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PubMed2004

Late pacemaker requirement after pediatric orthotopic heart transplantation may predict the presence of transplant coronary artery disease.

BACKGROUND: Few data are available regarding pacemaker implantation after pediatric orthotopic heart transplantation. The purpose of this study was to assess the incidence, indications and associations with regard to pacemaker placement in children who have undergone orthotopic heart transplantation. METHODS: We performed a retrospective study of all patients undergoing orthotopic heart transplantation at our institution from October 1984 to March 2001. Data obtained included demographics, indications for pacemaker, presence of transplant coronary artery disease and long-term follow-up. Patients were divided into: Group 1, patients requiring a pacemaker within 3 months of transplantation; and Group 2, patients requiring a pacemaker beyond 3 months. RESULTS: Pacemakers were required in 7 of 106 (6.6%) transplant recipients. Pacing indications for patients in Group 1 (n = 2) were persistent bradycardia with pause-related ventricular arrhythmia and atrial flutter with resultant sinus pauses of up to 4 seconds. In Group 2 patients (n = 5), indications for pacing were high-grade atrioventricular (AV) block in 1 patient and episodic sinus pauses up to 3.3 seconds associated with syncope/dizziness in the remaining 4 patients. All patients in Group 2 had transplant coronary disease diagnosed within 1 year of pacemaker implantation. All had resolution of symptoms and no complications after implantation. CONCLUSIONS: Pacemakers are infrequently required after cardiac transplantation in children. Despite not meeting classic symptomatic sinus bradycardia criteria, pacemaker placement should be considered post-transplantation in patients with episodic sinus pauses and dizziness or syncope. Patients who present with the aforementioned symptoms or high-grade AV block should be evaluated closely for the presence or development of transplant coronary artery disease, as it may be their first symptom.

Bradycardia↗
PubMed1999

Effect of immunosuppressive therapy, serum creatinine, and time after transplant on plasma total homocysteine in patients following heart transplantation.

OBJECTIVES: To determine the prevalence of hyperhomocysteinemia in heart transplant recipients, and to assess the effect of renal function and immunosuppressive medication on total plasma homocysteine (tHcy) levels. BACKGROUND: Elevated plasma tHcy levels have been associated with increased risk of mortality in patients with established coronary artery disease. Graft coronary disease is the major cause of morbidity and mortality in long-term survivors of heart transplantation. The tHcy has been found to be elevated in heart and kidney transplant patients, however, the etiologic factors have not been clearly delineated. METHODS: The study group consisted of 70 heart transplant recipients (56 males, 14 females, mean age 53+/-13 years [range 17 to 69 years]). The parameters evaluated were fasting tHcy level, cumulative cyclosporine (CyA) dose, cumulative prednisone dose, serum creatinine, and time from transplantation. RESULTS: The mean fasting tHcy level was 20.5+/-10.2 micromol/L (range 5.2 to 59.0 micromol/L). Sixty-one (87%) had fasting tHcy levels greater than the seventy-fifth percentile of the general population (>12.2 micromol/L in males, and >10.1 micromol/L in females). There was no difference in mean post-transplant tHcy level between patients with and without coronary artery disease before transplantation (21.0+/-11.4 vs. 19.3+/-6.7 micromol/L, p = NS). There were significant relationships between the tHcy level and the serum creatinine (r = 0.76, p<0.001), and cumulative exposure to CyA (r = 0.31, p<0.01). There were no significant relationships between tHcy levels and cumulative prednisone dose, or time from transplantation. CONCLUSIONS: Fasting tHcy levels are markedly elevated in the majority of patients following heart transplantation, and are correlated to serum creatinine. Further studies are needed to determine other etiologic factors of elevated tHcy following heart transplantation, and to examine the impact of elevated tHcy on clinical outcomes.

Adolescent↗
PubMed2002

Late post-transplant anemia in adult renal transplant recipients. An under-recognized problem?

Post-transplant anemia (PTA), a frequent complication during the first 3-6 months after transplant, is thought to be uncommon during the late post-transplant period. A study population of adults (> 18 years) transplanted during 1995 at Stanford University (n = 88) and University of North Carolina (n = 40) was selected. Data-collection points were 0, 1, 2, 3, 4 and 5 years post transplant. Anemia was defined as a hematocrit < 33 volume percentage. Thirty percent of patients were anemic at some time during the post-transplant period. The prevalence of PTA increased over time; by 5 years post transplant, 26% of the patients were anemic. Anemia occurred in 62.5% of patients converted from azathioprine to mycophenolate mofetil. A multivariate logistic regression model demonstrated a correlation between anemia and serum total CO2 (p = 0.002), BUN (p = 0.04), and creatinine (p = 0.045) at 1 year post transplant. At 5 years post transplant, only serum total CO2 (p = 0.0004) correlated with anemia. Thus, diminished renal excretory function and metabolic acidosis appear to be the most important correlates of late PTA. These findings should be interpreted in view of the fact that the newer immunosuppressive agents may have an even more profound effect on anemia and its recovery after transplantation.

Adult↗
PubMed2004

Post-transplant plasma cell myeloma and polymorphic lymphoproliferative disorder with monoclonal serum protein occurring in solid organ transplant recipients.

Post-transplant lymphoproliferative disorders are mostly Epstein-Barr virus-related, B-cell tumors that develop as a consequence of immunosuppressive therapy in recipients of solid organ or bone marrow transplants. These disorders range from reactive, polyclonal plasmacytic hyperplasia to those that are morphologically and genotypically indistinguishable from typical non-Hodgkin's lymphomas. Plasma cell myeloma occurring after solid organ transplantation is rare. We report three plasma cell myeloma post-transplant lymphoproliferative disorder cases and one polymorphic, monoclonal post-transplant lymphoproliferative disorder case associated with a monoclonal serum protein. All three plasma cell myeloma post-transplant lymphoproliferative disorder cases had clinical, radiologic, and pathologic features of conventional plasma cell myeloma. The one polymorphic post-transplant lymphoproliferative disorder case was associated with an IgM monoclonal serum protein and was morphologically indistinguishable from a lymphoplasmacytic lymphoma. Three of the four cases, including the one polymorphic post-transplant lymphoproliferative disorder case, were positive for Epstein-Barr virus encoded small RNA by in situ hybridization. One patient died of plasma cell myeloma post-transplant lymphoproliferative disorder. The remaining three patients are alive: two are completely free of post-transplant lymphoproliferative disorder, and one has shown partial response to therapy. We compare the clinicopathologic features of these cases with those in the literature.

Aged↗
PubMed1999

Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant.

BACKGROUND AND METHODS: The extent to which renal allotransplantation - as compared with long-term dialysis - improves survival among patients with end-stage renal disease is controversial, because those selected for transplantation may have a lower base-line risk of death. In an attempt to distinguish the effects of patient selection from those of transplantation itself, we conducted a longitudinal study of mortality in 228,552 patients who were receiving long-term dialysis for end-stage renal disease. Of these patients, 46,164 were placed on a waiting list for transplantation, 23,275 of whom received a first cadaveric transplant between 1991 and 1997. The relative risk of death and survival were assessed with time-dependent nonproportional-hazards analysis, with adjustment for age, race, sex, cause of end-stage renal disease, geographic region, time from first treatment for end-stage renal disease to placement on the waiting list, and year of initial placement on the list. RESULTS: Among the various subgroups, the standardized mortality ratio for the patients on dialysis who were awaiting transplantation (annual death rate, 6.3 per 100 patient-years) was 38 to 58 percent lower than that for all patients on dialysis (annual death rate, 16.1 per 100 patient-years). The relative risk of death during the first 2 weeks after transplantation was 2.8 times as high as that for patients on dialysis who had equal lengths of follow-up since placement on the waiting list, but at 18 months the risk was much lower (relative risk, 0.32; 95 percent confidence interval, 0.30 to 0.35; P<0.001). The likelihood of survival became equal in the two groups within 5 to 673 days after transplantation in all the subgroups of patients we examined. The long-term mortality rate was 48 to 82 percent lower among transplant recipients (annual death rate, 3.8 per 100 patient-years) than patients on the waiting list, with relatively larger benefits among patients who were 20 to 39 years old, white patients, and younger patients with diabetes. CONCLUSIONS: Among patients with end-stage renal disease, healthier patients are placed on the waiting list for transplantation, and long-term survival is better among those on the waiting list who eventually undergo transplantation.

Adolescent↗
PubMed2006

Aerobic capacity, muscle strength and health-related quality of life before and after orthotopic liver transplantation: preliminary data of an Austrian transplantation centre.

OBJECTIVE: Patients before orthotopic liver transplantation usually show a reduced physical performance status, which impacts on their daily life and social participation. This pilot study aimed to evaluate endurance capacity, muscle strength, and quality of life before and after orthotopic liver transplantation in patients in an Austrian transplantation centre. SUBJECTS: Fifteen patients (male/female = 10:5) were included in the pilot study. METHODS: Exercise testing, strength testing of knee extensor muscles and of handgrip, and quality of life (SF-36 health survey) were assessed before and after orthotopic liver transplantation (after 1-2 months). RESULTS: The oxygen uptake at the anaerobic threshold (VO2AT) and isokinetic strength testing of quadriceps femoris muscle did not change significantly from baseline, before transplantation to follow-up after orthotopic liver transplantation. Before orthotopic liver transplantation, quality of life was hampered concerning functional status, emotional role, vitality, and general health perception. Significant improvements of social functioning (p=0.032), vitality (p=0.006), mental health (p=0.004) and general health perception (p=0.002) could be found for this study population after orthotopic liver transplantation. CONCLUSION: The results of this pilot study including a population of an Austrian transplantation centre indicate deficits of physical performance as well as reduced quality of life in patients before and after orthotopic liver transplantation.

Adult↗
PubMed1998

The effect of felodipine on renal function and blood pressure in cyclosporin-treated renal transplant recipients during the first three months after transplantation.

BACKGROUND: Due to their vasodilatory effect, calcium antagonist may have a renoprotective against cyclosporin (CsA)-induced nephrotoxicity and rise in blood pressure (BP) seen in renal transplantation. METHODS: In order to evaluate the effect of the calcium antagonist felodipine on renal function and BP during cyclosporin treatment, 79 CsA-treated renal transplant recipients were investigated during the first 3 months after transplantation in a randomized, double-blind, placebo-controlled study with two parallel groups. Felodipine (ER tablets, 10 mg) or placebo was given prior to transplantation and each day during the study period. The patients were assessed twice, i.e. at 4-6 weeks and at 10-12 weeks after transplantation. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured by constant infusion technique. Tubular function was estimated from clearance of lithium. RESULTS: At 6 weeks after transplantation, felodipine caused a significantly higher RPF [felodipine: 219 +/- 70 ml/min; placebo: 182+/-56 ml/min (mean+/-1 SD); P=0.03]. No differences were found in GFR, filtration fraction (FF), tubular sodium handling, or sodium excretion. Felodipine lowered BP significantly. At 12 weeks after transplantation, felodipine caused a significantly higher GFR (felodipine: 49+/-18 ml/min; placebo: 40+/-16 ml/min; P=0.05) and RPF (felodipine: 225+/-77 ml/min; placebo: 175+/-48 ml/min; P<0.01). No difference was found in FF. Felodipine lowered BP significantly. No differences were found with regard to duration of primary anuria, hospitalization time, number of rejection episodes, plasma creatinine day 7 post-transplant, or treatment doses of CsA. CONCLUSIONS: It is concluded that in renal transplant recipients treated with CsA, felodipine significantly increased both GFR and RPF 3 months after transplantation when compared with placebo, despite a concomitant lowering of BP. A possible antagonizing affect of felodipine against CsA-induced nephrotoxicity in these patients is suggested.

Adolescent↗
PubMed1991

Graft thrombosis in pediatric renal transplant recipients. 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 incidence and possible causes of graft thrombosis in pediatric renal transplant recipients. Between January 1987, and November 1989, 1045 renal transplants in recipients less than 18 years of age were registered in the study, including 484 living-related donor and 561 cadaver donor transplants. There were 213 graft failures (67 LRD, 146 CAD), and of these 27 were caused by thrombosis (8 LRD, 19 CAD). Thrombosis occurred in 2.6% of all transplants and accounted for 22.5% (27/120) of all graft failures that occurred in the first 60 days following transplantation. Among the LRD recipients, there were 24 graft failures in those less than 6 years of age, and 7 of these were due to thrombosis, compared to 1 thrombosis in 43 graft losses in recipients greater than 6 years (P less than 0.01). In recipients less than 6 years old, the thrombosis rate for those who received transplants without prior dialysis was 4/32 (12.5%) versus 3/109 (2.8%) with prior dialysis. Among the CAD recipients, age of the recipient did not influence graft thrombosis. Donor age, however, was strongly associated with the risk of thrombosis, as was cold storage time. Donor age and cold storage time were not independently distributed within the population, with longer cold storage times required for younger donors. Both factors, however, independently affected outcome. Other factors, including prior nephrectomy, prior transplant, center size, and use of cyclosporine were not associated with increased risk of thrombosis in LRD or CAD recipients. We conclude that graft thrombosis is an important cause of renal graft loss in children. In LRD transplants the risk of graft thrombosis is increased in recipients less than 6 years old, and preliminary data suggest that the lack of prior dialysis may be associated with thrombotic risk in these patients. CAD transplant recipients who receive grafts from young donors, particularly those with long cold storage time, are at increased risk for graft failure due to thrombosis.

Adolescent↗
PubMed1997

Risk factors for vascular thrombosis in pediatric renal transplantation: a special report of the North American Pediatric Renal Transplant Cooperative Study.

Vascular thrombosis remains a major cause of graft failure, accounting for 12.2% of failed index transplants and 19.2% of repeat transplants. We conducted a special study to identify the risk factors for vascular thrombosis. A total of 4394 transplants (2060 living donor [LD] transplants and 2334 cadaver donor [CAD] source transplants) were evaluated. The respective vascular thrombosis rates for LD and CAD transplants were 38/2060 (1.8%) and 100/2334 (4.2%) (P<0.001). Univariate analysis showed that the rate of graft loss due to thrombosis was significantly higher in younger children (less than 2 years of age) as compared with older age groups (2-5 years, 6-12 years, and more than 12 years of age) (9.0% vs. 5.5%, 4.4%, and 3.5% for CAD transplant recipients and 3.5% vs. 3.4%, 0.7%, and 1.9% for LD graft recipients). Recipients of kidneys from cadaver donors less than 5 years of age had a significantly higher thrombosis rate (8.3%) than did recipients from older donor groups (5-10 years, 4.5%; greater than 10 years, 3.2%). Recipients of kidneys with cold ischemia time greater than 24 hr also had a higher thrombosis rate (5.6%), as compared with recipients of kidneys with a shorter cold ischemia time (3.2%). Recipients of antilymphocyte therapy on day 0 or day 1 were at dimished risk of graft loss due to thrombosis (2.2% vs. 4.1%, P=0.001). Comparable trends were seen for both LD and CAD organ recipients. LD organ recipients with a history of prior transplantation had a significantly higher rate of thrombosis as compared with those who received a primary transplant (4.6% vs. 1.6%, P=0.005). For both LD and CAD organ recipients, the occurrence of acute tubular necrosis was a significnat risk factor for the development of thrombosis. Regression analysis showed that for LD organ recipients, a history of prior transplantation increased the risk for thrombosis, whereas increasing recipient age had a linear decreasing risk effect. The use of antilymphocyte antibody or cyclosporine on day 0/1 decreased the risk for thrombosis. For CAD kidney recipients, organ cold ischemia time greater than 24 hr increased the risk for thrombosis. The use of antibody induction therapy, donors greater than 5 years of age, and increasing recipient age were factors that decreased the risk for thrombosis.

Age Factors↗
PubMed1998

Long-term outcome of kidney transplantation in patients with systemic lupus erythematosus: a multicenter study. Groupe Cooperatif de Transplantation d'île de France.

BACKGROUND: The outcome of 60 renal transplantations in 53 patients with end-stage renal disease (ESRD) because of lupus nephritis was studied retrospectively and compared with 106 controls matched for age, sex, maximum panel-reactive antibody (PRA) level, and date of transplantation. METHODS: The patients received their transplants over a 260-month period (21.5 years) between October 1971 and August 1993. The population was predominantly women (90%), and the mean age at the time of the transplantation was 33.2 years (range: 21-54 years). Fifty-six transplants (93%) were from cadaveric donors, and 4 (7%) were from living-related donors; 46 patients (86%) had primary allografts, and 7 (14%) received a second allograft. The duration of disease before transplantation was 93.6+/-6.2 months, and the duration of dialysis before transplantation was 48+/-6 months. RESULTS: No patient had clinically active systemic lupus erythematosus (SLE) at the time of transplantation. The 1-year graft and patient survival rates were 83% and 98%, and the 5-year graft and patient survival rates were 69% and 96%. Actuarial graft and patient survival rates in SLE patients were not significantly different from those of the matched control group. Chronic rejection was the major risk factor for graft loss. Lupus nephritis recurred in the graft of one patient 3 months after transplantation, and there were extrarenal manifestations of SLE in four others. CONCLUSIONS: The present study confirms that patients with SLE can receive transplants with excellent graft and patient survival rates and a low rate of clinical recurrent lupus nephritis.

Adult↗
PubMed2003

Comprehensive cost comparison of adult-adult right hepatic lobe living-donor liver transplantation with cadaveric transplantation.

BACKGROUND: An important long-term consideration for living-donor liver transplantation (LDLT) is the expense compared with cadaveric-liver transplantation. LDLT is a more complex procedure than cadaveric transplantation and the cost of donor evaluation, donor surgery, and postoperative donor care must be included in a cost analysis for LDLT. In this study, we compare the comprehensive cost of LDLT with that of cadaveric-liver transplantation. METHODS: All costs for medical services provided at our institution were recorded for 24 LDLT and 43 cadaveric recipients with greater than 1 year follow-up transplanted between August 1997 and April 2000. The donor costs include donors evaluated and rejected, donors evaluated and accepted, donor right hepatectomy costs, and donor follow-up costs (365 days postdonation). LDLT and cadaveric recipient costs include medical care 90 days pre-LDLT, recipient transplant costs, and recipient follow-up costs (365 days posttransplant) including retransplantation. Cost is expressed as an arbitrary cost unit (CU) that is a value between $500 to $1,500. RESULTS: Total LDLT costs (evaluations of rejected donors+evaluations of accepted donors+donor hepatectomy+donor follow-up care for 1 year+pretransplant recipient care [90 days pretransplant]+recipient transplantation+recipient 1-year posttransplant care)= 162.7 CU. Total mean cadaveric transplant costs (pretransplant recipient care [90 days pretransplant]+recipient transplantation [including organ acquisition cost]+recipient 1-year posttransplant care)= 134.5 CU, (P =ns). CONCLUSIONS: The total comprehensive cost of LDLT is 21% higher than cadaveric transplantation, although this difference is not significant.

Adult↗
PubMed2003

Health professionals' perceptions of health status after renal transplantation: a comparison with transplantation candidates' expectations.

BACKGROUND: Renal transplantation is frequently considered superior to other renal replacement therapy in terms of survival and quality-of-life outcome. In this study, it was examined whether physicians and nurses have accurate perceptions of health status after renal transplantation (RTX) and whether renal transplant candidates have realistic expectations about posttransplant quality of life. METHODS: A comparative descriptive design was used for the comparison of physicians' and nurses' perceived and patients' expected and actual health status after RTX. Health status perceptions were measured by means of the EQ-5D self-report questionnaire. RTX candidates (n=107) were followed longitudinally from November 1999 until July 2001. Transplant patients (n=29) were surveyed 14 days and 4, 8, and 12 months after discharge from hospital. All physicians and nurses (n=123) had regular contact with dialysis or RTX patients. RESULTS: Physicians' and nurses' perceptions of health status after RTX were significantly lower than patients' expectations. Transplant nurses' and physicians' valuations were closer to patients' actual health status after transplantation than valuations of nurses on the dialysis or nephrology ward or at the outpatient clinic. CONCLUSIONS: RTX candidates frequently have higher expectations about their quality of life after transplantation than physicians and nurses who have regular contact with renal transplant patients. Physicians' and nurses' perceptions are closer to the actual health state after transplantation than patients' expectations. Thus, physicians and nurses are a reliable source of information for patients about the health state they can expect after transplantation.

Comorbidity↗
PubMed2006

Transplant tourism: Outcomes of United States residents who undergo kidney transplantation overseas.

BACKGROUND: Although international commerce in kidney transplantation is a reality, little is known about U.S. residents who travel abroad for kidney transplantation. METHODS: We retrospectively reviewed the clinical outcomes of patients who were evaluated at the University of Minnesota Medical Center or Hennepin County Medical Center, but then surreptitiously underwent kidney transplantation overseas. RESULTS: We identified 10 patients who underwent kidney transplantation outside the United States between September 16, 2002 and June 30, 2006 and then returned for care in our programs. Eight were transplanted in Pakistan (all Somali), one was transplanted in China (Chinese), and one was transplanted in Iran (Iranian). All but one had a living donor. Mean age was 36.8+/-12.5 years with median follow-up of 2.0 years (range 0.4-3.7). Three patients communicated their intent to travel abroad before transplantation. Induction immunosuppressive therapy (if any) was available in 3/10, and initial maintenance immunosuppression was known in 5/10. Complications were primarily infectious, with six potentially life-threatening infections in four patients. At last follow-up, mean serum creatinine was 1.13+/-0.34 mg/dL, acute rejection occurred in 2/10, 1/10 grafts failed due to acute rejection, and 9/10 patients were alive. CONCLUSIONS: Kidney function and graft survival were generally good after surreptitious overseas kidney transplantation. Major problems included incomplete perioperative information communicated to the posttransplant care facility and a high incidence of posttransplant infections. Longer follow-up and detailed cost analysis are needed to better understand the implications of the growing phenomenon of transplant tourism.

Adult↗
PubMed2006

Value of soluble adhesion molecules and plasma coagulation markers in assessing transplant coronary artery disease in pediatric heart transplant recipients.

BACKGROUND: With an increasing number of heart transplantations (HTx) performed in children and an extended long-term survival of these patients, the importance of transplant coronary artery disease (TCAD) rises in this group of transplant recipients. Reliable serum markers for diagnosis or non-invasive monitoring of this disease in pediatric transplant recipients are still missing. We studied the systemic expression of adhesion molecules as well as plasma coagulation markers and the occurrence of TCAD and/or rejection in pediatric heart transplant recipients. METHODS AND RESULTS: The systemic plasma levels of soluble forms of sVCAM-1 and sICAM-1, d-dimer, tissue factor (TF), prothombin fragments F(1+2), and tissue factor pathway inhibitor (TFPI) were assessed in serial venous blood samples (2-4 per patient) in 50 pediatric transplant recipients children and 63 age- and sex-matched non-transplanted controls. TCAD and rejection were diagnosed angiographically or by combined histological, echocardiographic, or clinical signs, respectively. Plasma levels of sICAM-1 and sVCAM-1, d-dimers and prothrombin fragment F(1+2) but not TF and TFPI were significantly increased in children following HTx compared with non-transplanted controls (p<0.001). Among the transplanted patients, sICAM-1 levels were significantly higher in patients with angiographically detectable TCAD than in patients without evidence of TCAD (p<0.005). Plasma sICAM-1 levels above a cutoff value of 1500 ng/mL (95.5 percentile of control values) were indicative of the presence of TCAD (odds ratio 2.7; 95% confidence interval, 1.34-5.56, p = 0.022; Fisher's exact test). Only d-dimers were found to be significantly elevated in children with signs of myocardial rejection compared with those without rejection. CONCLUSIONS: Our results suggest that plasma sICAM-1 and d-dimer levels may be potentially useful to non-invasively assess TCAD and rejection, respectively, in pediatric heart transplant recipients.

Adolescent↗
PubMed2006

Heart transplantation across antibodies against human leukocyte antigen and ABO-post-transplant follow-up of donor reactive antibodies.

BACKGROUND: We have successfully performed heart transplantation despite the most unfavourable risk factors for graft and patient survival: the presence of a high level of antibodies (Abs) against the donor's human leukocyte antigens (HLA) class I/II and blood group A1 antigens. The present study concerns post-transplant follow-up and characterization of donor reactive antibodies (DRA). METHODS: Pre-transplant treatment consisted of mycophenolate mofetil (MMF), prednisolone, tacrolimus, intravenous immunoglobulin (IVIG), rituximab, protein-A immunoadsorption (PAIA) and per-operative plasma exchange. A standard triple-drug immunosuppressive protocol was used post-operatively. Abs were analyzed by the complement dependent cytotoxicity (CDC) test against donor and panel B/T cells and by flow cytometry (FlowPRA tests detecting isolated HLA class I/II antigens). Abs against the donor's erythrocytes were analyzed using a standard direct agglutination test for immunoglobulin M (IgM) Abs and a Bio-Rad AHG gel card test detecting IgG Abs and C3d. RESULTS: Pre-transplant treatment reduced Ab titers against the donor's lymphocytes from 128 to 16 and against the donor's blood group A1 antigen from 256 to 0. The patient was emergently transplanted with a heart from a blood group incompatible donor (A1 secretor to O). No hyperacute rejection was seen. DRA were present against all mismatched HLA class I and class II antigens at the time of transplantation; two of these DRA Abs disappeared within the first year post-transplant (anti-B62 and anti-DR4), one showed weakened reactivity (anti-A24) and one is still strongly reactive (anti-DQ3). The donor-specific CDC cross-match is still positive (titers 2 to 8). The level of panel reactive antibodies (PRA) remained unchanged from 6 months on post-transplant. Rising anti-A1 blood group Abs preceded the second rejection and were adsorbed by two blood group specific immunoadsorptions (Glycosorb)-ABO) and remained at a low level. IgM anti-A1 blood group Abs disappeared at 1 yr post-transplant and IgG Abs are still reactive with blood group A1 erythrocytes but at low titers (1 to 2). CONCLUSIONS: The patient is clinically well 2 years after heart transplantation despite the constant persistence of donor reactive IgG Abs against blood group A1 and HLA-DQ antigens. The reactivity of DRA against other mismatched HLA antigens disappeared or weakened during the follow-up period.

ABO Blood-Group System↗
PubMed2006

Post-transplant de novo malignancies in renal transplant recipients: the past and present.

Post-transplant de novo malignancies are reviewed in three time periods: (i) the azathioprine (AZA) era from 1962 to 1980-1981, (ii) the cyclosporine (CYA) era (1980 to present) in which the calcineurin inhibitors, CYA and tacrolimus (TAC), were the mainstay of recipient immunosuppression, and (iii) the TOR inhibitor era starting in the year 2000. Both transplant registry and transplant center reports on malignancies occurring in the AZA era are reviewed. Reports from transplant centers and from the Cincinnati Transplant Tumor Registry (CTTR) in both the early CYA era (1980s) and the 1900-2000 CYA era are reported. Cancer incidence associated with AZA versus CYA, CYA versus TAC, and AZA versus mycophenolate mofetil (MMF) is compared in both transplant center and registry reports including new, unreported Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) data from 1998 to 2003. The malignancy incidence associated with lymphocyte-depleting antibody and corticosteroid immunosuppression is discussed. Reduced malignancy incidence recently reported with TOR inhibitors is compared with that of conventional immunosuppression. Important nondrug factors influencing the incidence of post-transplant malignancies from seven single and three registry reports are detailed. The substantial role that de novo malignancies play in post-transplant mortality is discussed. Finally, management recommendations for recipients who develop de novo post-transplant malignancies are briefly presented.

Antilymphocyte Serum↗
PubMed2006

To transplant or not? The importance of psychosocial and behavioural factors before lung transplantation.

The gratifying results of lung transplantation in terms of survival and quality of life stimulate the referral of an ever-increasing number of patients with end-stage lung disease. This in turn compounds the organ shortage, which is the limiting factor in the transplantation rate. In the absence of good alternative treatment modalities, an evidence-based pretransplant screening process is a prerequisite to determine which patients will benefit most from transplantation. Within this evidence-based screening process, medical selection criteria are well established. There is a growing awareness that psychosocial and behavioural factors may determine outcome after transplantation as well. This paper reviews the available evidence for psychosocial and behavioural factors in the screening process for lung transplantation. The relation of various factors with post-transplant outcome was explored. Psychosocial characteristics before transplantation consist of 1) anxiety and depression, 2) personality disorders, 3) neurocognitive problems, and 4) lack of social support. Pretransplant behavioural factors include 1) noncompliance with medication, 2) alcohol abuse or dependence, 3) smoking, 4) noncompliance with dietary guidelines, and 5) noncompliance with monitoring of vital parameters and infections. It appears that the lack of rigorous studies limit the feasibility of an evidence-based screening process. Prospective studies are crucial to this further investigation of the relationship between psychosocial and behavioural determinants before transplantation and outcomes after transplantation, in terms of compliance, morbidity, and mortality. Identification of modifiable risk factors for poor outcome before transplantation is a first step in developing interventions.

Alcoholism↗
PubMed1995

The cost-effectiveness of lung transplantation. A pilot study. University of Washington Medical Center Lung Transplant Study Group.

OBJECTIVE: Lung transplantation is one of the fastest-growing solid organ transplant procedures in the world, yet its cost-effectiveness is unknown. We compared the costs and outcomes of the first 25 patients who received lung transplants at the University of Washington with 24 patients currently on the lung transplant waiting list. DESIGN: Inpatient and outpatient charges were obtained from the hospital billing service and home health agencies. Quality-adjusted life year scores (QALYs) were computed from the following: (1) utility scores obtained through standard gamble interviews, and (2) published survival data from an international lung transplant registry and from studies of patients on lung transplant waiting lists. RESULTS: Transplantation charges averaged $164,989 (median, $152,071). Average monthly charges posttransplant were $11,917 in year 1 and $4,525 thereafter, vs $3,395 for waiting-list patients. Posttransplant utility scores were significantly higher than waiting-list scores (0.80 vs 0.68; p < 0.001). Life expectancy was not greater for lung transplant vs waiting-list patients (5.89 vs 5.32 years; p > 0.05), although quality-adjusted life expectancy did improve significantly. After converting charges to costs, the incremental cost per QALY gained for posttransplant compared with waiting-list patients was $176,817. CONCLUSIONS: Lung transplantation is very expensive, although it can substantially improve quality of life. Two-thirds of care costs are incurred after transplantation. The principal barriers to cost-effectiveness at present are the high cost of postrecovery care and marginal gains in life expectancy compared with conservative care.

Adult↗