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PubMed2005

Incidence and prevalence of diabetes mellitus in patients with cystic fibrosis undergoing lung transplantation before and after lung transplantation.

Cystic fibrosis (CF) related diabetes mellitus (DM) occurs in 15% of adult pancreatic insufficient CF patients. Lung transplantation is a treatment option for end-stage CF. We hypothesized that the prevalence of DM increases after lung transplantation. The study population included adult patients undergoing lung transplantation from March 1988 to March 2002 for end-stage CF at the University of Toronto. Demographic data, exocrine pancreatic function, presence of DM before and after transplant, as well as timing of its development after transplant were collected. Eighty-six patients met the study criteria; 77 of 86 (89.5%) of patients were pancreatic insufficient and were further analyzed. Median follow-up post-transplant was 3.3 yr (interquartile range: 1.2-7.2). Their mean age was 29.7 +/- 8.1 yr and 46 of 77 (59.7%) were male. The prevalence of DM increased from 22 of 77 (28.6%) before transplant to 38 of 77 (49.4%) after transplant (p = 0.008). The median time of DM development after transplant was 80 d (range: 13-4352). Sixteen of 55 (29.1%) of pancreatic insufficient patients who were non-diabetic prior to transplant, developed DM after transplant. DM is common in CF patients undergoing lung transplantation and the prevalence increases after transplant.

Adult↗
PubMed2006

Survival after adult liver transplantation does not correlate with transplant center case volume in the MELD era.

It has been demonstrated that low-volume orthotopic liver transplant centers have poorer outcomes compared to high-volume centers. In light of the recent significant changes in liver transplantation, we performed an analysis of transplant center procedure volume and mortality with data from the Model for End-stage Liver Disease (MELD) era. We analyzed 9909 adult liver transplants performed in the United States since the beginning of the MELD allocation system. Transplant centers were categorized by volume of transplants performed per year. Multivariate survival models were constructed with raw survival as the primary endpoint for both high- and low-volume centers. Thirty percent of centers were categorized as low volume (< or =20 liver transplants per year) and 8.2% of all transplants were performed at low-volume centers. The unadjusted raw mortality rate at 1-year post-transplant at high-volume centers (9.5%, 95% CI 9.4-9.5) was significantly lower than the rate at low-volume centers (10.9%, 95% CI 10.4-11.4), p < 0.001. However, after adjusting for disease severity and multiple donor and recipient factors, transplant center volume was no longer a significant predictor of post-transplant survival (HR 0.99, 95% CI 0.99-1.00, p = 0.22). We conclude that transplant center case volume is no longer a significant predictor of post-transplant survival in the MELD era and factors which are currently unaccounted for in present survival models should be investigated.

Adult↗
PubMed2003

Equity of access to renal transplant waiting list and renal transplantation in Scotland: cohort study.

OBJECTIVE: To examine the access to the renal transplant waiting list and renal transplantation in Scotland. DESIGN: Cohort study. SETTING: Renal and transplant units in Scotland. PARTICIPANTS: 4523 adults starting renal replacement therapy in Scotland between 1 January 1989 and 31 December 1999. MAIN OUTCOME MEASURES: Impact of age, sex, social deprivation, primary renal disease, renal or transplant unit, and geography on access to the waiting list and renal transplantation. RESULTS: 1736 of 4523 (38.4%) patients were placed on the waiting list for renal transplantation and 1095 (24.2%) underwent transplantation up to 31 December 2000, the end of the study period. Patients were less likely to be placed on the list if they were female, older, had diabetes, were in a high deprivation category, and were treated in a renal unit in a hospital with no transplant unit. Patients living furthest away from the transplant centre were listed more quickly. The only factors governing access to transplantation once on the list were age, primary renal disease, and year of listing. A significant centre effect was found in access to the waiting list and renal transplantation. CONCLUSIONS: A major disparity exists in access to the renal transplant waiting list and renal transplantation in Scotland. Comorbidity may be an important factor.

Adolescent↗
PubMed1996

Post-transplantation lymphoproliferative disorder in the Epstein-Barr virus-naïve lung transplant recipient.

Post-transplantation lymphoproliferative disorder (PTLD) is a widely recognized and often catastrophic complication of organ transplantation. The incidence of PTLD after lung transplantation ranges from 6.2 to 9.4% and is two-fold higher than that seen after organ transplantation of other organs. Primary Epstein-Barr virus (EBV) infection is a major risk factor for PTLD, but the incidence of PTLD in EBV seronegative (EBV-) patients seems to vary with type of organ transplant. The goal of this study was to quantify the risk of PLTD based on pre-lung transplantation EBV serostatus in lung transplant patients. Pre- and post-lung transplant serostatus was defined in 80 patients, and our six cases of PTLD occurred in this group. Six of 94 lung transplant patients (6.4%) who survived > 1 mo developed PTLD. All cases of PTLD involved thoracic structures at presentation and occurred in the first post-operative year. Patients who were EBV- before lung transplant were much more likely to develop PTLD than those who were seropositive (EBV+) (five of 15 [33%] versus one of 60 [< 2%], p < 0.001). Consistent with the prevailing adult (donor) EBV+ rate (85%), two of our EBV-patients remained EBV-after lung transplant. Therefore, the rate of PTLD was 42% in those with primary EBV infection. As compared with EBV-patients that remained tumor-free, those who developed PLTD had similar levels of immunosuppressants and doses of anti-viral therapy. We conclude that PLTD occurs predominantly in EBV-naïve patients (risk approximately 1/3). EBV-patients should be monitored more closely after lung transplantation and, possibly, managed with lower immunosuppression. Our data also suggest that anti-viral therapy alone does not decrease the incidence of PTLD in high risk patients, PTLD can be successfully treated in most cases, and EBV-naïve patients should not be excluded from lung transplant because their risk of death from PTLD is < 15%.

Adolescent↗
PubMed2001

[Living donors for transplantation and bioethics laws. Survey with French transplantation professionals].

OBJECTIVES: Renewed interest in living donor transplantation in France led us to survey French transplanters to determine their opinion concerning this technique and the ethical issues involved. Their concerns and suggestions about current legislation were examined. METHODS: An anonymous questionnaire was sent to physicians working in the different kidney, liver and lung transplantation units operating in France. RESULTS: French transplanters expressed a wide range of opinions concerning living donor transplantation and possible broadening of the current regulations. Sixty-two percent of the transplanters had a positive opinion on living donor transplantation compared with 22% who expressed a negative opinion. For 23% of the transplanters, it is preferable to transplant with a living donor graft compared with 64% who preferred cadaveric grafts. A living donor transplantation program is under study in 65% of the units. There is some debate concerning the legitimate nature of the emergency donation situation for spouses. About one-half of the transplanters were in favor of controlled extension of potential donors to second degree relatives and to the recipient's spouse or living partner. CONCLUSION: There is no real consensus among French transplanters concerning living donor transplantation due to the complexity of the ethical issues involved. Their opinions reflect medical tradition with background marked by autonomy and paternalism. This leads to a wide range of opinions concerning current bioethics legislation and the usefulness of more flexible laws.

Bioethics↗
PubMed2004

[Limited prognostic value of surgical biopsy before transplantation of good quality renal transplants].

OBJECTIVE: The purpose of this study was to assess the correlations between histological examination of surgical biopsies before transplantation of good quality donor kidneys and delayed return of renal function and renal function at 1 year in order to determine whether histology could explain the various, sometimes surprising outcomes observed with these good quality transplants. MATERIAL AND METHOD: From November 1999 to March 2002, 110 consecutive renal transplantations were performed in our centre from 79 different donors, not including any "borderline" donors. During preparation of each transplant, a surgical wedge biopsy of the mid-renal cortex was performed. Biopsies were paraffin-embedded then stained with P.A.S. (Periodic Acid Shiff). Histological examination was performed by a single pathologist and focused on the glomeruli (number, morphology), and the morphology of the interstitial space and vessels. Delayed return of transplant renal function was defined by the need for dialysis during the first week after renal transplantation. Immunosuppression and surveillance protocols were standardized and uniform. Transplant function at 1 year was evaluated by serum creatinine and creatinine clearance calculated according to Cockcroft's formula. RESULTS: The mean number of glomeruli per biopsy was 15.0 +/- 10.8. 42 renal biopsies (39.2%). Histological examination did not reveal any vascular, interstitial or glomerular lesions. Among these 42 transplants with normal biopsies, 30 (71.4%) did not develop delayed return of renal function (vs 69% of the transplants with abnormal biopsies, p > 0.05). Mean serum creatinine at 1 year (168.5 +/- 63 micromol/l vs 166.9 +/- 40.5 micromol/l, p > 0.05) and mean creatinine clearance at 1 year (53.4 +/- 17.4 ml/min. vs 48.3 +/- 14.3 ml/min, p > 0.05) were not significantly different between the normal biopsy group and the abnormal biopsy group. CONCLUSION: Histological abnormalities are frequently observed in renal transplants derived from good quality donors. The biopsy result before renal transplantation from "non-borderline" donors was not significantly correlated with the risk of delayed return of transplant function or the renal function at 1 year Biopsy alone cannot constitute a reliable criterion for the selection of renal transplants from "non-borderline" donors.

Adolescent↗
PubMedDate not supplied

Study of the relative incidences of psychosocial factors before and after heart transplantation and the influence of posttransplantation psychosocial factors on heart transplantation outcome.

Psychosocial factors substance abuse, noncompliance, psychiatric problems, and obesity in relation to the outcome of heart transplantation have been investigated. Data were gathered at the time of initial assessment, and patients (n = 53) were monitored during the follow-up after heart transplantation (mean 18 months). Noncompliance, psychiatric problems, or excessive weight before heart transplantation continued after heart transplantation. Significantly fewer substance abusers exhibited similar behavior after heart transplantation (p < 0.01), although in many cases this exposed other psychiatric or compliance problems. Patients with psychiatric problems after heart transplantation had a higher risk of infection (p < 0.01). Both these patients and those who were noncompliant had higher incidences of hospital readmission (p < 0.01) which were reflected in higher medical costs (p < 0.01) during the second year after heart transplantation in both subgroups. We conclude that (1) heart transplant recipients do not alter previous behavior after heart transplantation except with regard to substance abuse, (2) patients exhibiting substance abuse before heart transplantation and abstaining after heart transplantation have other psychosocial problems, (3) psychosocial problems after heart transplantation do not increase the risk for medical complications in the early posttransplantation period except with regard to infection, and (4) the presence of noncompliance and psychiatric problems after heart transplantation is related to increased readmissions and higher total medical costs.

Age Factors↗
PubMed1997

Infection after pediatric heart transplantation: results of a multiinstitutional study. The Pediatric Heart Transplant Study Group.

BACKGROUND: Detailed information regarding the spectrum and predictors of infection after heart transplantation in children is limited because of relatively small numbers of patients at any single institution. We therefore used combined data obtained from the Pediatric Heart Transplant Study Group to gain additional information regarding infectious complications in the pediatric population. METHODS: To determine the time-related risk of infection and death related to infection in a large pediatric patient population, we analyzed data related to 332 pediatric patients (undergoing heart transplantation between January 1, 1993, and December 31, 1994) from 22 institutions in the Pediatric Heart Transplant Study Group. RESULTS: Among the 332 total patients, 276 infections were identified in 136 patients. Of those patients with development of infection, a single infection episode was reported in 54% of patients, 21% had two infections, and 25% had three or more infections. Of the 276 infections, 164 (60%) were bacterial, 51 (18%) were due to cytomegalovirus, 35 (13%) were other viral (noncytomegalovirus) infections, 19 (7%) were fungal, and 7 (2%) were protozoal. Bacterial infections were more common in infants younger than 6 months of age at time of transplantation, comprising 73% of all infections as compared with 49% in patients older than 6 months of age. The incidence of bacterial infection peaked during the first month after transplantation, with the actuarial likelihood of a bacterial infection among all patients reaching 25% at 2 months. The most common sites of bacterial infection were blood and lung (74% of bacterial infections). Cytomegalovirus accounted for 59% of viral infections, with a peak hazard occurring at 2 months after transplantation. Among all infections, cytomegalovirus was less common in infants younger than 6 months of age (8% of all infections) than in older patients (25%). By multivariate analysis, risk factors for early infection included younger recipient age (p = 0.05), mechanical ventilation at time of transplantation (p = 0.0002), positive donor cytomegalovirus serologic study result with negative recipient result (p = 0.004), and longer donor ischemic time (p = 0.04). The overall mortality rate from infection was 5%, with an actuarial freedom from death related to infection of 92% at 1 year after transplantation. The mortality rate was high in patients with fungal infections (52%), yet was low for those with cytomegalovirus infection (6%). Infections accounted for 27% of the overall mortality rate in infants younger than 6 months of age, compared with 16% for older patients. CONCLUSIONS: Although most infections in pediatric heart transplant recipients are successfully treated, infection remains an important cause of posttransplantation morbidity and death, especially in infants. Bacterial infections predominate within the first month after transplantation, whereas the peak hazard for viral infections occurs approximately 2 months after transplantation. Cytomegalovirus infections are common in the pediatric transplant population, but death related to cytomegalovirus is low.

Actuarial Analysis↗
PubMed2000

Second allogeneic transplantation after failure of first autologous transplantation.

We evaluated the outcome of second allogeneic bone marrow transplantations (BMTs) in 59 patients aged 1-57 years who relapsed after initial autologous transplantation. Patients received a second transplantation for recurrent acute myeloid leukemia (AML) (n = 24), acute lymphoblastic leukemia (ALL) (n = 13), lymphoma (n = 18), multiple myeloma (n = 3), or chronic myelogenous leukemia (n = 1) from an HLA-matched related (n = 14), mismatched related (n = 25), or matched unrelated (n = 20) donor. The probabilities of nonrelapse mortality, relapse, and disease-free survival (DFS) 2 years after the second BMT were 51%, 26%, and 23%, respectively. The 2-year DFS estimates for AML, ALL, and lymphoma were 46%, 23%, and 0%. Univariate analysis demonstrated that superior DFS was associated with age < or =17 years at the time of the second transplantation, remission before the second transplantation, total-body irradiation-based preparative regimen for the second transplantation, and the diagnosis of AML. These data demonstrate that an allogeneic transplantation after a failed autologous transplantation can result in disease-free survivors, especially in the young. The outcomes after a second transplantation for patients aged >17 years and for those with lymphoma were especially grim. These data suggest that pediatric patients may be appropriate candidates for a second transplantation. In adults, however, the use of an allogeneic transplantation as salvage therapy after failure of the initial autologous transplantation is generally unsuccessful. Alternative experimental strategies, such as low-dose nonmyeloablative allogeneic minitransplantations, should be considered.

Adolescent↗
PubMed2000

Second allogeneic stem cell transplantation using nonmyeloablative conditioning for patients who relapsed or developed secondary malignancies following autologous transplantation.

OBJECTIVE: Second allogeneic stem cell transplants for hematological malignancies are associated with a high incidence of transplant-related mortality due to the cumulative incidence of toxicity of the high-dose chemoradiotherapy traditionally used as an essential component of the conditioning. We have demonstrated previously that nonmyeloablative conditioning for primary allogeneic transplants from both sibling and unrelated donors results in minimal transplant-related toxicity and excellent stem cell engraftment. This study explores the possibility of using nonmyeloablative conditioning to minimize transplant-related toxicity in patients who have undergone second allogeneic transplants. PATIENTS AND METHODS: Twelve high-risk, heavily treated patients-five with acute myelogenous leukemia (AML); five with non-Hodgkin's lymphoma (NHL); one with Burkitt's lymphoma, and one with acute lymphoblastic leukemia (ALL)-underwent second allogeneic nonmyeloablative stem cell transplantation (NST) from human leukocyte antigen (HLA)-matched donors, 29 (median) (range 3-57) months following their first transplantation procedure. The conditioning consisted of fludarabine 30 mg/m(2) daily for 6 days, busulfan 4 mg/kg daily for 2 days, and anti-T-lymphocyte globulin 10 mg/kg daily for 4 days. Anti-graft-vs-host disease (anti-GVHD) prophylaxis consisted of cyclosporine A alone, 3 mg/kg. RESULTS: Engraftment was observed in all recipients, with complete and stable chimerism. None of the patients developed veno-occlusive disease of the liver or multi-organ failure. Five very high-risk patients with NHL (n = 3), Burkitt's lymphoma (n = 1), and AML (n = 1) relapsed 2 to 6 months post-transplant, and four of them died. Six patients appear to be disease-free after median follow-up of 23 months. One additional patient died from grade IV hemorrhagic cystitis. Actuarial survival and disease-free survival at 34 months are 56% and 50% respectively, with 95% confidence interval (25-78%). CONCLUSION: These results suggest that nonmyeloablative conditioning significantly reduces transplant-related toxicity, thus making a second transplant feasible.

Actuarial Analysis↗
PubMed1998

Pre-transplant donor-specific transfusions induce allograft rejection and IL-2 gene expression in the WKY-->F344 functional tolerance model of rat lung transplantation.

Our previous studies have shown that a spontaneous functional tolerance develops in a rat model of lung transplantation (WKY-->F344). The tolerance observed in this model may be due to the minor histocompatible differences in this combination, however, the possibility of a tolerogenic effect related specifically to the lung allograft must be considered. To further examine this model, the effect of pre-transplant donor-specific spleen cell transfusions (DSTs) was examined on the functional tolerance state seen in this model. F344 rats received WKY spleen cells on days -45 and -30 before lung transplantations. Control F344 rats received lung transplants without DSTs. Recipients in both groups were killed on day 7, 14, 21 and 49 post-transplant, and allograft rejection (AR) was graded histologically (stage 0-IV). Intragraft cytokine gene transcripts were examined on day 7 and 14 post-transplant using reverse transcriptase-polymerase chain reaction (RT-PCR) techniques to investigate the underlying immunological events occurring in each group. In addition, allogeneic (WKY) and third party (BN) skin grafts were placed on lung recipients at day 35 post-transplant to evaluate the development of systemic tolerance. It was seen that control animals showed moderate to severe lymphocytic infiltrations (stage II-III AR) in the first 3 weeks followed by spontaneous recovery with stage I-II AR on day 49. In marked contrast, DST-treated animals showed more aggressive AR with severe lymphocytic infiltration and haemorrhagic infarction (stage III-IV AR) by day 14-21, without any evidence of recovery on day 49. WKY skin grafts showed prolonged survival in control animals, but were promptly rejected in DST-treated animals. Intragraft cytokine gene expression in control animals was characterized by no or weak expression of IL-2 and high IL-10, while DST-treated animals showed high levels of IL-2 transcripts. IL-2:IL-10 and IL-2:IL-4 ratios were significantly increased in DST-treated animals compared with controls on day 7 post-transplant. It was concluded that pre-transplant DSTs did not enhance allograft survival, but actually induced AR and ablated any immunological benefit of the lung allograft on induction of tolerance in the WKY-->F344 lung transplant model. It was found that the DST-induced AR was associated with a deviation of cytokine immune responses from a predominant Th2 to Th1 profile characterized by increased IL-2 gene expression in the allografts. We also conclude that factors other than the degree of histocompatibility matching, such as the route and timing of alloantigen exposure, and the amount or nature of alloantigens associated specifically with lung allografts, are involved in deviating native immune responses toward acceptance or rejection of lung allografts in this model of lung transplantation.

Animals↗
PubMed2000

Are heart transplant recipients more likely to develop skin cancer than kidney transplant recipients?

Non-melanoma skin cancer is frequent in organ transplant recipients. The risk of posttransplant cutaneous squamous cell carcinoma in Norwegian heart transplant recipients (n = 148) and kidney transplant recipients (n = 1020) on triple immunosuppressive therapy with cyclosporine, azathioprine, and prednisolone, transplanted between 1983 and 1992, were studied. After adjustment for age at transplantation in multivariable Cox models, heart transplant recipients had a significantly 2.8-times higher risk of developing squamous cell carcinoma relative to kidney transplant recipients. The risk relative to the general population (standardized incidence ratio) was higher in heart transplant recipients than in kidney transplant recipients. The results indicate that heart transplant recipients are more likely to be diagnosed with skin cancer than kidney transplant recipients, probably due to the higher doses of cyclosporine and azathioprine after heart transplantation used at our center in the study period.

Azathioprine↗
PubMedDate not supplied

Mortality of cadaveric kidney transplantation versus combined kidney-pancreas transplantation in diabetic patients.

In the United States diabetes in now the principle cause of end-stage renal disease. For diabetic patients undergoing cadaveric kidney transplantation, a combined kidney-pancreas (KP) transplant is often recommended because this option is perceived to carry no additional risk. However, most transplant centres have restricted KP transplantation to patients with few diabetic complications and no coronary artery disease. We compared survival rates after KP transplantation with those after kidney transplantation alone in clinically similar though non-randomised patient groups. In 173 consecutive diabetic renal transplant candidates, 3-year patient survival in 54 KP recipients was 68%, versus 90% in 46 patients who received a cadaveric kidney alone (p = 0.01). The remaining patients had a living-related-donor kidney transplant, either alone (65) or followed 4-20 months later by a pancreas transplant (8), with survival similar to that with a cadaveric kidney. Independent variables associated with early death were age, history of congestive heart failure, and pancreas transplantation. A serious complication of pancreas transplantation was infection, or which 14 of 54 recipients required pancreatectomy; KP recipients had a higher death rate from infection in the first 12 months (p = 0.034). In view of the excess mortality associated with KP transplantation, we suggest that the combined operation should be reserved for young patients with no history of congestive heart failure, or for patients in whom hyperglycaemia is life-threatening. A randomised trial is needed to compare the long-term outcomes of these procedures.

Adult↗
PubMed2003

Low incidence and severity of transplant-associated coronary artery disease in heart transplants from live donors.

BACKGROUND: Hearts transplanted from patients undergoing heart-lung transplantation (domino hearts) are unique because they have not been subjected to the deleterious effects of brain-stem death. This study examines the incidence and severity of transplant-associated coronary artery disease in recipients of domino hearts. METHODS: We retrospectively reviewed angiographic and clinical data from 97 patients who survived more than 1 year after domino heart transplantation at our hospital. Duration of follow-up ranged from 1 to 11 years after transplantation. The diagnosis of coronary artery disease was based on angiographic criteria. RESULTS: At 1 year, freedom from angiographic coronary artery disease was 99% (70% confidence interval [CI], 97-100), at 5 years it was 83% (70% CI, 78-89), and at 10 years it was 77% (70% CI, 70-84). Donor age, cystic fibrosis in the donor, organ ischemia time during transplantation, and acute rejection after transplantation did not influence risk for the disease. We found an increased incidence of coronary disease in hearts from male donors compared with those from female donors: freedom from disease at 5 years was 72% (70% CI, 63-81) in men vs 93% (87-99) in women. Thirteen patients experienced coronary artery disease at a median of 3 years after transplantation; 4 patients died but most patients remained asymptomatic with angiographically mild disease at their last follow-up examination. CONCLUSIONS: We found decreased incidence and severity of transplant-associated coronary artery disease in recipients of domino hearts compared with that reported in recipients of cadaveric hearts. This data supports the continued practice of domino heart transplantation and also supports the hypothesis that brain death may contribute to the development of transplant coronary artery disease in recipients of hearts transplanted from cadaveric organ donors.

Actuarial Analysis↗
PubMed2001

Pre-transplant cardiac testing for kidney-pancreas transplant candidates and association with cardiac outcomes.

BACKGROUND: Coronary artery disease is a major cause of mortality following renal transplantation, especially in those patients with diabetes. The accurate prediction of cardiac risk is therefore a major focus of the pre-transplant evaluation. The objective of this study was to retrospectively evaluate the ability of non-invasive cardiac testing (standard echocardiography, stress echocardiography, exercise tolerance testing, and nuclear myocardial perfusion) performed within 1 yr of kidney-pancreas transplant to predict post-transplant myocardial infarction. METHODS: Clinical history and pre-transplant cardiac testing performed within 1 yr prior to transplantation were reviewed in a non-blinded fashion for 165 kidney-pancreas transplantation patients receiving allografts between June 1990 and May 1998. The predictive values of clinical symptoms and cardiac testing for cardiac events (fatal and non-fatal myocardial infarctions) up to 1 yr post-transplant were calculated. RESULTS: Clinical history had a negative predictive value of 98% for cardiac events occurring within 1 yr following testing and 97% within 1 yr post-transplant. Collectively, non-invasive testing had a negative predictive value of 97% for 1 yr post-testing and 1 yr post-transplant. CONCLUSION: Clinical history alone is highly suggestive but not sufficient for the prediction of post-kidney-pancreas transplant myocardial infarction. Although a useful supplement, cardiac testing does not predict all cardiac events out to 1 yr post-testing. In this high-risk patient population with diabetes and renal failure, other methods of risk assessment are needed to more accurately predict long-term cardiac outcome for patients awaiting transplantation.

Coronary Angiography↗
PubMed2000

Simultaneous pancreas-kidney transplantation and living related donor renal transplantation in patients with diabetes: is there a difference in survival?

OBJECTIVE: To compare the outcome of simultaneous pancreas-kidney transplantation (SPK) and living related donor renal transplantation (LRD) in patients with diabetes. SUMMARY BACKGROUND DATA: It remains unanswered whether diabetic patients with end-stage renal failure are better served by LRD or SPK. METHODS: Using a longitudinal database, data from all diabetic patients receiving LRD or cadaveric renal transplants or SPKs from January 1986 through January 1996 were analyzed. Patient and graft survival, early graft function, and the cause of patient and graft loss were compared for 43 HLA-identical LRDs, 87 haplotype-identical LRDs, 379 SPKs, and 296 cadaveric renal transplants. RESULTS: The demographic composition of the SPK and LRD groups were similar, but because of less strict selection criteria in the cadaveric transplant group, patients were 10 years older, more patients received dialysis, and patients had been receiving dialysis longer before transplantation. Patient survival was similar for the SPK and LRD groups but was significantly lower for the cadaveric renal transplant group. Similarly, there was no difference in graft survival between SPK and LRD recipients, but it was significantly lower for recipients in the cadaveric renal transplant group. Delayed graft function was significantly more common in the cadaveric renal transplant group. Discharge creatinine, the strongest predictor of patient and graft survival, was highest in the SPK group and lowest in the HLA-identical LRD group. The rate of rejection within the first year was greatest in SPK patients (77%), intermediate in the haplotype-identical LRD and cadaveric transplant groups (57% and 48%, respectively), and lowest (16%) in the HLA-identical LRD group. Cardiovascular disease was the primary cause of death for all groups. Acute rejection, chronic rejection, and death with a functioning graft were the predominant causes of graft loss. CONCLUSIONS: This study demonstrates that there was no difference in patient or graft survival in diabetic patients receiving LRD or SPK transplants. However, graft and patient survival rates in diabetic recipients of cadaveric renal transplants were significantly lower than in the other groups.

Adult↗
PubMed1997

Pre-transplant blood transfusion and renal allograft outcome: a report of the North American Pediatric Renal Transplant Cooperative Study.

Data from the North American Pediatric Renal Transplant Cooperative Study were analyzed to determine the effect of pre-transplant blood transfusions on graft survival and acute rejection for pediatric renal transplant recipients. Between January 1, 1987 and November 11, 1995, 4015 renal transplants in children <18 years of age (2007 living donor, 2008 cadaver) were registered in the study. Recipients were grouped by number of pre-transplant blood transfusions (0, n=1171; 1-5, n=1796; >5, n=1048). The risks of graft failure and acute rejection were related to number of pre-transplant transfusions by proportional hazards regression analysis. Models were adjusted for recipient age, sex, race, induction therapy, prior dialysis, prior transplant, HLA-DR mismatching, and transplant year. Additionally, the living donor (LD) model was adjusted for the use of donor-specific blood transfusion, and the cadaver donor (CAD) model was adjusted for donor age and cold storage time. The risk of graft failure was increased in LD (p<0.001) and CAD (p=0.001) recipients who received >5 pre-transplant transfusions. There was no significant difference in the causes of graft loss between groups. The risk of a first acute rejection decreased in LD recipients who received 1-5 blood transfusions compared with 0 (p=0.04) or >5 (p=0.003) and in CAD recipients who received 1-5 compared with 0 (p=0.05). We conclude that multiple (>5) pre-transplant blood transfusions are a risk factor for graft failure in pediatric recipients and should be avoided. However, limited blood transfusions (1-5) are associated with a decreased risk of acute rejection. Our data show that for pediatric recipients the number of pre-transplant blood transfusions is an important factor in transplant outcome.

Blood Transfusion↗
PubMed1999

HLA compatibility and organ transplant survival. Collaborative Transplant Study.

The influence of HLA compatibility on organ transplant survival was analyzed in more than 150,000 recipients transplanted from 1987 to 1997 at transplant centers participating in the Collaborative Transplant Study. A statistically highly significant effect of HLA matching on graft and patient survival rates was found in the analysis of kidney transplants (P < 0.0001). Ten years after transplantation, the graft survival rate of first cadaver kidney transplants with a complete mismatch (6 HLA-A+B+DR mismatches) was 17% lower than that of grafts with no mismatch. During the first post-transplant year, the class II HLA-DR locus had a stronger impact than the class I HLA-A and HLA-B loci. During subsequent years, however, the influence on graft survival of the three loci was found to be equivalent and additive. For optimal graft outcome, compatibility at all three HLA loci is, therefore, desirable. The excellent correlation of HLA matching observed in recipients of cadaver kidneys with very short ischemic preservation (0-6 hours) or recipients of kidneys from living unrelated donors contradicts reports that short ischemia can eliminate the influence of matching. Although HLA has a significant effect on graft outcome regardless of the state of presensitization, the matching effect is potentiated in patients with highly reactive preformed lymphocytotoxic antibodies. Among first cadaver transplant recipients with an antibody reactivity against > 50% of the test panel, the difference in graft survival at 5 years between patients with 0 or 6 mismatches reached 30%. A collaborative project, in which molecular DNA typing methods were employed, showed that the correction of serological HLA typing errors by more accurate DNA typing results in a significantly improved HLA matching effect. Moreover, matching for the class II locus HLA-DP, a locus that can be typed reliably only by DNA methods, showed a significant effect in cadaver kidney retransplants, especially in the presence of preformed lymphocytotoxic antibodies. The analysis of heart transplants showed a highly significant impact of HLA compatibility on graft outcome (P < 0.0001). This result is of particular interest because donor hearts are not allocated according to the HLA match. A biasing influence of donor organ allocation (i.e. a preferential allocation of good matches to good risk recipients) can, therefore, be excluded. In liver transplantation, neither matching for HLA class I nor HLA class II could be shown to influence transplant outcome.

Graft Survival↗