Cause and timing of first allograft failure in orthotopic liver transplantation: A study of 177 consecutive patients

The cause and timing of first liver allograft failure was evaluated in 177 patients who underwent a second liver transplant between January 1984 and December 1988. The population studied consisted of 94 men and 83 women with a mean age 41.3 ± 1.0 yr (mean ± S.E.M.). Mean first‐graft survival was 130.6 ± 22.9 days (range = 0 to 2,073 days). Sixty‐eight percent of the grafts failed in the first postoperative month, 26% failed between the second and twelfth month and only 6% failed beyond the twelfth month from the date of the initial transplant. Six principal causes of graft failure were identified. Early allograft losses occurred as a result of four major problems: primary graft nonfunction (30.0% of all grafts; mean graft survival = 3.4 ± 0.3 days); ischemic injury of the graft without overt vascular injury (9.6%; mean graft survival = 17.5 ± 1.9 days); acute rejection (10.7%; mean graft survival = 30.4 ± 6.4 days); and overt vascular complications (26.6%; mean graft survival = 59.6 ± 24.1 days). Late graft failures were the result of either chronic rejection (11.3%; mean graft survival = 496.3 ± 136.0 days) or recurrence of the primary liver disease (6.8%; mean graft survival = 550.5 ± 172.1 days). Graft failure occurred as a result of a variety of miscellaneous causes in 5% of the cases (mean graft survival in this group = 300.0 ± 110.6 days). Overall 6‐mo patient survival after a second liver transplant was 46.3%. Patients who had a retransplant because of chronic rejection and ischemic injury had the greatest (65%) and least (23%) 6‐mo survival rates respectively after second grafting (p < 0.05). Those who survived the second transplant procedure for 6 mo or more tended be younger (p < 0.01) and had a reduced first transplant requirement for red blood cells (p < 0.05), latelets (p < 0.01) and fresh frozen plasma (p < 0.01) than did those who died during the 6 mo after their second transplant procedure. (HEPATOLOGY 1991;14:1054–1062.) Copyright © 1991 American Association for the Study of Liver Disease

Preimplantation biopsy predicts delayed graft function, glomerular filtration rate and long-term graft survival of transplanted kidneys

Background The predictive value of preimplantation biopsies for long-term graft function is often limited by conflicting results. The aim of this study was to evaluate the influence of time-zero graft biopsy histological scores on early and late graft function, graft survival and patient survival, at different time points. Methods We retrospectively analyzed 284 preimplantation biopsies at a single center, in a cohort of recipients with grafts from live and deceased donors (standard and nonstandard), and their impact in posttransplant renal function after a mean follow-up of 7 years (range 1–16). Implantation biopsy score (IBS), a combination score derived from 4 histopathological aspects, was determined from each sample. The correlation with incidence of delayed graft function (DGF), creatinine clearance (1st, 3rd and 5th posttransplant year) and graft and patient survival at 1 and 5 years were evaluated. Results Preimplantation biopsies provided somewhat of a prognostic index of early function and outcome of the transplanted kidney in the short and long term. In the immediate posttransplantation period, the degree of arteriolosclerosis and interstitial fibrosis correlated better with the presence of DGF. IBS values between 4 and 6 were predictive of worst renal function at 1st and 3rd years posttransplant and 5-year graft survival. The most important histological finding, in effectively transplanted grafts, was the grade of interstitial fibrosis. Patient survival was not influenced by IBS. Conclusions Higher preimplantation biopsy scores predicted an increased risk of early graft losses, especially primary nonfunction. Graft survival (at 1st and 5th years after transplant) but not patient survival was predicted by IBS

The use of FK-506 for small intestine llotransplantation: Inhibition of acute rejection and prevention of fatal graft-versus-host disease

Small intestine allotransplantation in humans is not yet feasible due to the failure of the current methods of immunosuppression. FK-506, a powerful new immunosuppressive agent that is synergistic with cyclosporine, allows long-term survival of recipients of cardiac, renal, and hepatic allografts. This study compares the effects of FK-506 and cyclosporine on host survival, graft rejection, and graft-versus-host-disease in a rat small intestine transplantation model. Transplants between strongly histoincompatible ACI and Lewis (LEW) strain rats, and their Fi progeny are performed so that graft rejection alone is genetically permitted (F1→LEW) or GVHD alone permitted (LEW→F1) or that both immunologic processes are allowed to occur simultaneously (ACI—»LEW). Specific doses of FK-506 result in prolonged graft and host survival in all genetic combinations tested. Furthermore, graft rejection is prevented (ACI→LEW model) or inhibited (rejection only model) and lethal acute GVHD is eliminated. Even at very high doses, cyclosporine did not prevent graft rejection or lethal GVHD, nor did it allow long-term survival of the intestinal graft or the host. Animals receiving low doses of cyclosporine have outcomes similar to the untreated control groups. No toxicity specific to FK-506 is noted, but earlier studies by other investigators suggest otherwise. © 1990 by Williams & Wilkin

Cadaveric renal transplantation under cyclosporine-steroid therapy

Ninety-seven cadaveric renal transplants were performed upon 96 patients during 1981. The one year patient mortality was 2.1 per cent. Seventy of the recipients were undergoing trasplantation for the first time. Of these patients, 38 were treated with cyclosporine and steroids with a one year graft survival rate of 89.5 per cent. The other 32 primary recipients were treated with azathioprine and steroids with a one year graft survival rate of 50 per cent. The difference between the cyclosporine-steroid versus conventional therapy groups was significant. Cyclosporine and steroids were also used to treat 26 patients who underwent retransplantation with 27 cadaveric grafts. The one year graft survival time was 77.8 per cent; most of the graft losses were in presensitized patients. The results with retransplantation were twice as good as in historical control groups

5-Year survival of pediatric anterior cruciate ligament reconstruction with living donor hamstring tendon grafts

Background: It is well accepted that there is a higher incidence of repeat anterior cruciate ligament (ACL) injuries in the pediatric population after ACL reconstruction (ACLR) with autograft tissue compared with adults. Hamstring autograft harvest may contribute to the risk for repeat ACL injuries in this high functional demand group. A novel method is the use of a living donor hamstring tendon (LDHT) graft from a parent; however, there is currently limited research on the outcomes of this technique, particularly beyond the short term. Purpose/Hypothesis: The purpose was to determine the medium-term survival of the ACL graft and the contralateral ACL (CACL) after primary ACLR with the use of an LDHT graft from a parent in those aged less than 18 years and to identify factors associated with subsequent ACL injuries. It was hypothesized that ACLR with the use of an LDHT provides acceptable midterm outcomes in pediatric patients. Study Design: Case series; Level of evidence, 4. Methods: Between 2005 and 2014, 247 (of 265 eligible) consecutive patients in a prospective database, having undergone primary ACLR with the use of an LDHT graft and aged less than 18 years, were included. Outcomes were assessed at a minimum of 2 years after surgery including data on ACL reinjuries, International Knee Documentation Committee (IKDC) scores, and current symptoms, as well as factors associated with the ACL reinjury risk were investigated. Results: Patients were reviewed at a mean of 4.5 years (range, 24-127 months [10.6 years]) after ACLR with an LDHT graft. Fifty-one patients (20.6%) sustained an ACL graft rupture, 28 patients (11.3%) sustained a CACL rupture, and 2 patients sustained both an ACL graft rupture and a CACL rupture (0.8%). Survival of the ACL graft was 89%, 82%, and 76% at 1, 2, and 5 years, respectively. Survival of the CACL was 99%, 94%, and 86% at 1, 2, and 5 years, respectively. Survival of the ACL graft was favorable in patients with Tanner stage 1-2 at the time of surgery versus those with Tanner stage 3-5 at 5 years (87% vs 69%, respectively; hazard ratio, 3.7; P = .01). The mean IKDC score was 91.7. A return to preinjury levels of activity was reported by 59.1%. Conclusion: After ACLR with an LDHT graft from a parent in those aged less than 18 years, a second ACL injury (ACL graft or CACL injury) occurred in 1 in 3 patients. The 5-year survival rate of the ACL graft was 76%, and the 5-year survival rate of the CACL was 86%. High IKDC scores and continued participation in sports were maintained over the medium term. Importantly, there was favorable survival of the ACL graft in patients with Tanner stage 1-2 compared with patients with Tanner stage 3-5 over 5 years. Patients with Tanner stage 1-2 also had a significantly lower incidence of second ACL injuries over 5 years compared with those with Tanner stage 3-5, occurring in 1 in 5 patients. Thus, an LDHT graft from a parent is an appropriate graft for physically immature children

Diversity of gut microflora is required for the generation of B cell with regulatory properties in a skin graft model

B cells have been reported to promote graft rejection through alloantibody production. However, there is growing evidence that B cells can contribute to the maintenance of tolerance. Here, we used a mouse model of MHC-class I mismatched skin transplantation to investigate the contribution of B cells to graft survival. We demonstrate that adoptive transfer of B cells prolongs skin graft survival but only when the B cells were isolated from mice housed in low sterility "conventional" (CV) facilities and not from mice housed in pathogen free facilities (SPF). However, prolongation of skin graft survival was lost when B cells were isolated from IL-10 deficient mice housed in CV facilities. The suppressive function of B cells isolated from mice housed in CV facilities correlated with an anti-inflammatory environment and with the presence of a different gut microflora compared to mice maintained in SPF facilities. Treatment of mice in the CV facility with antibiotics abrogated the regulatory capacity of B cells. Finally, we identified transitional B cells isolated from CV facilities as possessing the regulatory function. These findings demonstrate that B cells, and in particular transitional B cells, can promote prolongation of graft survival, a function dependent on licensing by gut microflora

Cadaveric renal transplantation at the University of Pittsburgh: a two and one-half-year experience with the point system.

From January 1, 1986 to July 30, 1988, 530 consecutive cadaver kidney transplantations were performed with patient selection by a point system that took into account time awaiting an organ, donor-recipient matching, degree of presensitization, and some less important factors. The effect of the system was to diminish judgmental factors in case selection which in the past, had probably operated to the disadvantage of "undesirable" potential recipients, including older ones. Primary 1-year graft survival (74%) and graft survival after retransplantation (71%) were lower than in the earlier time. However, the results with triple-drug therapy using CsA, AZA and P demonstrated 88% 1-year graft survival for primary graft recipients and 74% in highly sensitized patients, with comparable patient mortality. These latter observations provide some assurance that the concepts of equitable access and efficient utilization of a scarce resource are not mutually exclusive

One hundred ten consecutive primary orthotopic liver transplants under FK 506 in adults.

An account is given of the 6- to 12-month survival, and causes of failure in 110 consecutive patients who underwent primary liver transplantation under treatment from the outset with FK 506 and steroids. The patient survival is 92.7%, and the first graft survival is 87.3%. At a very high frequency, the patients achieved good graft function, and they had a relatively low morbidity that was partially ascribable to minimal use and early discontinuance (in 60% of cases) of steroids. Renal dysfunction and other adverse findings were largely confined to patients with poor initial graft function and consequent apparent alteration of the kinetics of FK 506 elimination, causing functional overdosage. Results compare very favorably with our past record using conventional immunosuppression, and support the belief that FK 506 is a superior immunosuppressive agent which is suitable for chronic administration

"Suboptimal" kidney donors: The experience with tacrolimus-based immunosuppression

Female, pediatric, and older donors have been associated with inferior graft survival after renal transplantation. We analyzed these three subgroups in 397 patients receiving tacrolimus-based immunosuppression. There were no differences in recipient age, incidence of retransplantation, or percentage of sensitized patients. Female donors, compared with male donors, were associated with comparable 1- and 3-year patient survival rates (96% and 93% vs. 95% and 92%, respectively) and comparable 1- and 3-year graft survival rates (90% and 80% vs. 88% and 81%, respectively). Renal function was also similar. Recipients of pediatric en bloc kidneys, when compared with recipients of other cadaveric kidneys, also had comparable 1- and 3-year patient survival rates (94% and 94% vs. 95% and 91%, respectively) and comparable 1- and 3-year graft survival rates (84% and 84% vs. 89% and 79%, respectively). Renal function was better in recipients of en bloc kidneys, with a mean serum creatinine level of 1.4±1.8 mg/dl vs. 2.0±1.5 mg/dl (P=0.01). In contrast to the first two subgroups, donors over 60 years of age, when compared with donors under 60 years of age, were associated with worse 1- and 3-year patient survival rates (88% and 80% vs. 96% and 94%, respectively; P<0.03) and worse 1- and 3-year graft survival rates (74% and 62% vs. 91% and 83%, respectively; P<0.0001). Renal function was worse in the older donor group, with a serum creatinine level of 2.7±1.2 mg/ml vs. 1.9±1.5 mg/dl (P=0.01). We conclude that, under tacrolimus-based immunosuppression, kidneys from female or very young pediatric donors are not associated with adverse outcomes, whereas kidneys from donors over 60 years of age are associated with inferior outcomes