their patients underwent transplant more than once . The difference in the prevalence of kidney retransplants in different countries might be related to a difference in the level of health services provided to such specialized patients and the difference in the medical awareness that cases with chronic graft failure can receive a second or 3rd transplant.
In terms of retransplants with different donor sources, chronic glomerulonephritis represented the main identified original kidney disease in the two studied groups (20.7% in group 1 vs. 18.8% in group 2, respectively). This finding was in agreement with that reported in Thailand , India , and USA , where chronic glomerulonephritis was the main cause of ESKD (around 30%) among their retransplant recipients.
The percentage of Kuwaiti patients in group 2 (deceased donor group) was significantly higher (P=0.005), which could be explained by the worldwide policy adopted that prioritizes organs from deceased donors to patients of the same nationality. However, the percentage of non-Kuwaiti patients in group 1 was significantly higher (P=0.005).
Trebern-Launay et al.  reported that second transplant recipients received better HLA-matched transplants compared with the first transplant recipients (P=0.0001) and they were more frequently exposed to induction therapy with a lymphocyte-depleting agent (P=0.0001). In our cohort, the mean HLA (HLA-A, B, DR) mismatches were significantly higher in group 2 ([Table 1], P<0.05). This was associated with a significantly higher percentage of patients who received lymphocyte-depleting agents (our local policy of use in this group of patients) in the cadaver donor group (P=0.006). However, we found no significant difference between the two groups in the use of less potent induction therapies or maintenance immunosuppression ([Table 1], P>0.05).
We observed significantly better immediate posttransplant graft function in patients of group 1. Conversely, the percentage of patients with DGF was significantly higher in group 2 (31%) ([Table 1], P<0.001). This observation was is in agreement with the percentage of DGF (31 cases, 26.7%) among second transplant recipients reported by Ingsathit et al. , who stated that it was comparable to their first transplant DGF.
In our study, we found a higher prevalence of posttransplant diabetes mellitus among our retransplant recipients, especially in group 1 (22.7%,) compared with that reported in another study from Korea by Yeoa and colleagues, who showed that 13 (12.4%) out of 105 recipients were diagnosed as having posttransplant diabetes mellitus. This could be attributed to ethnic and lifestyle diabetogenic factors in our group of patients.
The percentage of patients who developed CMV viremia, 49/198 (24.7%), was higher than that reported by Yeoa et al.  in their study in 15 (14.2%) out of 105 recipients. This finding could be explained by the stronger immunosuppression used among our patients, especially in group 2, with significantly more prevalent CMV (38.8% in group 2 vs. 21.3% in group 1, [Table 2], P=0.049). We did not find a significant difference between the two groups in other infections such as BK viremia, BKV nephropathy, and recurrent urinary tract infection ([Table 2], P>0.05).
In terms of the prevalence of rejection episodes, we observed that the prevalence of both acute antibody-mediated rejection and T-cell-mediated rejection (16.6 and 18.7% in group 2 vs. 9.33 and 10% in group 1, respectively) was more frequent among patients in group 2, but this did not reach significance (P>0.05). The percentage of patients who developed acute rejection episodes was 21.33% in group 1 and 35.3% in group 2, which was higher than that reported by Trebern-Launay et al. , who reported cumulative probabilities of acute rejection episodes at 1, 3, and 12 months of 10, 13, and 19%, respectively, for second renal transplants. This finding could be related to the significantly higher HLA-AB-DR mismatches and higher percentage of DGF in the patients in group 2 (P<0.05) despite the significantly more potent induction therapy used in the same group.
The benefit of patients undergoing kidney retransplantation remains unclear. Some studies ,, have reported inferior outcomes, while other authors have reported acceptable results ,,. In our cohort, we observed that the percentage of patients with failed grafts was higher in group 2, but this did not reach statistical significance till their last follow-up, while the two groups were comparable in terms of patient outcomes (P>0.05). Patient survival rates, with a 95% confidence interval, at 1, 5, and 10 years were 100, 95.9, and 92%, while graft survival rates were 93.8, 80.9, and 69.4, respectively. This observation was is in agreement with the second transplant outcome reported by Yeoa et al. , who reported similar survival rates (patient survival rates at 1, 5, and 10 years were 100, 97.2, and 90.7% and graft survival rates were 97.0, 94.6, and 71.5%, respectively). Moreover, the rates were higher than those reported by Ingsathit et al.  and Coupel et al. , who reported lower survival rates.
| Conclusion|| |
Long-term outcomes of renal retransplant recipients, with different donor sources, have acceptable graft and patient survival, but will need optimized immunosuppressive regimens. Retransplant either from a living or a deceased donor is considered a good option after first renal allograft loss.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2]