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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.

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. 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.

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.

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.

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.

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

Two patients are presented with progressive invalidating uremic peripheral neuropathy. The peripheral neuropathy developed despite frequent hemodialysis with a polyacrylonitril membrane and afterwards in combination with CAPD. The first patient with a long history of progressive peripheral neuropathy before renal transplantation recovered incompletely after renal transplantation, whereas the second patient with a short history of a severe progressive UPN recovered completely after renal transplantation.

HE MAJORITY of the adult human population is infected with 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 neonates, 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. 1 We evaluated the diagnostic value of monitoring the expression of the CMV immediate early (IE) 1 mRNA using NASBA, in peripheral blood cells of kidney and liver transplant patients. The IE 1 mRNA is expressed directly after entrance of the virus into a cell. NASBA results were compared to the techniques which are routinely being used for the detection of CMV: pp65-antigenemia, virus culture, and serology.

Better evidence on the relative merits of various immunosuppressive regimens for reducing diabetes while preserving overall outcomes is needed. See also article by vincenti et al in this issue on page 1506.

Department of Internal Medicine, University Hospital Maastricht, The Netherlands.BACKGROUND: It has been hypothesized that correction of metabolic acidosis might improve the nutritional state of acidotic haemodialysis (HD) patients partly because of a reduced oxidation of branched-chain amino acids (BCAA). AIM: We investigated whether bicarbonate (Bic) supplementation in acidotic HD patients results in increased plasma levels of BCAA. METHODS: In a longitudinal study (run-in period, 2 months; study period, 6 months), the effect of Bic supplementation on plasma levels of BCAA was studied in 12 acidotic HD patients (7 men, 5 women, mean age 54 +/- 18 years) with a predialysis bicarbonate (Bic) concentration smaller or equal to 22 mmol/l. Bic was supplemented by increasing Bic concentration of the dialysate and by oral Bic supplementation. RESULTS: Predialysis Bic increased significantly during the study period (18.7 +/- 2.7 vs. 23.1 +/- 11.5 mmol/l). There was no change in nutritional parameters. However, plasma levels of the BCAA valine, leucine, and isoleucine increased significantly. CONCLUSIONS: In haemodialysis patients with metabolic acidosis, Bic supplementation over a 6-months period resulted in an increase in plasma levels of BCAA. Further study is needed to elucidate the mechanisms behind, and the clinical importance of the observed changes in plasma BCAA levels.

It is unknown to what extent preservation and/or reperfusion may damage islet cells in pancreas allografts. In this study, the release of insulin after reperfusion was used as a marker of injury to the islet cell and compared with the best insulin secretory response (ISR) after glucagon stimulation over a period of 100 days after pancreas transplantation.

The presence of human cytomegalovirus (HCMV) genome in spleen tissue was studied by using DNA hybridization techniques in seropositive and seronegative organ donors without clinical or laboratory confirmed HCMV infection. The serum samples of these patients were screened by latex agglutination test (LA) and enzyme linked immuno sorbent assay (ELISA) for the presence of HCMV antibodies, and confirmed by immunoblotting technique (IB). For the detection of HCMV sequences in spleen tissue dot blot DNA hybridization (DBH) using probes derived from immediate-early and late regions (ES and BH fragment respectively) of the HCMV genome were used. Samples positive in DBH were further tested by in situ DNA hybridization (ISH) using the ES probe. The number of spleen tissue specimens positive for HCMV nucleic acids indicated that HCMV may be present in human beings, even without serological evidence.

It has been shown that patients transfused with one unit of blood mismatched for both HLA DR antigens have an increased rate of formation of cytotoxic leukocyte antibodies compared to patients who received blood which differs in only one DR antigen. In the same study it was found that DR sharing of the blood transfusion donor and patient improved results of kidney and heart transplantation. However, the data were mostly collected in a retrospective manner and came from various centers. Furthermore, no information was available on whether these antibodies were directed to B- or T-cells. Therefore, the influence of DR match of recipient and blood donor on the formation of T- and B-cell antibodies as well as on clinical course after kidney transplantation was studied prospectively in patients transplanted in one centre.

It is generally accepted that HLA matching improves graft survival [1]. However, there is no consensus on whether this improvement is reflected on daily clinical course. Clinical course after renal transplantation depends on many factors, such as donor age, recipient age, ischemic score in the kidney [2], and HLA matching [3]. The relative contribution of these factors is unknown. Because management of the recipients in the various centers differs considerably, only a single centre study would reveal the relative contribution of all these factors. Therefore, in our centre we studied the influence of these parameters on the clinical course after renal allografting.

At the introduction of our Pancreas Transplant Program in 1985, we decided to try to prevent graft thrombosis by including the spleen in the graft (1). In those days the incidence of graft thrombosis was as high as 25% (2). We based our policy on the work of Starzl (3), who introduced the inclusion of the spleen in pancreatic transplantation. The assumption is, that preservation of the normal vascular architecture of the pancreas will maintain the normal flow pattern. We presume that the pancreas receive about 1% of the heart minute volume and the spleen about 5%, and therefore, inclusion of the spleen might increase several times the amount of flow through the graft. But the pathophysiology of the thrombotic episode is not totally clear and other factors as edema due to ischemia and preservation or pancreatic enzyme damage to vascular endothelium (4), and eventually the pancreas being a low-flow state organ (5), all may play a role.

Tacrolimus is a very potent drug for preventing all types of acute rejection after renal transplantation. The decrease of vascular rejection may have important long-term implications. This is demonstrated in the 3-year data of the U.S. multicentre trial, where a significant decrease of graft loss was observed in the tacrolimus patients compared to cyclosporine patients. Safety profiles of both drugs are the same, but there are some major differences in side effects. Hyperglycemia is more common during tacrolimus, but generally the induction of hyperglycemia is a dose-dependent reversible process, which leads generally to diabetes mellitus during high systemic exposure, in certain races and prediabetics. Gum hyperplasia and hirsutism are not seen during tacrolimus therapy and there is a more favorable cardiovascular risk profile during tacrolimus as compared to cyclosporine based immunosuppression.

Co-administration of tacrolimus and mycophenolate mofetil in cadaveric renal transplant recipients.

In a retrospective single-center study the influence of warm ischemia time and simultaneous influence of HLA (A and B) matching on one-year renal graft survival was analyzed in 170 adult recipients of primary cadaveric renal grafts. One-year survival of grafts with warm ischemia times longer than 50 min was only 40% (n = 10). When warm ischemia time was shorter than 50 min, a 1-min increase of warm ischemia time correlated with 1% decrease in one-year graft survival as a result of rejection. This detrimental effect of warm ischemia time on graft survival was not yet significant one month after transplantation, but became more evident as follow-up time was lengthened. Warm ischemia time also correlated with the number of reversible rejection episodes in patients with a graft functioning for longer than one year (P less than 0.04). The beneficial influence of HLA (A and B) matching on one-year graft survival was significant (P less than 0.05 log linear test). This influence was even more evident with longer warm ischemia times. It is concluded that warm ischemia has a detrimental influence on graft survival that is mediated by rejection, and it is suggested that this might be due in part to altered presentation or expression of HLA-antigens of ischemically damaged kidney tissues.

Two adult patients received both kidneys from neonatal donors. After grafting an accelerated growth of the kidneys was observed. Five weeks after transplantation the craniocaudal diameter had increased from 4 and 3.4 to 8.3 and 6.1 cm, respectively. Histological examination of the kidneys showed segmental glomerulosclerosis 24 and 3 months after grafting, respectively.

Graft prognosis in 435 leucocytotoxin-free recipients of a kidney graft was not significantly improved by matching for the serologically defined antigens. It could, however, be shown that 108 donor-recipient combinations which shared either the HL-A 1 and 8, or the HL-A 2-12, or the HL-A 3-7 antigens had a significantly better prognosis (70% after 18 months) than 40 combinations mismatched for these antigens (41% after 18 months, p

The dosages of corticosteroids applied after kidney transplantation were recently decreased in our hospital by approximately 50%. This led to a considerable decrease of the morbidity rate without a decrease of graft survival (1, 2). This change in our immunosuppressive regimen was one reason to undertake an analysis of factors contributing to an increased infection rate after cadaveric kidney transplantation.

The medical history of a 42-year-old patient with primary hyperoxaluria type I is presented. Primary hyperoxaluria was suspected after renal transplantation, when oxalate deposits were found in a biopsy of the kidney graft. Diagnosis of type I hyperoxaluria was confirmed by the finding that significantly increased amounts of glycolic acid and oxalic acid were excreted. Treatment of the patient with 500 mg pyridoxine daily resulted in a decrease of the excretion of oxalate to normal values.

In a prospective study, an analysis of risk factors for the development of cytomegalovirus (CMV) infection and disease was performed on 77 renal allograft recipients. Twenty-five out of the 77 recipients (32%) had a CMV infection. Twenty-two of the recipients received triple immunosuppressive therapy (cyclosporin A, prednisolone, and azathioprine) while the remaining 55 received standard therapy (cyclosporin A and prednisolone). In 23 recipients (30%) acute rejection was diagnosed and the first positive parameter of infection occurred 22 days after rejection therapy. Infection occurred in 10 out of 18 HLA-DR7-positive recipients (56%) and in 15 out of 59 HLA-DR7-negative recipients (25%; P< 0.02). In multiple regression analysis, HLA-DR7 was found to be a significant predictor of CMV infection (P< 0.005). CMV disease was diagnosed in only 9 out of 25 recipients with an acute infection. Six recipients (67%) with CMV disease received triple therapy for maintenance immuuosuppression; this was significantly correlated to CMV disease (P< 0.05) as compared to three recipients (33%) with CMV disease maintained with standard therapy. Our data suggest that HLA-DR7-positive recipients are more susceptible to CMV infection and that CMV disease is associated with triple immunosuppressive therapy.

4 observations semblables: 4 a 6 mois apres transplantation d'un rein de cadavre, sans rejet ni complications d'infection, les receveurs presentent des episodes d'hematurie macroscopique. La cystoscopie revele la presence de calculs au niveau de l'anastomose de l'uretere du greffon et de la paroi vesicale, qui est ulceree. Ces calculs sont formes par l'accumulation d'oxalate de calcium sur des fragments de sutures de vicryle. Apres lithotripsie tout rentre dans l'ordre