Poor Allograft Survival Research Articles

ALLOANTIBODY TESTING IN PANCREAS TRANSPLANTS AND ITS CORRELATION WITH PANCREAS REJECTION AND PANCREAS GRAFT LOSS

335 Preformed HLA antibodies have been associated with poor kidney allograft survival and the development of HLA alloantibodies post transplant has also been associated with rejection and subsequent graft loss. The purpose of this study was to evaluate the predictive nature of HLA antibody testing in identifying high risk patients receiving a pancreas transplants and to determine whether antibody detected by post transplant monitoring was associated with rejection events and graft outcomes. The group of patients selected were 150 pancreas transplants were performed between 6/18/90-9/11/96 for which we had stored serum and follow up > 1 yr.. 133 received SPK, 5 LRD kidney/CAD pancreas, and 12 pancreas alone. All were transplanted with negative AHG T cell crossmatches: 131 with negative T and B flow crossmatches (FXM). The median age was 35 yrs. & 43% were female. The mean HLA mismatches were 3.9 for ABDR and 1.9 for DRDQ. Kidneys and pancreata were transplanted using bladder drainage. Patients received induction OKT3 therapy with maintenance immunosuppression consisting of cyclosporine, Imuran and prednisone. The outcomes for this cohort were the following: pancreas, kidney and patient survival at one year were 86.7%, & 88.7% and 92.7%. The overall rejection rate was 86.7% as determined by protocol and dysfunction biopsies. The average rejection reoccurrence rate was 80%, mean number of rejections was 2.29, and average time to first rejection was 44.5 days. The presence of alloantibody in pre-transplant sera was determined using PRA-STAT and CDC-PRA; the presence of alloantibody specific for donor was determined using FXM techniques. Serum collected post-transplant was tested at 1,2,3,6, & 12, >12 mo. using PRA-STAT (82 patients) and FXM (78 patients). The outcomes evaluated included kidney and pancreas loss up to 1, 3, 6 and 12 mo., patient survival at 12 mo, the total number and severity of rejections, time to first rejection, and rejection reoccurrence. PRA was ranked at 5, 7, 10, 15, 20, 30 and 50% and PRA evolution was an increase of more than 9%. Alloantibody in pre-transplant serum detected by PRA-STAT, CDC-PRA or FXM was associated with higher incidence of early pancreas rejection and lower pancreas graft survival at one year and kidney loss in low risk patients at 120 days. PRA stat evolution was associated with pancreas graft loss. Alloantibody detected by FXM in post-transplant serum was highly correlated (p<0.01) with a pancreas rejection event in the first 6 weeks after transplant and with both pancreas and kidney rejection events occurring between 1 and 6 months post transplant (p<0.001). This correlation was not seen with PRA-STAT. Conclusions: 1) Alloantibody detected pre-transplant identifies patients at risk for early pancreas rejection and lower pancreas graft survival. 2) Alloantibody is generated post-transplant during pancreas and kidney rejection events and may be used to guide biopsy 3) Flow crossmatching appears to be more sensitive than PRA-STAT in detecting antibody after transplant.

Impact of acute rejection and early allograft function on renal allograft survival.

Both acute rejection and the function of a renal allograft early after transplantation correlate with long-term graft survival. In this study we assessed the relationship between these two factors in 843 adult recipients of first cadaveric renal grafts, transplanted at a single institution and followed for a minimum of 3.5 years. Patients were divided into four groups according to (1) history of acute rejection (AR) during the first 6 months after transplantation, and (2) concentration of serum creatinine at 6 months after transplantation (SCr(6mo) < or > or = 2 mg/dl). Death censored allograft survival was not significantly different among patients without AR and with low SCr(6mo) (group 1, n=376), patients without AR but with an elevated SCr(6mo) (group 2, n=117), and patients with AR but low SCr(6mo) (group 3, n=185). In contrast, graft survival was significantly worse in patients with AR and an elevated SCr(6mo) (group 4, n=165) compared with patients in the other three groups (Cox, P<0.0001). The elevated SCr(6mo) in group 4 patients was not necessarily the consequence of AR, as 32% of patients in group 4 had a SCr at 10 days after transplantation (SCr(10d)), before they had AR, that was equal to or higher than the SCr(6mo). Based on this observation we investigated the implications of the SCr(10d) concentration for graft prognosis. The SCr(10d) correlated weakly with graft survival (Cox, P=0.05). However, an elevated SCr(10d) correlated with other potential risk factors for graft survival including: Older donors (P<0.0001), male recipients (P<0.0001), and heavier recipients (P<0.0001, all by multivariate regression); and posttransplant factors such as, increasing numbers of AR (P<0.0001), higher posttransplant blood pressure (P<0.0001), and lower doses of cyclosporine (P<0.0001, all by multivariate regression). In conclusion, graft dysfunction predicts poor graft survival only when associated with AR. Similarly, AR predicts a poor renal allograft survival only when associated with graft dysfunction. The SCr(10d) is an indicator of risk factors from both the donor and recipient, and an elevated SCr(10d) predicts a higher risk of acquiring additional risk factors early after transplantation.

The Indications for and Outcome in Pediatric Keratoplasty: A Multicenter Study

A multicenter study was undertaken to delineate the indications for and outcome of pediatric keratoplasty. The authors retrospectively studied 164 grafts in 131 eyes of 108 children younger than 12 years of age, with an average follow-up of 45 months. Multivariate linear and logistic regression was performed to evaluate potential risk factors for poor visual outcome and graft failure. Graft survival was depicted in terms of the Kaplan-Meier survival curve. Corneal opacities were grouped into three diagnostic categories: congenital (64%), traumatic (17%), and acquired nontraumatic (19%) opacities. Overall graft survival was 80% at 12 months and 67% at 24 months postoperatively. There was no significant difference in retention of clarity among diagnostic groups. Vitrectomy-lensectomy, regrafts, and postoperative complications were associated significantly with poor allograft survival. Eighteen percent of all eyes had worse vision at the time of the last visit than preoperatively. Amblyopia treatment was the only independently significant prognosticator for visual improvement after surgery. Timing of keratoplasty was not demonstrated to be associated with visual outcome. Visual acuity in 33% of eyes that could be quantified was better than 20/200 at the last visit, whereas 62% of eyes retained full graft clarity. The authors conclude that keratoplasty can be successful in most children, especially when combined with appropriate amblyopia management.

Racial differences in renal allograft survival: The role of systemic hypertension

The rate of decline in the number of functioning renal allografts beyond the first year after transplantation has changed little in the last 25 years, and during long-term follow-up most allografts are lost due to chronic transplant rejection or patient death. The recipient race correlates with allograft survival, and African American recipients have a lower allograft survival than Caucasians. The goal of the present study was to identify clinical variables present during the first six months after transplantation that predict the loss of renal allografts beyond six months after transplantation, and in particular to determine the role of systemic hypertension on renal allograft survival in black and white recipients. This study includes 547 recipients of first cadaveric renal allografts performed at The Ohio State University. All patients were treated with a uniform immunosuppressive protocol and had a follow-up of at least three years. By multivariate analysis the following variables correlate with poor allograft survival: an elevated serum creatinine concentration measured six months after transplantation (SCr6mo) (P < 0.0001); black race (P < 0.0001); increasing numbers of acute rejection episodes (ATR) (P = 0.002); and young recipients (P = 0.026). Allograft survival is significantly worse in black (mean allograft half-life of 7.7 +/- 1.3 years) than in white recipients (24 +/- 3 years) (P < 0.0001). Black recipients also have a significantly higher six month average mean arterial blood pressure (MAP) (105 +/- 8 mm Hg) than white recipients (102 +/- 7 mm Hg) (P = 0.002). However, the prevalence of hypertension is not significantly different in black (33%) than in white recipients (26%).(ABSTRACT TRUNCATED AT 250 WORDS)

The course of HIV disease in renal allograft recipients

The clinical course of HIV seropositive renal allograft recipients is ill defined. Thus, a retrospective analysis of mortality, morbidity and graft survival was performed in two groups of HIV-positive patients. Group 1 (nine patients), seropositive for an indefinite period of time prior to transplantation (eight IV drug abusers, one homosexual), all lost their grafts after a mean period of 23 ± 11 months from chronic rejection (six), complicated by focal glomerular sclerosis and nephrotic syndrome in three cases, sepsis (two) and death with a functioning graft (one). Four patients died, two from sepsis, one from Kaposi's sarcoma and one from fluid overload. Of the remaining five patients, all on hemodialysis, one had AIDS and four were asymptomatic after a mean period of 44 months following graft failure. Prolonged hospitalizations for both infections and acute rejection were common. Group 2 (six patients) seroconverted in the perioperative period, and two had functioning allografts at 78 and 100 months post-transplant. Causes of allograft loss, patient death and infection-related complications were similar to those of group 1, but acute rejection was rare. In conclusion, HIV infection in renal allograft recipients was associated with poor allograft survival due mainly to rejection, mostly chronic, often complicated by glomerular sclerosis and nephrotic syndrome. Infectious complications requiring hospitalization were also increased.

The course of HIV disease in renal allograft recipients.

The clinical course of HIV seropositive renal allograft recipients is ill defined. Thus, a retrospective analysis of mortality, morbidity and graft survival was performed in two groups of HIV-positive patients. Group 1 (nine patients), seropositive for an indefinite period of time prior to transplantation (eight i.v. drug abusers, one homosexual), all lost their grafts after a mean period of 23 +/- 11 months from chronic rejection (six), complicated by focal glomerular sclerosis and nephrotic syndrome in three cases, sepsis (two) and death with a functioning graft (one). Four patients died, two from sepsis, one from Kaposi's sarcoma and one from fluid overload. Of the remaining five patients, all on hemodialysis, one had AIDS and four were asymptomatic after a mean period of 44 months following graft failure. Prolonged hospitalizations for both infections and acute rejection were common. Group 2 (six patients) seroconverted in the perioperative period, and two had functioning allografts at 78 and 100 months post-transplant. Causes of allograft loss, patient death and infection-related complications were similar to those of group 1, but acute rejection was rare. In conclusion, HIV infection in renal allograft recipients was associated with poor allograft survival due mainly to rejection, mostly chronic, often complicated by glomerular sclerosis and nephrotic syndrome. Infectious complications requiring hospitalization were also increased.

Effect of Blood Transfusion on Renal Allograft Survival: Immunologic Considerations

DETERMINATION of immunologic factors relevant to renal allograft survival may allow identification of high risk potential recipients who will experience poor allograft survival. These factors may include histocompatibility matching, determination of recipient anti donor immune responsiveness and finally, the general, nonspecific state of recipient immunocompetence. Well matched cadaveric grafts, in recipients with no known donor alloantigen pre sensitivity , may be rejected because the recipient is a high-risk strong immune responder. 1 We cannot yet determine whether these recipients are strong responders to all alloantigens or whether they are presensitized to a donor antigen not tested for, such as kidney specific or enothelial antigens. For recipients of living related donor (LRD) organs a high donor specific mixed lymphocyte culture (MLC) stimulation index (SI) is a risk factor. As has been reported by the UCSF transplant group and others, graft survival, in haplotype matched related renal allograft recipients with a high MLC SI, is comparable to the results of cadaveric transplantation with a l-yr graft survival rate of 45%-55%.2 The data imply that high MLC responders are at risk when they receive the LRD organ. Potential recipients of LRD grafts, with strong donor specific MLC responsiveness, may be relegated to receive a cadaveric allograft as one alternative. A second alternative is to be transplanted with the LRD graft and to be treated with adjunctive immunosuppressive medications postoperatively, such as antithymocyte globulin (ATG) or cyclosporin A, to dampen the potentially destructive immune response. These medications may modify the immune response and improve strong immune responder graft survivals so that they are comparable to weak MLC LRD graft survivals. 1 However, the patient morbidity and mortality attendant with the use of these medications is still to be determined. A third alternative is for the strong MLC responder recipient to be treated with purposeful blood transfusions from the prospective kidney donor prior to transplant. Transfused recipients who do not respond by developing deleterious anti-Tor B antibodies can be transplanted and a clear cut positive influence on allograft survival has been reported. 3•4 However, before recommending wholesale donor specific transfusions (DST) of strong responder recipients of LRD grafts, a detailed examination of the protocol is necessary to determine the appropriateness of such a protocol to other patients and to compare these data with data obtained from random donor transfusions in cadaveric transplantation. It is possible that consideration of these points may result in an appreciation of what has been accomplished, arid more significantly, may direct our attention to improving graft survival for those positive responders who are excluded from receiving an LRD graft following transfusion and for recipients of cadaveric grafts. Since initiating the DST protocol, the UCSF transplant team has reported that approximately 30% of the transfused patients developed donor specific anti-T or B antibodies, which was taken as a contraindication to transplantation. Recipients v.'ith a negative cross-match who received a kidney from their blood donors had approximately a 95% graft survival. 3.4 As indicated, the mechanism(s) operative in the DST protocol may be: (1) selection and segregation of responders from nonresponders by antibody development; or (2) modification of the host immune response by the development of suppressor cells or the development of antiidiotypic (enhancing) antibodies. As reported, approximately 65% of the patients receiving DST also received random donor transfusions. 3 It is now widely accepted that increasing numbers of random pretransplant transfusions can improve cadaveric allograft survival. 5 Moreover, haplotype matched recipients of LRD