Heart transplant coronary artery disease in Chinese recipients

BACKGROUND: Transplant coronary artery disease is the principle limiting factor for long-term survival of heart transplantation (HTx) recipients. We reviewed our data to assess the incidence of this disorder among Chinese HTx recipients and to compare it with the results of Western studies. MATERIAL AND METHODS: From July 1988 to May 2002, 182 patients received 184 orthotopic HTx. One hundred sixty-three recipients survived for at least 1 year with available SPECT scans or coronary angiogram studies. The data set included donor characteristics, recipient characteristics, active cytomegalovirus (CMV) infection rate, rejection episodes, immunosuppressants, and human leukocyte antigen (HLA) mismatches. RESULTS: Surgical mortality in our program was 4.3% and the actuarial freedom from coronary artery disease at 1, 3, and 5 years was 99%, 95%, and 92%, respectively. Angiogram results were stratified into coronary artery disease (n = 15) or absence of the disorder (n = 148) groups. Only older donor age showed statistical significance between the groups. Compared with the Western series, the present data show higher actuarial survival rates and freedom from coronary artery disease. There were statistically significant differences in regard to graft ischemia time, proportion of male recipients, ischemic heart disease, rejection episodes during the first year, and incidence of CMV infection. CONCLUSIONS: SPECT scan can detect coronary artery disease before there is significant stenosis of the coronary artery with acceptable survival rates. Chinese HTx recipients show a lower incidence of the disorder, lower rates of ischemia heart disease, lower proportion of male gender, lower incidence of CMV infection, fewer rejection episodes during the first year, and less ischemic time than Western recipients, which maybe the contributing factors to their better survival.     

Differential characteristics of heart transplantation in patients older than 60 years

BACKGROUND: The effect of advanced age on the results of heart transplantation (HTx) is still controversial. The few articles addressing this issue have not been conclusive, due to either short follow-up periods or small numbers of patients. METHODS: We present a retrospective study of 560 HTx which were divided into group A, including patients of 60 or less years at HTx (n=465, 83%), and group B, of 95 recipients older than 60 years. A subgroup of the latter, named B1, includes 24 patients older than 65. More than 100 recipient, donor and surgical procedure variables were analyzed for their impact on actuarial survival and incidence of common causes of posttransplant morbidity and mortality during a follow-up period longer than 10 years. RESULTS: Group B showed a lower number of acute rejection episodes than group A, (1.53+/-1.87 versus 1.96+/-1.81, P<.04). Both groups showed a similar incidence of infection episodes, malignancies or graft vasculopathy, but older patients experienced fewer viral infections than younger ones (9% in group A versus 18% in group B, P<.05). Log-rank test showed a trend to shorter survival in group B (P=.08), a disadvantage that reached significance (P=.01) among patients older than 65 years. CONCLUSIONS: Patients who were older than 60 at HTx displayed a lower incidence of acute rejection episodes and viral infections, but a trend toward shorter long-term survival. This disadvantage in prognosis was statistically significant among recipients older than 65 years.     

Medium-term results of heart transplantation using donors over 63 years of age

BACKGROUND: The continual shortage of hearts for transplantation (HTx) led to the expansion of the donor pool by accepting older donors. We compared the medium-term follow-up of patients after HTx with older hearts (over the age of 63 years) with those of patients after HTx with younger hearts. PATIENTS AND METHODS: Since April 1994 we have used hearts for HTx from donors older than the age of 63 years. Until November 1998, 309 HTx and 9 re-HTx were performed in 309 adults with a mean age of 50.7+/-10.9 years (range 17-68 years). There were 252 men and 57 women. The patients were divided into two groups: group I--donor age under 63 years (296 patients, mean age 50.4+/-11 years; mean donor age 38.1+/-13 years; mean follow-up 1.7+/-1.6 years); group II-donor age of more than 63 years (13 patients, mean age 57.4+/-5.6 years; mean donor age 65.1+/-2.1; mean follow-up 2.2+/-1.6 years). There were no differences in the etiology of heart failure, gender, or ischemia time between the groups. The patients in group II were significantly older (P = 0.008). Multiple factors were analyzed in the groups, which included changes in the left/right ventricle ejection fraction, early postoperative mortality (up to 30 days), cumulative survival rates and cardiac-dependent morbidity [myocardial infarction, malignant arrhythmias, coronary stenosis (>50% in one of the main coronary arteries) and transplant vasculopathy]. Additionally, freedom from cytomegalovirus infection (rise of titer or seroconversion) and freedom of acute rejection episodes grade > or =2 (International Society of Heart & Lung Transplantation [ISHLT]) were analyzed. RESULTS: After 1 year mean left and right ventricle ejection fraction were good in both groups and did not significantly change for up to 2 years. No Re-HTx was performed in group II. The early postoperative mortality was similar in both groups (P = 0.8). Also, the cumulative survival rates were similar in both groups (P = 0.87). Long-term cardiac morbidity was lower in group I (P = 0.03). The long-term freedom from cytomegalovirus infection in group I was significantly higher when compared with group II (P = 0.0002). The long-term freedom from severe rejection episodes was similar in both groups (P = 0.3) CONCLUSION: The study found a significant increase in long-term cardiac morbidity due to more focal coronary stenosis in group II, and freedom from cytomegalovirus infection, but did not find significant differences in the long-term survival between patients who received hearts from donors of up to 63 years of age and from those more than 63 years. The acceptance of donors older than 63 years old for HTx does not worsen the outcome of the recipients. The careful selection of older donors, with close monitoring of the coronary situation after HTx and expanded indications for revascularization of older hearts, could make HTx with older hearts, even in older recipients, a safe option.     

Comparison of enteric-coated mycophenolate sodium with mycophenolate mofetil in living renal allograft transplantation

OBJECTIVE: Enteric-coated mycophenolate sodium (MPS) has been developed to decrease the GI side effects of mycophenolate mofetil (MMF). We did a retrospective analysis of 112 patients to compare the safety and efficacy of enteric coated MPS vs MMF in living renal transplantation. METHODS: Patients were divided into two groups. Group A who received MPS [Novartis, Basel, Switzerland] [1.08-1.44 g/d] included 53 patients of mean age 33.5 +/- 11.9 yrs, and M:F gender ratio 37:15 with a mean donor age of 43.2 +/- 9.9 years. Group B who received MMF [1.5-2.0 g/d] included 59 subjects of mean age 33.2 +/- 9.9 yrs and M:F gender ratio 57:6, with a mean donor age of 41.4 +/- 10.9 years. All patients received cyclosporine and prednisolone in addition to mycophenolate. Mean follow-up in the two groups was 11.6 +/- 7.0 and 12.6 +/- 8.5 months, respectively. RESULTS: There were 11 (20.7%) rejection episodes in Group A and 12 (20.3%) rejection episodes in Group B (P = NS). Incidence of CMV disease was 9.61% and 10.1%, and of other infections, 88.7% and 74.7% in Groups A and Group B, respectively [P = NS]. The incidence of GI (18.9% & 20.3%) and hematologic toxicities (9.4% & 5.1%) were similar in the groups. Patient and graft survivals in Group A were 91.9% & 86.6%, and in Group B was 91.3% & 91.3%, respectively [P = NS]. CONCLUSION: Mycophenolate sodium is an alternative immunosuppressant to mycophenolate mofetil in kidney transplant recipients with a similar efficacy and safety profile.     

Coronary atherosclerosis in cardiac transplant patients treated with total lymphoid irradiation.

BACKGROUND: Multiple episodes of rejection following cardiac transplantation have been associated with an increased incidence of coronary atherosclerosis. Total lymphoid irradiation (TLI) has been shown to be a successful treatment for persistent allograft rejection, but its effect on coronary arterial disease has yet to be evaluated. METHODS: From 1987 to 1999, 40 patients required TLI for persistent or recurrent allograft rejection following heart transplantation. Each patient's (Group 1, n = 31) post-transplant coronary angiograms were examined and compared with those of a control group (Group 2, (n = 32) matched for time of transplantation. Degree of coronary stenosis was assessed on a 6-point scale. All patients received induction therapy (rabbit anti-thymocyte globulin or OKT3) and standard triple immunosuppressive therapy. TLI (80 cGy x 10 fractions) was used for the treatment of recurrent or persistent rejection on the basis of clinical indications. Actuarial survival, number and treatment of rejection episodes, and severity of coronary artery disease were compared in each group. RESULTS: Recipient gender, age, race and cytomegalovirus (CMV) status at time of transplant, along with donor gender, CMV status and graft ischemia time, were similar in both groups. Group 1 donor age was younger than that of Group 2 (22.2 +/- 11.2 vs 31.5 +/- 13.6 years, p = 0.004), and the indication for surgery in Group 1 patients was more likely to be ischemic heart disease (15 of 31 vs 6 of 32, p = 0.02). Mean follow-up was 5.7 +/- 3.5 years in Group 1 vs 6.9 +/- 3.8 in Group 2 (p = NS). Group 1 had more rejection episodes (4.4 +/- 2.2 vs 2.3 +/- 2.0, p = 0.0002) and more steroid treatments (9.78 +/- 4.0 g vs 5.14 +/- 4.7 g, p < 0.0001), but less coronary artery disease compared with Group 2 (p = 0.035). CONCLUSIONS: Despite multiple episodes of rejection, patients treated with TLI after cardiac transplant appear to develop less coronary atherosclerosis than appropriately matched controls.     

A strategy to achieve donor-specific hyporesponsiveness in cadaver renal allograft recipients by donor haematopoietic stem cell transplantation into the thymus and periphery.

INTRODUCTION: We designed a prospective, randomized clinical trial to evaluate the immune response to thymic and peripheral infusions of donor haematopoietic stem cells (HSCs) to create tolerance in recipients of cadaver renal allografts. METHOD: We divided 24 patients into two equal groups. For group A, 350 ml of unfractionated bone marrow (BM) was aspirated from the anterior iliac crests of donor cadavers. A 2 ml aliquot of concentrated marrow was infused into the thymus of the subject and 100 ml into the BM before surgery; the remaining 250 ml was infused peripherally post-transplantation. The mean nucleated cell count inoculated into the thymus was 3.3 x 10(4) cells/cm(3) and into the periphery 8.6 x 10(7) cells/kg body weight. Group B (controls) underwent renal transplantation directly. Recipients were lymphocytotoxicity cross-match negative in both groups. Group A received low dose prednisolone and cyclosporin; controls also received azathioprine. RESULTS: Over a mean follow-up of 703 days for both groups, group A had significantly better graft function with minimum acute rejection episodes or cytomegalovirus (CMV) infections, a mean serum creatinine (SCr) of 1.23 mg/dl and no graft or patient loss. Group B, with a mean SCr of 2.19 mg/dl had three patients with single acute rejection episodes, two of whom died following uncontrolled rejection-associated infections. The third patient maintained an SCr of 2.5 mg%. Actuarial graft survival was 87.5% in controls at the end of 2 years compared with group A with 100% graft survival at the end of 2 years. CONCLUSION: This novel approach of introducing unfractionated HSCs into the thymus and periphery to create tolerance is safe and efficacious and gives significantly better graft function, minimum acute rejection and no CMV disease with monotherapy.     

Valganciclovir as preemptive therapy for cytomegalovirus in cytomegalovirus-seronegative liver transplant recipients of cytomegalovirus-seropositive donor allografts.

The efficacy of valganciclovir as preemptive therapy for the prevention of cytomegalovirus (CMV) disease and its impact on indirect sequelae of CMV were assessed in recipient-negative/donor-positive (R-/D+) liver transplant recipients. Of 187 consecutive liver transplant recipients at our institution since July 2001, 36 (19.2%) belonged to the R-/D+ group. Surveillance tests for CMV were performed on all patients at weeks 2, 4, 6, 8, 10,12, and 16. In all, 27 patients with asymptomatic viremia received preemptive therapy with valganciclovir. At a total follow-up of 62.8 patient years (median: 19 months, range: 3 months to 5.6 years), no episodes of CMV disease were documented in these patients. The incidence of rejection, retransplantation, and bacterial or fungal infections and the probability of survival did not differ for R-/D+ patients and all non-R-/D+ patients treated preemptively with valganciclovir (P > 0.20 for all variables). Thus, preemptive therapy with valganciclovir in R-/D+ patients was not associated with CMV disease during the period of surveillance monitoring or at anytime thereafter (late-onset CMV disease). The indirect outcomes with the use of valganciclovir in R-/D+ patients were comparable to the outcomes of other subgroups of liver transplant recipients receiving preemptive therapy.     

Cytomegalovirus infection in kidney transplant patients: Prevalence,risk factors,and impact on outcome – A local multicentre experience

BackgroundCMV infection prevalence in kidney transplant recipients (KTR) is reported to be high in the literature, reaching rates of over 80%.ObjectivesThe primary endpoints were the evaluation of the prevalence, the risks factors, and the effects of CMV infection on graft function and survival, as well as patient survival at three years after kidney transplantation.Material and methodsWe retrospectively reviewed the medical records of 288 kidney transplant patients operated in three Lebanese transplant centers between 1998 and 2017 with three years of follow-up. The patients were divided into two groups: those free of any CMV infection (271 patients (94%); Group I) and those who suffered from CMV infection (17 patients (6%); Group II).ResultsBaseline demographics of the two groups were similar, including recipient and donor gender and age, cause of renal disease, recipient body mass index, pre-transplant fasting blood sugar and dialysis duration, HLA matching between donor and recipient, degree of sensitization in the recipient, type of CMV prophylaxis, maintenance immunosuppression and immunological characteristics. The prevalence of CMV infection is 5.9% among KTR. There were significant differences between the two groups concerning the type of induction therapy and the duration of anti-CMV prophylaxis. The rate of infected patients and infectious episodes were significantly higher in Group II. At 3-years, graft function and survival, patient survival, and the rate of new-onset diabetes were similar between the two groups.ConclusionThe present study is the first to explore the incidence and risk factors of CMV in kidney transplant patients in Lebanon. Comprehensive nationwide studies are therefore necessary to determine the epidemiology and risk factors of CMV infection after kidney transplantation in Lebanon.     

Cytomegalovirus infection in simultaneous pancreas-kidney transplantation

INTRODUCTION: In this open-label multicenter study, 205 simultaneous pancreas-kidney (SPK) transplant recipients between 1998 and 2000 were randomly assigned to tacrolimus or cyclosporine-microemulsion (ME). All patients received concomitant rATG induction therapy, mycophenolate mofetil and short-term corticosteroids. We report the 3-year data related to the occurrence, severity and effect of cytomegalovirus (CMV) infections. The type of CMV prophylaxis and treatment was at the discretion of the investigator. RESULTS: The overall incidence of CMV infection was 34% with no difference in incidence between the tacrolimus and cyclosporine-ME treatment arms. Statistically significant fewer CMV infections occurred among patients who received ganciclovir (22%) than those who did not receive prophylaxis (42%; P = .0075) or were treated with acyclovir (43%; P = .0066). The CMV infection rate according to donor recipient CMV serological status was: D-/R- group 11%, which was lower than the D-/R+ group at 40% (P = .0035), the D+/R+ group at 37% (P = .0024), or the D+/R- group at 52% (P = .00001). Among the last three groups, the infection rate was lower in patients on ganciclovir than those with no prophylaxis or on acyclovir (22% vs 64%; P = .00001). The incidence of acute rejection episodes was higher among patients without ganciclovir prophylaxis. No difference was observed in actuarial patient, kidney, or pancreas survival rates between patients with versus without infection. CONCLUSIONS: Ganciclovir prophylaxis effectively prevented CMV infection in SPK transplant recipients, especially in higher risk groups. An effect of CMV prophylaxis on the incidence of rejection is possible.     

Does cytomegalovirus status influence acute and chronic rejection in heart transplantation during the ganciclovir prophylaxis era?

BACKGROUND: The effect of cytomegalovirus (CMV) status on acute rejection in heart transplantation is not well understood. Furthermore, there is some evidence to suggest that CMV antibody positivity is associated with cardiac allograft vasculopathy (CAV). METHODS: This study compared the effect of CMV antibody status in heart transplant donors (D) and recipients (R) on acute and chronic rejection episodes during the ganciclovir prophylaxis era. RESULTS: All heart transplant recipients at Papworth Hospital during the ganciclovir prophylaxis era were included (n = 374). They were grouped according to recipients and their respective donor CMV serology: R(-)/D(-) (n = 82); R(+)/D(-) (n = 114); R(-)/D(+) (n = 73); and R(+)/D(+) (n = 105). Ganciclovir prophylaxis was administered to the R(-)/D(+) group. The mean (SD) recipient and donor ages were 46 (11), 51 (9), 47 (11) and 52 (8) years (p < 0.001), and 32 (11), 33 (14), 36 (12) and 38 (14) years (p = 0.01), respectively, for the CMV groups. The mean number of acute rejection episodes (as confirmed by cardiac biopsy) per 100 patient-days was 0.13 (0.36), 0.11 (0.34), 0.12 (0.34) and 0.12 (0.34), respectively (p > 0.05) There was no statistical difference in the development of CAV as assessed by angiography (p = 0.92). At 2 years, the "freedom from CAV" rates were 96%, 97%, 97% and 98%, respectively. The 5-year post-operative survival rates were 83%, 79%, 67% and 73% (p = 0.08 overall). CONCLUSIONS: CMV status of heart transplant recipients and their respective donors does not influence acute or chronic rejection in terms of cardiac allograft vasculopathy.     

Pregnancy after heart transplantation: a well‐thought‐out decision? The Quebec provincial experience – a multi‐centre cohort study

Despite reports of successful pregnancies in heart transplant (HTx) recipients, many centers recommend their patients against maternity. We reviewed our provincial experience of pregnancy in HTx recipients by performing charts review of all known gestations following HTx in the province of Quebec (Canada), stratified between planned and unplanned pregnancies. Long‐term survival was compared to HTx recipient women of childbearing age who did not become pregnant. Eighteen pregnancies, 56% unplanned, occurred in eight patients, 10.1 (2.6–27.0) years after HTx. Immunosuppression was CNI‐based, with a mean dose increase of 48.3% (tacrolimus) and 26.5% (cyclosporine), without rejection. Cardiometabolic complications were high compared to the general Canadian population, including preeclampsia (15.4% vs. 5.5%), hypertension (38.5% vs. 4.6%), and diabetes (15.4% vs. 5.6%). Mean gestational age was 35.1 (23.4–39.6) weeks (72.2% live births; 53.8% prematurity). Mean birthweight was 2418 (660–3612) g. Serum creatinine increased during pregnancy, becoming significant after delivery (P = 0.0239), and returning to preconception level in all but three patients within a year. After 4.6 (1.2–17.2) years of follow‐up, two rejection episodes occurred in one patient. Long‐term mortality was similar to overall HTx women (Kaplan–Meier; P = 0.8071). Pregnancy in HTx carries high cardiometabolic complications and decreased kidney function, but is feasible with acceptable outcomes and no impact on mother's survival.     

Risk factors among donor characteristics which affect graft outcome in paired kidney transplantation

OBJECTIVE: The goal of this study was to identify risk factors among donor characteristics which affect short- and long-term graft outcomes and patient survivals. MATERIALS AND METHODS: This is a retrospective analysis of cases where the kidneys were retrieved from the same donor. We evaluated donor variables including age, sex, cytomegalovirus (CMV) status, infection, blood pressure, electrolyte, urine output, transfusion, cause of death, creatinine level, and cold ischemia time. We also analyzed recipient outcomes and graft function. RESULTS: We analyzed 21 donor and 42 recipient records. The majority of donors (85.0%) were <50 years old. The mean donor urine output was 169 mL/h. Delayed graft function was not affected by donor variables. The serum Na and CMV status of the donor were related to the occurrence of an acute rejection episode, but only CMV status showed a significant influence in the multivariate analysis. Among different groups of donor creatinine, better donor function (creatinine <1.0 vs >1.0 mg/dL) was associated with better posttransplantation graft function (creatinine 1.18 vs 2.26 mg/dL). In long-term graft function and survival, donor creatinine showed no significant impact. According to the sequence of transplantation, recipients were divided into group 1 (first kidney transplantation: mean ischemia time, 207 minutes) vs group 2 (second kidney transplantation: mean ischemia time, 441 minutes). Group 1 showed better graft function and survival time. CONCLUSIONS: Only CMV status of the donor was related to acute rejection episodes after renal transplantation. The donor creatinine data also affected initial posttransplantation creatinine. There was no significant difference in long-term graft survival among various levels of donor kidney function.     

Effect of donor age on long-term survival following cardiac transplantation

BACKGROUND AND AIM: The current shortage of donor hearts has forced the criteria of organ procurement to be extended, leading to increased use of older donor hearts to bridge the gap between demand and availability. Our objective was to analyze the effect of donor age on outcomes after cardiac transplantation. METHODS: We retrospectively studied 864 patients who underwent cardiac transplantation at New York Presbyterian Hospital - Columbia University between 1992 and 2002. Patients were divided into two groups; donor age <40 years (Group A, n = 600) and donor age > or =40 years (Group B, n = 264). RESULTS: Characteristics including gender, body mass index, and cytomegalovirus (CMV) status were significantly different between the two donor age groups. Race, CMV status, toxoplasmosis status, left ventricular assist device prior to transplant, diabetes mellitus, and retransplantation were similar in both the recipient groups, while age, gender, and BMI were different. Early mortality was lower in Group A, 5%, versus 9.5% in Group B. Multivariate analysis revealed recipient female gender (odd ratio (OR) = 1.71), retransplantation (OR = 1.63), and increased donor age (OR = 1.02) as significant predictors of poor survival in the recipient population. Actuarial survival at 1 year (86.7% vs 81%), 5 years (75% vs 65%), and 10 years (56% vs 42%) was significantly different as well with a log rank p = 0.002. CONCLUSIONS: These findings suggest that increased donor age is an independent predictor of long-term survival. However, the shortage of organs makes it difficult to follow strict guidelines when placing hearts; therefore, decisions need to be made on a relative basis.     

Infectious complications in kidney transplant recipients: a single-center experience

To determine the patterns of infectious complications in renal transplant recipients in our center, we evaluated 48 patients (29 men and 19 women) who were transplanted between 1994 and 2003. The average age of the patients was 29 years. Thirty (62.5%) and 18 (37.5%) transplants were from living related and cadaveric donors, respectively. Posttransplant immunosuppression consisted of azathioprine or mycophenolate mofetil (MMF), prednisone, antithymocyte globulin (ATG), and cyclosporine or tacrolimus. The acute rejection episodes were treated with pulse doses of methylprednisolone; steroid-resistant rejection was treated with ATG or muromonab (OKT3). All patients received prophylaxis with sulfadoxine-pyrimethamine; none received prophylaxis against cytomegalovirus (CMV) infection. Thirty-nine (81%) recipients developed 77 confirmed episodes of infection; 35 (46%) episodes occurred in the early postoperative period, 28 (36%) in the first month and 14 (18%) after 6 months. According to the type of infection, there were 24 urinary tract, 16 CMV, seven herpetic, nine general septic, six fungal, four pneumonia, one disseminated nocardial, and 10 miscellaneous episodes. All 26 (100%) patients who had acute rejection episodes developed infections compared with 13/22 (59%) who did not have rejection (P < .01). There was a significant correlation between CMV disease and acute rejection and/or tacrolimus or MMF use. CMV infection occurred after the additional immunosuppressive treatment for acute rejection in 10 patients or during the use of tacrolimus or MMF in six patients. We conclude that CMV infection was the most frequent opportunistic pathogen in our renal transplant population and related to the intensive antirejection therapy, followed by urinary tract infections within 3 months after surgery.     

Early and Late Infections in Lung Transplantation Patients

Infections are an important cause of morbidity and mortality among transplanted patients. Their pathophysiology is associated with anatomic factors, immunosuppression, and pretransplant viral exposure. The aim of this investigation was to characterize infections following lung transplantation. We retrospectively analyzed the charts of 51 lung transplant recipients, who were transplanted between 1999 and 2008. Infections were classified according to their origin, etiology, occurrence time, and risk factors. The patient mean age was 55 years (range 13-71), 65% were male, and pulmonary fibrosis was the lung disease etiology in 59% of cases. Seventy-one episodes of infection were reported in the 51 patients, including (75%) during the first year after transplantation and 30 within the first 3 months (42%). Between the 4th and 11th months the number of infections decreased to 23 (32%), and afterwards there were 18 additional cases. The original site of infection was pulmonary in 43 episodes (60%), and the etiology was bacterial in 34 (48%), with Pseudomonas in 12 instances (35% of bacterial infections). Viruses were involved in 25 episodes, especially cytomegalovirus (CMV) in seronegative patients. The nine infections of fungal etiology (13%) were all caused by Aspergillus and always associated with either an acute rejection episode or suture damage. Three cases of tuberculosis were diagnosed, including two in the late post-transplant period. Three patients died of early infections.

Conclusions

The critical period for infections in lung transplantation patients is the first 3 months, especially for those of bacterial etiology. CMV diseases were more common in seronegative patients and fungal infections in airway injury cases.     

Risk Factors for Rejection and Infection in Pediatric Liver Transplantation

Rejection and infection are important adverse events after pediatric liver transplantation, not previously subject to concurrent risk analysis. Of 2291 children (<18 years), rejection occurred at least once in 46%, serious bacterial/fungal or viral infections in 52%. Infection caused more deaths than rejection (5.5% vs. 0.6% of patients, p < 0.001). Early rejection (<6 month) did not contribute to mortality or graft failure. Recurrent/chronic rejection was a risk in graft failure, but led to retransplant in only 1.6% of first grafts. Multivariate predictors of bacterial/fungal infection included recipient age (highest in infants), race, donor organ variants, bilirubin, anhepatic time, cyclosporin (vs. tacrolimus) and era of transplant (before 2002 vs. after 2002); serious viral infection predictors included donor organ variants, rejection, Epstein-Barr Virus (EBV) naivety and era; for rejection, predictors included age (lowest in infants), primary diagnosis, donor-recipient blood type mismatch, the use of cyclosporin (vs. tacrolimus), no induction and era. In pediatric liver transplantation, infection risk far exceeds that of rejection, which causes limited harm to the patient or graft, particularly in infants. Aggressive infection control, attention to modifiable factors such as pretransplant nutrition and donor organ options and rigorous age-specific review of the risk/benefit of choice and intensity of immunosuppressive regimes is warranted.     

Improved Late Graft Survival and Half-Lives in Pediatric Kidney Transplantation: A Single Center Experience

We evaluated variables associated with improved late graft survival in 290 children transplanted between 11/1/1984 and 12/31/1997, and who had > 1 year graft survival. We studied the following variables: age, gender, race, primary disease (diseases prone to recurrence, i.e. hemolytic uremic syndrome, focal segmental glomerulosclerosis or oxalosis vs. others), primary vs. retransplant; donor source, acute tubular necrosis, acute rejection episodes in the first year, transplant era and discharge serum creatinine. Graft half-life was defined as the time taken for 1/2 of the grafts functioning at 1 year to fail. There were 205 living donor and 85 cadaveric transplant. The cumulative graft survival at 5 and 10 years was 88% and 75% for living donor, and 72% and 46% for cadaveric, respectively. Multivariate analyses showed a higher late graft survival to be associated with: no acute rejection episodes (risk ratio 0.16, p = 0.0001), age 2-5 years (risk ratio 0.24, p = 0.0007), living donor (risk ratio 0.46, p = 0.017), primary nonrecurrent disease (risk ratio 0.29, p = 0.001), Caucasian race (risk ratio 0.40, p = 0.006). A high half-life was seen with living donor transplant (21.3 years) and the age group 2-5 years (27.5 years). Further, living donor patients with no acute rejection episodes had the best half-life of 37.6 years, while children with hemolytic uremic syndrome, focal segmental glomerulosclerosis or oxalosis had the lowest overall half-life of 5.6 years. This study finds that living donor, no acute rejection episodes, age 2-5 years, Caucasian race and having a disease not prone to recurrence are strong predictors of late graft survival. Hence, preferential use of living donor and prevention of acute rejection episodes in the first year are key variables that can improve long-term renal graft survival in children.     

The Impact of Infection on Chronic Allograft Dysfunction and Allograft Survival After Solid Organ Transplantation

Infectious diseases after solid organ transplantation (SOT) are a significant cause of morbidity and reduced allograft and patient survival; however, the influence of infection on the development of chronic allograft dysfunction has not been completely delineated. Some viral infections appear to affect allograft function by both inducing direct tissue damage and immunologically related injury, including acute rejection. In particular, this has been observed for cytomegalovirus (CMV) infection in all SOT recipients and for BK virus infection in kidney transplant recipients, for community‐acquired respiratory viruses in lung transplant recipients, and for hepatitis C virus in liver transplant recipients. The impact of bacterial and fungal infections is less clear, but bacterial urinary tract infections and respiratory tract colonization by Pseudomonas aeruginosa and Aspergillus spp appear to be correlated with higher rates of chronic allograft dysfunction in kidney and lung transplant recipients, respectively. Evidence supports the beneficial effects of the use of antiviral prophylaxis for CMV in improving allograft function and survival in SOT recipients. Nevertheless, there is still a need for prospective interventional trials assessing the potential effects of preventive and therapeutic strategies against bacterial and fungal infection for reducing or delaying the development of chronic allograft dysfunction.     

The adverse impact of cytomegalovirus infection on clinical outcome in cyclosporine-prednisone treated renal allograft recipients

Cytomegalovirus (CMV) infection was diagnosed in 28% (n = 144) of 516 renal allograft recipients treated with cyclosporine-prednisone (CsA-Pred) immunosuppressive therapy. The majority of infections produced either asymptomatic (n = 37) or mild-to-moderate (n = 75) clinical disease, while 10% were lethal (n = 14). Transplantation from a seropositive donor to a seronegative recipient was associated with an increased incidence of (CMV) infection but did not predispose to more severe clinical disease. Similarly, donor source (cadaver [CAD] vs. living-related donor [LRD]), age greater than or equal to 45 years, and antecedent pulse steroid therapy for the treatment of acute rejection were not correlated with clinically more severe disease. An increase in serum creatinine to greater than or equal to 25% of preinfection nadir values occurred in association with CMV infection in 106 patients, returning to nadir values or below in 74.5% of these individuals. CMV infection did not impact on actual patient survival among recipients of LRD or CAD allografts or on actual 1-year HLA-haploidentical or HLA-identical LRD graft survival. In contrast, actual 1-year cadaveric graft survival was significantly lower among CMV-infected (n = 95) vs. uninfected (n = 198) patients (75.8% vs. 87.8%, P = .01). In association with the finding of reduced actual 1-year CAD graft survival, CMV-infected patients were found to be more predisposed to develop acute rejection episodes. Of the CMV-infected CAD graft recipients, 48.4% developed greater than or equal to 1 acute rejection episode during the first year following transplantation vs. 25.3% of their uninfected counterparts (P less than .001). The impact of CMV infection in CsA-Pred treated renal transplant recipients does not differ substantially from that reported historically in association with prednisone-azathioprine immunosuppressive therapy.     

The influence of histocompatibility on graft rejection and graft survival within a single center population of heart transplant recipients.

BACKGROUND: We report a consecutive single center series of 261 patients who received first orthotopic heart transplants from 1986 to 1997. The 1- and 5-year graft survivals were 78 and 68%. The influence of histocompatibility was investigated by comparing graft survival and numbers of treated rejection episodes with HLA-A, -B, and -DR mismatches over different time periods. FINDINGS: Recipients with six mismatches for HLA-A+-B+-DR combined (13.4%) had reduced survival at 7 years (47%) when compared with other recipients (64%). In the first year of transplant, recipients with four HLA-A+-B mismatches had significantly reduced actuarial graft survival (P=0.03) with the greatest influence apparent at 6 months [0-3 mismatches (n=193) 85% versus 4 mismatches (n=68) 69%; P=0.005, OR=2.1]. For 182 recipients with functioning hearts at 1 year, the number of rejection episodes treated within this time was strongly influenced by HLA-DR mismatch [0 DR mismatch (n=15) mean 1.2 rejection episodes versus 1 DR mismatch (n=76) mean 2.7 rejection episodes versus 2 DR mismatches (n=91) mean 3.8 rejection episodes: P=0.0002]. Of these 182 transplants, recipients who had more than four treated rejection episodes during the first year had a significantly reduced 7- year survival [<5 rejection episodes (n=133) 85% versus more than four rejection episodes (n=49) 66%; P=0.02, OR=3.4], as did those with two HLA-DR mismatches [0+1 mismatch (n=91) 87% versus 2 mismatches (n=91) 70%; P<0.05, OR=2.4]. INTERPRETATION: We show that graft loss in the first 6 months of transplant is significantly influenced by four HLA-A+-B mismatches. HLA-DR mismatch significantly increases the number of rejection episodes within the first year, without influencing graft survival. After 12 months both >4 rejection episodes in the first year and two HLA-DR mismatches are markers for late graft loss. We postulate that immunological graft loss in the first 6 months is dominated by the direct allorecognition pathway driven by HLA-DR mismatch. This mechanism is later lost or suppressed. Our data highlight HLA-DR mismatch as a marker for late graft loss and we show an advantage to avoiding transplanting hearts with six HLA-A+-B+-DR mismatches and to minimizing HLA-DR mismatches whenever possible.