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Francis L Delmonico

Publications and source records attributed to Francis L Delmonico.

At least 37 records · Page 2Linked to original sources
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↗
PubMed2003

A prospective, randomized, clinical trial of intraoperative versus postoperative Thymoglobulin in adult cadaveric renal transplant recipients.

BACKGROUND: Delayed graft function (DGF) is frequently observed in recipients of cadaveric renal transplants. Previous retrospective or nonrandomized studies have suggested that intraoperative administration of polyclonal antithymocyte preparations may reduce the incidence of DGF, possibly by decreasing ischemia-reperfusion injury. METHODS: We performed a prospective randomized study of Thymoglobulin induction therapy in adult cadaveric renal transplant recipients. Between January 2001 and January 2002, 58 adult cadaveric renal transplant recipients were randomized to receive intraoperative or postoperative Thymoglobulin induction therapy. Three to six doses of Thymoglobulin (1 mg/kg/dose) were administered during the first week posttransplant. Baseline immunosuppression consisted of tacrolimus (54 of 58) or cyclosporine A (4 of 58), steroids, and mycophenolate mofetil. DGF was defined by the requirement for hemodialysis within the first week posttransplant. RESULTS: There were no significant differences between the two groups in recipient demographics, donor age, cold ischemia time, or total number of doses of Thymoglobulin administered. Intraoperative Thymoglobulin administration was associated with significantly less DGF and a lower mean serum creatinine on postoperative days 10 and 14 (P<0.05). Posttransplant length of stay was also significantly shorter for the intraoperative Thymoglobulin patient group. The acute rejection rate was also lower in the intraoperative treatment group but this did not achieve statistical significance. There was no difference in the incidence of cytomegalovirus disease between the two groups. CONCLUSIONS: The results of this study indicate that intraoperative Thymoglobulin administration, in adult cadaveric renal transplant recipients, is associated with a significant decrease in DGF, better early allograft function in the first month posttransplant, and a decreased posttransplant hospital length of stay.

Acute Disease↗
PubMed2003

A prospective, randomized clinical trial of cyclosporine reduction in stable patients greater than 12 months after renal transplantation.

BACKGROUND: For stable kidney-transplant recipients receiving triple drug therapy with cyclosporine (CsA), prednisone, and mycophenolate mofetil (MMF), it remains unclear what is the optimal dose of CsA beyond the first 6 to 12 months after transplantation. Complete CsA withdrawal has been associated with a significant incidence of acute rejection and, in some studies, chronic rejection as well. METHODS: We performed an open, prospectively randomized, controlled clinical trial to determine whether CsA could be safely reduced by 50%. At 1 year or more posttransplant, 64 patients were randomized to either continue their stable-maintenance CsA dose (control group, n=32) or to lower their CsA dose by 50% over a 2 month period (CsA reduction group, n=32). All patients had stable renal-allograft function at the time of enrollment. RESULTS: Within 6 months of randomization, no episode of acute rejection or graft loss occurred in either group. Patients in the CsA reduction group had a slight but significant increase in their glomerular filtration rate and a trend towards lower serum creatinine. There was also a significant decrease in mean systolic blood pressure, triglycerides, and serum uric acid levels in the CsA reduction group. No significant changes in any of these parameters were observed in the control group. CONCLUSIONS: This study suggests that a strategy consisting of a 50% CsA reduction is safe and is not associated with the increased risk of acute rejection observed in CsA withdrawal studies. It also has the potential to improve short-term allograft function and appears to reduce cardiovascular risk factors such as hypertension and hyperlipidemia.

Adult↗
PubMed2003

Hormonal resuscitation yields more transplanted hearts, with improved early function.

BACKGROUND: Brain death results in cardiovascular instability and poor organ perfusion in many brain-dead donors. Hormonal resuscitation stabilizes certain brain-dead donors and is associated with significant increases in the numbers of organs transplanted per donor. The goal of this study was to examine the quality of hearts recovered from donors treated with hormonal resuscitation. METHODS: A retrospective analysis of 4,543 recipients of hearts recovered from brain-dead donors, reported to the United Network for Organ Sharing/Organ Procurement and Transplantation Network database between November 1, 1999, and December 31, 2001, was conducted. Hormonal resuscitation consisted of a methylprednisolone bolus and infusions of vasopressin and either triiodothyronine or l-thyroxine. Univariate and multivariate analyses were used to evaluate the quality of hearts from donors who received three-drug hormonal resuscitation (3HR) treatment versus donors who did not receive all three drugs (non-3HR). Death within 30 days and early graft dysfunction were used as endpoints. RESULTS: Hearts from 3HR donors demonstrated a 1-month survival rate of 96.2%, compared with a 92.1% survival rate for non-3HR donor hearts (P<0.01). Early graft dysfunction occurred in 5.6% of 3HR donor hearts and 11.6% of non-3HR donor hearts (P<0.01). Multivariate results demonstrated a 46% reduced odds of death within 30 days and a 48% reduced odds of early graft dysfunction. Steroids alone and steroids plus triiodothyronine/l-thyroxine also significantly reduced prolonged graft dysfunction. CONCLUSIONS: This study suggests that 3HR treatment of brain-dead donors results in increased numbers of transplanted hearts, with improved short-term graft function.

Adult↗
PubMed2003

Aggressive pharmacologic donor management results in more transplanted organs.

BACKGROUND: Brain death results in adverse pathophysiologic effects in many cadaveric donors, resulting in cardiovascular instability and poor organ perfusion. Hormonal resuscitation (HR) has been reported to stabilize and improve cardiac function in brain-dead donors. The goal of this study was to examine the effect of HR on the brain-dead donor on the number of organs transplanted per donor. METHODS: A retrospective analysis of all brain-dead donors recovered in the United States from January 1, 2000, to September 30, 2001, was conducted. HR consisted of a methylprednisolone bolus and infusions of vasopressin and either triiodothyronine or L-thyroxine. Univariate analyses and multivariate logistic regression analyses were used to detect differences between the HR group and those donors who did not receive HR. RESULTS: Of 10,292 consecutive brain-dead donors analyzed, 701 received three-drug HR. Univariate analysis showed the mean number of organs from HR donors (3.8) was 22.5% greater than that from nonhormonal resuscitation donors (3.1) (P <0.001). Multivariate analyses showed that HR was associated with the following statistically significant increased probabilities of an organ being transplanted from a donor: kidney 7.3%, heart 4.7%, liver 4.9%, lung 2.8%, and pancreas 6.0%. Extrapolation of these probabilities to the 5,921 brain-dead donors recovered in 2001 was calculated to yield a total increase of 2,053 organs. CONCLUSION: HR stabilizes certain brain-dead donors and is associated with significant increases in organs transplanted per donor.

Adult↗
PubMed2003

The report of a national conference on the wait list for kidney transplantation.

In March, 2002, over 100 members of the transplant community assembled in Philadelphia for a meeting designed to address problems associated with the growing number of patients seeking kidney transplantation and added to the waiting list each year. The meeting included representatives of nine US organizations with interests in these issues. Participants divided into work groups addressing access to the waiting list, assigning priority on the list, list management, and identifying appropriate candidates for expanded criteria donor kidneys. Each work group outlined problems and potential remedies within each area. This report summarized the issues and recommendations regarding the waiting list for kidney transplantation addressed in the Philadelphia meeting.

Congresses as Topic↗
PubMed2003

Acute humoral rejection in hepatitis C-infected renal transplant recipients receiving antiviral therapy.

The use of interferon-alpha (IFN) in hepatitis C (HCV)-infected renal recipients has been associated with acute rejection and graft loss. We reviewed our recent experience in HCV (+) renal recipients treated with antiviral therapy for biopsy proven chronic hepatitis C. Twelve HCV (+) recipients who recently received antiviral therapy were analyzed. Post-treatment sera were tested for donor-specific human leukocyte antigen (HLA) antibodies (DSA). Within 6 months of initiating antiviral therapy, two of 12 patients (17%) developed acute rejection, which was characterized as acute humoral rejection (de novo DSA in serum and C4d deposits in peritubular capillaries). Both progressed to graft failure. Nine of the remaining 10 patients tested did not have DSA. The use of IFN was associated with severe acute humoral rejection (C4d +, DSA +). The recognition of IFN-associated acute humoral rejection in this series may explain the high rate of graft loss reported previously in renal recipients receiving IFN.

Adult↗
PubMed2003

Morbidity and mortality after living kidney donation, 1999-2001: survey of United States transplant centers.

There have been two recent trends in living kidney donation: increased acceptance of living donors and increased acceptance of laparoscopic nephrectomy (LN). We surveyed 234 UNOS-listed kidney transplant programs to determine current living donor morbidity and mortality for open nephrectomy, hand-assisted LN, and non-hand-assisted LN. Of the 234 centers, 171 (73%) responded. Between 1/1/1999 and 7/1/2001, these centers carried out 10 828 living donor nephrectomies: 52.3% open, 20.7% hand-assisted LN, and 27% non-hand-assisted LN. Two donors (0.02%) died from surgical complications and one is in a persistent vegetative state (all after LN). Reoperation was necessary in 22 (0.4%) open, 23 (1.0%) hand-assisted LN, and 21 (0.9%) non-hand-assisted LN cases (p = 0.001). Complications not requiring reoperation were reported for 19 (0.3%) open, 22 (1.0%) hand-assisted LN, and 24 (0.8%) non-hand-assisted LN cases (p = 0.02). Readmission rate was higher for LN (1.6%) vs. open (0.6%) donors (p < 0.001), almost entirely as a result of an increase in gastrointestinal complications in LN donors. Morbidity and mortality for living donor nephrectomy at transplant centers in the United States remain low. We provide current data from which comprehensive informed consent can be obtained from donors.

Humans↗
PubMed2002

Induction of kidney allograft tolerance after transient lymphohematopoietic chimerism in patients with multiple myeloma and end-stage renal disease.

BACKGROUND: Two patients with end-stage renal disease secondary to multiple myelomas were treated with combined kidney and bone marrow transplantation in an effort to achieve donor-specific allotolerance through the induction of mixed lymphohematopoietic chimerism. METHODS: Two female patients (55 and 50 years of age) with end-stage renal disease secondary to kappa light-chain multiple myelomas received a nonmyeloablative conditioning regimen that consisted of 60 mg/kg cyclophosphamide intravenously (IV) on days -5 and -4; 15 mg/kg equine anti-thymocyte globulin (ATGAM) IV on days -1, +1, and +3; and thymic irradiation (700 cGy) on day -1. On day 0, the recipients underwent kidney transplantation, followed by IV infusion of donor bone marrow (2.7x10(8) and 3.8x10(8) /kg nucleated cells, respectively) obtained from a human leukocyte antigen (HLA)-matched sibling. Cyclosporine A was administered IV at a dose of 5 mg/kg on day -1, then continued orally at 8 to 12 mg/kg per day until days +73 and +77, respectively, after which no further immunosuppression was given. Donor leukocyte infusions (1x10(7) /kg CD3+ T cells) were administered in an attempt to enhance the graft-versus-myeloma effect (days +66 and +112 in the first patient and day +78 in the second patient). Hematopoietic chimerism was monitored weekly by microsatellite assays. RESULTS: Multilineage lymphohematopoietic chimerism (5%-80% donor CD3+ or CD3- cells, or both) was first detected during the second posttransplant week and was maintained for approximately 12 weeks, after which there was a gradual decline to undetectable levels (<1% donor cells) after day 105 in the first patient and after day 123 in the second patient. In both recipients, the blood urea nitrogen and creatinine levels returned to normal within 3 days. No rejection episodes have occurred. Quantification of urinary kappa light chains revealed a decline from 28 mg/dL to undetectable levels (<2.5 mg/dL) within 29 days in the first case and from 99.8 mg/dL to <10 mg/dL within 50 days in the second case. Both patients continue with normal kidney function and sustained anti-tumor responses, while receiving no immunosuppression for nearly 4 years and 2 years, respectively. CONCLUSIONS: This nonmyeloablative regimen followed by combined HLA-matched donor bone marrow and renal allotransplantation is the first example of an intentional and clinically applicable approach to inducing renal allograft tolerance and achieving potent and sustained antitumor effects in patients with multiple myeloma.

Bone Marrow Transplantation↗
PubMed2002

Donor characteristics associated with reduced graft survival: an approach to expanding the pool of kidney donors.

BACKGROUND: Availability of cadaveric kidneys for transplantation is far below the growing need, leading to longer waiting time and more deaths while waiting. METHODS: Using national data from 1995 to 2000, we evaluated graft survival by donor characteristics and the rate of discard of retrieved organs, with the goal of increasing use of kidneys that are associated with increased risk of graft failure, that is, expanded donor kidneys. RESULTS: Cox models identified four donor factors that independently predicted significantly higher relative risk of graft loss compared with a low-risk group. These factors included donor age, cerebrovascular accident as the cause of death, renal insufficiency (serum creatinine >1.5 mg/dL), and history of hypertension. Expanded donor kidneys were defined as those with relative risk of graft loss greater than 1.70 and included all donors aged 60 years and older and those aged 50 to 59 years with at least two of the other three conditions (cerebrovascular cause of death, renal insufficiency, hypertension). The expanded donor group accounted for 14.8% of transplanted kidneys. Among organs procured from expanded donors, 38% were discarded versus 9% for all other kidneys. The risk of graft loss of expanded donor kidneys was increased in both older and younger recipients but to a greater extent in those recipients older than 50 years. CONCLUSION: By identifying donor factors associated with graft failure, these analyses may help to expand the number of transplanted kidneys by increasing the utilization of retrieved cadaveric kidneys.

Adolescent↗
PubMed2002

Living kidney donors in need of kidney transplants: a report from the organ procurement and transplantation network.

BACKGROUND: Our aim was to use the Organ Procurement and Transplantation Network (OPTN) database to determine the number of renal waitlist candidates who previously had been living donors. METHODS: All living renal donors in the OPTN database were cross-checked against the renal waitlist history files. Additionally, renal transplant programs were contacted that had listed candidates as qualified for four additional allocation points available to patients who previously had donated an organ. Confirmatory phone calls to transplant programs yielded additional cases previously unreported to the United Network for Organ Sharing. RESULTS: A total of 56 previous living donors were identified as having been subsequently listed for cadaveric kidney transplantation. Forty-three have received transplants; 36 currently have functioning grafts. One died after transplantation. Two candidates died while waiting. CONCLUSIONS: Living renal donation has long-term risks that may not be apparent in the short term. The numbers here reported underestimate the actual number of living donors with renal failure, because they include only patients listed for a kidney transplant. To determine risk factors for postdonation renal failure, long-term living-donor follow-up data are needed.

Databases as Topic↗
PubMed2002

The nondirected live-kidney donor: ethical considerations and practice guidelines: A National Conference Report.

BACKGROUND: The success of kidney transplantation from a genetically unrelated living spouse or friend has influenced transplant physicians to consider the requests of individuals wishing to volunteer to be a kidney donor who have no intended recipient specified. Representatives of the transplant community gathered in Boston, MA, on May 31, 2001, to deliberate on the experience of live kidney donation from such volunteers, currently termed nondirected donors (NDD). OBJECTIVE OF CONFERENCE PARTICIPANTS: The objective of the conference was to recommend ethical and practice guidelines for health care professionals considering the transplantation of a kidney from a live NDD. CONFERENCE PARTICIPANTS: This conference was convened under the sponsorship of The National Kidney Foundation, with representation from The American Society of Transplantation and The American Society of Transplant Surgeons, The American Society of Nephrology, The United Resource Networks, The United Network for Organ Sharing, The Association of Organ Procurement Organizations, The National Institutes of Health, and The Division of Transplantation of the Health Resources and Services Administration (see Appendix). CONFERENCE REPORT: The suggested content of screening interviews, which provide information regarding the donation process, elicits pertinent medical and psychosocial history, and assesses NDD motivation are presented in this report. Approaches to identifying the center that would evaluate the suitability of the NDD, to performing the kidney recovery, and to selecting the NDD recipient are also proposed. Other ethical issues such as the use of prisoners as an NDD, compensation for the NDD, media involvement, and communication between the NDD and recipient are discussed. CONCLUSION: The willingness of health care professionals to consider NDD volunteers is driven by the compelling need to provide organs for an ever-expanding list of patients awaiting a kidney transplant. However, the psychological impact and emotional reward of donation has yet to be determined for NDD who may not have any relationship to the recipient or knowledge of the recipient's outcome. Transplant centers that accept NDD should document an informed consent process that details donor risks, assures donor safety, and determines that the goals and expectations of the NDD and the recipient can be realized.

Communication↗