James F. Whiting

Effect of Dipyridamole plus Aspirin on Hemodialysis Graft Patency

BACKGROUND Arteriovenous graft stenosis leading to thrombosis is a major cause of complications in patients undergoing hemodialysis. Procedural interventions may restore patency but are costly. Although there is no proven pharmacologic therapy, dipyridamole may be promising because of its known vascular antiproliferative activity. METHODS We conducted a randomized, double-blind, placebo-controlled trial of extended-release dipyridamole, at a dose of 200 mg, and aspirin, at a dose of 25 mg, given twice daily after the placement of a new arteriovenous graft until the primary outcome, loss of primary unassisted patency (i.e., patency without thrombosis or requirement for intervention), was reached. Secondary outcomes were cumulative graft failure and death. Primary and secondary outcomes were analyzed with the use of a Cox proportional-hazards regression with adjustment for prespecified covariates. RESULTS At 13 centers in the United States, 649 patients were randomly assigned to receive dipyridamole plus aspirin (321 patients) or placebo (328 patients) over a period of 4.5 years, with 6 additional months of follow-up. The incidence of primary unassisted patency at 1 year was 23% (95% confidence interval [CI], 18 to 28) in the placebo group and 28% (95% CI, 23 to 34) in the dipyridamole-aspirin group, an absolute difference of 5 percentage points. Treatment with dipyridamole plus aspirin significantly prolonged the duration of primary unassisted patency (hazard ratio, 0.82; 95% CI, 0.68 to 0.98; P=0.03) and inhibited stenosis. The incidences of cumulative graft failure, death, the composite of graft failure or death, and serious adverse events (including bleeding) did not differ significantly between study groups. CONCLUSIONS Treatment with dipyridamole plus aspirin had a significant but modest effect in reducing the risk of stenosis and improving the duration of primary unassisted patency of newly created grafts. (ClinicalTrials.gov number, NCT00067119.)

The expanded criteria donor dilemma in cadaveric renal transplantation

Background. Outcomes of expanded criteria donor (ECD) kidney transplants are known to be superior to dialysis but inferior to transplant with a standard donor. Because of recent policy changes, ECD kidneys will be offered only to patients who have agreed to consider such an organ in advance. There is wide variation in opinion concerning the composition of ECD wait lists. However, the relative benefits of accepting an ECD versus waiting for a standard donor have not been quantified. Methods. A Markov model was developed to determine when an individual patient should accept or reject an offer of an ECD kidney to optimize their personal expected quality-adjusted life years (QALY). Input variables were estimated from the United States Renal Data System (USRDS) database using a sample of 35,030 recipients. Results. Recipients of ECD kidneys waited 77 days longer for transplant than recipients of standard donors. The average patient could wait 3.2 years longer, in addition to the time they have already waited, for a standard donor than an ECD and expect equivalent QALYs. Selected subsets revealed differences in wait times that equated QALYs for ECD and standard donors: African American, 4.4 years; age under 30, 4.0 years; age over 60, 11 months. Conclusions. Existing policy is likely to be in the best interests of only certain sets of patients awaiting cadaveric kidney transplantation unless ECDs dramatically reduce expected waiting for transplantation. This is most possible in elderly patients because of the short wait-time reduction required to make ECDs beneficial. Data reported here have been supplied by the USRDS. The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as an official policy or interpretation of the US Government. The data and analyses reported in the 2001 Annual Report of the United States Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients have been supplied by the United Network for Organ Sharing and University Renal Research and Education Association under contract with Health and Human Services. The authors alone are responsible for reporting and interpreting of these data.

Cost-Effectiveness of Organ Donation: Evaluating Investment into Donor Action and Other Donor Initiatives

Initiatives aimed at increasing organ donation can be considered health care interventions, and will compete with other health care interventions for limited resources. We have developed a model capable of calculating the cost‐utility of organ donor initiatives and applied it to Donor Action, a successful international program designed to optimize donor practices.

The Life-Years Saved by a Deceased Organ Donor

Understanding the additional life‐years given to patients by deceased organ donors is necessary as substantial investments are being proposed to increase organ donation. Data were drawn from the Scientific Registry of Transplant Recipients. All patients placed on the wait‐list as eligible to receive or receiving a deceased donor solid organ transplant between 1995 and 2002 were studied. The benefit of transplant was determined by the difference in the expected survival experiences of transplant recipients and candidates expecting transplant soon. An average organ donor provides 30.8 additional life‐years distributed over an average 2.9 different solid organ transplant recipients, whereas utilization of all solid organs from a single donor provides 55.8 additional life‐years spread over six organ transplant recipients. The relative contribution of the different organs to the overall life‐year benefit is higher for liver, heart and kidney, and lowest for lung and pancreas. The life‐year losses from unprocured and unused organs are comparable to suicide, congenital anomalies, homicide or perinatal conditions and half that of HIV. Approximately 250 000 additional life‐years could be saved annually if consent for potential deceased donors could be increased to 100%. Therefore, increasing organ donation should be considered among our most important public health concerns.

Economic cost of expanded criteria donors in cadaveric renal transplantation: Analysis of medicare payments.

Background. The use of expanded criteria donors (ECDs) in cadaveric renal transplantation is increasing in the US.We assess the economic impact of the use of ECDs to the Medicare end stage renal disease program. Methods. The United Nations for Organ Sharing renal transplant registry was merged to Medicare claims data for 42,868 cadaveric renal transplants performed between 1991–1996 using USRDS identifiers. Only recipients for whom Medicare was the primary payer were considered, leaving 34,534 transplants. An ECD was defined as (1) age ≤5 or ≥55 years, (2) nonheart-beating donors, donor history of (3) hypertension or (4) diabetes. High-risk recipients (HRR) were age >60 years, or a retransplant. Medicare payments from the pretransplant dialysis period were projected forward to provide a financial “breakeven point” with transplantation. Results. There were 25,600 non-HRR transplants, with 5,718 (22%) using ECDs, and 8,934 HRR transplants, of which 2,200 (25%) used ECDs. The 5-year present value of payments for non-ECD/non-HRR donor/recipient pairings was

Transporting live donor kidneys for kidney paired donation: initial national results.

121,698 vs.

Donor postextubation hypotension and age correlate with outcome after donation after cardiac death transplantation.

143,329 for ECD/non-HRR pairings (P <0.0001) and, similarly was

Design of the Dialysis Access Consortium (DAC) clopidogrel prevention of early AV fistula thrombosis trial

134,185 for non-ECD/HRR pairings vs.

The use of granulocyte colony-stimulating factor after liver transplantation

165,716 for ECD/HRR pairings (P <0.0001). The break even point with hemodialysis ranged from 4.4 years for non-ECD/non-HRR pairings to 13 years for the ECD/HRR combinations but was sensitive to small changes in graft survival. Transplantation was always less expensive than hemodialysis in the long run. Conclusions. The impact of ECDs on Medicare payments is most pronounced in high-risk recipients. Cadaveric renal transplantation is a cost-saving treatment strategy for the Medicare ESRD program regardless of recipient risk status or the use of ECDs.

Clinical results of an organ procurement organization effort to increase utilization of donors after cardiac death.

Optimizing the possibilities for kidney‐paired donation (KPD) requires the participation of donor–recipient pairs from wide geographic regions. Initially it was envisaged that donors would travel to the recipient center; however, to minimize barriers to participation and simplify logistics, recent trends have involved transporting the kidneys rather than the donors. The goal of this study was to review outcomes of this practice. KPD programs throughout the United States were directly queried about all transplants involving live donor kidney transport. Early graft function was assessed by urine output in the first 8 h, postoperative serum creatinine trend, and incidence of delayed graft function. Between April 27, 2007 and April 29, 2010, 56 live donor kidneys were transported among 30 transplant centers. Median CIT was 7.2 h (IQR 5.5–9.7, range 2.5–14.5). Early urine output was robust (>100 cc/h) in all but four patients. Creatinine nadir was <2.0 mg/dL in all (including the four with lower urine output) but one patient, occurring at a median of 3 days (IQR 2–5, range 1–49). No patients experienced delayed graft function as defined by the need for dialysis in the first week. Current evidence suggests that live donor kidney transport is safe and feasible.