Showing papers in "Clinical Transplantation in 1999"

The UNOS Scientific Renal Transplant Registry.

Abstract: Based upon data reported to the UNOS Scientific Renal Transplant Registry regarding transplants performed between 1994-1998, the one- and 3-year graft survival rates for 16,288 recipients of living donor kidneys were 93% and 86%, respectively, with a half-life of 17 years Among those were 2,129 transplants from HLA-identical siblings with one- and 3-year graft survival rates of 96% and 93% and a 39-year half-life, 3,140 sibling donor grafts matched for one HLA haplotype with 94% and 87% one- and 3-year survival rates and a 16-year half-life and 2,071 transplants from living unrelated donors with 92% and 86% one- and 3-year graft survival rates and a 17-year half-life The overall results of 35,289 cadaver donor kidney transplants were 87% and 76% graft survival at one- and 3-years with a 10-year half-life There was a 13% difference in 3-year graft survival rates when recipients of kidneys from donors over or under age 55 were considered separately and the half-life was 11 years for younger donors and 6 years when the donor was older (p < 0001) A total of 4,688 (14%) of cadaver kidney recipients received an HLA-matched transplant Their graft survival rates were 89% and 83% at one and 3 years and their graft half-life was 16 years compared with 86% and 76% one- and 3-year graft survival and a 10-year half-life for recipients of HLA-mismatched kidneys (p < 0001) The recipient's age affected both graft survival and the cause of graft loss Recipients aged 19-45 had a 78% 3-year graft survival rate compared with 72% for recipients over age 60 or under 18 (p < 0001) However, 65% of graft losses after the first year among older recipients were due to death with a functioning graft compared with 18% among 19-45-year olds Acute rejections accounted for 16% of graft failures after the first year when the recipient was aged 6-18 Immune failures decreased with increasing recipient age The recipient's race also influenced graft survival rates Asian recipients of cadaver kidneys had the highest graft survival rates of 91% and 85% at one and 3 years with a half-life of 18 years The result for Whites and Blacks were significantly lower (87-86% at one year and 78% and 70% at 3 years, respectively; p < 0001) The graft half-life was 12 years for Whites and 7 years for Blacks DGF and acute rejection episodes during the early posttransplant period reduced 3-year survival of cadaveric transplants by 20% and reduced graft half-lives by 2 years (rejections) or 4 years (DGF) When rejections occurred in recipients with DGF, 3-year graft survival was 64% Induction therapy with anti-T-cell reagents did not affect graft survival rates among patients with DGF, but reduced the incidence of early rejections from 27-14% Rejections that occurred within the first 6 months had a more pronounced effect on subsequent graft half-lives (116 years without and 76 years with; p < 001) and increased the proportion of kidneys that failed because of chronic rejection from 31-43% between 1-3 years More than 50% of diabetics received a simultaneous pancreas kidney transplant during this period and the graft and patient survival rates were significantly higher for recipients of the SPK transplants When deaths with a functioning graft were censored, however, the graft failure rates were not significantly different The major causes of death among cadaver kidney transplant recipients were cardiovascular (26%) and infections (24%) during the first posttransplant year Between 1-3 years, the percentage of deaths due to infection fell to 15% and malignancies accounted for 13% of patient deaths

Delayed graft function: risk factors and the relative effects of early function and acute rejection on long-term survival in cadaveric renal transplantation.

Abstract: Delayed graft function (DGF) and acute rejection have both been associated with reduced renal allograft survival. In some studies, they have been shown to have an interactive effect. We studied the risk factors for DGF and the relative impact of DGF and rejection on both short- and long-term survival in recipients of cadaveric renal transplants. Data from the Oxford Transplant Centre Database were assessed on 710 cadaver allografts over a 10-yr period, during which time all recipients received cyclosporin-based immunosuppressive protocols. The interaction between DGF and acute rejection was examined using logistic and Cox multivariate regression. Long cold ischaemia time (CIT), sensitisation and older donor age were found to be independent predictors of DGF. The occurrence of DGF resulted in a reduced 5-yr survival (56 vs. 75%). However, the effect of DGF was confined to the first year post-transplant, as there was no significant difference in survival, as measured by half-life (t 1/2 ) of grafts functioning at 1 yr, with DGF alone and a group with good early function (t 1/2 = 21.3 vs. 20.0 yr). There was no increase in acute rejection in grafts with DGF. However, the combination of DGF and acute rejection resulted in the worst short-term graft survival (68% at 1 yr, compared to 92.3% in those grafts with no DGF or acute rejection) and this continued over the long term (t 1/2 = 10.5 yr). These data suggest that early function is critical to the success of renal transplantation. The effects of DGF are limited to the first year post-transplant. Long-term graft survival may be improved by efforts to limit CITs, particularly for grafts from older donors and sensitised recipients.

Increased early morbidity and mortality with acceptable long-term function in severely obese patients undergoing liver transplantation.

Abstract: The effect of obesity on outcomes following liver transplantation remains unclear. We reviewed our experience with 302 liver transplants in 277 patients from September 1989 to September 1996 to determine the effect of body mass on outcome. Two-hundred and seventeen transplants were performed in patients with a body mass index (BMI) 35 kg/m2 (severely obese). Non-weight related pre-operative demographics were similar between groups with the exception of an increased frequency of cryptogenic cirrhosis among the obese and severely obese patients. Intra-operative transfusion requirements were greater for the severely obese group (16.2 +/- 3.5 units versus 9.1 +/- 0.8 units for the non-obese, p = 0.0004), though not when normalized to body weight (0.14 +/- 0.03 units/kg versus 0.13 +/- 0.01 units/kg, p > 0.05). Post-operatively, severely obese patients had a higher rate of wound infection (20 versus 4%, p = 0.0001) and death attributed to multisystem organ failure (15 versus 2%, p = 0.0001), although overall mortality prior to discharge and total complications were not different between groups. Actual 1-yr graft survival showed a negative trend in the severely obese group (67 versus 81% for non-obese, p = 0.07), but both 3-yr graft survival and patient survival were similar to non-obese patients (p = 0.12 and 0.17, respectively by the Cox-Mantel test). Liver transplantation in severely obese patients is associated with wound infection and early death from multisystem organ failure, but has similar long-term outcomes when compared to non-obese controls.

Cyclosporine and tacrolimus (FK506): a comparison of efficacy and safety profiles.

Abstract: Multicenter clinical trials conducted in the United States and Europe to compare the efficacy and safety of cyclosporine with tacrolimus (FK506) have demonstrated comparable long-term patient survival and graft survival in liver and renal transplant recipients. Importantly, treatment with tacrolimus was associated with reductions in the incidence and severity of acute rejection episodes. However, tacrolimus-based therapy was also associated with increased toxicities in comparison to conventional cyclosporine-based therapy. It is becoming increasingly accepted that earlier trials may have employed high or supratherapeutic doses of tacrolimus and may have been unbalanced with respect to study design. In addition, these pivotal comparative trials were performed with the original formulation of cyclosporine, and not the cyclosporine microemulsion preparation. This critical review of the literature focuses on the United States and European tacrolimus multicenter clinical trials and examines the efficacy and safety of the two primary immunosuppressants, cyclosporine and tacrolimus, obtained in these and other studies. The preliminary findings of ongoing studies comparing the efficacy and safety of the improved formulation, cyclosporine microemulsion, with tacrolimus are also discussed. The overall efficacy of the two agents appears to be similar. The safety profile shows differing toxicities of the two medications. The availability of these two immunosuppressants allows the clinician improved options when choosing an immunosuppressive regimen in solid organ transplantation.

Correlates of support for organ donation among three ethnic groups

Abstract: Telephone interviews about organ donation were conducted with 4880 white respondents, 634 African-American respondents and 566 Hispanic respondents Forty-three percent (429%) of whites, 312% of Hispanics and 226% of African-Americans reported that they were willing to donate their organs after their death (p < 0001) Logistic regression analysis revealed three significant correlates of willingness to donate across all ethnic groups: having had a family discussion about end-of-life issues; the belief that a doctor does all he or she can to save a life before pursuing donation; and concerns about surgical 'disfigurement' of a relative's body after donation Concerns in relation to body disfigurement were more prevalent among African-American and Hispanic respondents (p < 0001) than among white respondents Public education should: a) stress the need for family communication about end-of-life issues including organ donation; b) underline the fact that donation is considered only after all efforts to save the life of the patient are exhausted; and c) reassure minorities that the body of the donor is treated respectfully and not disfigured

Patient survival after renal transplantation: II. The impact of smoking.

Abstract: Renal transplant recipients have significantly higher mortality than individuals without kidney disease and the excess mortality is mainly due to cardiovascular causes. In this study, we sought to determine the impact of smoking, a major cardiovascular risk factor, on patient and renal graft survival. The study population included all adult recipients of first cadaveric kidney transplants done in our institution from 1984 to 1991. By selection, all patients were alive and had a functioning graft for at least 1 yr after transplantation. Smoking history was gathered prior to transplantation. The follow-up period was 84.3 + 41 months and during this time 28%, of the patients died and 21%, lost their graft. By univariate and multivariate analysis, patient survival, censored at the time of graft loss, correlated with these pre-transplant variables: age (p < 0.0001); diabetes (p = 0.0002); history of cigarette smoking (p = 0.004); time on dialysis prior to the transplant (p = 0.0005); and cardiomegaly by chest X-ray (p = 0.0005). Post-transplant variables did not correlate with patient mortality. By Cox regression, patient survival time was significantly shorter in diabetics (p < 0.0001), smokers (p = 0.0005), and recipients older than 40 yr. However, there were no significant differences between the survival of smokers, non-diabetics, diabetics, and older recipients. Patient death was the most common cause of renal transplant failure in smokers, in patients older than 40 yr, and in diabetics, but these patient characteristics did not correlate with graft survival. The prevalence of different causes of death was not significantly different between smokers and non-smokers. In conclusion, a history of cigarette smoking correlates with decreased patient survival after transplantation, and the magnitude of the negative impact of smoking in renal transplant recipients is quantitatively similar to that of diabetes.

An alternate mechanism of glucocorticoid anti‐proliferative effect: promotion of a Th2 cytokine‐secreting profile

Abstract: Glucocorticoids (GCs) are used as immunosuppressive and anti-inflammatory agents in organ transplantation and in treating autoimmune diseases and inflammatory disorders and they exert their effects by several mechanisms, the most significant of which is inhibition of cytokine production and action. Recent reports suggested that GCs inhibit cytokine expression indirectly through promotion of a T helper cell type 2 (Th2) cytokine-secreting profile, thereby resulting in preferential blockade of pro-inflammatory monokine and T helper cell type 1 (Th1) cytokine expression. The target of GCs appeared to be monocytes macrophages, whereby altered regulation of interleukin (IL)-1/IL-1 receptor antagonist (IL-1ra), coupled with profound blockade of IL-12 synthesis and inhibition of interferon (IFN)-gamma-induced major histocompatibility complex (MHC) class II expression, lead to a preferential cognate stimulation of Th2 cells at the expense of Th1 cells. It is possible that this may have involved the expansion of a Th2-cell pool or, in addition, frank stimulation of uncommitted naive CD4 + T cells toward the Th2 lineage. In addition, GCs may have blocked Th1 cytokine expression, thereby inhibiting ongoing Th1 cytokine secretion, and consequently provided for the unimpeded production of Th2 cytokines. Collectively, this indicates that, in exerting their anti-proliferative effects, GCs act indirectly by altering Th1/Th2 cytokine balance, blocking the (pro-inflammatory) Th1 program and favoring the (anti-inflammatory) Th2 program.

Renal transplantation for end-stage renal disease following bone marrow transplantation: a report of six cases, with and without immunosuppression.

Abstract: UNLABELLED BACKGROUND. Over 12000 bone marrow transplantations (BMT) are performed in the USA each year. This procedure is associated with significant morbidity including acute and chronic renal failure (CRF). CRF after BMT is usually secondary to radiation nephropathy and,or cyclosporine (CsA) toxicity. Survival on dialysis therapy for patients with radiation nephropathy is poor and renal transplantation may be a preferable form of renal-replacement therapy. METHODS We report our experience with renal transplantation in 6 patients with end-stage renal disease (ESRD) following BMT: 4 as a result of radiation nephropathy; one secondary to hemolytic uremic syndrome; and 1 as a result of antitubular basement membrane nephritis. Ages at the time of BMT ranged from 26 to 40 yr. ESRD developed after a mean period of 94 months (range 42-140 months) after BMT. The kidney source was from a living donor in 5 patients, and a cadaveric donor (CAD) in 1 patient. In 3 recipients, the bone marrow and kidney were from the same donor. They are managed without any immunosuppressive therapy. The other 3 were initiated on triple therapy (prednisone, mycophenolate mofetil/azathioprine and cyclosporine/tacrolimus). RESULTS These patients have been followed for up to 31 months (range 3-30 months) after kidney transplant, and 5 out of 6 are alive with functioning bone marrow and renal transplants. Their plasma creatinines range from 70 to 160 micromol/L (mean 97 micromol/L). One patient died following metastatic squamous cell cancer of the genital tract. CONCLUSIONS 1) Renal transplant is a feasible alternative for patients with ESRD following BMT: 2) if bone marrow and kidney are from the same donor, the recipient requires little or no maintenance immunosuppression; 3) short-term results show good survival, but long-term follow-up is needed: 4) infections and malignancy post-renal transplantation were seen in recipients who needed immunosuppression; and 5) reduction in immunosuppression may be needed in such post-BMT patients who undergo kidney transplants.

Diabetic retinopathy after combined kidney-pancreas transplantation

Abstract: Diabetic retinopathy (DR) is amenable to good diabetic control; however, only successful pancreas transplantation can achieve sustained normoglycaemia. The aim of this long-term study was to examine the course of DR in insulin-dependent diabetic recipients of a simultaneous kidney and pancreas transplant (SPK). Successful SPK recipients (n = 46) and failed pancreas transplant with a functioning kidney transplant (n = 8) were assessed by baseline and regular post-transplant ophthalmic examinations (n = 432) for up to 10 yr after SPK. At the time of SPK (n = 108 eyes), the mean duration of diabetes was 25 +/- 7 yr, ten eyes were blind, and 79% of eyes had advanced DR that had panretinal laser (panretinal photocoagulation, PRP. Successful SPK recipients had normal glucose control with a mean HBA1C of 5.2 +/- 0.6%. DR remained stable in 75% of both the study and control groups, with no difference between groups. The DR mostly evolved towards inactive proliferative DR. After SPK, 14% of non-blind eyes showed improvement of DR, 76% remained stable and 10% progressed. Early vitreous haemorrhage occurred in 6.1% of eyes, and was related to established DR. Cataract of all types increased after transplantation (p < 0.01), which reduced visual acuity (VA) in affected eyes. The mean overall VA remained unchanged for the study duration. In summary, uremic patients from diabetic nephropathy had a high prevalence of severe proliferative DR and blindness at the time of presentation for SPK. This was subsequently stabilised to inactive proliferative DR by appropriate laser therapy followed by metabolic control achieved by SPK.

Clostridium difficile colitis after kidney and kidney-pancreas transplantation.

Abstract: Objective - To determine the timing and risk factors involved in the development of Clostridium difficile (CD) colitis in kidney and kidney-pancreas transplant recipients. background data - The incidence of CD colitis after kidney and kidney-pancreas transplantation has not been studied in detail. The question of whether the immunosuppressed transplant recipient is more prone to CD colitis and its complications (i.e., megacolon, perforations) and the risk factors involved have not been determined. Methods - We retrospectively reviewed our experience in kidney and kidney-pancreas recipients who received transplants between January 1, 1985 and December 31, 1994. We divided these recipients into three groups: pediatric kidney recipients, adult kidney recipients, and kidney-pancreas recipients. For each group, we assessed the timing of infection, primary disease, colitis treatment, and any concurrent complications or risk factors. Results - Of 1932 transplants, 159 recipients developed post-transplant CD colitis. 132 charts were available for review. Forty-three pediatric kidney recipients developed CD colitis. Their mean age was 3.2 yr; 74% (n = 37) of them developed their colitis during their initial hospital stay, with the mean timing of infection being 33 d. Forty-one (95%) had undergone intra-abdominal placement of the graft, with renal artery anastomoses to the aorta. Fifty adult kidney recipients developed CD colitis. Thirteen (26%) developed colitis during their initial hospital stay, with the mean timing of infection (for all adult kidney recipients) being 15 months. Thirty-nine kidney-pancreas recipients developed CD colitis. Mean timing of infection was 6 months. The overall incidence of CD colitis was 8%, with 16% in the pediatric kidney group, 15.5% in the kidney-pancreas group, and 3.5% in the adult kidney group. The difference in mean timing of infection was significant between the three groups (p < 0.001 for pediatric versus adult kidney recipients, p = 0.002 for pediatric kidney versus kidney-pancreas recipients, and p = 0.2846 for adult kidney versus kidney-pancreas recipients). Conclusion - The incidence of CD colitis is increased in pediatric kidney and kidney-pancreas recipients. Young recipient age ( < 5 yr), female gender, treatment of rejection with monoclonal antibodies, antibiotic use, and intra-abdominal graft placement have been shown to increase the incidence of this disease. Further studies concerning prevention in the high-risk groups are needed.

Human parvovirus B19 infection in organ transplant recipients

Abstract: We report a 61-yr-old kidney transplant recipient with human Parvovirus B19 (HPV B19) infection presenting as a severe pancytopenia 1 month after transplantation. Bone marrow aspiration revealed severe erythroid hypoplasia with giant and dystrophic proerythroblasts. Bone marrow cells were positive for HPV B19 DNA detected by polymerase chain reaction (PCR). Pancytopenia resolved shortly after administration of intravenous immunoglobulins. Nineteen cases of HPV B19 infection in organ transplant recipients have been so far reported in the literature. Immunocompromised patients should be considered at risk from developing symptomatic HPV B19 infections. In such patients, specific anti-HPV B19 IgM and IgG antibodies may be absent or transient and therefore their negativity cannot rule out the diagnosis of HPV B19 infestation. Bone marrow smear morphological findings may suggest the diagnosis but testing for viral DNA by PCR is mandatory. Patients may spontaneously recover. However, since specific anti-viral therapy is not currently available, intravenous immunoglobulin administration appears to be the more efficacious treatment.

Bronchoalveolar lavage in lung transplantation. State of the art.

Abstract: Fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) has become a crucial tool in the management of lung transplant recipients. Detection of pulmonary infectious pathogens by culture, cytology, and histology of BAL, protected brush specimens, and transbronchial biopsies (TBB) is highly effective. Morphologic and phenotypological analyses of BAL cells may be suggestive for certain complications after lung transplantation. For interpretation of BAL findings, the natural course of BAL cell morphology and phenotypology after lung transplantation must be considered. During the first 3 months after pulmonary transplantation, elevated total cell count in BAL and neutrophilic alveolitis are common, representing the cellular response to graft injury and interaction of immunocompetent cells of donor and recipient origin. With increasing time after transplantation the CD4/CD8 ratio decreases due to lowered percentages of CD4 cells in BAL. During bacterial pneumonias, the cellular profile of BAL is characterized by a marked granulocytic alveolitis. Lymphocytic alveolitis with a decreased CD4/CD8 ratio is suggestive of acute rejection, but is also found in viral pneumonias and obliterative bronchiolitis. In the case of a combined lymphocytosis and neutrophilia without any evidence of infection, obliterative bronchiolitis should be considered. Functional analyses of BAL cells can give additional information about the immunologic status of the graft, even before histologic changes become evident but have not been established in routine transplant monitoring. However, functional studies suggest an important role of activated, alloreactive and donor-specific T lymphocytes in the pathogenesis of acute and chronic lung rejection. Investigations of soluble components in BAL have given further insight into the immunologic processes after lung transplantation. In this overview, the characteristics of BAL after lung transplantation will be summarized, and its relevance for the detection of pulmonary complications will be discussed.

The public's willingness to discuss their preference for organ donation with family members.

Abstract: We sought to assess the public's willingness to discuss their preference for organ donation with family members and to identify factors associated with willingness to discuss donation. We categorized individuals (N = 4365) with a preference for donation according to their willingness to discuss donation and used ordinal logistic regression analysis to identify factors related to their level of willingness. About half of those who want to donate have discussed this with a family member. Others were at various stages with respect to their commitment to discuss donation. Those in the more committed stages were more likely than others to have signed an organ donor card, to have seen information about organ donation, to be male, to be white or Hispanic, to know about donation issues, and to be comfortable with the idea of their own death. The decision to donate is ultimately made by family members of a suitable candidate for donation, yet nearly half of those who wish to donate have not made their wishes known. Interventions targeted to individuals at different stages of commitment are needed so that more family members can respond in accordance with their loved one's wishes.

Peripheral vascular disease and renal transplant artery stenosis: a reappraisal of transplant renovascular disease

Abstract: Background: Renal transplant artery stenosis (RTAS) continues to be a problematic, but potentially correctable, cause of post-transplant hypertension and graft dysfunction. Older transplant recipients, prone to peripheral vascular disease (PVD), may have pseudoRTAS with PVD involving their iliac system. Methods: We retrospectively analyzed 819 patients who underwent kidney transplantation between 1993 and 1997 to determine the contribution of pseudoRTAS to renal transplant renovascular disease. Univariate analyses were performed for donor and recipient variables, including age, weight, gender, race, renal disease, cholesterol and creatinine values, human leukocyte antigen (HLA) matching, cytomegalovirus (CMV) infection, and immunosuppressive medications. Significant variables were then analyzed by a Cox proportional hazards model. Results: Ninety-two patients (11.2%) underwent renal transplant arteriogram (Agram) or magnetic resonance angiography (MRA) for suspected RTAS. RTAS or pseudoRTAS, defined as one or more hemodynamically significant lesions in the transplant artery or iliac system, was evident in 44 patients (5.4%). Variables significantly associated with RTAS by univariate analysis were weight at the time of transplant (p = 0.0258), male gender (p = 0.034), discharge serum creatinine > 2 mg/dL (p = 0.0041), and donor age (p = 0.0062). Variables significantly associated with pseudoRTAS by univariate analysis were weight at the time of transplant (p = 0.0285), recipient age (p = 0.0049), insulin-dependent diabetes mellitus (IDDM; p = 0.0042), panel reactive antibody (PRA) at transplant (p = 0.018), and body mass index (p = 0.04). Weight at transplant and donor age remained significantly associated with an increased risk for RTAS in a multivariate stepwise Cox proportional hazards model. IDDM, transplant PRA, weight at transplant, and donor age were significantly associated with an increased risk for pseudoRTAS in a multivariate stepwise Cox proportional hazards model. Importantly, both RTAS and pseudoRTAS were associated with poorer graft survival (p < 0.007 for each). Conclusions: Renal transplant renovascular disease encompasses pre-existing PVD acting as pseudoRTAS, as well as classical RTAS. Efforts to identify and correct renal transplant renovascular disease of either nature are important. given its negative impact on graft survival.

Influence of hyperglycemia and hyperuricemia on long-term transplant survival in kidney transplant recipients.

Abstract: Long-term prognosis in kidney transplant recipients depends on multiple factors. The purpose of this study was to quantify the influence of hyperuricemia and hyperglycemia (elements of the so-called 'syndrome X', i.e., a combination of metabolic disorders like hyperuricemia, diabetes mellitus, hyperlipidemia, and hypertension) on organ function in 350 kidney transplant recipients who had received 375 kidney transplants up to 1990 and in whom sex, age of recipient and donor, nephrologic disease, duration of dialysis, human leukocyte antigen (HLA) classification, and duration of transplant ischemia had been well matched. We found the influence of hyperuricemia on graft survival to be statistically significant (p 100 mg,dL) kidney transplant recipients (p > 0.05). Transplant survival in hyperuricemic patients (male, > 8 mg dL; female, > 6.2 mg/dL) 2, 4, and 5 yr post-transplantation was significantly reduced (92.2, 70.6, and 68.8% vs. 98.1, 85.6, and 83.3%), as compared to normouricemic recipients. A combined presence of both hyperuricemia and hyperglycemia probably influencing the prognosis post-kidney-transplantation failed to reach the level of statistical significance. We found a significant correlation between age of recipients and plasma glucose (p < or = 0.01) and between serum uric acid concentrations and diuretic therapy (p < or = 0.05) and gender (p < or = 0.(5). In conclusion, hyperuricemia after kidney transplantation seems to reduce graft survival, whereas an influence of the carbohydrate metabolism has to be denied.

Review of immunosuppressive usage in pancreas transplantation.

Abstract: Throughout 1997, nearly 10,000 pancreas transplants have been performed worldwide, with 88% being simultaneous kidney transplants (SKPT). The current 1 yr patient survival rate exceeds 90% and pancreas graft survival (complete insulin independence) rate exceeds 80% for SKPT, 70% for sequential pancreas after kidney transplant (PAKT), and 65% for pancreas transplant alone (PTA). According to registry data, rejection accounts for 32% of graft failures in the first year after pancreas transplantation. However, improvements are expected to continue with the evolution of treatment protocols. Most pancreas transplant centers employ quadruple drug immunosuppression with anti-lymphocyte induction with either a monoclonal or polyclonal antibody agent. In recent years, there has been an overall decline in the use of antibody induction therapy from 90% during the period 1987-1993 to 83% of pancreas transplants performed during 1994-1997. Maintenance immunosuppression is triple therapy consisting of a calcineurin inhibitor (cyclosporine or tacrolimus), corticosteroids, and an anti-metabolite (AZA or MMF). Prior to 1995, nearly all pancreas transplant recipients were managed with Sandimmune. In the last 2 yr, tacrolimus-based therapy has been used in approximately 20% of cases and a new microemulsion formulation of cyclosporine (Neoral) has replaced Sandimmune in contemporary post-transplant immunosuppression. In addition, MMF is replacing AZA as part of the standard immunosuppressive regimen after pancreas transplantation. At present, a number of centers are conducting various trials with new drug combinations including either Neoral or tacrolimus in combination with steroids and MMF with or without antibody induction therapy. From 1994 to 1997, the 1 yr rates of immunologic graft loss have decreased to 2% after SKPT, 9% after PAKT, and 16% after PTA. The current array of new immunosuppressive agents are providing more effective control of rejection and permitting solitary pancreas transplantation to become an accepted treatment option in diabetic patients without advanced complications. The apparent potency of new drug combinations has also resulted in a resurgence of interest in steroid withdrawal. Immunosuppressive strategies will continue to evolve in order to achieve effective control of rejection while minimizing injury to the allograft and risk to the patient. In addition, new regimens must not only address the issue of specific drug toxicities but also long-term economic, metabolic, and quality of life outcomes. Pancreas transplantation will remain an important alternative in the treatment of diabetic patients until other strategies are developed that can provide equal glycemic control with less immunosuppression and overall morbidity.

Functional, life-threatening disorders and splenectomy following liver transplantation.

Abstract: Splenectomy (SPL) in cirrhotic patients undergoing liver transplantation (LTx) may resolve specific problems related to the procedure itself, in case of functional and life-threatening clinical situations often occurring as a result of liver cirrhosis and portal hypertension. Methods. A single-center experience of ten splenectomies in a series of 180 consecutive adult liver transplant patients over a period of 6 yr is reported. The mean patient age was 46.8±9.5 yr (range 25–57 yr). Indications for SPL were post-operative massive ascitic fluid loss (n=3), severe thrombocytopenia (n=3), acute intra-abdominal hemorrhage (n=2), infarction of the spleen (n=1), and multiple splenic artery aneurysms (n=1). Results. Extreme ascites production due to functional graft congestion disappeared post-SPL, with an improvement of the hepatic and renal functions. SPL was also effective in cases of thrombocytopenia persistence post-LTx, leading to an increase in the platelet count after about 1 wk. Bleeding episodes related to left-sided portal hypertension or trauma were also resolved. The rejection rate during hospitalization was 0%, and no other episodes were recorded in the course of the long-term follow-up. However, sepsis with a fatal outcome occurred in 4 patients, i.e. between 2 and 3 wk post-SPL in three cases and 1 yr after the procedure as a result of pneumococcal infection in the last case. Fatal traumatic cranial injury occurred 3 yr post-LTx in another case. Five patients (50%) are still alive and asymptomatic after a median follow-up period of 36 months. Conclusions. The lowering of the portal flow appears to resolve unexplained post-operative ascitic fluid loss as a result of functional graft congestion following LTx. However, because of the enhanced risk of SPL-related sepsis, a partial splenic embolization (PSE) or a spleno-renal shunt could be used as an alternative procedure because it allows us to preserve the immunological function of the spleen. SPL is indicated in case of post-transplant bleeding due to left-sided portal hypertension and trauma, spleen infarction, and to enable prevention of hemorrhage in liver transplant patients with multiple splenic artery aneurysms. Severe and persistent thrombocytopenia could be treated with PSE. Because the occurrence of fatal sepsis post-SPL is a major complication in LTx, functional disorders, such as ascites and thrombocytopenia, should be treated with a more conservative approach.

Does subclinical rejection contribute to chronic rejection in renal transplant patients

Abstract: Renal allograft biopsies have traditionally been performed in the setting of acute graft dysfunction. However, several groups have performed graft biopsies at times of stable graft function, and more recently, after treatment of rejection episodes. Surprisingly, unequivocal histologic criteria for acute rejection have been demonstrated in a high proportion of these protocol biopsies. The Winnipeg Transplant Group has documented the high prevalence of clinically silent inflammatory infiltrates in early protocol biopsies, and demonstrated their inflammatory and cytotoxic potential by immunohistochemical and molecular biological techniques. Furthermore, in a randomized trial, our group has demonstrated that subclinical rejection, if untreated, is associated with the development of early chronic pathology and late graft dysfunction. In this overview, we will summarize the early data on subclinical allograft inflammation, present the experience of the Winnipeg Transplant Group, and discuss the possible implications of subclinical rejection on the development of chronic rejection.

Pain and health related quality of life after heart, kidney, and liver transplantation

Abstract: No study has focused particularly on the sensory and affective experience of bodily pain among transplanted patients. The aim of this study was to explore pain and other factors that influence health related quality of life (HRQOL) in heart, kidney, and liver transplant recipients during the first 2 yr after transplantation, and to define similarities and/or differences in the three groups. A total of 76 patients, 18-60 yr old, undergoing heart, kidney, or liver transplantation between 1995 and 1997 with a follow-up of 6-24 months were included. HRQOL and pain were investigated by using the Short-Form-36 items (SF-36), the Hospital Anxiety and Depression Scale (HAD), and the Pain-O-Meter (POM). Overall, the patients show satisfactory HRQOL. There were no differences in experienced HRQOL 6 24 months after transplantation between kidney, liver, and heart transplant recipients except in the area of Role-Physical (RP). Fifty-three percent of all patients reported bodily pain. The most common locations were the hands, feet, and back, and sensory experiences were burning, stabbing, or dull pain. There was a correlation between number of rejections and total score for POM-VAS (p < 0.05) (rho = 0.47). There was also a correlation between the number of rejection episodes and the total pain intensity score for POM-WDS (p < 0.05) (rho = 0.48). Patients with pain scored higher in the area of depression (p < 0.05). Bodily pain is an important problem after organ transplantation, affecting daily living even in patients with good allograft function and it limits physical function. vitality, and general health.

Male recipients of kidneys from female donors are at increased risk of graft loss from both rejection and technical failure

Abstract: The aim of the present retrospective study was to uncover the factor(s) responsible for the poor outcome of cadaver kidney grafts from female donors in male recipients. The 741 transplantations performed at our center from August 1983 to September 1997 were distributed into four groups according to recipient and donor gender: female donor to female recipient (F to F: n = 117), male donor to female recipient (M to F: n = 172), female donor to male recipient (F to M: n = 170), and male donor to male recipient (M to M: n = 282). All the patients received immunosuppressive therapy based on corticosteroids and cyclosporine, associated or not with either azathioprine or prophylactic anti-lymphocyte globulin. Overall graft survival was lower in the F to M group than in the three other groups (p = 0.009). Failures due to rejection were more frequent during the 1st post-transplant trimester in female than in male donor grafts, irrespective of recipient gender (p = 0.025). All failures due to technical problems occurred during the first 3 months post-transplantation: they were more frequent in the F to M group than in the three other groups (p = 0.040): this could be related to the older age of the donors in the former group. After the first post-transplant year, failures due to causes other than rejection remained low in the F to F group but increased steadily in the three other groups (p = 0.007). Specific survival rates were not correlated with the time-evolution of mean serum creatinine values, daily doses and trough levels of cyclosporine in the four groups of grafts. In conclusion, the poor outcome of F to M grafts results from combined immunologic and technical factors exerting their effects early in the course of transplantation.

Clinical risk factors for recurrence of IgA nephropathy.

Abstract: No clinical risk factors for recurrence of immunoglobulin A (IgA) nephropathy in kidney transplants have been defined. This is a single-centre retrospect analysis of recurrence in 104 first kidney transplant patients with biopsy-verified IgA nephropathy. Fifty patients had living donors. All but an identical twin were treated with cyclosporin A. The median follow-up time was 5 yr. Graft biopsies had been obtained from 35 grafts later than 6 months after transplantation, due to deteriorating graft function or gross proteinuria. Thirteen biopsies showed mesangial glomerulopathy proliferative in eleven cases with IgA deposits. Recurrence caused failure of six grafts. Eleven grafts with recurrence were from living donors (p = 0.005). No specific human leukocyte antigen (HLA) was identified as a risk factor. Known duration of original disease until end-stage renal failure was significantly shorter in patients with recurrence (median 5 yr, range 0-25 yr) compared with those without (median of 10 yr, range of 0-37 yr) (p = 0.015). Cumulative graft survival was not reduced in living versus cadaveric donor recipients.

Analyses of pancreas transplant outcomes for United States cases reported to the United Network for Organ Sharing (UNOS) and non-US cases reported to the International Pancreas Transplant Registry (IPTR).

Abstract: As of September 1999, almost 13,000 pancreas transplants had been reported to the IPTR, > 9,000 in the US and > 3,000 outside the US. An era analysis of US cases from 1987 to 1997 showed a progressive improvement in outcome (p 44 years old increased from 5% to 24%, and the improved outcomes encompassed the older patients as well. In patients > 44 years old, SPK pancreas GSRs at one year increased from 69% for 1987-89 cases to 79% for 1996-97 cases (p or = 95% in each recipient category, with one year pancreas GSRs of 84% for SPK (n = 2,502), 76% for PAK (n = 404), and 72% for PTA (n = 176) (p = 0.0001). The immunological graft failure rates for 1996-99 US SPK, PAK and PTA cases were 2%, 6%, and 10% at one year (p = 0.001). There was a progressive increase in the use of ED (as opposed to BD) for duct management, up to nearly 60% of US pancreas transplants by 1998. Approximately 18% of SPK ED transplants had venous drainage via the portal system. Pancreas GSRs were not significantly different for 1996-99 ED (n = 1,170) and BD (n = 1,203) US SPK transplants (84% and 85%, respectively, at 1 year), nor was there any difference in pancreas GSRs for systemic (n = 437) versus portal (n = 194) venous drained ED SPK transplants (84% and 83%, respectively, at 1 year). Interestingly, kidney GSRs were significantly higher for ED versus BD US SPK cases, 93% versus 84% at one year (p = 0.003). Duct management did matter for solitary (PAK and PTA) pancreas transplants. PAK pancreas GSRs were 80% at one year for BD (n = 238) versus 68% for ED (n = 156) US transplants. PTA pancreas GSRs were 78% at one year for BD (n = 98) versus 63% for ED (n = 73) US transplants. However, BD transplants were associated with a 12% conversion rate to ED by 2 years after transplantation. Analyses of outcome by immunosuppression for US cases showed pancreas GSRs to be higher in SPK recipients given MMF (87% at 1 year) than in those who were not (76% at 1 year). For PAK and PTA recipients, those given anti-T cell for induction and TAC and MMF for maintenance immunosuppression had the highest GSRs: 86% and 83%, respectively, at one year for BD pancreas transplants; not significantly different from the pancreas GSR (87% at 1 year) in BD SPK recipients also given anti-T cell for induction and TAC and MMF for maintenance immunosuppression. Analyses of US pancreas transplant outcome according to HLA matching showed no effect at all in the SPK category, while for PAK and PTA transplants an effect was seen at the A and B loci, strongest at the B loci. Matching for at least one antigen at both loci was associated with one-year pancreas GSRs of 85% for PAK and 74% for PTA, versus 70% and 60%, respectively, at one year for those who were not matched for at least one antigen at both the A and B loci. In regard to non-US cases, the overwhelming majority were in the SPK category (n = 528 for 1996-99), with one-year pancreas GSR of 79%, not significantly different from US cases. Approximately 40% of non-US SPK cases were ED (n = 204), and, as in the US, the pancreas GSRs were similar for ED and BD transplants in this category. (ABSTRACT TRUNCATED)

Pre-transplant identification of risk factors that adversely affect length of stay and charges for renal transplantation

Abstract: BACKGROUND In the current era of renal transplantation, increasing attention is being focused on resource utilization. The purpose of this study was to identify demographic, medical and immunologic risk factors that are associated with changes in length of stay (LOS) and charges for renal transplantation. METHOD The study was a retrospective analysis of 311 consecutive renal transplants performed at a single institution. Univariate and multivariate analyses were used to examine relationships between risk factors, LOS, charges and post-operative complications. RESULTS The following pre-transplant variables were found to be independently significant in predicting increased LOS and/or charges: African-American race, obesity for women, chronic obstructive pulmonary disease (COPD), presence of cardiac disease or previous stroke, pre-transplant dialysis time > or = 1 yr, a 10% increase in panel reactive antibody (PRA), cadaver donor and retransplantation. The analyses were performed with and without adjustment for key outcome variables such as delayed graft function (DGF) and use of induction antibody therapy. Increased LOS or charges for specific risk factors could be attributed to increased complication rates, including delayed graft function seen with various co-morbidities, or increased immunologic risk and more frequent use of induction antibody therapy. CONCLUSION Analysis of linked financial and clinical databases can reveal demographic, medical and immunologic risk factors that correlate with LOS, charges and complications for renal transplantation. Efforts to establish quantitative relationships for various risk factors relative to resource utilization will become important in managed care and/or capitated healthcare delivery systems.

Transmission of malaria tertiana by multi-organ donation.

Abstract: In this report, transmission of malaria via a liver, a kidney, and possibly a heart allograft from a single donor is described. The donor had immigrated from Cameroon to Germany 18 months before, but had no clinical signs of active malaria infection. The liver transplant recipient and one of the two kidney transplant patients developed febrile illness with the appearance of Plasmodium vivax in blood smears 5 and 6 wk after transplantation, respectively. In the heart transplant recipient, a subclinical malaria infection was suspected based on a rise of malaria antibodies late after transplantation, whereas the recipient of the second kidney allograft had no clinical or laboratory evidence of malaria. Both liver and kidney recipients with active malaria responded to medical treatment. However, the liver transplant patient developed progressive cholestasis and died 5 months after transplantation from liver failure possibly due to side effects of the malaria medication. Other cases of malaria in solid organ recipients are briefly reviewed.

Differences in Type 1 and Type 2 intracytoplasmic cytokines, detected by flow cytometry, according to immunosuppression (cyclosporine A vs. tacrolimus) in stable renal allograft recipients

Abstract: Recent multicenter, randomized clinical trials have shown that in renal transplant patients tacrolimus (FK506) was more efficient than cyclosporine A (CsA) at preventing acute rejection. In order to try and evaluate whether this difference was related to a different in vivo T-cell suppression we assessed, in a prospective study, the frequencies of interleukin (IL)-2-, IL-4-, IL-5-, IL-6-, IL-10-, interferon-gamma (IFN-gamma)- and double-positive IL-2/IFN-gamma-producing whole T cells, CD4 + and CD8 + T-cell subsets by means of cytokine flow cytometry. This was performed after in vitro stimulation of peripheral blood mononuclear cells (PBMCs) with phorbol myristate acetate (PMA) and ionomycin, in the presence of monensin, in 14 healthy volunteers (controls) and in 14 renal transplant patients. The immunosuppression of the latter was based either on CsA (n = 7) or on FK506 (n = 7). Cytokine-expressing T-cell frequencies were assessed immediately pretransplantation (DO), and subsequently 3 months (M3) and 6 months (M6) afterwards in fasting patients prior to the morning intake of the immunosuppressive drug. We found that at DO the frequencies of IL-2-(22 +/- 2% vs. 22.2 +/- 2%), IFN-gamma-(26 +/- 3% vs. 29 + 3.4%) and IL-4-(0.8 +/- 0.2% vs. 1.4 +/- 0.2%)-expressing T lymphocytes were not significantly different between the controls and the patients, respectively. Conversely, the frequency of IL-2/IFN-gamma double positive cells was higher in the latter (9.3 +/- 1.6%) than in the controls (5.6 +/- 0.8); p = 0.06. Finally, on D0 the frequencies of IL-5-, IL-6-, and IL-10-producing T lymphocytes were lower than 1%, in both groups, as well as after grafting, i.e. on M3 and M6. As compared to baseline (DO): (a) chronic immunosuppression significantly decreased the frequencies of IL-2-, IL-4- and IL-2/IFN-gamma-expressing T cells, whereas those of IFN-gamma, IL-5, IL-6, and IL-10 were not significantly affected; (b) the frequencies of cytokine-expressing T cells were not statistically different between M3 and M6; (c) the decrease in the frequencies of IL-2- and IL-2/IFN-gamma-expressing T cells affected CD4 + and CD8 + cells equally; (d) there was a marginal decrease in the frequency of IFN-gamma-expressing cells only in the CD4 + subset but not in the CD8 population; and (e) for CsA, but not for FK506, the frequency of the IL-2-expressing T cells was negatively correlated with the whole blood trough levels. When we compared the frequencies of cytokine-expressing cells in FK506- and CsA-treated patients, we found that the frequency of IL-2-expressing T cells was significantly lower with FK506 (10.9+/-1.61%) than with CsA (16.3 +/- 1.8%; p = 0.03), whereas the frequencies of the other cytokine-expressing cells were not statistically different between the two groups. In conclusion, our study clearly demonstrated that studied ex vivo, FK506 and CsA decrease the frequencies of cells expressing IL-2, IL-4 and IL-2/IFN-gamma in vivo but do not affect those expressing IFN-gamma. Meanwhile, the frequency of IL-2-producing T cells was more affected with FK506 than with CsA and was negatively correlated with the CsA trough level. Finally, our results regarding IL-2 might explain to some extent the higher efficiency of FK506 in vivo than CsA.

The prognostic importance of severity and type of post-transplant proteinuria.

Abstract: Proteinuria, developing after renal transplantation may influence allograft and patient outcomes. This study aimed to investigate the effect of proteinuria on patient and allograft survival. Among 514 patients, 56 (11%) patients with good allograft function and proteinuria were evaluated retrospectively. Patients with proteinuria were classified as group P (20 patients with permanent proteinuria, Male/Female: 16/ 4) and group T (36 patients with temporary proteinuria, M/F: 29/7) according to the type of proteinuria. Also, considering the amount of proteinuria, patients were classified as group M (32 patients with massive proteinuria, M/F: 29/3) and group NM (24 patients with non-massive proteinuria, M/F: 16/8). The mean time interval between transplantation and appearance of proteinuria was 23.7 months (range 0-121 months) and no difference was found between groups. Two- and 5-yr allograft survival rates were found to be 85 and 80% in group M, and 95 and 82% in group NM, respectively (p = 0.24). In terms of type of proteinuria, 2- and 5-yr allograft survival rates were found to be 70 and 58% in group P and 92 and 87% in group T, respectively. The difference between groups P and T was found to be statistically significant (p = 0.02). Most (85%) of the patients with permanent proteinuria also had massive proteinuria. In conclusion, we found a significant relation between type and severity of proteinuria. The type of post-transplant proteinuria had a stronger effect on allograft outcome than the severity of proteinuria.

Expression of γ-IFN mRNA in bronchoalveolar lavage fluid correlates with early acute allograft rejection in lung transplant recipients

Abstract: Various cytokines are upregulated in acute allograft rejection (AR). Local production of Th-1 cytokines is suggested to play a pathogenic role in AR, and Th-2 cytokines in the development of allograft tolerance. The purpose of this study was to correlate the expression of Th-1 [interleukin-2 (IL-2) and gamma-interferon (gamma-IFN)], and Th-2 [interleukin-10 (IL-10)] cytokines in bronchoalveolar lavage (BAL) fluid with AR in lung transplant (LT) recipients. The role of Th-1 dominance expressed as IgG2/IgG1 ratio in BAL in AR was also examined. The mRNA expression for IL-2, gamma-IFN and IL-10 was examined in 64 BAL specimens from 23 LT recipients using reverse transcriptase-polymerase chain reaction (RT-PCR). IgG1 and IgG2 levels were measured in 55 BAL specimens by enzyme-linked immunosorbent assay (ELISA). The expression on mRNA for these cytokines, and the ratio of IgG2/IgG1 was correlated with AR (early AR occurring within 3 months of transplant and late AR occurring after 3 months). Ten patients had 17 episodes of biopsy proven AR. Twelve episodes of AR (6 patients) occurred within the first 3 months of transplantation. In 5 patients, AR was diagnosed 4, 5, 6, 9 and 24 months post-transplantation. Detection of gamma-IFN mRNA correlated significantly with early AR (p < 0.001), whereas it lacked correlation with late AR. Expression of IL-2 and IL-10 mRNA did not correlate with AR. IL-10 was present in most samples irrespective of the presence or absence of AR. The ratio of IgG2/IgG1 was similar in patients with or without AR. Our findings suggest that the detection of gamma-IFN mRNA in BAL by RT-PCR is useful for immune monitoring of early AR in LT recipients. Absence of elevated IgG2/IgG1 ratio, and presence of IL-10 in BAL during AR suggests that Th-1 cytokines may not be the sole mediator of rejection in LT recipients.

Peritubular capillary deposition of C4d complement fragment in ABO-incompatible renal transplantation with humoral rejection.

Abstract: In ABO-incompatible renal transplantation complement activation may be related to antibody-associated humoral rejection. However, immune deposits within the vasculature have been infrequently demonstrated in biopsy specimens. Whether deposition of complement fragment C4d is correlated with graft outcome and pathological findings (as measured by the severity of antibody-associated humoral rejection) is investigated in this study. Nineteen ABO-incompatible and 9 ABO-compatible renal graft biopsy specimens were selected. Four out of 19 ABO-incompatible patients lost their grafts within I yr. Ten out of 19 ABO-incompatible and just 1 out of 9 ABO-compatible patients, had prominent C4d deposition in peritubular capillaries. ABO-incompatible patients with predominant C4d deposition showed few tubulitis, accumulation of polymorphonuclear cells and thrombosis in peritubular and glomerular capillaries. The severity of the humoral rejection was correlated to C4d deposition in peritubular capillaries. Three out of four graft losses in ABO-incompatible renal transplantation showed severe humoral rejection and profuse deposition of C4d complement fragments in peritubular capillaries. Immunosuppression therapy was discontinued in the 4th patient, who lost his graft because of his lethal intestinal bleeding. C4d deposition in peritubular capillaries would be helpful for differential diagnosis between humoral rejection and drug-induced nephrotoxicity, and may serve as a sensitive marker of ABO-incompatible humoral rejection for patients with unsatisfactory (no glomeruli) biopsy specimens.

Liver transplantation in the United States: a report from the UNOS Liver Transplant Registry.

Abstract: Transplants and centers Between 1988 and 1998 the number of liver transplants performed in the US more than doubled from 1,713 to 4,487; the number of centers increased from 59 to 116. The number of living donor, segmental, and multiple organ transplants also increased over time. The rate of increase in the number of centers has slowed over the last few years. Outcomes. Survival among pediatric recipients. The one- and 7-year graft survival rates for pediatric recipients were 72% and 62%, respectively. The one- and 7-year patient survival rates were 85% and 79%. Patient survival did not decrease much after the first 2 years and graft survival stabilized after 4 years posttransplant. Some of the factors associated with increased odds of graft failure and patient death at 6 months posttransplant included having a previous transplant; being hospitalized, in the ICU, or on life support at the time of transplant; creatinine > 2 mg/dl; donor age and race/ethnicity; and transplant type. Factors associated with decreased odds of graft failure or patient death were recipient gender, recipient race/ethnicity, having a metabolic disease and receiving a living donor liver. Among grafts/recipients surviving the first 6 months after transplantation, recipient race/ethnicity, primary liver disease, having a previous transplant, donor age and race/ethnicity, and transplant type were associated with a greater relative risk of graft failure and mortality. Survival among adult recipients. The one- and 7-year graft survival rates among adult recipients were 77% and 57%, respectively. The one- and 7-year patient survival rates were 85% and 67%. Survival rates decreased steadily at all time points following transplantation. Some of the factors associated with increased odds of graft failure and mortality at 6 months after transplantation were recipient age and race/ethnicity; primary liver disease; having a previous transplant; being hospitalized, in the ICU, or on life support at the time of transplant; longer cold ischemia time; older donor age, race/ethnicity, or gender; and having a non-identical recipient/donor blood type match. Having cholestatic liver disease/cirrhosis and shorter cold ischemia times were associated with decreased odds of graft failure and mortality. Many of these characteristics also affected grafts and patients surviving the first 6 months, including recipient race/ethnicity, primary liver disease, previous transplant, and donor age.

Impact of solid organ transplantation and immunosuppression on fever, leukocytosis, and physiologic response during bacterial and fungal infections.

Abstract: Immunosuppressed solid organ transplant patients may exhibit a blunted response to infection compared to non-transplant patients. To test this hypothesis, we prospectively identified all episodes of bacterial and fungal infection on the in-patient abdominal organ transplant service in our hospital, in 1997, and compared them to infected general surgery and trauma admissions treated simultaneously on the same wards. Eighty-two infections occurred in transplant patients versus 463 in non-transplant patients. Transplant patients demonstrated an overall greater physiologic response [Acute Physiology and Chronic Health Evaluation (APACHE II) and Acute Physiology Scores (APS) at the time of infection of 17.0+/-0.7 and 10.3+/-0.6, respectively, vs. 12.2+/-0.4 and 8.0+/-0.3 for non-transplant patients, p < 0.003], with a similar maximum temperature (38.0+/-0.1 vs. 38.2+/-0.1 degrees C, p = 0.2) and white blood cell (WBC) count (12.1+/-1.0 vs. 13.9+/-0.4 k/mL, p = 0.08). Upon further analysis of subgroups, patients receiving mycophenolate or azathioprine had significantly lower maximum temperatures (37.9+/-0.2 degrees C) and WBC counts (11.0+/-0.9 k/mL) when compared to non-transplant patients, while steroids appeared to have little effect on the systemic inflammatory response. Overall mortality was similar between groups. In general, solid organ transplant recipients exhibit a physiologic response to bacterial or fungal infection (as measured by the APS) at least as great as that seen in non-transplant surgical patients, although mycophenolate and azathioprine appear to slightly depress the ability to respond with fever and leukocytosis. None of these differences appeared to affect overall mortality.