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.     

Pediatric cardiac retransplantation: intermediate-term results

BACKGROUND: Cardiac retransplantation (re-CTx) in children is a controversial therapy, yet it remains the best treatment option to recipients with failing grafts. Our objective was to determine the incidence of re-CTx in a large pediatric population of recipients and evaluate the outcome of such therapy. METHODS: Between November 1985 and November 1999, 347 children underwent cardiac transplantation at the Loma Linda University Medical Center. Of these, 32 children were listed for re-CTx. Ten patients died while waiting, and 22 recipients underwent re-CTx. Median age at re-CTx was 7.1 years (range, 52 days to 20.1 years). RESULTS: Indications for re-CTx were allograft vasculopathy (n = 16), primary graft failure (n = 5), and acute rejection (n = 1). Two patients with primary graft failure underwent retransplantation within 24 hours of the first transplantation procedure while on extracorporeal membrane oxygenation support. Median time interval to re-CTx for the others was 7.2 years (range, 32 days to 9.4 years). Operative mortality for all cardiac re-CTx procedures was 13.6%. Causes of hospital mortality were pulmonary hypertension with graft failure (n = 2) and multiorgan failure (n = 1). Median hospital stay after re-CTx was 14.1 days (range, 6 to 45 days). There was one late death from severe rejection. Actuarial survival at 3 years for re-CTx was 81.9% +/- 8.9% compared with 77.3% +/- 2.6% for primary cardiac transplantation recipients (p = 0.70). CONCLUSIONS: Elective re-CTx can be performed with acceptable mortality. Although the number of patients undergoing retransplantation in this report is small and their long-term outcome is unknown, the intermediate-term survival after re-CTx is similar to that of children undergoing primary cardiac transplantation.     

Liver retransplantation in children in Poland

An average of 15% of patients require retransplantation due to irreversible liver graft failure due to primary graft nonfunction, chronic rejection, vascular and biliary complications, or infections. The survival of patients and grafts after retransplantation is inferior to that after primary transplantation. The purpose of the present study was to examine the incidence, indications, and outcome of retransplantation in children. In our center 169 liver transplantations had been performed in 154 patients, and 14 patients (9%) required 15 retransplantations: nine in the early postoperative period, five late after primary transplantation, and one late after the second transplantation. One-year patient survival after primary transplantation was 82%, but after early retransplantation it was 55%.     

Early and late outcomes after cardiac retransplantation

Background

Cardiac retransplantation remains the most viable option for patients with allograft heart failure; however, careful patient selection is paramount considering limited allograft resources. We analyzed clinical outcomes following retransplantation in an academic, tertiary care institution.

Methods

Between 1981 and 2011, 593 heart transplantations, including 22 retransplantations were performed at our institution. We analyzed the preoperative demographic characteristics, cause of allograft loss, short- and long-term surgical outcomes and cause of death among patients who had cardiac retransplantations.

Results

Twenty-two patients underwent retransplantation: 10 for graft vascular disease, 7 for acute rejection and 5 for primary graft failure. Mean age at retransplantation was 43 (standard deviation [SD] 15) years; 6 patients were women. Thirteen patients were critically ill preoperatively, requiring inotropes and/or mechanical support. The median interval between primary and retransplantation was 2.2 (range 0–16) years. Thirty-day mortality was 31.8%, and conditional (> 30 d) 1-, 5- and 10-year survival after retransplantation were 93%, 79% and 59%, respectively. A diagnosis of allograft vasculopathy (p = 0.008) and an interval between primary and retransplantation greater than 1 year (p = 0.016) had a significantly favourable impact on 30-day mortality. The median and mean survival after retransplantation were 3.3 and 5 (SD 6, range 0–18) years, respectively; graft vascular disease and multiorgan failure were the most common causes of death.

Conclusion

Long-term outcomes for primary and retransplantation are similar if patients survive the 30-day postoperative period. Retransplantation within 1 year of the primary transplantation resulted in a high perioperative mortality and thus may be a contraindication to retransplantation.     

Cardiac retransplantation: is it justified in times of critical donor organ shortage? Long-term single-center experience

Objective: Survival after heart transplantation has improved significantly over the last decades. There are a growing number of patients that require cardiac retransplantation because of chronic allograft dysfunction. With regard to the critical shortage of cardiac allograft donors the decision to offer repeat heart transplantation must be carefully considered. Methods: Since 1983 a total of 807 heart transplantations have been performed at our institution. Among them 41 patients received cardiac retransplantation, 18 patients because of acute graft failure and 23 because of chronic graft failure. Data were analyzed for demographics, morbidity and risk factors for mortality. The acute and chronic retransplant group was compared to those patients undergoing primary transplantation. Results: The mean interval between primary transplantation and retransplantation was 1.9 days in the acute and 6.7 years in the chronic retransplant group. Mean follow-up was 6.9 years. Baseline characteristics were similar in the primary and retransplant group. Actuarial survival rates at 1, 3, 5 and 7 years after primary cardiac transplantation compared to retransplantation were 83, 78, 72 and 64% vs 53, 50, 47 and 36%, respectively (p < 0.001). Early mortality after acute retransplantation was significantly higher compared to late retransplantation (10/18, 55.6% vs 4/23, 17.4%, p = 0.011). Major causes of death were acute and chronic rejection, infection and sepsis. Conclusions: Cardiac retransplantation is associated with lower survival rates compared to primary transplantation. However, results after retransplantation in chronic graft failure are significantly better compared to acute graft failure. Therefore, we consider cardiac retransplantation in chronic graft failure a justified therapeutic option. In contrast, patients with acute graft failure seem to be inappropriate candidates for cardiac retransplantation.     

Should we perform heart retransplantation in early graft failure?

Cardiac retransplantation represents the gold standard treatment for a failing cardiac graft but the decision to offer the patient a second chance is often made difficult by both lack of donors and the ethical issues involved. The aim of this study was to evaluate whether retransplantation is a reasonable option in case of early graft failure. Between November 1985 and June 2008, 922 patients underwent cardiac transplantation at our Institution. Of these, 37 patients (4%) underwent cardiac retransplantation for cardiac failure resulting from early graft failure ( n  = 11) or late graft failure (acute rejection: n  = 2, transplant-related coronary artery disease: n  = 24). Survival at 1, 5 and 10 years of patients with retransplantation was 59%, 50% and 40% respectively. An interval between the first and the second transplantation of less than ( n  = 11, all in early graft failure) or more than ( n  = 26) 1 month was associated with a 1-year survival of 27% and 73%, and a 5-year survival of 27% and 65% respectively ( P  = 0.01). The long-term outcome of cardiac retransplantation is comparable with that of primary transplantation only in patients with transplant-related coronary artery disease. Early graft failure is a significant risk factor for survival after cardiac retransplantation and should be considered as an exclusion criteria.     

Long-term outcome of liver retransplantation in children

BACKGROUND: Retransplantation of the liver is the only means of prolonging survival in children whose initial graft has failed. Patient and graft survival rates after retransplantation in most series have been inferior to rates after first transplantation. PATIENTS AND METHODS: Of 450 pediatric liver transplantations performed between January 1990 and March 2001, 50 were first retransplantations, 9 were second retransplantations, and 1 was a third retransplantation. The overall retransplantation rate was 13.3% (median age at retransplantation 4 years and median weight 15 kg). The median post-retransplantation follow-up was 73 (range, 6-139) months. RESULTS: Kaplan-Meier patient survival rates for the group (n=50) were 71.7%, 64.7%, and 64.7% at 1, 3, and 5 years, respectively. Graft survival rates were 65.6%, 56.7%, and 56.7% at 1, 3, and 5 years, respectively. This is significantly worse than rates for children undergoing first liver transplantation. There were 17 deaths, of which 9 occurred in the first month. Biliary complications occurred in 5 (10%) patients and vascular complications in 6 (12%). Improved patient and graft survival rates were observed in the later phase of the program, although the difference was not significant. Higher preoperative serum creatinine (P=0.001) and serum bilirubin (P=0.02) levels were associated with a higher postoperative mortality. CONCLUSION: Results of retransplantation in children remain inferior to those after first transplantation. There is a trend toward improving results. Liver retransplantation makes an important contribution to overall survival in children.     

The influence of nephrectomy of the primary allograft on retransplant graft outcome in the cyclosporine era.

The present analysis was undertaken to evaluate the influence of primary allograft nephrectomies on the early function, incidence of rejection, and short-term graft survival of subsequent renal retransplants. Among 95 consecutive cyclosporine treated retransplant recipients, 52 were retransplanted without primary allograft nephrectomy; 35 had removal of their primary grafts prior to retransplantation for fever and graft tenderness (30 patients) and persistent hematuria (5 patients); and 8 patients had an elective primary graft nephrectomy at the time of retransplantation. Demographic characteristics and immunosuppressive regimens were otherwise similar in all three groups. Nephrectomy of the primary allograft prior to retransplantation was associated with a significant subsequent rise in preformed cytotoxic antibody levels (57% having PRA greater than 30% compared with 33% in those with retention of primary grafts), a significantly higher incidence of delayed graft function among retransplants (63% compared with 30% in those who did not undergo primary allograft nephrectomy) and a trend toward decreased allograft survival in the subgroup who lost their primary allografts in the first year posttransplant. The incidence of acute rejection and 3-year posttransplant renal function in retransplants were not, however, influenced by nephrectomy of the primary allograft.     

Long-term experiences on cardiac retransplantation in adults

Background: It remains disputed whether cardiac retransplantation should be performed. This study aimed to evaluate our long-term experiences on cardiac retransplantation in adults. Patients and methods: Between March 1989 and December 2004, 2% (28/1290) of cardiac retransplantations were performed. Results: The reasons for cardiac retransplantation were cardiac allograft vasculopathy (n = 13; 47%), primary graft failure (n = 11; 39%), and refractory acute rejection (n = 4; 14%). The 30-day mortality risk was 29% (acute rejection: 50%; primary graft failure: 36%; cardiac allograft vasculopathy: 15%, p = 0.324), compared to 8.5% for primary cardiac transplantation (p < 0.001). The causes of early death were acute rejection (n = 3; 37%), multiorgan failure (n = 3; 37%), primary graft failure (n = 1; 13%), and right ventricular failure (n = 1; 13%). The late mortality rate was 96/1000 patient-years. The causes of late death were acute rejection (n = 4; 50%), cardiac allograft vasculopathy (n = 2; 25%), multiorgan failure (n = 1; 13%), and infection (n = 1; 13%). The 1-, 5-, 10-, and 15-year survival was respectively 78, 68, 54, and 38% (primary cardiac transplantation), and 46, 41, 32, and 32% (cardiac retransplantation) (p = 0.003). The short-term survival for cardiac retransplantation due to cardiac allograft vasculopathy was likely better than primary graft failure and refractory acute rejection (p = 0.09). Conclusion: The overall outcomes of cardiac retransplantation are significantly inferior to primary cardiac transplantation. Cardiac retransplantation should be only performed for selected patients.     

Successful ABO-incompatible pediatric liver transplantation utilizing standard immunosuppression with selective postoperative plasmapheresis.

Transplanting blood group A, B, or O (ABO)-incompatible (ABO-I) liver grafts has resulted in lower patient and graft survival with an increased incidence of vascular and biliary complications and rejection. We report that, without modification of our standard immunosuppression protocol, crossing blood groups is an acceptable option for children requiring liver transplantation. In our study, ABO-I liver grafts -- regardless of recipient age -- have comparable long-term survival (mean follow-up of 3.25 yr) with ABO-compatible grafts without any difference in rejection, vascular or biliary complications. From January 1, 1999 to October 1, 2005, we studied 138 liver transplants in 121 children: 16 (13.2%) received an ABO incompatible liver allograft. One-year actuarial patient survival for ABO-matched grafts vs. ABO-I grafts was 93.0% and 100%, respectively, whereas graft survival was 83.4% and 92.3%. Additionally, 6 of 16 (37.5%) ABO-I transplanted children had 8 rejection episodes, whereas 47 patients (44.8%) had 121 rejection episodes in the ABO-compatible group. There were no vascular complications and 2 biliary strictures in the ABO-I group. Plasmapheresis was not used for pretransplantation desensitization and was only required in 1 posttransplantation recipient. No child was splenectomized. Six of the 16 children were older than 13 yr of age, suggesting the possibility of successfully expanding this technique to an older population. In conclusion, our outcomes may support the concept of using ABO-I grafts in a more elective setting associated with split and living donor liver transplants.     

Pediatric liver retransplantation: indications and outcome

INTRODUCTION: Liver transplantation is the only treatment for end-stage liver disease. Not all patients have a favorable outcome. Graft failure secondary to primary nonfunction, vascular complications, or chronic rejection among other problems may lead to retransplantation. Retransplantation represents 8% to 29% of liver transplantations in the pediatric population. The aim of this study was to present our experience with retransplanted children by analyzing the indications and the results. METHODS: All patients were prospectively included in our database, including 125 children. We included the indications for retransplantation, complications, and mortality. Kaplan-Meier curves were used for survival analysis. RESULTS: Since 1994, 125 patients were transplanted and 25 were retransplanted (20%), including 5 who received a third graft. Primary nonfunction represented 30% of the indications for retransplantation and hepatic artery thrombosis, 20%. Six of 25 patients who received a first retransplantation and 2 of 5 who received a second retransplantation died. The most frequent cause of death was multiorgans failure. The survivals at 1 and 5 years were 82% and 76% for children receiving a first retransplantation, and 60% at 1 and 5 years for those who received a second retransplantation. CONCLUSIONS: Organ failure after liver transplantation was a common event in pediatric transplantation. Survival was similar between patients transplanted once and those who received one retransplantation. Survival decreased among patients who received a third graft but was maintained at 60%, which is better than most published results for first retransplanted patients. Retransplantation is a valid option with good results for selected pediatric cases.     

Treatment of refractory cholestatic pruritus with molecular adsorbent recirculating system (MARS)

Pruritus is a common complication of cholestatic liver diseases or liver graft dysfunction. Current medical therapies lack efficacy. The molecular adsorbent recirculating system (MARS) represents an interesting therapeutic option. Our objective was to report our experience in the management of four patients with intractable pruritus with MARS. PATIENTS AND METHODS: The MARS treatment cycle included three consecutive treatments, each of 8 hours duration. The four patients with intractable pruritus who were treated had primary biliary cirrhosis/autoimmune hepatitis overlap syndrome (n = 1), ductopenic allograft rejection (n = 2), or posttransplant cholestatic HCV recurrence (n = 1). Intensity of pruritus was documented 24 hours before as well as 24 hours, 7 and 30 days after MARS therapy, and at the end of follow-up. We measured complete blood cell counts, glucose, BUN, creatinine, sodium, potassium, AST, ALT, GGT, alkaline phosphatase, bilirubin, prothrombin activity, and activated partial thromboplastin time. RESULTS: MARS therapy was well tolerated. Patient 1 experienced temporal relief of pruritus, but needed another MARS cycle because of relapse. Patient 2 experienced partial and temporary relief of pruritus, was listed for retransplantation, and received a liver graft 2 months later. Patient 3 showed a dramatic reduction in the degree of pruritus with MARS. Pruritus in patient 4 decreased promptly with MARS therapy and conversion of immunosuppression to tacrolimus, thereby avoiding retransplantation. CONCLUSION: MARS therapy is a promising, safe therapeutic option to treat refractory pruritus caused by cholestatic liver disorders.     

Cardiac retransplantation in the cyclosporine era

Between December 1980, when immunosuppression with cyclosporine was introduced, and May 1988, 288 patients underwent primary transplantation for end-stage cardiac disease (group TX). Fourteen patients underwent retransplantation for accelerated graft atherosclerosis (group RTXAGA), and 9 underwent retransplantation for intractable acute allograft rejection (group RTXREJ). Cumulative patient follow-up was 724 patient-years (range, 1 month to 7.5 years; mean, 2.3 years). Within the first 3 postoperative months, no differences were noted between groups for linearized rates of infection or rejection except between the rate of rejection for group TX (1.69 +/- 0.09 events/100 patient-days) and group RTXAGA (0.94 +/- 0.3 events/100 patient-days) (p less than 0.02). No significant differences existed between groups for actuarial rates of remaining rejection-free or infection-free for more than 7.5 years. No significant differences in actuarial survival existed except between group TX (81% +/- 2% at 1 year and 58% +/- 4% at 5 years) and group RTXREJ (44% +/- 17% at 1 year and 44% +/- 0% at 5 years) (p less than 0.05). We conclude that patients who undergo retransplantation for accelerated graft atherosclerosis experience a lower rate of early rejection and similar rates of infection and survival compared with patients who receive primary transplants. Cardiac retransplantation for rejection incurs rejection and infection at rates similar to those of primary procedures. However, patients who undergo retransplantation for rejection survive these complications significantly less often than do patients who receive primary transplants. This information should be considered when scarce donor hearts become available and retransplantation is contemplated.     

Effect of histological damage on long-term kidney transplant outcome

BACKGROUND: Chronic renal allograft failure remains a major challenge to overcome. Factors such as donor quality, delayed graft function (DGF), acute rejection, and immunosuppression are known to affect long-term outcome, but their relationship to histological damage to graft outcome is unclear. METHODS: Protocol kidney biopsies (n=112) obtained at 3 months after transplantation yielded 102 with adequate tissue. Histology was scored by the Banff schema, and compared with implantation biopsies (n=91), repeat 12-month histology (n=39), decline in serum creatinine and serial isotopic glomerular filtration rate, onset of chronic allograft nephropathy (CAN), and actuarial graft survival censored for death with a functioning graft. RESULTS: At a median follow-up of 9.3 years, 20 patients had graft failure and 26 died with a functioning graft. Banff chronic nephropathy was present in 24% of 3-month biopsies, and was predicted by microvascular disease in the donor, cold ischemia, DGF, and acute vascular rejection (P<0.001). Acute glomerulitis at 3 months correlated with segmental glomerulosclerosis at 12 months, subsequent recurrent glomerulonephritis, and graft failure (P<0.01). Subclinical rejection at 3 months occurred in 29% of biopsies, correlated with prior acute rejection and HLA mismatch, and led to chronic histological damage by 12 months (r=0.25-0.67, P<0.05-0.001). Subclinical rejection, arteriolar hyalinosis, and tubulitis present at 3 months had resolved by 12 months. The 10-year survival rates for Banff chronic nephropathy were 90.4% for grade 0, 81.0% grade 1, and 57.9% for grades 2 or greater (P<0.01). Early tubulointerstitial damage at 3 months profoundly influenced graft survival beyond 10 years. CAN was predicted by kidney ischemia, 3-month chronic intimal vascular thickening, tubular injury, proteinuria, and late rejection. Chronic fibrointimal thickening of the small arteries and chronic interstitial fibrosis at 3 months independently predicted graft loss and decline in renal function (P<0.05-0.001). CONCLUSIONS: Early transplant damage occurs in the tubulointerstitial compartment from preexisting donor kidney injury and discrete events such as vascular rejection and DGF. Subsequent chronic damage and graft failure reflect accumulated previous injury and chronic interstitial fibrosis, vascular impairment, subclinical rejection, and injury from late rejection. CAN may be conceptualized as the sequelae of incremental and cumulative damage to the transplanted kidney. The duration of graft survival is dependent and predicted by the quality of the transplanted donor kidney combined with the intensity, frequency, and irreversibility of these damaging insults.     

再次肝移植22例的指征与疗效分析

目的 分析我院再次肝移植患者的手术指征和移植效果.方法 2001年6月至2004年11月,22例患者因各种原因行再次肝移植.原因分别为：胆道并发症10例,肝动脉血栓形成4例,其中1例合并胆漏,慢性排斥反应4例,急性排斥反应2例,原发性移植肝无功能2例.并对再次肝移植患者进行随访.结果 在22例再次移植患者中,存活12例,死亡10例,住院期间死亡率为45%（10/22）.死亡病例术后生存时间3～35 d,平均12.6 d.死于脓毒败血症7例;手术出血性休克2例;脑血管意外1例.在存活者中,并发症发生率为25%（3/12）,其中胆道并发症2例,伤口裂开1例,院内感染11例,感染率为92%（11/12）.随访2～28个月,中位随访时间18个月.存活3～31个月,中位生存时间为16个月.结论 再次肝移植主要指征为胆道并发症、肝动脉栓塞、慢性及急性排斥反应,原发性移植肝无功能.导致再次肝移植死亡原因主要为脓毒败血症.     

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.     

The safety and efficacy of early withdrawal of calcineurin inhibitors in kidney transplant recipients 6 months' posttransplant

INTRODUCTION: The introduction of calcineurin inhibitors (CNIs) in clinical transplantation has resulted in dramatic reduction in acute rejection rate and improvements in short-term allograft survival. However, CNI-induced chronic nephrotoxicity is a clinical concern since it is a major cause of chronic allograft failure. Recent studies suggest that withdrawal or reduction of CNI dosage results in improvement in graft function and survival. The aim of this study was to evaluate the safety and efficacy of substituting CNIs with mycophenolate mofetil (MMF) at 6 months' postkidney transplant. METHODS: Kidney transplant recipients of first or second grafts (n = 20) maintained on CNI-based therapy and with no history of irreversible acute or vascular rejection were included in the study. Primary end points were the incidence of biopsy-proven acute rejection or treatment failure. Secondary end points included changes in mean serum creatinine and estimated GFR (Cockroft and Gault, CG) over time, incidence of infection, cardiovascular risk factors (blood pressure, cholesterol), graft and patient survival rates, as well as incidence of biopsy-proven chronic allograft nephropathy (CAN). Study patients were compared to a matched control group (n = 20) who remained on CNI-based therapy at equivalent time points. RESULTS: Incidence of acute rejection following CNI withdrawal was 15%. All episodes reversed with steroid pulses. There was no significant difference in mean serum creatinine or estimated GFR during the follow-up period. No significant change occurred in blood pressure or antihypertensive agents between the groups; however, there was a trend toward lower cholesterol levels after CNI withdrawal. No graft or patient loss was seen during the study period. Biopsy-proven CAN was diagnosed in 2 control patients (10%) at 6 to 8 months' posttransplant. CONCLUSIONS: Withdrawal of CNI at 6 months following kidney transplantation is associated with an increased risk of rejection and a trend toward lower serum creatinine and cholesterol levels. Further follow-up is needed to establish the long-term results of CNI-sparing regimens on the development of CAN.     

An analysis of pretransplantation variables associated with long-term allograft outcome in pediatric liver transplant recipients receiving primary tacrolimus (FK506) therapy.

BACKGROUND: The present study analyzes pretransplantation variables associated with long-term liver allograft survival in 278 children who underwent transplantation under primary tacrolimus (FK506) therapy at a single center between October 1989 and October 1996. METHODS: The influence of 17 pretransplantation variables on long-term liver allograft outcome was analyzed. Donor variables included age, weight, gender, and cold ischemia time. Recipient variables included age, weight, gender, original liver disease, pretransplantation waiting time, previous abdominal surgery, United Network of Organ Sharing (UNOS) status, ABO blood group, bilirubin level, prothrombin time, ammonia level, creatinine level, and reduced-size/split liver grafts. RESULTS: Overall actuarial graft survival was 79.9% at 1 year, 79.1% at 2 years, and 78.3% at 3, 4, and 5 years. Retransplantation rate was 10.8%. Pretransplantation variables with a significant adverse effect on graft survival by univariate analysis were donor age < or = 1 year (P<0.004), donor weight < or = 10 kg (P<0.003), UNOS status I and II (P<0.007), ABO type O, B, and AB (P<0.03), and reduced-size/split liver grafts (P<0.02). Pretransplantation variables significant by multivariate analysis and therefore independent predictors of inferior graft outcome were donor weight '10 kg (relative risk [RR] 2.91, confidence interval [CI] 1.53-5.51); reduced-size/split liver grafts (RR 2.53, CI 1.30-5.64); and UNOS status I (RR 2.22, CI 1.11-4.43). CONCLUSIONS: Pediatric liver transplant recipients receiving primary tacrolimus therapy have long-term graft survival rates approaching 80%. UNOS status, donor weight, and the use of reduced-size/split liver grafts are the most important factors affecting survival.     

Liver transplantation for primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease that progresses to end-stage liver disease. This report is a retrospective analysis of a Canadian centre experience with liver transplantation (LT) for PSC. Of 1107 LTs performed between 1984 and 2002, 132 were performed on 111 patients with PSC. Patient survival at 1, 3, 5, and 10 years was 84.5%, 84.5%, 83.4%, and 68.9%, respectively. Graft survival at 1, 3, 5, and 10 years was 80.8%, 79.8%, 72.7%, and 55.3%. These were not significantly different from overall patient survival (P =.91) or graft survival (P =.28) in non-PSC patients transplanted over the same time period. Early mortality was predominantly related to primary nonfunction and multi-organ failure; late mortality was predominantly related to malignancy. No patient with known cholangiocarcinoma (CCA) underwent LT, but three patients had an incidental CCA noted on explant pathology. All three died of widespread metastatic disease (10.8, 38.0, and 39.8 months after LT). Nineteen patients lost their primary grafts requiring retransplantation, and two of these patients required a third transplant. Recurrent PSC was detected in six patients and suspected in another six. Four patients have been retransplanted for recurrent PSC. Chronic rejection was detected in nine patients. Eight have required retransplantation. The incidence of biliary complications was 16.2%. CONCLUSIONS: LT is effective therapy for PSC. Patient and graft survival is comparable to that seen in patients transplanted for indications other than PSC, but long-term graft survival may be lower. Recurrent PSC and chronic rejection are the major determinants of graft loss.