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Kidneys from old donors after cardiac death (DCD) may increase the donor pool but the prognosis of these kidneys is unsatisfactory. To improve these results, we retrospectively evaluated the diagnostic utility of published selection algorithms for old donor kidneys. We studied all DCD kidney transplantations between January 1, 1994 and July 1, 2005 at our institution (n = 199). Selection algorithms were evaluated in the subset of kidney transplantations from donors aged 60 years or older (n = 52). For histological assessment of kidney biopsies, glomerulosclerosis, tubular atrophy, interstitial fibrosis and vascular narrowing were blindly scored. Functional kidney weight was calculated as renal mass multiplied by the fraction of nonsclerosed glomeruli. Graft function and survival of kidneys from DCD aged 60 years or older were inferior to those from younger DCD. Histological scores were associated with kidney function and graft survival of old DCD kidney transplantations. Functional kidney weight was associated with kidney function but not graft survival, while donor glomerular filtration rate (GFR), donor age and machine perfusion characteristics were associated with neither of the clinical outcomes of interest. We conclude that histological assessment of preimplantation biopsies may improve the selection of kidneys from old DCD and may therefore contribute to expansion of the donor pool.

An update is given about some factors leading to loss of renal allograft, especially in relation to the use of tacrolimus and cyclosporine. We discuss both immunological, such as suboptimal immunosuppression, acute rejection, and noncompliance, as well as nonimmunological factor's such as hypertension, hyperlipidemia, chronic toxic effects of immunosuppressants, older donors, and delayed graft function.

BACKGROUND: Donor-directed antibodies (DDA) can be formed in recipients after transplantation. There is not much known about their appearance in relation to the time after transplantation, nor the duration between transplantation and failure. METHODS: DDA formation was retrospectively analyzed in patients transplanted between 1992 and 2004. Thirty-two nonimmunized first transplant recipients with transplantectomy within 4 weeks (median 6 days) were analyzed. Posttransplant sera were screened for HLA class I and II by flow cytometry (FC), ELISA, and cytotoxicity. All patients except one were treated with CNI (calcineurin inhibitor)-based immunosuppression. RESULTS: Analysis was performed on the basis of FC results. In total, 16 of 32 patients became positive for DDA class I and/or II (50%). All antibodies were detected after transplantectomy. Class I and II antibodies were produced in 15 and 10 recipients, respectively. Multivariate regression analysis showed DDA positivity to be predicted by donor age (P=0.05). DDA were shown in patients who lost their graft due to immunological reasons but in a comparable percentage also in patients with nonimmunological graft loss. CONCLUSIONS: DDA after early transplantectomy appeared frequently but later than expected. In view of the growing number of marginal donors and the possible necessity of retransplantation, it is considered important to prolong the time of serum sampling and screening to at least 4 months. Immunization might escape attention when serum screening is restarted only from the time the patient is again referred to the waiting list.

The impact and evaluation of two school-based interventions on intention to register an organ donation preference.Reubsaet A, Brug J, Kitslaar J, van Hooff JP, van den Borne HW.Department of Health Education and Promotion, Universiteit Maastricht, The Netherlands. a.reubsaet@gvo.unimaas.nlThe present paper describes the impact and evaluation of two intervention components-a video with group discussion and an interactive computer-tailored program-in order to encourage adolescents to register their organ donation preference. Studies were conducted in school during regular school hours. The video with group discussion in class had a positive impact on the intention to register an organ donation preference as well as on the intention to register as a posthumous organ donor. The computer-tailored program had no surplus value when compared to reading an extensive brochure with general information on organ donation. However, participants appreciated the tailored information more than the brochure. It may be that having provided general information before exposure to the tailored program, the tailored intervention will be more effective. This needs to be tested in a further experiment.

Process evaluation of a school-based education program about organ donation and registration, and the intention for continuance.Reubsaet A, Reinaerts EB, Brug J, van Hooff JP, van den Borne HW.Maastricht University, Department of Health Education and Promotion, PO Box 616, 6200 MD Maastricht, The Netherlands. a.reubsaet@gvo.unimaas.nlThis paper describes the process evaluation of an organ donation education program for high school students aged 15-18 years of which the effectiveness was established. The program consisted of three components: a video with group discussion, an interactive computer-tailored program and a registration training session. A cross-sectional survey was conducted among 50 teachers who had recently worked with the program. The results show that all teachers reported to have implemented at least two of the three intervention components, while a majority of teachers reported to have implemented all components. Teachers' attitudes toward the program were generally positive. They reported that the opinions of students and colleagues in their own department were most influential in their decision to provide the education program. Furthermore, teachers were very confident about their ability to apply the different parts of the education program. The educational quality of the program was evaluated as moderately positive and almost all teachers had the intention to use the program again in the future. Because of the positive evaluations and intentions for future implementation by teachers, and justified by its previously established effectiveness, the education program should be considered for large-scale dissemination among high schools in The Netherlands

The effects of FK778 in combination with tacrolimus and steroids: a phase II multicenter study in renal transplant patients.Vanrenterghem Y, van Hooff JP, Klinger M, Wlodarczyk Z, Squifflet JP, Mourad G, Neuhaus P, Jurewicz A, Rostaing L, Charpentier B, Paczek L, Kreis H, Chang R, Paul LC, Grinyo JM, Short C.Inwendige Geneeskunde-Nefrologie, Universitaire Ziekenhuizen Gasthuisberg, Leuven, Belgium. yves.vanrenterghem@uz.kuleuven.ac.beBACKGROUND: In animal and in vitro models, FK778 inhibits acute rejection, modifies vasculopathy, and shows anti-viral activity. We report first efficacy and safety data of FK778 in human kidney transplant recipients at two concentration-controlled ranges. METHODS: In a double-blind manner, 149 patients were randomized to a 12-week treatment with FK778 in combination with tacrolimus (Tac) and corticosteroids (S). Of the high-level group (H), 49 patients received 2 x 600 mg/day FK778 and continued on 150 mg/day, 54 patients of the low-level group (L) got 1 x 600 mg/day followed by 75 mg/day, and 46 patients received placebo (P). Subsequent FK778 doses were adjusted to trough levels of 100-200 microg/mL (H) and 10-100 microg/mL (L). The primary endpoint was the incidence of biopsy proven acute rejection (AR). RESULTS: In 93% of the patients in group L, targeted plasma trough levels were reached by Day 3; in half of the patients in group H, the targeted levels were reached by Day 9. Graft survival at week 16 was 89.7%, 88.8%, and 91.3%, and the incidences of AR were 26.5%, 25.9%, and 39.1% for groups H, L, and P. For the subgroup of patients in which target levels were reached by week 2, incidences were 7.7%, 27.1%, and 39.1%, respectively. Anemia, the most frequently reported adverse event especially in group H, was reversible. Mean total cholesterol and LDL-cholesterol levels were reduced during FK778 treatment compared with group P. CONCLUSION: FK778 is pharmacologically active, well-tolerated, and safe. To fully benefit from this promising new drug, FK778 dosing will be optimized in subsequent studies

BACKGROUND: Supplementation of immunosuppressive therapy with mycophenolate mofetil (MMF) has been found to reduce the rate of acute rejection in renal transplantation. We report a dose-finding study for MMF when administered in combination with low-dose tacrolimus and corticosteroid prophylaxis in cadaveric renal transplant recipients. METHODS: Two hundred thirty-two patients at 16 centers were enrolled in this randomized, parallel-group study. The three treatment groups were tacrolimus and corticosteroids (MMF-0 group, n=82); tacrolimus, corticosteroids, and 1 g of MMF daily (MMF-1 g group, n=79); and tacrolimus, corticosteroids, and 2 g of MMF daily (MMF-2 g group, n=71). Study duration was 6 months, and patients were followed up for patient and graft survival for 12 months. RESULTS: At 6 months posttransplantation, daily doses of 1 g and 2 g of MMF were associated with significantly lower rates of acute rejection compared with tacrolimus alone. The Kaplan-Meier rates were 48.5%, 24.9%, and 22.9%, respectively, for the three treatment groups when acute rejection was determined by clinical criteria (P=0.007). At month 12, patient survival rates were 100%, 97.5%, and 97.2% and graft survival rates were 90.2%, 92.4%, and 93.0% for the MMF-0 group, MMF-1 g group, and the MMF-2 g group, respectively. Gastrointestinal adverse events and leukopenia were higher in the MMF groups, especially in the MMF-2 g group (P

Background Fat mass is increased in renal transplant (RTx) patients, which may have untoward metabolic and cardiovascular effects. The influence of steroids on body composition (BC), resting energy expenditure (REE), and substrate oxidation rates was assessed in stable RTx patients in a cross-sectional design. Also, the relation between physical activity and nutrient intake, respectively, and body composition was studied. Methods 77 RTx patients (42 males, 35 females) were studied. Twenty-one patients were on 10 mg and 27 patients on 5 mg maintenance steroid dose; 29 patients were receiving steroid-free immunosuppression. Assessed were BC (DEXA, anthropometry), REE and substrate oxidation (indirect calorimetry), physical activity (Baecke questionnaire), and nutrient intake (dietary records). Results BC was not different between the 0-, 5-, and 10-mg steroid group, and no relationship existed between cumulative dose of steroids and BC. REE and substrate oxidation also did not differ between the various groups, apart from a small increase in glucose and decrease in lipid oxidation in female patients using 5-mg steroids. Especially in females, leisure time physical activity was positively related with the percentage lean body mass (r=0.571, P=0.004) and inversely related with fat mass (r= -0.588, P=0.003). Nutrient intake and BC (corrected for physical activity) were not related. Conclusions No relation was observed between daily and cumulative steroid dosage and BC and between daily steroid dose and REE and substrate oxidation in RTx patients. Especially in female patients, physical activity level and the percentage of lean body mass concluded and body fat were significantly related.

Background. The early detection of human cytomegalovirus infection after organ transplantation is a prerequisite for effective antiviral therapy. We evaluated the diagnostic value of monitoring the viral immediate-early (IE) 1 mRNA expression in blood leukocytes by nucleic acid sequence-based amplification (NASBA). Methods. Nucleic acids were isolated from 489 blood samples collected from 42 kidney transplant recipients and subjected to amplification by IE NASBA The IE NASBA results were compared to those from pp67 NASBA, pp65 antigenemia, cell culture (DEAFF and CPE), and serology. Results. IE NASBA provedl to be the most sensitive assay which detected the onset of both primary and secondary cytomegalovirus infection significantly earlier than the other assays. Conclusions. The early detection of cytomegalovirus infection with IE NASBA would enable the start of effective antiviral therapy at an early state of infection to prevent cytomegalovirus disease in patients at risk.

Whether multifrequency bioelectrical impedance analysis (MF-BIA), a relatively new method for measuring body composition, is also applicable for accurate body composition measurements in renal transplant (RTx) patients is not known. Therefore, the use of MF-BIA is validated in 77 RTx patients with a stable renal function at least 2 yr posttransplantation. MF-BIA is compared to isotope dilution techniques for measurement of body water compartments, and to dual energy x-ray absorptiometry (DEXA) and anthropometry for measurement of fat and fat free mass. Finally, DEXA and anthropometry are compared to each other. Method agreement is assessed by intraclass correlation coefficients (ICC) and plotted by Bland and Altman analysis. MF-BIA significantly underestimates total body water (TBW, 0.7+/-2.1 L) and overestimates the extracellular water (ECW, 3.3+/-1.8 L) compared to isotope dilution; the ICC between both techniques is 0.943 for TBW and 0.846 for ECW. The percentage body fat (BF) measured by MF-BIA is significantly higher than both BF measured by DEXA (3.4+/-4.7%) or by anthropometry (5.5+/-5.2%). The ICC between MF-BIA and DEXA is 0.887 and between MF-BIA and anthropometry 0.856. BF measured by DEXA is significantly higher than BF measured by anthropometry (2.1+/-4.4%); their ICC is 0.913. In conclusion, MF-BIA seems to be suitable for measurement of TBW in RTx patients; however, method agreement between isotope dilution and MF-BIA for the measurement of ECW is not satisfactory. In the assessment of fat and fat free mass, the reliability of MF-BIA appears to be questionable. Method agreement between DEXA and anthropometry seems to be slightly better.

Background. Pretransplant blood transfusions are reported to decrease acute rejection rate and increase graft survival after renal transplantation. This has been attributed to matching for HLA-DR with the transfusion donor, which also results in a lower rate of sensitization. Methods. The development of donor-specific T- and B-cell antibodies was measured by National Institutes of Health and two-color fluorescence assays after one transfusion in 247 naive patients. Auto-cross-matches were performed to exclude autoantibodies. Patients were grouped according to DR-matching (n=107) or nonmatching (n=140) with the transfusion donor. In 103 renal allograft recipients, acute rejection rate and graft survival were analyzed by Cox regression. Results. T-cell antibodies developed in 6.5% of the patients. There was no difference between the DR-matched and nonmatched group. No auto-antibodies against T-cells developed, whereas one quarter of the sera had a positive B-cell auto-cross-match. There was no difference with regard to B-cell antibodies (autoantibody-positive sera excluded) between the DR-matched (15.8%) and nonmatched (18.6%) group. Sharing of HLA A and/or B antigens did not result in a lower frequency of donor-directed T- or B-cell antibodies. None of the risk factors, including DR sharing with transfusion donor, contributed significantly towards graft survival (odds ratio for DR sharing: 1.02; 95% confidence interval: 0.45-2.32; P=0.97). DR sharing was no risk factor towards acute rejection either, in contrast to DR mismatch with kidney donor (odds ratio: 2.9), and use of cyclosporine versus tacrolimus (odds ratio: 4.4). Conclusions. Development of donor-directed T-cell antibodies after one transfusion of leukocyte-poor blood is low and irrespective of HLA-DR match with transfusion donor. B-cell antibodies develop more frequently and independent of HLA-DR match. In 26% of the sera, B-cell auto-antibodies are detected. Rejection rate and graft survival are not significantly different between HLA-DR-matched and nonmatched transfusions.

To evaluate the diagnostic value of nucleic-acid-sequence-based amplification (NASBA) for the detection of cytomegalovirus (CMV) infection in transplant recipients, we compared immediate early 1 (IE1) and late pp67 mRNA detection by NASBA with the antigenemia assay, PCR and viral culture in 72 renal transplant (RTx) recipients and with antigenemia and serology in 25 liver transplant (LTx) recipients. Antigenemia, viral culture and pp67 NASBA were almost equivalent for the detection of CMV in RTx recipients. In LTx recipients, antigenemia detected more positive samples and more positive recipients compared to pp67 NASBA. In RTx recipients, PCR detected more positive samples and positive recipients compared to pp67 NASBA, antigenemia and viral culture. Also the first day of detection was slightly earlier for PCR. However, IE1 NASBA was the most sensitive test and detected 96% of all positive samples and positive transplant recipients. In addition, IE1 NASBA preceded PCR and all other positive results. This makes IE1 NASBA a very attractive screening test for the early detection of CMV infection.

Publication Types: Clinical Trial Multicenter Study Randomized Controlled Trial

Department of Internal Medicine, University Hospital Maastricht, The Netherlands.BACKGROUND: There is no consensus on the role of donor-directed antibodies after renal transplantation detected by complement-dependent cytotoxicity (CDC) or by flow cytometry (FC). METHODS: Therefore, antibody formation was studied by FC and correlated with clinical course in a group of patients who received transplants between 1983 and 1993. All had a negative current CDC crossmatch and were treated with cyclosporine. Current and posttransplant sera from 143 donor-recipient combinations were studied retrospectively. Antibodies were considered present in FC if the fluorescence ratio between serum and negative control was > 2.65. RESULTS: Of 143 patients, 17 (11.9%) were found to be positive in the posttransplant FC crossmatch and 126 (88.1%) were negative. Of the positive patients, 3 were already positive in the current FC crossmatch, whereas 14 demonstrated a positive posttransplant FC crossmatch after a negative current FC crossmatch. It was noteworthy that, from 16 patients with a positive current FC crossmatch, 13 turned negative in the posttransplant crossmatch. In 113 recipients (79%), both pre- and posttransplant FC crossmatches were negative. The development of a positive FC crossmatch after transplantation was a significant risk factor for graft survival in Cox regression analysis (P = 0.01). The results were also studied as relative change in fluorescence ratio (RCFR). RCFR was determined by classifying the recipients in quartiles according to their change in flow cytometric value from current to posttransplant serum. Quartiles were defined as follows: quartile 1, decrease > 10%; quartile 2, decrease 0-10%; quartile 3, increase > 0-30%; and quartile 4, increase > 30%. RCFR proved to be the only significant risk factor for graft survival (odds ratio for quartile 4 vs. quartile 1, 3.27; P < 0.02). More rejections were shown for increasing quartile numbers (P < 0.001). CONCLUSIONS: Classification of patients by RCFR detected more patients with unfavorable clinical outcome (25% vs. 11%) than by FC crossmatch.

The aim of combined pancreas-kidney transplantation (PKT) in type I diabetic patients with end-stage nephropathy is to restore both functions. Quality of life (QoL) is supposed to improve as a result of this combined transplantation. The objectives of this study are to evaluate QoL before and after PKT and to compare the results with patients in whom the pancreas graft failed soon after the transplantation (PKT-P). The trial is a prospective controlled multicenter study. The control group consists of patients before transplantation and patients who received a PKT in whom the pancreas rejected or thrombosed soon after the transplantation. (PKT-P). A standardized home-based interview is done during dialysis, and repeated 5, 12, and 18 months after transplantation in both groups by the same interviewer. The interview consisted of disease-specific questions (RSCL), general questionnaires (NHP I and II, ABS), the Visual Analogue Scale, a specific questionnaire (Anxiety), and evaluative questions about social support and transplantation. Patients in whom the PKT is successful (n=17) improve significantly or show a strong tendency toward improvement on many aspects of quality of life. Patients in whom the pancreas failed (n=5) still demonstrate improvement, although this is not statistically significant in most cases. Intergroup comparison shows that PKT patients are less anxious, suffer of less itching, have better average daily living conditions, have no diet restrictions, and have a better [correction of have and] global quality of life.

Uniparental maternal disomy 6 in a renal transplant patient.van den Berg-Loonen EM, Savelkoul P, van Hooff H, van Eede P, Riesewijk A, Geraedts J.Tissue Typing Laboratory, University Hospital Maastricht, The Netherlands.HLA analysis of the family of a renal transplant patient revealed an extremely rare condition. On repeated typings the only demonstrable HLA antigens shown in the propositus were from the maternal haplotype, HLA-A11,-B46,-CW1,-DR14,-DQ1. No paternal antigens could be demonstrated either by serologic or by DNA-typing methods. A paternity investigation was carried out to exclude the possibility of the legal father not being the biological father. The results of this investigation showed a paternity index I = > 20000 and a fatherhood probability W = > 99.995%. Karyotyping of the patient showed two normal chromosomes 6 and no other chromosomal abnormalities. Maternal isodisomy was demonstrated from the analysis of polymorphic DNA markers, involving the short as well as the long arm of chromosome 6. These data are consistent with this patient having the first uniparental maternal disomy 6 reported (inheritance of two identical chromosome 6 haplotypes from the mother and none from the father).

In this study, we investigated soluble tumor necrosis factor receptor (sTNF-R) levels in plasma of patients with either a kidney or cardiac allograft when clinical suspicion of acute rejection was raised. In plasma of patients with acute renal graft rejection, the sTNF-R levels were strongly enhanced (20–150 ng/ml) as compared to plasma of patients with stable renal function. Following successful treatment of the rejection, a gradual decline in sTNF-R levels occurred with improving renal function, and an inverse correlation between creatinine clearance and sTNF-R was found. To determine whether the increase was caused by an accumulation of constitutively released sTNF-R and lack of clearance by the kidney, or whether the immunological process of the rejection caused the enhancement, we measured sTNF-R in patients suffering from acute cardiac graft rejection but with predominantly stable kidney function. Rejection of a cardiac graft did not lead to a significant enhancement of sTNF-R levels. However, treatment with ATG or OKT3 did cause enhanced sTNF-R levels, followed by a decline that reached starting values after 7 days. These results provide evidence that the immune reaction that occurs during rejection of a graft does not per se induce discernible changes in sTNF-R levels, whereas that induced by ATG or OKT3 does. Thus, sTNF-R levels are not a reliable marker in transplant recipient monitoring.

Because of the decreased venous compliance in hypertensive dialysis patients, it was investigated whether their venous system exhibited structural abnormalites. Venous samples were taken during transp

Early graft thrombosis and rejection of the graft are the two major causes of graft failure in pancreas transplantation. Inclusion of the spleen in the pancreatic graft has been purported as a possible solution to both complications, but severe graft-versus-host disease led to abolishment of this procedure. By irradiating the donor spleen ex vivo during cold storage, we successfully prevented graft-versus-host disease, allowing us to evaluate the advantages of clinical pancreaticosplenic transplantation. This study reports our experience with 12 pancreaticosplenic transplantations. Using Doppler flow measurements, we have been able to examine the hemodynamic advantages. Our results confirm the purported benefit. Vascular resistance indices in the pancreatic graft are significantly lower when the donor spleen is included. This, however, did not lower the incidence of thrombosis (2 out of 12 cases) in our study. Serial radionuclide studies with 99mTc-hexamethyl propylene amine oxime were performed for further evaluation of graft perfusion. With time the spleen uptake diminishes, compatible with atrophy of the organ. This was confirmed histologically. No indication of an immunologic advantage of transplanting the pancreas together with the spleen was found. All patients went through severe rejection crises. A transient reduction in platelet count (55-88%, mean 71%) of preoperative values was observed. This platelet drop is not seen in patients with a pancreas without spleen transplantation. We conclude that in pancreas transplantation, inclusion of the irradiated spleen has no obvious advantages for early graft thrombosis and rejection of the graft.

THE MAJORITY of the adult human population is seropositive for cytomegalovirus (CMV), a member of the b-herpesvirus family. Normally, infection of immunocompetent individuals does not cause disease. In contrast, infection of immunocompromised individuals, such as patients with AIDS and transplant recipients, can cause severe complications and can even lead to death. Therefore, early detection of active CMV infection is necessary to start effective antiviral treatment. Nucleic Acid Sequence-Based Amplification (NASBA) has been developed for the specific amplification of RNA. In previous studies, we evaluated the diagnostic value of monitoring the expression of the CMV immediate early (IE) 1 and late pp67 mRNA using NASBA, in peripheral blood cells of kidney transplant (Tx) patients. The IE 1 mRNA is expressed directly after entrance of the virus into a cell, while pp67 mRNA is expressed in a late stage in the replication cycle. NASBA results were compared to the techniques that are routinely being used for the detection of CMV: pp65-antigenemia, virus culture, and serology. From this study it was concluded that IE NASBA is a very sensitive assay that detects the onset of CMV infection significantly earlier than the other assays. This is especially valuable for patients that are at risk for symptomatic CMV infection, i.e., seronegative patients with an organ of a seropositive donor and/or intense immunesuppression. The sensitivity and specificity values of pp67 NASBA were comparable to those of the antigenemia assay. We set up a similar study to evaluate the diagnostic value of IE and pp67 NASBA for liver Tx patients. The liver Tx patients are usually severely ill, immunesuppression is more intense compared to the kidney Tx patients and they often have anti-rejection therapy. The results for IE NASBA are presented in this report. The evaluation of pp67 NASBA is still in progress.

Bicarbonate as a physiological buffer should be preferred in haemodialysis treatments. The use of bicarbonate dialysis, however, varies from 30 to 100% in the different industrialised countries. Except for the many advantages using bicarbonate dialysate, there are also clinical pitfalls in the use of the bicarbonate buffer substrate. Furthermore, technical problems can be expected in the use of varying dialysate bicarbonate concentrations, as in the concomitant use of acetate and bicarbonate dialysate in the same dialysis unit. This paper deals with the clinical and technical aspects of bicarbonate dialysis.

In 9 chronic hemodialysis patients, treated with recombinant human erythropoietin (rHuEpo), longitudinal studies were performed to investigate possible changes in macro- and microcirculatory parameter

Changes of macro- and microcirculation during haemodialysis and fluid removal are probably dependent on ultimate fluid status and on the efficacy of various regulation mechanisms, especially the catecholamines. This was studied in 20 chronic dialysis patients. Pre- and postdialysis stroke volume, mean arterial pressure, heart rate and systemic vascular resistance were measured. Furthermore, microcirculation was studied by Laser Doppler flow and by intravital microscopy of finger nail fold, measuring red blood cell velocity and capillary density. Pre- and postdialysis noradrenaline and adrenaline were measured. Nine patients proved to be hypovolaemic after dialysis (group I) and 11 patients proved to be normovolaemic or less hypervolaemic (group II) according to vena cava inferior parameters. There was a significant decrease of mean arterial pressure and stroke volume in group I, and an increase of heart rate, whereas in group II there was only a decrease of mean arterial pressure. Systemic vascular resistance did not change in both groups. Noradrenaline decreased although not significantly in both groups, whereas in group I adrenaline increased significantly. There was a significant decrease of skin perfusion in group I, whereas in group II there was a significant increase. Capillary density increased significantly in group II after reaching normovolaemia. Underhydration was leading to a decrease of skin microcirculation on the basis of a decrease of stroke volume and an increase of adrenaline levels. In hypervolaemic patients, who were ultrafiltrated to normovolaemia, skin microcirculation improved on the basis of a decrease of arterial and venous pressure and consequently a decrease of the myogenic response as a local autoregulatory effect.

In a preliminary investigation an assay for tacrolimus based on fingerprick sampling and consecutive application as a blood spot on sampling paper has been developed. The dried blood spot was analysed by HPLC-tandem mass spectrometry. The validated range was 1-30 microg/l. Intra- and inter-assay variability for precision and accuracy was

Non-heart-beating donor (NHBD) kidneys may substantially expand the donor pool, but many transplant centers are reluctant to use these kidneys because of the relatively high incidence of primary nonfunction (PNF). In heart-beating donor kidneys, intravascular fluid depletion during transplant surgery is associated with delayed graft function (DGF). Therefore, we studied the effect of the recipients' hemodynamic status on the outcome of 177 NHBD kidney transplantations. Independent statistically significant predictors of PNF were average central venous pressure (CVP) below 6 cmH(2)O (adjusted odds ratio (AOR) 3.1 (95% CI: 1.4-7.1), p=0.007), average systolic blood pressure below 110 mmHg (AOR 2.6 (95% CI: 1.1-5.9), p=0.03) and pre-operative diastolic blood pressure below 80 mmHg (AOR 2.4 (95% CI: 1.0-5.9), p=0.05). Donor characteristics were not independently associated with PNF (p>0.10). In a subgroup analysis of 56 paired kidneys, 29% of the recipients with the lower CVP of the pair experienced PNF compared with 11% of their counterparts with higher CVP (p=0.09). Our study indicates that recipient hemodynamics during transplant surgery are major predictors of PNF. Therefore, improving recipient hemodynamics by expansion of the intravascular volume is expected to enhance the results of NHBD kidney transplantations and may enlarge the donor pool by increasing the acceptance of NHBD kidneys.

Early detection of active cytomegalovirus (CMV) infection after organ transplantation is necessary to start effective antiviral treatment. In the present study, blood specimens of kidney transplant recipients (n = 38) were monitored for the expression of CMV immediate early (IE) and late (L) mRNA using nucleic acid sequence-based amplification (NASBA). Results were compared with virus isolation, pp65 antigenemia and serology. In patients developing active CMV infection, pp65 antigen and L mRNA were detected simultaneously. At the same time, positive cell culture results could be reported to the clinic. CMV was detected significantly earlier with IE NASBA than with the other assays. However, the specificity of IE NASBA is lower than that of antigenemia, late NASBA and cell culture. Early detection of IE mRNA is especially useful for patients at high risk of developing symptomatic CMV infection in order that early, adequate antiviral therapy may be started. Late NASBA can be used to monitor further development of CMV infection, comparable to antigenemia.

Lipoprotein patterns in renal transplant patients: a comparison between FK 506 and cyclosporine A patients.

Although acceptable outcomes have been reported in both non-heart-beating (NHB) and elderly donors individually, the large pool of elderly NHB donors has not yet been fully utilized. In 1994, we expanded our transplant protocol to include NHB donors aged over 65 years and this study compares the clinical outcomes with regular NHB transplantations. Up to June 2005, 24 patients were transplanted at our center with kidneys from NHB donors aged 65 years or more, whereas 176 patients received grafts from conventional NHB donors during the same period. Grafts from older donors were associated with inferior glomerular filtration rates (29 vs. 44 mL/min after 1 year, p = 0.01) and graft survival (52% vs. 68% after 5 years, p = 0.19) compared to younger NHB donor grafts, although the difference in graft survival was not statistically significant. Exclusion of older NHB donor kidneys with severe vascular pathology resulted in similar graft survival of older and younger NHB donor kidneys. We conclude that the use of elderly NHB donors in order to expand the donor pool was associated with unacceptable clinical outcomes and cannot be justified without further refinement in their selection, for example, by histological assessment of pretransplant biopsies.

In 1998, a new organ donor registration system was implemented in the Netherlands to increase the number of potential donors. A high school education program was developed to prepare adolescents to make an informed decision about organ donation. A post-test only randomised controlled trial was conducted in 39 high schools including 2868 students. Students within schools were randomly allocated to either attend the organ donation education program or not. The impact of the program on students’ intention to register their organ donation preference (and determinants thereof) were analysed using multivariate multileveling modelling (MlwiN). The results show that students who were exposed to the education program had more favourable registration intentions ( B = . 40 ), were more often willing to be donors ( OR = 1.45 ), and had greater knowledge about ( B = 3.84 ) and more positive social outcome expectations ( B = . 09 ) and self-efficacy regarding organ donation registration ( B = . 22 ). Lastly, they experienced significantly less negative outcome expectations related to organ donation registration ( B = - . 15 ). Students’ evaluation of the school-based education program was favourable. The present organ donation registration program proved to be effective in changing determinants of organ donation registration, and a large-scale implementation in the Dutch high school curriculum is planned.

Safe withdrawal of corticosteroids or mycophenolate mofetil: results of a large, prospective, multicenter, randomized study.Squifflet JP, Vanrenterghem Y, van Hooff JP, Salmela K, Rigotti P; European Tacrolimus/MMF Transplantation Study Group.Cliniques Universitaires Saint-Luc, University of Louvain Medical School, Saint Luc Hospital, 10 Hippocrates Avenue, B-1200 Brussels, Belgium. Jean-Paul.Squifflet@chir.ucl.ac.be

BACKGROUND: In 1998, a new organ donor registration scheme was implemented in the Netherlands in order to increase the number of potential donors and to facilitate decisions and procedures concerning organ donation. However, registration rate and registration choices failed to meet the expectations. METHODS: A cross-sectional survey among a random sample of 1,731 Dutch adolescents of 18 and 19 years was conducted to study potential determinants of organ donor registration choices. RESULTS: Almost one fifth of the adolescents indicated that they did not return their organ donation registration form. Among subjects who registered, 57% were willing to donate their organs or tissues posthumously. More positive social influences, fewer negative outcome beliefs, and a low level of organ donation anxiety were significant predictors of returning a completed registration form and registration as an organ donor. In addition, religion was a significant predictor of returning a completed registration form, and positive outcome beliefs contributed to the prediction of registration as an organ donor. CONCLUSIONS: The results give clear suggestions for tailoring organ donation registration interventions to specific characteristics, beliefs, and misconceptions of adolescents. The results also suggest that it is important to encourage adolescents to discuss issues related to organ donation with their parents and friends in order to increase donor registration.

Anti-class I IgG can be detected by complement-dependent cytotoxicity (CDC) and by ELISA. We compared ELISA and CDC for both class I and class II antibodies on method agreement and relation to rejection-free and graft survival.Peak, current, and posttransplant sera (n=429) of 143 renal allograft patients were tested by National Institutes of Health technique (NIHT), two-color fluorescence (TCF), and ELISA. Method agreement was assessed by intraclass correlation coefficient (ICC). Rejection and graft survival were analyzed by uni- and multivariate techniques. The screening results for each serum were compared, as was the change in result of current to posttransplant serum.The ICC of ELISA and NIHT was insufficient; it was lower for TCF than NIHT. Graft survival was not related to the result of any assay. Rejection-free survival was related to ELISA and NIHT in current and posttransplant serum. With the NIHT, the change in percent panel-reactive antibody (%PRA) correlated better with rejection than it did with ELISA. The combined antibody status of current and posttransplant serum was a risk factor for rejection in all assays, and for TCF also in multivariate analysis. The rejection rate was higher if the posttransplant serum was ELISA-negative/CDC-positive, rather than ELISA-positive/CDC-negative. For ELISA, class I specificities (and not %PRA) in peak and current sera were related to rejection, even if the antibodies were not donor-directed. In the case of the National Institutes of Health technique (NIHT), %PRA and not specificity was related to rejection. Class II antibodies were never related to rejection.ELISA and NEIT are complementary screening techniques in this patient population. They are of equal predictive value for rejection. The optimal strategy in combining these techniques must be determined.