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Biomedical subjects

Francis L Delmonico

Publications and source records attributed to Francis L Delmonico.

At least 19 recordsLinked to original sources
PubMed2006

Increasing the opportunity of live kidney donation by matching for two- and three-way exchanges.

BACKGROUND: To expand the opportunity for paired live donor kidney transplantation, computerized matching algorithms have been designed to identify maximal sets of compatible donor/recipient pairs from a registry of incompatible pairs submitted as candidates for transplantation. METHODS: Demographic data of patients who had been evaluated for live donor kidney transplantation but found to be incompatible with their potential donor (because of ABO blood group or positive crossmatch) were submitted for computer analysis and matching. Data included ABO and HLA types of donor and recipient, %PRA and specificity of recipient alloantibody, donor/recipient relationship, and the reason the donor was incompatible. The data set used for the initial simulation included 29 patients with one donor each and 16 patients with multiple donors for a total of 45 patients and 68 donor/patient pairs. In addition, a simulation based on OPTN/SRTR data was used to further assess the practical importance of multiple exchange combinations. RESULTS: If only exchanges involving two patient-donor pairs were allowed, a maximum of 8 patient-donor pairs in the data set could exchange kidneys. If three-way exchanges were also allowed, a maximum of 11 pairs could exchange kidneys. Simulations with OPTN/SRTR data demonstrate that the increase in the number of potential transplants if three-way exchanges are allowed is robust, and does not depend on the particular patients in our sample. CONCLUSIONS: A computerized matching protocol can be used to identify donor/recipient pairs from a registry of incompatible pairs who can potentially enter into donor exchanges that otherwise would not readily occur.

Algorithms↗
PubMed2005

Living-donor kidney transplantation: a review of the current practices for the live donor.

The first successful living-donor kidney transplant was performed 50 yr ago. Since then, in a relatively brief period of medical history, living kidney transplantation has become the preferred treatment for those with ESRD. Organ replacement from either a live or a deceased donor is preferable to dialysis therapy because transplantation provides a better quality of life and improved survival. The advantages of live versus deceased donor transplantation now are readily apparent as it affords earlier transplantation and the best long-term survival. Live kidney donation has also been fostered by the technical advance of laparoscopic nephrectomy and immunologic maneuvers that can overcome biologic obstacles such as HLA disparity and ABO or cross-match incompatibility. Congressional legislation has provided an important model to remove financial disincentives to being a live donor. Federal employees now are afforded paid leave and coverage for travel expenses. Candidates for renal transplantation are aware of these developments, and they have become less hesitant to ask family members, spouses, or friends to become live kidney donors. Living donation as practiced for the past 50 yr has been safe with minimal immediate and long-term risk for the donor. However, the future experience may not be the same as our society is becoming increasingly obese and developing associated health problems. In this environment, predicting medical futures is less precise than in the past. Even so, isolated abnormalities such as obesity and in some instances hypertension are no longer considered absolute contraindications to donation. These and other medical risks bring additional responsibility in such circumstances to track the unknown consequences of a live-donor nephrectomy.

Humans↗
PubMed2005

Impact of the expanded criteria donor allocation system on the use of expanded criteria donor kidneys.

BACKGROUND: The U.S. Organ Procurement and Transplantation Network recently implemented a policy allocating expanded criteria donor (ECD) kidneys by waiting time alone. ECD kidneys were defined as having a risk of graft failure > or = 1.7 times that of ideal donors. ECDs include any donor > or = 60 years old and donors 50 to 59 years old with at least two of the following: terminal creatinine >1.5 mg/dL, history of hypertension, or death by cerebrovascular accident. The impact of this policy on use of ECD kidneys is assessed. METHODS: The authors compared use of ECD kidneys recovered in the 18 months immediately before and after policy implementation. Differences were tested using t test and chi2 analyses. RESULTS: There was an 18.3% increase in ECD kidney recoveries and a 15.0% increase in ECD kidney transplants in the first 18 months after policy implementation. ECD kidneys made up 22.1% of all recovered kidneys and 16.8% of all transplants, compared with 18.8% (P<0.001) and 14.5% (P<0.001), respectively, in the prior period. The discard rate was unchanged. The median relative risk (RR) for graft failure for transplanted ECD kidneys was 2.07 versus 1.99 in the prepolicy period (P=not significant); the median RR for procured ECD kidneys was unchanged at 2.16. The percentage of transplanted ECD kidneys with cold ischemia times (CIT) <12 hr increased significantly; the corresponding percentage for CIT > or = 24 hr decreased significantly. CONCLUSIONS: The recent increase in ECD kidney recoveries and transplants appears to be related to implementation of the ECD allocation system.

Humans↗
PubMed2005

Prevalence and significance of anti-HLA and donor-specific antibodies long-term after renal transplantation.

Post-transplant circulating anti-human leukocyte antigens (HLA)-antibodies and C4d in allograft biopsies may be important in chronic rejection in renal transplant recipients (RTR). We determined the prevalence and significance of anti-HLA-antibodies and donor-specific antibodies (DSA). Sera were collected from 251 RTR >6 months post-transplant. Sera were tested using enzyme-linked immunosorbent assay (ELISA) screening for anti-HLA antibodies. Positive sera were retested with ELISA-specific panel for antibody specificity. A 11.2% of patients had anti-HLA antibodies and 4.4% had DSA. Anti-HLA antibodies were significantly associated with pretransplant sensitization, acute rejection and in multivariate analysis, higher serum creatinine (2.15 +/- 0.98 vs. 1.57 +/- 0.69 mg/dl in negative anti-HLA antibodies group). Allograft biopsies performed in a subset of patients with anti-HLA antibodies revealed that 66% had C4d in peritubular capillaries (0% in patients without antibodies). Anti-HLA antibodies were associated with a worse allograft function and in situ evidence of anti-donor humoral alloreactivity. Long-term RTR with an increase in creatinine could be screened for anti-HLA antibodies and C4d in biopsy.

Adolescent↗
PubMed2005

Organ donation and utilization in the United States, 2004.

This article discusses issues directly related to the organ donation process, including donor consent, donor medical suitability, non-recovery of organs, organs recovered but not transplanted, expanded criteria donors (ECD), and donation after cardiac death (DCD). The findings and topics covered have important implications for how to evaluate and share best practices of organ donation as implemented by organ procurement organizations (OPOs) and major donor hospitals in the same donation service areas (DSAs). In 2002 and 2003, US hospitals referred more than one million deaths or imminent deaths to the OPOs of their DSA. Referrals increased by nearly 10% from 2002 to 2003 (1,022,280 to 1,121,392). Donor consents have increased by about 5% and the number of total deceased donors has risen from 6,187 to 6,455. Since multiple organs are recovered from most donors, this increase allowed more than 500 additional wait-listed candidates to receive an organ transplant than in the prior year. Non-traditional donor sources have experienced a large rate of increase; in 2003 the number of ECD kidney donors increased by 8% and the number of DCD donors increased by 43%, from 189 donors in year 2002 to 271 donors in 2003.

Ethnicity↗
PubMed2005

Research to practice: a national consensus conference.

PURPOSE: To gain consensus on aspects of the process of gaining consent for organ donation that should be mainstream daily practice. METHODS: A 3-day consensus conference of transplant professionals that provided a forum for research and innovative ideas about gaining consent for organ donation. Four work groups were assembled to address issues of gaining consent from organ and tissue donors: (1) demystifying first-person consent (donor authorization): is it a matter of law?, (2) recovery coordinators: getting from green to great, (3) maximizing the process: old views and new, and (4) donor family support: mother or smother? RESULTS: Participants reached a consensus about major consent-related practices, identified areas of practice variance, and defined topics in need of further research. CONCLUSIONS: The conference participants agreed that (1) the primary role of the organ procurement organization is to recover organs for transplantation from deceased donors and to facilitate distribution of those organs to the appropriate recipients; (2) early referral of potential donors from the hospital to the organ procurement organization is desirable; (3) a score less than 5 on the Glasgow Coma Scale should initiate end-of-life discussions with family members; a procurement coordinator from the organ procurement organization who is physically housed within the hospital is the most successful model for accommodating early referral of potential donors and optimizing family support practices; and (3) a decedent's right to donate should take precedence in the donation process and such designation by the donor before death is irrevocable and does not require the consent or concurrence of any person after the donor's death.

Humans↗
PubMed2004

Cardiovascular risk profile after conversion from cyclosporine A to tacrolimus in stable renal transplant recipients.

BACKGROUND: Cardiovascular disease is a major cause of morbidity and mortality in renal recipients. In addition to steroids, cyclosporine A (CsA) has been implicated in contributing to increased cardiovascular risk. Conversion from CsA to tacrolimus (TAC) has been shown to improve hyperlipidemia and hypertension, but little is known about the differential effects of CsA versus TAC on other cardiovascular risk factors. We investigated overall cardiovascular risk profile after conversion from CsA to TAC. METHODS: This was an open-label, single-arm prospective study; 22 adult renal recipients who were receiving CsA-based immunosuppression with serum total cholesterol greater than 200 mg/dL more than 1 year after transplantation were enrolled. CsA was replaced by TAC. Blood pressure, fasting lipid profile, homocysteine, fibrinogen, C-reactive protein, hemoglobin A1c, and creatinine were measured at baseline and at 3 and 6 months after conversion. RESULTS: There was a significant improvement in fibrinogen (366 +/- 81 - 316 +/- 65 mg/dL, P <0.001), total cholesterol (250 +/- 50 - 207 +/- 29 mg/dL, P <0.001), and low-density lipoprotein cholesterol (155 +/- 43 - 121 +/- 24 mg/dL, P <0.001) after conversion. No new onset or worsening of diabetes mellitus was observed after conversion. There were no significant differences in HDL cholesterol, triglycerides, homocysteine, C-reactive protein, hemoglobin A1c levels, serum creatinine, mean blood pressure, and mean number of antihypertensive medications required before and after conversion. CONCLUSIONS: Our results indicate that conversion to low-dose TAC may be preferable over CsA for chronic maintenance immunosuppression because it improves the overall cardiovascular risk profile without any apparent adverse effects.

Adult↗
PubMed2004

Summary report of a national conference: Evolving concepts in liver allocation in the MELD and PELD era. December 8, 2003, Washington, DC, USA.

A national conference was held to review and assess data gathered since implementation of MELD and PELD and determine future directions. The objectives of the conference were to review the current system of liver allocation with a critical analysis of its strengths and weaknesses. Conference participants used an evidence-based approach to consider whether predicted outcome after transplantation should influence allocation, to discuss the concept of minimal listing score, to revisit current and potential expansion of exception criteria, and to determine whether specific scores should be used for automatic removal of patients on the waiting list. After review of data from the first 18 months since implementation, association and society leaders, and surgeons and hepatologists with wide regional representation were invited to participate in small group discussions focusing on each of the main objectives. At the completion of the meeting, there was agreement that MELD has had a successful initial implementation, meeting the goal of providing a system of allocation that emphasizes the urgency of the candidate while diminishing the reliance on waiting time, and that it has proven to be a powerful tool for auditing the liver allocation system. It was also agreed that the data regarding the accuracy of PELD as a predictor of pretransplant mortality were less conclusive and that PELD should be considered in isolation. Recommendations for the transplant community, based on the analysis of the MELD data, were discussed and are presented in the summary document.

Adult↗
PubMed2004

Analysis of the cardiovascular risk profile in stable kidney transplant recipients after 50% cyclosporine reduction.

BACKGROUND: Long-term use of cyclosporine (CsA) contributes to post-transplant cardiovascular disease (CVD). Hence, a reduction in CsA dosage in kidney transplant recipients (KTR) may improve long-term outcomes. We analyzed the effects of 50% CsA dose reduction on the CVD risk profile in stable KTR. METHOD: Thirty-one KTR on a regimen of CsA, prednisone and mycophenolate mofetil (MMF) were studied. Patients were randomized to either a) continue their previously determined CsA dose (control group, n = 15) or b) lower their CsA dose by 50% (CsA reduction group, n = 16). Renal function, blood pressure, lipid profile, plasma homocysteine (HCY), C-reactive protein (CRP), fibrinogen, and uric acid were compared at baseline and at 6 months. RESULTS: At 6 months, there was a significant improvement in allograft function, systolic blood pressure, number of anti-hypertensive medications and serum uric acid levels in the CsA reduction group. No significant decrease in plasma HCY, CRP, fibrinogen or improvement in lipid profile was found. In contrast, in the Control group, there was a significant increase in HCY, uric acid, and triglycerides. No acute rejection occurred in either group. CONCLUSIONS: A greater reduction in CsA dose could further improve CVD risk profiles, although this may increase the risk of acute or subclinical rejection.

Adult↗
PubMed2004

Organ donation and utilization in the USA.

The processes leading to donor identification, consent, organ procurement, and allocation continue to dominate debates and efforts in the field of transplantation. A considerable shortage of donors remains while the number of patients needing organ transplantation increases. This article reviews the main trends in organ donation practices and procurement patterns from both deceased and living sources in the USA. Although there have been increases in living donation in recent years, 2002 witnessed a much more modest growth of 1%. Absolute declines in living liver and lung donation were also noted in 2002. In 2002, the number of deceased donors increased by only 1.6% (101 donors). Increased donation from deceased donors provides more organs for transplantation than a comparable increase in living donation, because on average 3.6 organs are recovered from each deceased donor. The total number of organs recovered from deceased donors increased by 2.1% (462 organs). Poor organ quality continued to be the major reason given for nonrecovery of consented organs from deceased donors. The kidney is the organ most likely to be discarded after recovery. Over the past decade the discard rate of recovered kidneys has increased from 6% to 11%. Many of these are expanded criteria donor kidneys.

Cadaver↗
PubMed2004

National conference to assess antibody-mediated rejection in solid organ transplantation.

The process of humoral rejection is multifaceted and has different manifestations in the various types of organ transplants. Because this process is emerging as a leading cause of graft loss, a conference was held in April 2003 to comprehensively address issues regarding humoral rejection. Though humoral rejection may result from different factors, discussion focused on a paradigm caused by antibodies, typically against donor HLA antigens, leading to the term 'antibody-mediated rejection' (AMR). Conference deliberations were separated into four workgroups: The Profiling Workgroup evaluated strengths and limitations of different methods for detecting HLA reactive antibody, and created risk assessment guidelines for AMR; The Diagnosis Workgroup reviewed clinical, pathologic, and serologic criteria for assessing AMR in renal, heart and lung transplant recipients; The Treatment Workgroup discussed advantages, limitations and possible mechanisms of action for desensitization protocols that may reverse AMR; and The Basic Science Workgroup presented animal and human immunologic models for humoral rejection and proposed potential targets for future intervention. This work represents a comprehensive review with contributions from experts in the fields of Transplantation Surgery, Medicine, Pathology, Histocompatibility, Immunology, and clinical trial design. Immunologic barriers once considered insurmountable are now consistently overcome to enable more patients to undergo organ transplantation.

Antibodies↗
PubMed2004

Donor kidney exchanges.

Kidney transplantation from live donors achieves an excellent outcome regardless of human leukocyte antigen (HLA) mismatch. This development has expanded the opportunity of kidney transplantation from unrelated live donors. Nevertheless, the hazard of hyperacute rejection has usually precluded the transplantation of a kidney from a live donor to a potential recipient who is incompatible by ABO blood type or HLA antibody crossmatch reactivity. Region 1 of the United Network for Organ Sharing (UNOS) has devised an alternative system of kidney transplantation that would enable either a simultaneous exchange between live donors (a paired exchange), or a live donor/deceased donor exchange to incompatible recipients who are waiting on the list (a live donor/list exchange). This Regional system of exchange has derived the benefit of live donation, avoided the risk of ABO or crossmatch incompatibility, and yielded an additional donor source for patients awaiting a deceased donor kidney. Despite the initial disadvantage to the list of patients awaiting an O blood type kidney, as every paired exchange transplant removes a patient from the waiting list, it also avoids the incompatible recipient from eventually having to go on the list. Thus, this approach also increases access to deceased donor kidneys for the remaining candidates on the list.

Cadaver↗
PubMed2004

Transplantation in the diabetic patient with advanced chronic kidney disease: a task force report.

On May 7 to 8, 2003, more than 60 physicians, surgeons, nurses, and allied health professionals met in Chicago, IL, to discuss state-of-the-art approaches to transplantation in the clinical management of patients with diabetes and advanced chronic kidney disease. Four work groups addressed pretransplantation evaluation and management, therapeutic alternatives for treatment of patients with chronic kidney disease, posttransplantation diabetes mellitus, and improving long-term kidney transplant outcomes in patients with diabetes. This report summarizes the deliberations and recommendations of the task force.

Coronary Disease↗
PubMed2003

Is this live-organ donor your patient?

The transplant community is in the midst of an ethical reflection regarding the manner in which live-organ transplantation should be practiced. There is a fundamental aspect to be addressed and reaffirmed. It is the doctor-patient relationship between the transplant surgeon and the live-organ donor. This relationship brings a mutual responsibility to the physician and the donor patient to each other, which should not be abrogated by the claim of donor autonomy nor the obligation fostered by the recipient's needs. If equipoise is not affirmatively achieved in the risk-benefit calculation for the donor and the recipient, then sound medical judgment should override all other concerns.

Humans↗