Factors related to success or failure of second renal transplants.

From January 1, 1968 to December 31, 1973, 50 patients received two or more kidney transplants. Patient and graft survival was highly dependent upon the source of the donor and to a lesser extent the functional duration of the first transplant and the elapsed time between first and second graft. Survival (patient and graft) was best in patients receiving two related grafts and worst in patients receiving two sequential cadaver grafts. Intermediate rates of success followed cadaver transplantation after rejection of a related graft. The highest failure rate was encountered when those patients who sustained an early loss of the first cadaver graft received a subsequent cadaver graft within a few months. We recommended removal of the acutely rejected graft and delay prior to retransplantation of patients who rapidly reject cadaver grafts in the face of maximal doses of immunosuppression. A delay will permit recovery from both the immunosuppression and any underlying subclinical infections, and will permit the recognition of anti-HL-A antibodies which may not be manifest soon after rejection. Retransplantation of the patient who is slowly rejecting the first kidney does not require prior removal of the rejected graft or delay in retransplantation.     

Recent results of cadaver kidney retransplantation

The results of secondary cadaver renal transplantation in 42 patients treated from 1980 to 1986 have been reviewed. The initial graft was from a cadaver donor in all cases. All patients were managed with a maintenance immunosuppressive regimen, including either antilymphoblast globulin and/or cyclosporine. The over-all 1 and 2-year patient survival rates were 97 and 94 per cent, respectively. The over-all 1 and 2-year graft survival rates were 69 and 63 per cent, respectively. Graft success was not influenced by patient age greater than 50 years, diabetes, initial graft removal, interval between initial graft removal and retransplantation, duration of initial graft function, level of presensitization or HLA-Dr antigen matching. Currently, cadaver renal retransplantation can be performed safely and with an improved opportunity for graft success. Patients who return to dialysis after losing an allograft should be encouraged to consider another transplant for the same reasons that prompted initial transplantation.     

Heart Retransplantation

Retransplants comprise only a small minority (3-4%) of heart transplants, however outcome following retransplantation is compromised. Risk factors for a poor outcome following retransplantation include retransplantation early (<6 months) after primary transplant, retransplantation for acute rejection or early allograft failure, and retransplantation in an earlier era. The incidence of rejection and infection is similar following primary transplant and retransplantation. The compromised outcomes and risk factors for a poor outcome are similar in adult and pediatric heart retransplantation. However, due to the short half-life of the transplanted heart, it is an expectation that patients transplanted in childhood may require retransplantation. Based on the data available and the opinion of the working group, indications for heart retransplantation are (i) chronic severe cardiac allograft vasculopathy with symptoms of ischemia or heart failure (should be considered) or asymptomatic moderate or severe left ventricular dysfunction (may be considered) or (ii) chronic graft dysfunction with symptoms of progressive heart failure in the absence of active rejection. Patients with graft failure due to acute rejection with hemodynamic compromise, especially <6 months post-transplant, are inappropriate candidates for retransplantation. In addition, guidelines established for primary transplant candidacy should be strictly followed.     

Management of the Patient with a Failed Renal Transplant

The management of the failed renal transplant depends upon the clinical circumstances. In most instances of failure secondary to acute rejection or structural lesions, transplant nephrectomy is necessary. When failure is due to chronic rejection, grafts often can be left in place and removed only for the indications of fever, pain, swelling, infection, or refractory hypertension. Once dialysis has been reinstituted, immunosuppression should be tapered in accordance with standard principles; this often does not result in the need to remove the failed allograft so long as it is clinically quiet. The presence of a nonfunctioning graft does not preclude retransplantation. With the use of cyclosporine, the results of retransplantation are beginning to look similar to the statistics for first transplants. The quality of life in patients who have failed transplantation has not been definitely proven to be worse than that of patients on dialysis or those who have a functioning graft. However, patients with a failed transplant will need emotional support in their readjustment to dialysis.     

Successful retransplantation after renal allograft loss to polyoma virus interstitial nephritis

BACKGROUND: Although polyoma virus infection is being increasingly recognized as a cause of renal allograft dysfunction and failure, the risk of polyoma recurrence in a subsequent transplant is unknown. We present the first reported case of successful retransplantation after polyoma virus-induced renal allograft loss. CASE REPORT: A 40-year-old Caucasian woman received a cadaveric kidney transplant. Baseline immunosuppression included corticosteroids, mycophenolate mofetil, and tacrolimus. Her post-transplant clinical course was complicated by an early acute rejection episode on posttransplant day (PTD) 6, that warranted treatment with OKT3. A biopsy performed on PTD 154 to evaluate a rise in creatinine revealed polyoma virus interstitial nephritis. Despite reduction in immunosuppression, the renal function progressively worsened and dialysis was initiated by PTD 160, followed by transplant nephrectomy on PTD 184. Four months later, she received a living related kidney from her sister. Immunosuppression was initiated with prednisone, azathioprine, and tacrolimus. She had immediate graft function with a decrease in serum creatinine from 12.8 to 1.1 mg/dl. Three and one-half years after her second renal transplant, her allograft functions well, with a serum creatinine of 1 mg/dl. Both quantitative and qualitative assays of blood and urine (by PCR) remain negative for BK virus, indicating the absence of virus reactivation. CONCLUSION: Judicious retransplantation should be considered as a therapeutic option in the management of polyoma virus induced graft failure. Previous graft loss secondary to polyoma virus infection is not a contraindication to retransplantation.     

Investigation into the onset and progression of transplant arteriosclerosis in a mice aortic retransplantation model

Long-term function of vascularized human organ grafts is often limited by transplant arteriosclerosis and can lead to graft failure. Here, we have analyzed the impact of an initial rejection episode on the later development of transplant arteriosclerosis. Following transplantation of allogeneic abdominal aortic segments in mice, aortic grafts were retransplanted into either immunodeficient or syngeneic recipients. Retransplantation of grafts from immunocompetent into immunodeficient mice as early as 2 days after the primary transplant resulted in intimal proliferation and obstruction of the graft lumen 30 days after the primary transplant. In contrast, retransplantation of the grafts into donor syngeneic B10 recipients within 7 days did not result in the development of transplant arteriosclerosis. These data suggest that the adaptive immune system can induce intimal proliferation by an initial lethal hit that is sustained by the innate response. However our data demonstrate that development of chronic rejection can be inhibited, in this case by retransplantation into a syngeneic host.     

100 second renal allografts from a single transplantation institution.

Between January 1, 1968 and March 1977, 100 of 131 patients who lost their first transplant at the University of Minnesota received a second renal allograft. Overall patient survival in the retransplanted group was 10% less than that in the dialysis group. The best results (graft function and patient survival were seen in young patients, nondiabetics, patients who received two sequential living related groups, and in those whose first graft was lost secondary to chronic rejection. The poorest results were seen in older patients (greater than 40 years), diabetics, and patients with acute rejection during the initial graft. Shared donor antigens do not affect graft outcome. These findings, although not the product of a randomized prospective study, may be useful in advising patients of the relative risks of retransplantation or hemodialysis.     

Retransplantation in 7,290 primary transplant patients: a 10-year multi-institutional study.

BACKGROUND: Cardiac retransplantation is a controversial procedure due to the disparity between donor heart demand and supply. METHODS: Of 7,290 patients undergoing primary cardiac transplantation between January 1990 and December 1999 at 42 institutions contributing to the Cardiac Transplant Research Database (CTRD), 106 patients later underwent a second and 1 patient a third cardiac transplant procedure. RESULTS: The actuarial freedom from retransplantation was 99.2% and 96.8% at 1 and 10 years, respectively. Reasons for retransplantation included early graft failure (n = 34), acute cardiac rejection (n = 15), coronary allograft vasculopathy (CAV, n = 39), non-specific graft failure (n = 7), and miscellaneous (n = 10). The only risk factor associated with retransplantation was younger age, reflecting the policy of preferential retransplantation of younger patients. Survival after retransplantation was inferior to that after primary transplantation (56% and 38% at 1 and 5 years, respectively). Risk factors associated with death after retransplantation included retransplantation for acute rejection (p = 0.0005), retransplantation for early graft failure (p = 0.03), and use of a female donor (p = 0.005). Survival after retransplantation for acute rejection was poorest (32% and 8% at 1 and 5 years, respectively) followed by retransplantation for early graft failure (50% and 39% at 1 and 5 years, respectively). Survival after retransplantation for CAV has steadily improved with successive eras. CONCLUSIONS: The results of retransplantation for acute rejection and early graft failure are poor enough to suggest that this option is not advisable. However, retransplantation for CAV is currently associated with satisfactory survival and should continue to be offered to selected patients.     

Cyclosporine versus azathioprine: a review of 200 consecutive cadaver renal transplant recipients

Most renal transplant centers report an increase in graft survival when cyclosporine is used as a primary immunosuppressant. We report the outcome of 200 consecutive cadaver renal transplant recipients among whom initial immunosuppression and risk factors were similar except for the substitution of cyclosporine for azathioprine in the second 100 recipients. Azathioprine-treated recipients had significantly increased (p less than 0.05) mean hospital stays (31.9 versus 18.3 days), incidence of first rejection episodes (85 versus 31) and methylprednisolone dose (3.38 versus 0.06 gm. per patient). Cyclosporine-treated recipients had a significantly higher 1-year mean serum creatinine level (1.85 versus 1.56 mg. per dl.) and 1-year actual graft survival (83 versus 58 per cent). Despite mild nephrotoxicity, cyclosporine is superior to azathioprine as a primary immunosuppressant in cadaver kidney transplantation.     

Effect of acute rejection episode on occurrence of chronic rejection after kidney transplantation

Chronic rejection is the most prevalent cause of renal transplant failure in the late post-transplant period. The clinical significance of acute rejection episodes on occurrence of chronic rejection is controversial. We analyzed 503 cases of the first renal transplantation maintained by calcinurine inhibitor for the correlation of acute rejection and clinical chronic rejection. The later the first episode of acute rejection occurred, the shorter was the half-life of graft. The acute rejection occurring within 3 post-transplant months worsens long-term graft survival if the peak creatinine level exceeds 2 mg/dl. Multivariate analysis by the Cox proportional hazard model for factors affecting cadaver graft loss by chronic rejection, revealed that the risk factor of acute early rejection was lower than those of donor age and post-transplant hypertension.     

Cardiac retransplantation: a viable option? The Registry of the International Society for Heart and Lung Transplantation.

To evaluate cardiac retransplantation as an appropriate utilization of scarce donor organs we analyzed data from the registry of the International Society for Heart and Lung Transplantation (ISHLT) (n = 449) and the Utah Cardiac Transplant Program (n = 20). Actuarial survival among retransplants was lower than in patients who received only one transplant in both the ISHLT registry patients (1 year survival, 48% versus 78%; p = 0.001) and the Utah series (1 year survival, 74% versus 88%; p = 0.06). Uncontrolled rejection, short interval (< 6 months) between transplantations, and the need for mechanical circulatory support were identified as risk factors for retransplantation. The incidence of rejection and infection was similar in first and second transplant recipients. Second transplant recipients had a higher level of sensitization, a greater incidence of donor-specific positive crossmatches, and an increased early mortality. Repetition in the second donor of mismatched HLA antigens present in the first donor did not adversely affect survival. If patients who underwent retransplantation within 6 months of their initial transplantation, those receiving transplants for uncontrolled rejection, and those requiring mechanical assistance were eliminated from the study, the short-term and long-term survival after cardiac retransplantation does not differ from that in patients having a single transplant.     

Retransplantation of a cardiac allograft inadvertently harvested from a donor with metastatic melanoma

Donor-derived melanoma is easily transmitted through organ transplants and is highly aggressive in transplant recipients. The best treatment-withdrawal or reduction of immunosuppression-permits tumor rejection but risks allograft rejection. In recipients of nonrenal allografts, the prognosis is particularly grim, with transmission rates and mortality approaching 100%. Retransplantation has been proposed as a possible strategy but has never been performed for a cardiac allograft. This is the first report of cardiac retransplantation and only the second case of retransplantation of any nonrenal organ. Our patient received a heart transplant from a donor found to have occult metastatic melanoma at autopsy. He underwent retransplantation 17 days later. Close clinical and radiographic follow-up reveal no evidence of melanoma 22 months after transplantation. Based on the rapid development of donor-derived melanoma in previous reports, our patient is likely to remain free of donor cancer. Retransplantation and low-dose immunosuppression may have been lifesaving.     

Hepatic ischemia/reperfusion injury can be modulated with thymoglobulin induction therapy

BACKGROUND: Thymoglobulin induction therapy has been shown to ameliorate delayed graft function and possibly decrease ischemia reperfusion injury in cadaver renal transplant recipients. This controlled randomized trial was designed to assess whether thymoglobulin also protects liver transplant recipients from ischemia reperfusion injury. PATIENTS AND METHODS: Twenty-two cadaver liver transplant recipients were randomized to receive either thymoglobulin (1.5 mg/kg per dose) during the anhepatic period and two doses every other day or no thymoglobulin. No differences in recipient or donor demographics were present. Maintenance immunosupression consisted of tacrolimus (or cyclosporine) and steroids for both groups. Donor biopsies were obtained during organ procurement, cold storage, and 1 hour after revascularization. Postoperative liver function tests were monitored. Early graft function, length of stay, patient and graft survival rates, incidence of primary nonfunction, and rate of rejection were assessed. RESULTS: Patient and graft survival at 3 months was 100%. There was no incidence of primary graft nonfunction and no need for retransplantation. The incidence of acute rejection was similar between the two groups. Although donor livers randomized to thymoglobulin had less optimal preimplantation biopsies, these recipients had significant decreases in ALT at day 1 compared to the control group (P = .02), near significant decreases of total bilirubin at day 5, and shorter length of hospitalization. CONCLUSION: Thymoglobulin allowed for more compromised liver grafts to be transplanted with less clinical evidence of ischemia reperfusion injury and improved function.     

Treatment of renal transplant rejection episodes in patients receiving prednisone and azathioprine. A cost-effective approach

Antilymphocyte globulin (ALG) has been advocated for the treatment of renal transplant rejection episodes in patients maintained on prednisone and azathioprine. Treatment with steroids (outpatient) is considerably less expensive than with ALG (inpatient), so we studied whether routine ALG was necessary. Between 3/82 and 11/83, 54 cadaver transplant recipients maintained on prednisone and azathioprine who developed a first rejection episode were randomized to receive--for treatment of their first, and if necessary second, rejection--methylprednisolone (MP) plus ALG (n = 24), or MP alone, with ALG added if treatment failed (n = 30). Treatment failure was defined as continuing deterioration on T131 iodohippuran scan, rising serum creatinine level, or lack of improvement within 7 days. There was no significant difference in patient survival, graft survival, mean number of rejections, and infection rate between the two groups: 60% (18/30) of first and 50% (10/10) of second rejection episodes responded to MP alone. We conclude that patients are not penalized by initial rejection treatment with MP. Many rejection episodes respond to steroids alone; elimination of routine ALG use will save hospitalization time and expense.     

Kidney retransplantation in the cyclosporine era

The results of kidney retransplantation in the cyclosporine era remain to be determined. Over a 42-month period, 76 nonprimary renal transplants (66 second, 7 third, 3 fourth allografts) were performed in 73 recipients under cyclosporine immunosuppression. The patient population was predominantly white (90.4%) with a mean age of 32.3 years. Twenty-one recipients (28.8%) were diabetic, and 36 (49.3%) were highly sensitized (panel-reactive antibody [PRA] greater than 50%). Sixty-two patients received cadaver donor grafts while the remaining donations were living-related (12) or living-unrelated (2). A sequential antilymphocyte globulin/cyclosporine protocol was employed, with cyclosporine therapy delayed until adequate renal function occurred. Overall patient and graft survival is 92.1% and 60.5%, respectively, after a mean follow-up of 20.0 months. The mean serum creatinine is 1.64 mg/dl in the 46 functioning allografts. Graft survival is 63.6% for secondary grafts, 28.6% for tertiary grafts, and 66.7% for fourth kidney transplants. In second transplants, recipients of cadaver donor kidneys have a graft survival of 58.5%, while living-related donor graft survival is 84.6% (P = 0.07). In the cadaver retransplant population, duration of previous transplant function greater than one year and HLA-DR matching were associated with increased graft survival, while age over 39 and presence of diabetes mellitus with reduced graft survival. However, these trends were not significant. Peak PRA above 50% did demonstrate a significant negative impact on graft survival both in the univariate and multivariate analyses of risk factors. Acute rejection occurred in 50 patients (65.8%), and was successfully reversed 50% of the time. Of the 30 grafts lost, 25 (83.3%) occurred within four months of retransplantation. Transplant nephrectomy was performed in 20 patients. Cyclosporine was not administered in 21 (70%) of these early graft failures, negating any potential beneficial effect. Retransplantation can be performed safely, with living-donor graft survival superior to cadaver retransplant rates. Rejection and early graft loss are common, especially in the highly sensitized patient. The impact of cyclosporine immunosuppression in renal retransplantation is much less dramatic than in primary transplantation in a protocol that delays cyclosporine therapy until allograft function is demonstrated.     

Total lymphoid irradiation in heart transplantation: adjunctive treatment for recurrent rejection

In the face of recurrent heart transplant graft rejection refractory to all conventional immunotherapy, retransplantation is customary treatment. The case of a heart transplant recipient unsuitable for retransplantation whose recurrent rejection was successfully treated with postoperative total lymphoid irradiation is described.     

Potential benefits of living donor kidney transplantation

Living donor kidney transplantation is the best therapeutic option for endstage renal failure. In spite of being an underused option in our country, it acquires an important role reducing the waiting lists for transplantation because cadaver donation is not enough. Living donor kidney transplantation offers multiple advantages when compared with cadaver donor transplantation: longer graft and patient survival on the short, mid and long-term; the fact that a scheduled procedure allows us to optimize donor and receptor's conditions; and ischemia time between nephrectomy and transplantation can be shortened to a minimum. A good initial function without need of dialysis (up to 90%) and lower incidence of rejection, which diminishes the need of antirejection drugs, should also be emphasized.     

Post-transplant renal function in the first year predicts long-term kidney transplant survival

BACKGROUND: Improvements in long-term kidney graft survival have been recently noted. However, the reasons for this were unclear. This study examined post-transplant renal function within the first year as an independent variable influencing long-term survival. METHODS: The influence of demographic characteristics (age, sex, race); transplant variables (cadaver versus living donor, cold ischemia time, HLA mismatching, delayed graft function and transplant year), and post-transplant variables (immunosuppressive agents for the prevention of acute rejection, clinical acute rejection and post-transplant renal function in the first year) on graft survival were analyzed for 105,742 adult renal transplants between 1988 and 1998. Renal function in the first year was expressed as serum creatinine at six months and one year and delta creatinine (change in serum creatinine between 6 months and 1 year). Graft half-life was used to measure long-term survival. RESULTS: During this 11-year period, the one-year serum creatinine values for cadaver recipients steadily improved, from 1.82 +/- 0.82 mg/dL in 1988 to 1.67 +/- 0.82 mg/dL in 1998 (P < 0.001), as did the graft half-life. There was a progressive decline in graft half-life for each incremental increase of six month, one year and Delta creatinine for living and cadaver donor transplants as well for cadaver transplants with donor age > and < or =50 years. The Relative Hazard (RH) for graft failure was 1.63 (1.61, 1.65; P < 0.0001) with each increment of 1.0 mg/dL of serum creatinine at one year post-transplant and it increased to 2.26 (2.2, 2.31; P < 0.0001) when the Delta creatinine was 0.5 mg/dL. The RH reduction for graft failure was substantially lower for the years 1993, 1996, 1997 and 1998 when post-transplant renal function was not included in the model (P < 0.05). However, the RH reduction per year was not different when post-transplant creatinine was included in the model, 1.01 (0.94 to 1.05; P = 0.89). CONCLUSION: In conclusion, one-year creatinine and Delta creatinine values predict long-term renal graft survival. Recent improvements in graft half-life are related to conservation of renal function within the first year post-transplantation.     

再次肾移植的临床研究

目的对再次肾移植进行临床总结。方法回顾性分析86例再次移植患者的临床资料,并与86例首次肾移植患者进行对比分析。首次肾移植失败的原因,17例为超急性排斥反应,9例为急性排斥反应,55例为慢性移植肾肾病,4例为移植肾破裂,1例为严重肾结核;再次移植前,31例群体反应性抗体(PRA)或补体依赖细胞毒(CDC)阳性;再次移植后,16例采用泼尼松(Pred)和硫唑嘌呤(Aza)预防急性排斥反应,70例采用环孢素A(或他克莫司)、Aza(或霉酚酸酯)及Pred组成的三联用药方案,32例再次移植前后接受抗体诱导治疗。结果再移植组人/肾1、3和5年存活率分别为84.8%/61.6%、79.1%/45.3%和58.1%/41.9%,对照组分别为89.5%/79.1%、81.4%/74.4%和67.4%/58.1%,两组人存活率的差异无统计学意义,而各时间段的肾存活率的差异均有统计学意义(P<0.05);术前使用抗体诱导治疗者以及术后采用环孢素A(或他克莫司)预防排斥反应者移植肾1年存活率明显优于未用抗体诱导治疗者和仅用Aza、Pred治疗者;术后排斥反应发生率,再移植组明显高于首次移植组(P<0.05);再移植组术后感染发生率明显高于首次移植者。结论再次移植的肾存活率明显低于首次移植,术后排斥反应和感染的发生率较高;采用抗体诱导治疗有利于再移植肾的存活。     

Outcomes of kidney retransplantation in recipients with prior posttransplant lymphoproliferative disorders: An analysis of the 2000–2019 UNOS/OPTN database

This study utilized the UNOS database to assess clinical outcomes after kidney retransplantation in patients with a history of posttransplant lymphoproliferative disease (PTLD). Among second kidney transplant patients from 2000 to 2019, 254 had history of PTLD in their first kidney transplant, whereas 28,113 did not. After a second kidney transplant, PTLD occurred in 2.8% and 0.8% of patients with and without history of PTLD, respectively (p = .001). Over a median follow-up time of 4.5 years after a second kidney transplant, 5-year death-censored graft failure was 9.5% vs. 12.6% (p = .21), all-cause mortality was 8.3% vs. 11.8% (p = .51), and 1-year acute rejection was 11.0% vs. 9.3% (p = .36) in the PTLD vs. non-PTLD groups, respectively. There was no significant difference in death-censored graft failure, mortality, and acute rejection between PTLD and non-PTLD groups in adjusted analysis and after propensity score matching. We conclude that graft survival, patient survival, and acute rejection after kidney retransplantation are comparable between patients with and without history of PTLD, but PTLD occurrence after kidney retransplantation remains higher in patients with history of PTLD.