Renal Retransplantation Research Articles

Kidney re-transplantation in the ipsilateral iliac fossa: a surgeon's perspective on perioperative outcome.

Compared with primary transplantation, ipsilateral renal re-transplantation is associated with an increased risk of surgical complications and inferior graft outcomes. This study investigates whether an ipsilateral re-transplantation approach per se is an independent risk factor for surgical complications and early graft loss. In this retrospective, single-centre analysis, surgical complications and early graft outcomes of ipsilateral kidney re-transplantations from January 2007 to December 2017 were compared with primary transplantations and contralateral re-transplantations. Univariate and multivariate binary logistic regression analyses were performed to identify risk factors for surgical complications requiring surgical revision and graft loss within the first year after transplantation. Of the 1489 kidney transplantations, 51 were ipsilateral, 159 were contralateral re-transplantations and 1279 were primary transplantations. Baseline characteristics did not differ between the ipsilateral and contralateral re-transplant recipients except for current and highest panel reactive antibody levels. Major complications requiring surgical revision were significantly more frequent in ipsilateral re-transplantations (P=.010) than in primary transplantations but did not differ between ipsilateral and contralateral re-transplantations (P=.217). Graft loss within the first year after transplant was 15.7% in the ipsilateral versus 8.8% in the contralateral re-transplant group (P=.163) versus 6.4% in the primary transplantation group (P=.009). In a multivariate regression model, ipsilateral re-transplantation was not identified as an independent risk factor for complications requiring surgical revision or first-year graft loss. Ipsilateral renal re-transplantation is not a risk factor for inferior outcomes. Graft implantation into a pre-transplanted iliac fossa is a feasible and valid therapeutic option.

P.169: Renal re-transplantation: An ideal treatment for primary allograft failure.

P.169: Renal re-transplantation: An ideal treatment for primary allograft failure.

Successful Deceased Donor Kidney Transplantation in a Highly Sensitized Patient after Reclassification of Unacceptable Antigens Based on HLA Epitope Analysis

For patients with end stage renal disease, kidney transplant offers significant survival and quality-of-life advantages compared with dialysis. But for patients seeking transplant who are highly sensitized, waiting times have traditionally been long and options limited. We present the case of a 34-year-old hypersensitized female who underwent renal retransplantation. Histocompatibility tests revealed a calculated panel-reactive antibody of 99.53% with multiple antibodies against class I and II human leucocyte antigens and an eplet analysis was performed. The donor’s potential unacceptable antigens were re-defined and the calculated panel-reactive antibody decreased to 88.38%. After one month the patient received a deceased-donor kidney transplant. Complement dependent cytotoxicity crossmatch was negative; virtual crossmatch and flow cytometry crossmatch with historical serum were positive. High-dose intravenous immunoglobulin and rituximab were added to the thymoglobulin-based induction immunosuppression. Three donor-specific antibodies were detected and plasmapheresis was performed. Renal allograft biopsy revealed no manifestations of rejection. Repeated testing observed a decrease in donor-specific antibodies median fluorescence intensity values. Four months post-transplant, the patient remained with normal graft function without proteinuria. She is receiving a standard maintenance immunosuppression regime with prednisolone, mycophenolate mofetil and tacrolimus. The careful discussion among the transplantation center and histocompatibility laboratory in association with intense immunosuppression and close laboratory monitoring allowed a successful human leukocyte antigen-incompatible deceased donor kidney transplantation in the most critical phase for the occurrence of humoral rejection. It is noteworthy that the new histocompatibility and immunogenetics methodologies provide a more affirmative and comprehensive assessment of mismatch acceptability.

Effect of Nephrectomy After Allograft Failure on Inflammation, Erythropoiesis, Donor-Specific Antibodies, and Outcome of Re-Transplantation

BackgroundMorbidity and mortality rates are high for patients returning to dialysis after renal graft failure. Keeping failed kidney transplants in situ with concomitant minimization or withdrawal of immunosuppression is standard of care in many transplant centers. It is unclear, however, whether the resulting allospecific immune response can cause a microinflammatory milieu. The present work investigated the impact of allograft nephrectomy on systemic inflammation, erythropoiesis, and donor-specific antibodies (DSA).Material/MethodsWe performed a retrospective analysis evaluating C-reactive protein (CRP), hemoglobin concentration (Hb), ferritin, iron substitution dosages, erythropoietin dosages, and DSA in 92 transplant recipients with allograft failure, of whom 49 did not (Group A) and 43 did undergo transplant nephrectomy (Group B). Blood samples and clinical data were obtained 3–6 months after returning to dialysis. We additionally assessed outcome of kidney re-transplantation in a 10-year follow-up.ResultsThere was no significant difference in Hb concentrations, ferritin concentrations, CRP concentrations, iron, and EPO substitution dosages between the 2 groups. Patients undergoing nephrectomy had a significantly higher prevalence of DSA (65.1% vs 38.8%, P<0.0001). In the 10-year follow-up, 3 patients (12%) of Group B and none in Group A had allograft failure after primary successful re-transplantation.ConclusionsKeeping a kidney graft in situ after returning to dialysis did not lead to an increase in microinflammation. Although DSA develops in more than 50% of patients after an allograft nephrectomy, the outcome of a renal re-transplantation seems to be unaffected. Thus, both strategies are feasible options in kidney transplant recipients after return to dialysis.

Alemtuzumab in Renal Retransplantation – Transplant Outcomes and Associated Infections

Renal retransplant patients have decreased graft survival compared with primary renal transplant patients. Alemtuzumab induction is often used at the time of retransplant; however, the literature surrounding alemtuzumab induction in renal retransplant patients is limited. In this single-center, retrospective, observational study, we aimed to determine the 1-year incidence of infections and transplant outcomes in renal retransplant patients who received alemtuzumab induction. Thirty-four patients who received alemtuzumab met inclusion criteria and were included in the final analysis. Twenty-two (64.7%) of these patients acquired infections. Of these, 7 patients (31.8%) acquired infections that resulted in hospitalization or intravenous antibiotics. The most common infections were urinary tract infections (n=10; 29.4%), cytomegalovirus DNAemia (n=7; 20.6%), and BK virus (n=6; 17.6%). The use of steroid maintenance therapy after alemtuzumab induction did not increase the number of infections compared with patients with a steroid-free interval after alemtuzumab induction. The number of patients who developed de novo donor-specific antibodies (DSA) was 11 (32.4%) with only 1 of these patients having DSA before retransplantation. The incidence of acute cellular rejection was 2.9% (n=1). There was no graft loss, and patient survival was 97% (n=33). There were no significant differences in infection rate or DSA development between alemtuzumab and the other induction agents, antithymocyte globulin and basiliximab, among retransplanted patients. Alemtuzumab induction in renal retransplant patients resulted in similar bacterial and viral infection rates as previously reported in the literature and did not negatively impact graft and patient survival.

Elevated Donor-Derived Cell-Free DNA (dd-cfDNA) Attributed to Angiotensin II Type 1 Receptor Antibodies (AT1R-Ab) in Renal Re-Transplantation

Elevated Donor-Derived Cell-Free DNA (dd-cfDNA) Attributed to Angiotensin II Type 1 Receptor Antibodies (AT1R-Ab) in Renal Re-Transplantation

Hematopoietic Mononuclear Cell Transplant with Minimal Gvhd in up to Completely Mismatched Unrelated Recipients

37 patients have been transplanted in a phase 2 protocol to establish chimerism to induce tolerance in up to 0 of 6 matched related and unrelated recipients of living donor renal allografts (KTx). The protocol is based upon tolerogenic CD8+/TCR- facilitating cells (FC) and nonmyeloablative conditioning. Recipients were conditioned with fludarabine (30mg/m2 days -5,-4,-3), cyclophosphamide (50mg/kg day-3 and+3), 200 cGy TBI (day-1) followed by KTx (day0). G-CSF mobilized peripheral blood mononuclear cells were apheresed from the donor &gt;2 weeks before kidney transplantation, processed to remove graft-versus-host disease (GVHD)-producing cells yet retain CD34 +cells and FC, and cryopreserved until transplantation on day+1 after kidney transplantation. Immunosuppression consisted of mycophenolate mofetil and tacrolimus. 36 patients have reached at least 1 year of follow up (range 12-105 months) and are the focus of this analysis. Patients ranged in age from 18-65 yrs. Enrollment was agnostic to degree of HLA match; 2 were 6/6 and 3 5/6 matched related using high resolution allele level typing, with the remainder 4/6 to 0/6 matched related (n=15) or unrelated (n=16) Two of the recipients were renal re-transplants. Tacrolimus/MMF immunosuppression (IS) was weaned and discontinued at 1 year if chimerism (&gt;50% whole blood and T cell), normal renal function and normal kidney transplant biopsy were noted. 34 of 36 subjects exhibited peripheral blood donor chimerism at one month post KTx. Durable chimerism allowing for full IS withdrawal developed in 26 (time off IS from 1- 88 months); the majority (23/26) showed &gt;95% donor whole blood/T cell chimerism. Three have exhibited stable-mixed chimerism ranging between 40% - 60%. Three patients failed to develop chimerism. Transient chimerism occurred in 8 patients. Durably chimeric patients retained chimerism after removal of IS, remain rejection-free without donor-specific antibody (DSA) and show immunocompetence to vaccinations. None have had to resume immunosuppression. Transiently chimeric subjects resumed endogenous hematopoiesis and are maintained on low-dose IS with stable renal function. There have been two cases of GVHD: one grade 2 lower GI acute GVHD that developed during conversion from tacrolimus to sirolimus that responded to steroids; this patient has developed moderate chronic GVHD of the skin. He is off IS. The second presented late following development of severe gastrointestinal symptoms and manifested treatment-resistant lower GI GVHD with associated tissue-invasive CMV colitis that proved fatal at 11 months post-Tx. There have been two additional kidney graft losses, both related to early infections. A second subject death occurred in a heavy (&gt;100 pack yr) smoker who developed advanced stage lung cancer 4.5 years after Tx. A third subject developed pneumococcal sepsis &gt; 4 years after transplant. He had not undergone the recommended pneumococcal vaccination post HSCT. Overall patient survival is 91.8% and death censored graft survival 94.1%. These rates compare favorably to treatment-related mortality rates after standard of care renal transplant. In summary, high levels of durable chimerism and tolerance with a low (5.5%) incidence of GVHD has been achieved in up to 0 of 6 matched related and unrelated recipients of FCR001 + kidney transplant. Figure Disclosures Ildstad: Talaris Therapeutics Inc: Employment, Equity Ownership, Other: Founder and CSO.

Double Obstruction Following Third Renal Transplant: A Case Report

As the field of transplant evolves and patients with chronic disease live longer, retransplant for end-stage renal disease becomes more common because kidney allografts have a limited lifespan. In renal retransplant, graft and patient survival is near equivalent to first-time transplant; however, these procedures present a unique surgical risk profile, especially third and subsequent transplants, which are reviewed in this manuscript. The risk of bowel obstruction in primary kidney transplant recipients is much lower than patients who have undergone laparotomy for second or third transplant because of the retroperitoneal location of the transplanted kidney. Internal hernia is an uncommon cause of small bowel obstruction, particularly after kidney transplant, and often diagnosis and intervention are delayed because of diagnostic uncertainty. We report a case of a 34-year-old man with acute kidney injury and bowel obstruction, whose final diagnosis was an internal hernia around the transplanted ureter of an intra-abdominally placed third renal transplant resulting in ureteric obstruction associated with small bowel obstruction—a case of double obstruction.

Long-Term Outcome of Kidney Retransplantation in Comparison With First Transplantation: A Propensity Score Matching Analysis

BackgroundAdvances in renal transplantation have improved graft survival. However, many patients experience graft failure due to chronic renal allograft nephropathy. Although renal retransplantation is increasingly performed, its outcome is controversial. The aim of this study was to evaluate outcomes of renal retransplantation compared with those of first renal transplantation. MethodsFrom March 1969 to August 2018, there were 3000 cases of renal transplantation performed at Seoul St. Mary’s Hospital, Korea. Because the number of third renal transplantation was too small, only first and second renal transplantation groups were compared using propensity score matching. Outcomes of the third renal transplantation were then added. Graft survival rates were determined using Kaplan-Meier survival curves and assessed for significance using log-rank test. ResultsFive- and 10-year patient-graft survival rates for the first renal transplantation were 82.6% and 72.8%, respectively. Those for the second renal transplantation were 78.4% and 73.9%, respectively (P = .588). Five- and 10-year patient survival rates were 91.2% and 85.1%, respectively, for the first renal transplantation. These were 87.8% and 85.5%, respectively, for the second renal transplantation (P = .684). Five- and 10-year death-censored graft survival rates were 88.8% and 80.6%, respectively, for the first renal transplantation. These were 84.6% and 80.5%, respectively, for the second renal transplantation (P = .564). ConclusionsThis study showed that graft survival of second renal transplantation was not significantly different from that of first renal transplantation. Therefore, renal retransplantation might be a reasonable option for patients who lost the first renal graft.

Clinical Prognosis of Renal Retransplant Patients: A Single-Center Experience

BackgroundRetransplantation is a treatment option in patients with end-stage renal failure due to graft loss. Outcomes of these patients due to high immunologic risk remain unclear. The aim of this study was to evaluate outcomes of renal retransplantation patients retrospectively. MethodsRenal retransplant patients in our unit were evaluated retrospectively between 2010 and 2018. Patients’ demographic characteristics, primary diseases, the causes of prior graft loss, immunologic status, desensitization protocols, the induction and maintenance treatments, the complications during the follow-up period, numbers of acute rejections, and the clinical prognosis were all detected from the patients’ files. ResultsWe retrospectively evaluated 17 patients who underwent a second or third renal allograft. Of these, 16 received a second and the remaining 1 patient received a third renal allograft. Immunologically, all of the 17 patients had negative flow cytometry crossmatch, 1 patient had a positive complement-dependent cytotoxicity crossmatch (Auto 12%), 16 patients had positive panel reactive antibody, the median HLA-mismatch was 3.5, and the score of donor-specific antibody relative intensity score (RIS) was 6.4 ± 6.3. Ten pretransplant patients had desensitization treatment. While scores for HLA-MM and HLA-RIS in the patients who had a desensitization therapy were determined higher, no statistical difference was observed (respectively, P = .28 and .55). No acute rejection episode developed. BK virus DNA viremia was detected in 4 patients during the posttransplant 6th month. We observed no patient death or no graft loss during the follow-up period. ConclusionAlthough the retransplant patients who had a graft loss previously have high immunologic risks, retransplantation is reliable in these patients, but they should be followed up carefully in terms of BKV nephropathy.

Evaluation of graft function in renal retransplantation at Hue Central Hospital

This study aims to assess the results of kidney retransplantations and the survival of second kidney allografts performed in our center. Methodology: of 550 kidney transplantations performed since July 2001, 26 were second kidney transplants. Many recipients were sensitized. All patients were treated with the same immunosuppressive regimen. Results: grafts were functionally effective in all patients with kidney retransplantations one month after the transplant. Graft survival was 100% after one year (17/17) and after five years (1/1). Graft survival was similar for second and primary kidney transplants performed during the same period of time. There were three cases of acute rejection, but all of these cases responded to the anti-rejection treatment. Conclusions: the rate of acute rejection was similar for both second and primary transplantations in our hospital, and the second graft outcome demonstrated effectiveness 12 months after transplantation.

Strategy and clinical outcome of deceased donor kidney transplantation for presensitized recipients

Objective: To explore the management strategy and clinical outcome of renal transplantation in presensitized recipients using deceased donor kidneys. Methods: From January 2011 to June 2018, twenty-one presensitized patients, including 8 with positive donor specific antibodies (DSA) and 13 with positive panel-reactive antibodies (PRA) but no DSA, received renal retransplantation from deceased donors in our center. The incidence of delayed graft function (DGF) and acute rejection (AR), changes of DSA, and the graft and patient survival were retrospectively analyzed. Results: None of the renal allografts had primary non-function (PNF) and DGF after transplantation. Four of the 13 recipients with PRA(+)/DSA-had a total of 5 episodes of acute cell-mediated rejection (CMR), while 5 of 8 recipients with pre-existing DSA(+) developed AR, including 3 cases with CMR alone and 2 cases with mixed AR. All episodes of rejection were successfully reversed after targeted treatment. Interestingly, of the 8 recipients with positive preformed DSA, 4 cases with positive DR-DSA and/or class Ⅰ-DSA had their DSA disappeared after transplantation, whereas DQ-DSA remained positive in 4 of 5 recipients. After a median follow-up of 26 months, all recipients maintained normal renal allograft function, and the survival rates of both graft and recipient were 100%. Conclusions: With the use of deceased donors, kidney transplantation can be successfully performed in presensitized patients by appropriate HLA-matching screening, choosing donor kidneys with good quality, and the combination of optimal perioperative treatment.

Impact of renal allograft nephrectomy on graft and patient survival following retransplantation: a systematic review and meta-analysis.

It is not clear whether renal allograft removal affects the outcome of renal retransplantation. This study aimed to determine the effect of allograft nephrectomy (AN) and no-AN (No AN) on renal retransplantation. A systematic review and meta-analysis were conducted using MEDLINE, Embase and the Cochrane Library. Observational studies or randomized controlled trials including renal retransplantation recipients with AN or No-AN were included. The primary outcomes were graft survival, patient survival, acute rejection (AR) and delayed graft dysfunction; the secondary outcomes were positive panel reactive antibody rate and serum creatinine level at 1 year after retransplantation, cold ischemia time and time of hemodialysis before recent transplantation. Pooled estimates of odds ratios (ORs) and the weighted mean difference for outcomes were calculated. A total of 13 studies divided into 20 trials including 1923 patients were analyzed. The No-AN group had a significantly higher 3-year graft survival rate {OR 0.48 [95% confidence interval (CI) 0.34-0.69], 10 studies, n = 1030} and 5-year graft survival rate [OR 0.65 (95% CI 0.44-0.97), 16 studies, n = 1878] than the AN group. The rates of 5-year patient survival [OR 1.82 (95% CI 1.14-2.90), 5 studies, n = 749], positive panel reactive antibody [OR 3.08 (95% CI 2.08-4.56), 12 studies, n = 1225], AR [OR 1.59 (95% CI 1.21-2.09), 15 studies, n = 1388] and delayed graft dysfunction [OR 1.66 (95% CI 1.20-2.03), 8 studies, n = 879] were all significantly higher in the AN group. Compared with the No-AN group, cold ischemia time was longer in the AN group [weighted mean difference 1.84 (95% CI 0.90-2.79), 7 studies, n = 919]. The rate of 1-year graft survival and 10-year graft survival, serum creatinine levels at 1 year after retransplantation and the time of hemodialysis before recent transplantation were similar between the AN and No-AN groups. We recommend allowing the failed graft to remain unless symptoms dictate the need for surgery. We also suggest donor-specific antibody dynamic monitoring and better human leukocyte antigen matching for improved long-term outcome of retransplantation.

Successful Renal Re-transplant in a Patient with Alport Syndrome: A Case Report

Successful Renal Re-transplant in a Patient with Alport Syndrome: A Case Report

REPEAT KIDNEY TRANSPLANTATION

Nowadays, kidney transplantation is the best approach of renal replacement therapy for the majority of patients with end-stage renal disease that significantly improves the quality and length of life. Advances in the field of organ donation, immunosuppression, transplant surgery and immunology have improved short-term graft and patient survival. But the long-term graft survival remains static over last two decades. The disparity between low graft and high patient long-term survival led to increasing number of transplant recipients with failed grafts. Repeat renal transplant is presumed to be a good option for many patients losing their grafts, but it is associated with higher complication rates. Unfortunately, there are no evidence-based recommendations or guidelines for renal retransplantation procedure. This review is based on 100 scientifi c publications related to various aspects of the kidney retransplantation and provides the recent data on this matter.

Successful renal retransplantation after graft loss from BK polyomavirus infection in a human immunodeficiency virus‐positive patient

We report the case of a human immunodeficiency virus-seropositive patient whose initial kidney transplant failed because of BK polyomavirus-induced nephropathy, and who underwent a second transplantation 3years later. BK viruria was detected 1day after transplantation. After 1month, BK viremia developed along with a donor-specific antibody. After decreasing tacrolimus and mycophenolic acid and 2 courses of intravenous immunoglobulins, BK viremia and donor-specific antibody permanently disappeared, with stable renal function.

A Novel Surgical Option for Urinary Tract Reconstruction in Third Renal Transplantation

A Novel Surgical Option for Urinary Tract Reconstruction in Third Renal Transplantation

Patterns of Early Rejection in Renal Retransplantation: A Single-Center Experience.

It has been reported that kidney retransplant patients had high rates of early acute rejection due to previous sensitization. In addition to the acute antibody-mediated rejection (ABMR) that has received widespread attention, the early acute T-cell-mediated rejection (TCMR) may be another important issue in renal retransplantation. In the current single-center retrospective study, we included 33 retransplant patients and 90 first transplant patients with similar protocols of induction and maintenance therapy. Analysis focused particularly on the incidence and patterns of early acute rejection episodes, as well as one-year graft and patient survival. Excellent short-term clinical outcomes were obtained in both groups, with one-year graft and patient survival rates of 93.9%/100% in the retransplant group and 92.2%/95.6% in the first transplant group. Impressively, with our strict immunological selection and desensitization criteria, the retransplant patients had a very low incidence of early acute ABMR (6.1%), which was similar to that in the first transplant patients (4.4%). However, a much higher rate of early acute TCMR was observed in the retransplant group than in the first transplant group (30.3% versus 5.6%, P < 0.001). Acute TCMR that develops early after retransplantation should be monitored in order to obtain better transplant outcomes.

Pre-Emptive Retransplantation in Patients With Chronic Kidney Graft Failure

IntroductionThe aim of this study was to compare the group of patients receiving a new kidney transplant before starting dialysis again (pre-reTR) with a group of patients receiving a new kidney transplant after restarting dialysis (reTR). MethodsThis retrospective cohort included all the kidney retransplantations (second transplantations) between 2000 and 2012 performed at our center and their follow-up until July 2014. We analysed graft and patient survival, rejection rates, and immunologic parameters of these patients. ResultsWe studied 18 patients who had pre-reTR and 83 who had reTR. In the pre-reTR group no patient had panel-reactive assay (PRA) >10% at any time. In the reTR group 26.5% had PRA >10% at the time of transplantation (P = .014) and 54.2% had a historical highest PRA >10% (P < .001). The rejection rate was 11.1% in the pre-reTR group and 27.7% in the reTR group during the first year post-retransplantation (P = .227). Patient survival rate was 100% in the pre-reTR group at 5 years of follow-up, whereas in the reTR group at 1 year it was 95.2% and 85.9% at 5 years after retransplantation. Allograft survival at 1 and 5 years was 88% and 89%, respectively, in the pre-reTR group. On the other hand, in the reTR group it was 89% after the first year and 65% at 5 years post-retransplantation. ConclusionPre-emptive renal retransplantation is a feasible option that should be assessed in patients with kidney graft failure and may help to minimize the morbidity associated with dialysis reinitiation.

Different risk factor profiles distinguish early-onset from late-onset BKV-replication.

Two of three reactivations of latent BKV-infection occur within the first 6months after renal transplantation. However, a clear differentiation between early-onset and late-onset BKV-replication is lacking. Here, we studied all kidney transplant recipients (KTRs) at our single transplant center between 2004 and 2012. A total of 103 of 862 KTRs were diagnosed with BK viremia (11.9%), among which 24 KTRs (2.8%) showed progression to BKV-associated nephropathy (BKVN). Sixty-seven KTRs with early-onset BKV-replication (65%) and 36 KTRs with late-onset BKV-replication (35%) were identified. A control group of 598 KTRs without BKV-replication was used for comparison. Lymphocyte-depleting induction, CMV-reactivation, and acute rejection increased the risk of early-onset BKV-replication (P<0.05). Presensitized KTRs undergoing renal retransplantation were those at increased risk of late-onset BKV-replication (P<0.05). Among KTRs with BK viremia, higher doses of mycophenolate increased the risk of progression to BKVN (P=0.004). KTRs with progression to BKVN showed inferior allograft function (P<0.05). KTRs with late-onset BK viremia were more likely not to recover to baseline creatinine after BKV-replication (P=0.018). Our data suggest different risk factors in the pathogenesis of early-onset and late-onset BKV-reactivation. While a more intensified immunosuppression is associated with early-onset BKV-replication, a chronic inflammatory state in presensitized KTRs may contribute to late-onset BKV-replication.