Donald C. Dafoe

Effect of Towne Live Virus Vaccine on Cytomegalovirus Disease after Renal Transplant: A Controlled Trial

OBJECTIVE To test the efficacy of vaccination with the Towne live attenuated cytomegalovirus vaccine. DESIGN A double-blind, randomized, placebo-controlled trial in candidates for renal transplantation. The cytomegalovirus serologic status of both recipients and donors were determined, and the recipients were followed for periods of 6 months to 7 years after transplant. SETTING A university transplant center. PATIENTS The analyses were made on 237 patients who were given either vaccine or placebo, received renal transplants, and were followed for at least 6 months. INTERVENTION Subcutaneous inoculation with Towne live attenuated virus or with placebo. MAIN OUTCOME MEASURES The presence of cytomegalovirus infection was defined by virus isolation and antibody tests. If infection occurred, a prearranged scoring system for cytomegalovirus disease was used to objectify disease severity. RESULTS The vaccine was well tolerated, and there were no discernible long-term adverse effects. Recipients who were originally seropositive did not clearly benefit from vaccination. Protective efficacy was analyzed in the group at highest risk for cytomegalovirus disease; recipients who were seronegative at the time of vaccination and who received a kidney from a seropositive donor. Compared with placebo recipients, vaccinated patients in this group had significantly less severe cytomegalovirus disease, with a significant reduction in disease scores (P = 0.03) and 85% decrease in the most severe disease (95% CI, 35% to 96%), although infection rates were similar. Graft survival at 36 months was improved in vaccinated recipients of cadaver kidneys (8 of 16) compared with unvaccinated recipients (4 of 16) (P = 0.04). CONCLUSIONS Previous vaccination of seronegative renal transplant recipients with live cytomegalovirus results in reduction of disease severity mimicking the action of naturally derived immunity.

Evaluation of the older cadaveric kidney donor: the impact of donor hypertension and creatinine clearance on graft performance and survival.

Background. The use of older donors for cadaveric renal transplantation (CRT) remains controversial because older donors are associated with decreased graft survival, yet offer the opportunity for donor pool expansion.We investigated the impact of two age-related donor factors, hypertension and calculated creatinine clearance (C Cr), as predictors of graft outcome in recipients of CRTs from donors ≥55 years of age. Methods. We reviewed 33,595 recipients of CRTs reported to UNOS since 4/1/94, of which 4,732 were from donors aged ≥55 years. Outcome measures were graft survival, serum creatinine, and incidence of delayed graft function with 3 years of follow-up. We first analyzed the effect of hypertension on outcome from donors ≥55 years: 2679 donors had no hypertension, 1058 had hypertension ≤10 years, and 557 had hypertension >10 years. Next, the effect of donor C Cr as a risk predictor was investigated. Based on this analysis, recipients of older donors were grouped into two cohorts for comparison: 2570 donors with C Cr <80 ml/min and 2162 donors with C Cr ≥80 ml/min. Results. Actuarial graft survival from donors aged <55 years was 88.0, 83.4, and 78.5% at 1, 2, and 3 years, vs. 80.6, 73.5, and 65.3% from donors ≥55 years (P <0.0001). When stratified by hypertension, older donors hypertensive >10 years had survivals of 77, 66, and 57% vs. 81, 73, and 65% from donors without hypertension (P <0.017) and 80, 74, and 66% from donors hypertensive <10 years (P <0.017). When stratified by C Cr, older donors with C Cr <80 ml/min had survivals of 77, 69, and 62% vs. 83, 76, and 66% from donors with C Cr ≥80 (P <0.0001). Finally, older donors with both hypertension >10 years and C Cr <80 ml/min had survivals of 77, 61, and 53%. Conclusions. Long-standing hypertension and low calculated creatinine clearance are risk factors for decreased graft survival of CRTs from older donors. When both factors are present, graft survival is significantly decreased.

The use of bilateral adult renal allografts - a method to optimize function from donor kidneys with suboptimal nephron mass.

Alternatives to traditional organ donor usage has allowed expansion of the organ donor pool to help compensate for the increasing disparity between recipients and donors. The use of bilateral adult renal transplants is a novel idea to salvage older donor kidneys with suboptimal nephron mass that would otherwise be destined for discard. Ten renal transplants were performed utilizing both kidneys from adult cadaver donors with diminished nephron mass determined by calculated glomerular filtration rate or biopsy evidence of significant glomerulosclerosis (>10%). Nine of ten (90%) recipients have satisfactory renal function at a mean follow-up of 7 months. The single case of graft failure was due to documented medical non-compliance. Mean serum creatinine at 6 months was 1.5 mg/dl. Mean measured creatinine clearance was 43.2+/-3.4. These preliminary findings suggest that the use of bilateral renal transplants provide satisfactory early function and allows salvage of older donor kidneys with suboptimal nephron mass.

Percutaneous transluminal angioplasty. The procedure of choice in the hypertensive renal allograft recipient with renal artery stenosis.

A retrospective review of 547 renal transplants performed over a six-year period revealed allograft renovascular hypertension secondary to RTAS in 39 (7.1%) patients. Percutaneous transluminal angioplasty (PTA) resulted in immediate cure or improvement in 76% of the patients, increasing to 83% in patients with functioning kidneys at a mean follow-up period of 30 months (1–72 months). The renal artery stenosis (RTAS) was equally distributed between living-related and cadaver kidney recipients and did not appear to be more prevalent in end-to-end or end-to-side anastomoses. The blood pressures fell from pre-PTA levels of 167 ± 22 mmHg systolic to 141 ± 23.7 post-PTA and 102 ± 11 mmHg diastolic pre-PTA to 88 ± 12 mmHg post-PTA (P < 0.01). Of 25 cured or improved patients, 24 are on significantly less hypertensive medication. Two patients died of causes unrelated to the PTA and only one patient lost a kidney because of the procedure. Compared with operation, PTA is a safer and more effective procedure for the initial treatment of RTAS.

Financial incentives for cadaver organ donation: An ethical reappraisal

A panel of ethicists, organ procurement organization executives, physicians, and surgeons was convened by the sponsorship of the American Society of Transplant Surgeons to determine whether an ethically acceptable pilot trial could be proposed to provide a financial incentive for a family to consent to the donation of organs from a deceased relative. An ethical methodology was developed that could be applied to any proposal for monetary compensation to elucidate its ethical acceptability. An inverse relationship between financial incentives for increasing the families’ consent for cadaver donation that clearly would be ethically acceptable (e.g., a contribution to a charity chosen by the family or a reimbursement for funeral expenses) and those approaches that would more likely increase the rate of donation (e.g., direct payment or tax incentive) was evident. The panel was unanimously opposed to the exchange of money for cadaver donor organs because either a direct payment or tax incentive would violate the ideal standard of altruism in organ donation and unacceptably commercialize the value of human life by commodifying donated organs. However, a majority of the panel members supported reimbursement for funeral expenses or a charitable contribution as an ethically permissible approach. The panel concluded that the concept of the organ as a gift could be sustained by a funeral reimbursement or charitable contribution that conveyed the appreciation of society to the family for their donation. Depending on the amount of reimbursement provided for funeral expenses, this approach could be ethically distinguished from a direct payment, by their intrusion into the realm of altruism and voluntariness. We suggest that a pilot project be conducted to determine whether this kind of a financial incentive would be acceptable to the public and successful in increasing organ donation.

When should expanded criteria donor kidneys be used for single versus dual kidney transplants

BACKGROUND To increase the utilization of cadaveric donor kidneys, we have recently expanded our acceptable criteria to include aged donors (frequently with a history of hypertension), by selectively using both donor kidneys (dual transplant) into a single recipient. METHODS To define when these expanded criteria donor (ECD) kidneys should be used as a single versus a dual kidney transplant, we retrospectively reviewed 52 recipients of ECD kidneys that had been turned down by all other local centers between 1/1/95 and 11/15/96. Fifteen patients received dual transplants, whereas the remaining 37 received single kidneys. Of the dual kidney recipients, 14 of 15 ECD were > or = 59 years of age, 10 of 15 were hypertensive, and 9 of 15 were both. Of the single recipients, 11 of 37 ECD were > or = 59 years of age, 11 of 37 were hypertensive, and 7 of 37 were both. All patients received cyclosporine-based triple-drug therapy. We compared seven donor (D) and sixteen recipient outcome variables in single versus dual kidney transplants as subgrouped by: (1) donor admission creatinine clearance (D-AdC(Cr)) < 90 ml/min; (2) D-age > or = 59 years; and (3) cold storage (Cld Stg) < or > 24 hr. RESULTS In the group with D-AdC(Cr) < 90, there was a significantly higher incidence of delayed graft function (DGF) in single versus dual recipients (9 of 20 [45%] vs. 1 of 11 [9%]; P=0.04) and worse early graft function based upon mean serum creatinine at 1 and 4 weeks (5.3+/-3.3 and 2.8+/-2.0 vs. 1.7+/-0.6 and 1.4+/-0.5 mg] dl; P<0.05). In the group with D-age > or = 59, recipients of single kidneys had significantly higher mean serum creatinine at 1, 4, and 12 weeks versus recipients of dual kidneys (5.1+/-3.3, 3.4+/-2.1, 2.8+/-1.5 versus 2.8+/-2.5, 1.5+/-0.6, 1.6+/-0.5 mg/dl; P<0.05). Cld Stg time also had an impact on DGF and early outcome. Recipients of dual kidneys stored less than 24 hr had a significantly lower incidence of DGF versus single kidneys stored more than 24 hr (10% vs. 46%; P<0.05) and better early graft function based on mean serum creatinine at 1, 4, and 12 weeks (1.9+/-0.8, 1.3+/-0.4, 1.5+/-0.2 vs. 6.6+/-3.4, 3.0+/-1.6, 2.9+/-1.9 mg/dl; P<0.05). The overall 1-year patient and graft survivals were 96% and 81% vs. 93% and 87% (P=NS) in recipients of single ECD versus dual ECD kidneys. CONCLUSIONS In conclusion, we believe that kidneys from ECD with D-AdC(Cr) < 90 ml/min and D-age > or = 59 should be used as dual kidney transplants, keeping the Cld Stg time at < 24 hr to minimize the effect of Cld Stg on early graft function.

Percutaneous transluminal angioplasty treatment of renal transplant artery stenosis.

Since June 1979, percutaneous transluminal angioplasty (PTA) has been the procedure of choice for renal transplant artery stenosis (RTAS) at the Hospital of the University of Pennsylvania. Of 241 renal allograft recipients, 17 (7%) when studied by arteriogram because of suspected RTAS proved to have

Dual-kidney transplantation with organs from expanded criteria donors: a long-term follow-up.

Background. Since 1995, dual-kidney transplantation using organs from marginal donors has been used at our center to expand the organ donor pool and decrease the waiting time for deceased donor kidney transplantation. This approach has allowed for a shorter waiting period without compromising outcome in the early posttransplant period. We now have 8-year follow-up in the first recipients. Older individuals were offered this option preferentially, because we reasoned that they would stand to benefit most from the shorter waiting period. Methods. Patients aged 55 years or more who underwent either dual-kidney transplantation with expanded criteria donors or single-kidney transplantation with standard donors were included in this study. All expanded criteria donor organs were those that were refused by all other local transplant centers. The primary endpoints were recipient death and graft failure. Results. Waiting time for dual-kidney transplantation was 440±38 days versus 664±51 days for single-kidney transplantation (P<0.01). The 8-year actuarial patient survivals for the single- and dual-kidney transplants were 74.1% and 82.1%, respectively. The 8-year actuarial graft survivals for the single- and dual-kidney transplants were 59.4% and 69.7%, respectively. Conclusions. Eight-year actuarial patient and graft survivals in older individuals who underwent dual-kidney transplantation are equivalent to those who underwent standard single-kidney transplantation. With the continuing organ shortage and increasing waiting times for cadaver kidney transplantation, dual-kidney transplantation using organs that would otherwise be discarded offers a good option for older individuals who may not withstand a long waiting period.

A recent decrease in the time to development of monomorphous and polymorphous posttransplant lymphoproliferative disorder.

&NA; We have noted a decrease in the time to development of posttransplant lymphoproliferative disorder (PTLD) over the last two and one-half years in our multiorgan transplant program. From February 1965 until December 1990, 1622 transplants were performed including 1489 kidneys (KTxp), 87 livers (LTxp), and 46 pancreata. Between February 1965 and July 1988 (group 1), there were 1260 transplants performed and nine cases of either monomorphous PTLD (M-PTLD, n=8) or polymorphous PTLD (P-PTLD, n=1) were diagnosed. The mean time to development of PTLD was 163±128 weeks, all after KTxp. Five of these nine patients received haploidentical living-related grafts. All patients had presented with advanced disease, none had transplant nephrectomy, and all died of their disease. Between July 1988 and December 1990 (group 2), 362 transplants were performed, and four cases of M-PTLD and three cases of P-PTLD were recognized. Of the seven cases of PTLD in group 2, six developed within 90 days posttransplant (early PTLD). The mean time to development of PTLD was 11±16 weeks. This was significantly earlier than group 1 (P<.01). Four of the five cases after KTxp had a 1 or 2 DR-matched donor. Five of these seven patients had serological evidence of recent Epstein-Barr Virus infection, and four of these five had received OKT3 and then developed early PTLD. In group 2, three patients are alive 7–15 months after KTxp nephrectomy, the remaining four have died. We hypothesize that risk factors for the development of PTLD may include heavy immunosuppression, including the use of OKT3, good DR matching, and active EBV infection. Treatment should include graft removal, if applicable, and reduction or cessation of immunosuppression.

Outcome in recipients of dual kidney transplants: An analysis of the dual registry patients

BACKGROUND A novel but controversial method to increase the utilization of aged donor kidneys is the transplantation of both kidneys as a dual transplant. Initial single-center reports demonstrated outcomes similar to single kidneys from younger donors. In this report, we compare outcome in recipients of kidneys from donors > or =54 years of age who received a single kidney transplant reported to the United Network for Organ Sharing Scientific Registry versus a dual kidney transplant reported to the Dual Kidney Registry. METHODS A retrospective analysis was performed, comparing four donor and nine recipient and outcome variables between recipients of a single versus a dual transplant between March 1993 and March 1999. RESULTS Dual versus single transplants from donors > or =54 years of age have a significantly decreased incidence of delayed graft function, and lower serum creatinines up to 2 years after transplant despite having kidneys from significantly older donors with poorer HLA matching. CONCLUSIONS Dual kidney transplants improve graft performance and outcome in recipients of kidneys from donors > or =54 years of age.