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PubMedDate not supplied

Oversizing of donor hearts: beneficial or detrimental?

To determine the effects of donor/recipient weight mismatch on allograft function and survival after orthotopic heart transplantation, we retrospectively compared the clinical and the hemodynamic characteristics of recipients weighing more than their donor ("undersized") with those of recipients weighing less than their donor ("oversized"). The median follow-up period was 24 months (range, 0 to 67 months). In 88 patients (59%) donor weight was 1% to 46% less than recipient weight (13.5 +/- 8.9 means +/- SD). In 61 patients (41%) donor weight exceeded recipient weight by 0% to 139% (20% +/- 23%). When recipient ideal body weight was used in the analysis, 75 patients (51%) were undersized by 1% to 59% (13% +/- 10%), and 72 patients (49%) were oversized by 0% to 67% (19% +/- 18%). Preoperative transpulmonary gradient, ventricular function, and exercise tolerance were similar in the two groups. The number and severity of episodes of rejection and infection after transplantation were also similar in the two groups 1, 6, and 12 months after transplantation. When recipient ideal weight was used in the analysis, right ventricular (RV) and left ventricular (LV) ejection fractions (EFs) were within normal limits (RVEF greater than 40%; LVEF greater than or equal to 45%) and similar in the two groups. When recipient actual weight was used in the analysis, the LVEF measured at 12 months after heart transplantation was higher in the oversized than in the undersized group (52 +/- 11 vs 46 +/- 10; p less than 0.05). Postoperative hemodynamic values and exercise tolerance were similar in the two groups regardless of whether recipient weight or ideal body weight were used in the analysis. Forty-six recipients died 0 to 46 months (median, 7 months) after orthotopic heart transplantation. In a Cox regression model, recipients with donor weight greater than recipient ideal weight had a significantly greater risk of death within the follow-up period than did recipients with donor weight less than recipient ideal weight (relative risk = 2.19; p less than 0.05). When percent donor weight/recipient ideal weight mismatch was used as a continuous variable, donor heart oversizing was negatively related to survival, independent of preoperative transpulmonary gradient values (p less than 0.05). In contrast to common belief, oversizing of donor hearts does not improve the outcome of orthotopic heart transplant recipients who have reversible preoperative pulmonary hypertension. Acceptance of undersized donor hearts is not detrimental to allograft function and recipient survival. Use of undersized donor hearts may maximize the use of critically scarce donor organs.

Adult↗
PubMed1992

A preliminary report of the HTK randomized multicenter study comparing kidney graft preservation with HTK and EuroCollins solutions. HTK Study Group.

The main goal of transplantation is to restore good renal function and to improve the quality of life of thousands of dialysis patients, something which can only be achieved by providing them with well functioning grafts. Delayed renal allograft function is a serious problem. It is important to prevent this complication because it makes the diagnosis of acute rejection in the early postoperative period difficult, increases the necessity for diagnostic procedures, introduces dialysis treatments and prolongs hospital stay. The aetiology of delayed graft function (DGF) is multifactorial, and factors including donor management, technique used for organ procurement and preservation, age, anatomical variations in the graft, ischemia periods, use of cyclosporine A (CyA) or recipient immunological reactions have been implicated. Using different preservation solutions DGF rates vary from 30% to 60%. Recent clinical data have demonstrated better preservation and improved renal function posttransplant with HTK and University of Wisconsin (UW) solutions compared to EuroCollins solution. In a randomized multicenter study in collaboration with the Eurotransplant organ exchange organization, the efficacy of the HTK solution in renal transplantation was compared to EuroCollins and UW solutions in two parallel prospective randomized trials. The first preliminary results comparing HTK and EuroCollins solutions are reported here.

Creatinine↗
PubMed2005

Renal allograft tolerance in DLA-identical and haploidentical dogs after nonmyeloablative conditioning and transient immunosuppression with cyclosporine and mycophenolate mofetil.

BACKGROUND: Canine models of bone marrow and renal transplantation have provided important preclinical data relevant to developing novel therapeutic protocols for hematopoietic and solid organ transplantation in human beings. Nonmyeloablative transplantation has been shown to induce stable mixed hematopoietic chimerism in normal dogs and correct the phenotype of canine pyruvate kinase deficiency and Glanzman's thrombasthenia. In this study, we investigated the potential for inducing renal allograft tolerance using a nonmyeloablative bone marrow transplantation strategy that induces mixed chimerism in DLA-identical dogs. METHODS: Reciprocal renal allografts were performed in 4 DLA-identical and 4 DLA-haploidentical dogs with nonmyeloablative conditioning (200 cGy total body irradiation [TBI]) and transient immunosuppression with cyclosporine (CSP) and mycophenolate mofetil (MMF) with and without simultaneous bone marrow transplantation. Two DLA-identical control dogs received reciprocal renal allografts without TBI or immunosuppression with CSP and MMF. Serum creatinine (Cr) concentration was monitored to assess renal allograft function. RESULTS: The renal allografts were acutely rejected in the 2 DLA-identical dogs without TBI or immunosuppression. There was long-term (>1 year) renal allograft survival as evidenced by a normal (<2.0 mg/dL) serum Cr concentration in both the DLA-identical and DLA-haploidentical dogs that underwent 200 cGy TBI and transient immunosuppression with CSP and MMF either with or without simultaneous bone marrow transplantation. CONCLUSIONS: Nonmyeloablative conditioning (200 cGy TBI) and transient immunosuppression with CSP and MMF induce renal allograft tolerance in DLA-identical and DLA-haploidentical dogs without donor/host mixed hematopoietic chimerism. These findings suggest it may be possible to induce tolerance to solid organ transplants without the need for chronic immunosuppressive therapy or stable hematopoietic chimerism in the setting of both DLA-matched and haploidentical transplants.

Animals↗
PubMed2003

Growth hormone therapy before and after pediatric renal transplant.

Children undergoing successful renal transplantation anticipate optimal growth and development. The use of rhGH pre- and post-Tx has been evaluated and supported by randomized control trials. Several strategies are required to maximize the potential benefit of this treatment in the renal population including provision of adequate nutrition intake, following bone parameters with appropriate interventions, and strategies to reduce steroid therapy including utilization of alternate day steroid treatment. Studies are required to further assess the impact of rhGH on renal allograft function, rejection risk, and allograft ultrastructural changes.

Child↗
PubMed1998

Analysis of the relationship between chimerism and the allgeneic humoral response.

BACKGROUND: Persistence of antigens has been suggested to play a role in two opposing immunological phenomena: tolerance and memory. Therefore, we studied the impact of chimerism on alloreactive antibody (allo-Ab) production in kidney transplant patients. METHODS: Thirty-five female renal transplant recipients of male donor organs were classified into the following groups: group 1, 13 sensitized uremic patients on dialysis; group 2, 5 nonsensitized uremic patients on dialysis; group 3, six sensitized patients experiencing graft rejection (3 acute vascular, 1 acute cellular, and 2 chronic); and group 4, 11 nonsensitized with functioning allografts (9 with good function, 1 with acute cellular rejection, and 1 with chronic rejection). Mean duration of dialysis after graft failure was similar in groups 1 (56+/-29.7 months) and 2 (41.8+/-42.4 months), as was dialysis efficiency. Chimerism was measured indirectly in the peripheral blood lymphocytes by polymerase chain reaction amplification of a specific Y chromosome DNA gene sequence with a detection sensitivity limit of 1 male cell per 1 million female cells. Allo-Ab production was measured by the PRA-STAT enzyme-linked immunosorbent assay (Sangstat) method. RESULTS: Chimerism was observed in 60% of groups 1 and 2, 83% of group 3, and 82% of group 4. Among all groups, graft existence, irrespective of its function, positively predicted chimerism in 92% with a sensitivity of 88% and a specificity of 78%. In group 3, all three patients with acute vascular rejection had chimerism and donor-specific allo-Abs. In group 4, eight of the nine patients with no rejection had chimerism. CONCLUSION: Chimerism relates to persistence of allogeneic stimulus irrespective of its function. Chimerism did not confer protection against allo-Ab production or vascular rejection, and its existence was not crucial for sustenance of allo-Ab production.

Adult↗
PubMed2004

Proteomic-based detection of urine proteins associated with acute renal allograft rejection.

At present, the diagnosis of renal allograft rejection requires a renal biopsy. Clinical management of renal transplant patients would be improved by the development of non-invasive markers of rejection that can be measured frequently. This study sought to determine whether such candidate proteins can be detected in urine using mass spectrometry. Four patient groups were rigidly defined on the basis of allograft function, clinical course, and allograft biopsy result: acute clinical rejection group (n = 18), stable transplant group (n = 22), acute tubular necrosis group (n = 5), and recurrent (or de novo) glomerulopathy group (n = 5). Urines collected the day of the allograft biopsy were analyzed by mass spectrometry. As a normal control group, 28 urines from healthy individuals were analyzed the identical manner, as well as 5 urines from non-transplanted patients with lower urinary tract infection. Furthermore, sequential urine analysis was performed in patients in the acute clinical rejection and the stable transplant group. Three prominent peak clusters were found in 17 of 18 patients (94%) with acute rejection episodes, but only in 4 of 22 patients (18%) without clinical and histologic evidence for rejection and in 0 of 28 normal controls (P < 0.001). In addition, the presence or absence of these peak clusters correlated with the clinicopathologic course in most patients. Acute tubular necrosis, glomerulopathies, lower urinary tract infection, and cytomegalovirus viremia were not confounding variables. In conclusion, proteomic technology together with stringent definition of patient groups can detect urine proteins associated with acute renal allograft rejection. Identification of these proteins may prove useful as non-invasive diagnostic markers for rejection and the development of novel therapeutic agents.

Acute Disease↗
PubMed1979

Thrombocytopenic episodes in patients with well-functioning renal allografts. Inverse relationship between platelet count and platelet size pointing to intermittent platelet destruction.

20 out of 50 patients with well-funcioning renal allograft displayed at least one platelet count below 110 X 10(9)/1 (mean -2 SD of controls). For estimation of platelet production during thrombocytopenic episodes, the percentage of large platelets in the peripheral blood was determined which revealed an inverse relationship (p less than 0.01) to the platelet count, indicating that these thrombocytopenias were due to increased platelet consumption. Immunosuppressive treatment as well as rejection processes could be excluded as major pathogenetic factors whereas anti-platelet autoantibodies may contribute to this phenomenon.

Autoantibodies↗
PubMed1997

Spirometry values in stable lung transplant recipients.

To clarify the usefulness of spirometry to assess the function of the lung allograft post-transplant, we retrospectively reviewed 351 sequential spirometry measurements performed by 65 healthy recipients after the 80th postoperative day when the clinical evaluation and fiberoptic bronchoscopy with transbronchial biopsies and bronchoalveolar lavage excluded significant rejection or infection in the allograft. The mean coefficients of variation (CV) and significant values for change (SC) for the FVC, FEV1, and FEF25-75% were calculated according to the type of transplant procedure (heart-lung and double-lung [HL-DL] versus single-lung [SL]), and to the time after transplant when the spirometry measurements were obtained < or = 1 yr versus > 1 yr). The SC for the FVC decreased with time after transplantation for both HL-DL (< or = 1 yr: 17% versus > 1 yr: 7%) and SL recipients (< or = 1 yr: 13% versus > 1 yr: 8%). The higher degree of variability within the first year was primarily due to increasing values especially in the HL-DL recipients. The SC for the FEV1 also decreased over time for HL-DL recipients (< or = 1 yr: 18% versus > 1 yr: 9%) but was similar for SL recipients at both intervals (13%). Our results suggest that decreases of > or = 11% in FVC or 12% in FEV1 in HL-DL recipients and > or = 12% in FVC or 13% in FEV1 for SL recipients indicate a significant decrease in allograft function that may be due to infection or rejection.

Forced Expiratory Volume↗