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Background: Sensitive screening methods have revealed that many patients have donor-specific human leucocyte antigen antibodies (DSAs) prior to transplantation, regardless of negative crossmatch results. The clinical significance of pre-transplant (pre-Tx) DSAs for early graft function has remained unclear. Our aim was to examine the association of DSAs with delayed graft function (DGF)., Methods: Pre-Tx sera of 771 patients who received kidney transplants in our single-centre study were retrospectively screened. All transplantations were performed after negative complement-dependent cytotoxicity (CDC) crossmatch., Results: DSAs were detected in 13% of the patients. The overall DGF rate in our study was 29%. Patients with DSAs had a higher incidence of DGF when compared with non-sensitized patients (48 and 26%, respectively; P < 0.0001). Third-party antibodies had no effect for DGF incidence (28%; P = 0.6098). The relative risk (RR) of DGF for patients with DSAs in the multivariate analysis was 2.039 (95% CI 1.246-3.335; P = 0.0046). Analyses of the cumulative mean fluorescent intensity (MFI) value of the DSAs revealed a rate of DGF more than two times higher in patients with a cumulative value of 3000-5000 MFI compared with a cumulative value of 1000-3000 (65 versus 31%; P = 0.0351). DSAs against any loci showed an elevated DGF incidence of 44-69% when compared with patients without DSA (27%)., Conclusions: The risk of DGF is twice as high in patients having pre-formed DSAs. Pre-Tx DSAs is a modifiable risk factor that can be obviated with careful organ allocation relying on careful pre-Tx analysis of non-accepted mismatches determined with sensitive solid phase methods., (© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Although longer pretransplant dialysis has been associated with poor kidney transplant outcome, no data about this association exist from the current era or from Europe. We studied the association of pretransplant dialysis duration on outcomes after kidney transplantation across two different time periods., Methods: All recipients of first kidney transplantation between 1990 and 2010 in Finland were included (N=3,105) in this observational follow-up study of an inception cohort. The association of the duration of pretransplant dialysis with patient and graft survival after transplantation was analyzed with multivariable Cox regression and competing risk analyses. The association of pretransplant dialysis duration with the risk of specific causes of death (cardiovascular, infectious, or other) was analyzed using competing risk analysis., Results: Longer duration of pretransplant dialysis was an independent risk factor for patient death after transplantation (risk ratio [RR] 1.14 per 1-year increase) in the whole study population, but not for graft loss. Risk of death was increased in patients with greater than 12 months of pretransplant dialysis. After further adjustment in patients transplanted in 2000 to 2010, longer duration of dialysis remained an independent risk factor (RR 1.23 per 1-year increase). Longer duration of dialysis was an independent predictor of death resulting from cardiovascular diseases (RR 1.14 per 1-year increase), but not for other causes., Conclusions: The risk of death associated with longer duration of dialysis has not decreased over time, but remains an independent predictor of patient death after kidney transplantation because of increased risk of death resulting from cardiovascular diseases.

Background: Neutrophil gelatinase-associated lipocalin (NGAL) is a marker for acute kidney injury. We studied whether serum NGAL predicts delayed graft function (DGF) and recovery of kidney function after transplantation., Methods: Serum NGAL was analyzed using commercial ELISA and point-of-care (POC) (Triage®, Biosite) methods. Serum samples were collected from 176 consecutive, deceased-donor kidney recipients just before transplant surgery and on day 1 and 14 after transplantation. The first 132 samples were analyzed with both methods and the remaining samples with the POC method., Results: The correlation between the ELISA and POC methods was 0.89, p < 0.0001 and hence the POC method was used for the remaining analyses. DGF was seen in 66/176 patients. Day 1 sNGAL was significantly higher in DGF (588 ng/ml, SD 189.6) compared to early graft function (355 ng/ml, SD 166.2, p < 0.0001) and this difference persisted on day 14. Day 1 sNGAL predicted DGF with an area under the curve (AUC) of 0.853 (CI 0.792-0.914, p < 0.0001). At the optimal cutoff level of 423 ng/ml the sensitivity was 87% and the specificity 77%. In a multivariate analysis, day 1 sNGAL emerged as an independent predictor of DGF. The sNGAL also predicted DGF lasting longer than 14 days with an AUC of 0.825 (CI 0.751-0.899, p < 0.0001). At the optimal cutoff level of 486 ng/ml, the sensitivity was 80% and specificity 75%., Conclusion: Serum NGAL predicts clinically significant DGF and is useful in the care of kidney transplant recipients.

Adenine phosphoribosyltransferase deficiency is a rare autosomal recessive disorder manifesting as urolithiasis or crystalline nephropathy. It leads to the generation of large amounts of poorly soluble 2,8-dihydroxyadenine excreted in urine, yielding kidney injury and in some patients, kidney failure. Early recognition of the disease, institution of xanthine analog therapy to block the formation of 2,8-dihydroxyadenine, high fluid intake, and low purine diet prevent CKD. Because of symptom variability and lack of awareness, however, the diagnosis is sometimes extremely deferred. We describe a patient with adenine phosphoribosyltransferase deficiency who was diagnosed during evaluation of a poorly functioning second kidney allograft. This report highlights the risk of renal allograft loss in patients with undiagnosed adenine phosphoribosyltransferase deficiency and the need for improved early detection of this disease.

The annual number of kidney transplantations in Finland is 150 to 200. Successful kidney transplantation improves the patient's quality of life and prognosis and is cost-effective as compared with dialytic therapy. Only a few per cent of transplantations are made from a living donor. Waiting times for kidney transplantations have become longer in the last few years. Whereas attempts should be made to better identify potential brain-dead organ donors in order to increase kidney transplantations, transplantations from living donors could also reduce the disproportion between the availability and the need of organs.

The incidence and clinical course of polyomavirus-associated nephropathy (PyVAN) in our well-HLA-matched kidney transplant population mainly on low-dose cyclosporine-based triple-drug immunosuppression has not been described in detail. We aimed to characterize our patients with PyVAN and BK virus (BKV) viremia. Among 166 kidney transplantations between January 2007 and February 2011 followed up at Helsinki University Hospital nephrology clinic, 136 were screened for BKV viremia by quantitative analysis of BKV DNA in plasma. PyVAN was diagnosed by biopsy histopathology and SV40 T-antigen detection. BKV viremia or PyVAN were treated by reducing immunosuppression. BKV viremia was detected in 12 (9%) patients. PyVAN was diagnosed in six patients (4%). In the six patients with no PyVAN, four had low-level viremia (<10,000 copies/mL) of short duration (<2 months), one had high-level viremia, and one had sustained low-level viremia. After reduction of immunosuppression, all except one patient were able to clear viremia. No grafts were lost due to PyVAN. Even in a low-risk population, BKV viremia and PyVAN occur, highlighting the importance of monitoring viral loads. Reduction of immunosuppression was successful, and no grafts were lost due to PyVAN., (© 2012 John Wiley & Sons A/S.)

Background: Long-term use of corticosteroids is associated with considerable morbidity, including cardiovascular and metabolic adverse effects., Methods: This study evaluated the long-term efficacy and safety of two steroid-free regimens compared with a triple immunosuppressive therapy in renal transplant recipients. This was a 3-year follow-up to a 6-month, open-label, randomized, multicenter study., Results: Data from 3 years were available for 421 (93.3%) of 451 patients in the original intent-to-treat population (143 tacrolimus/basiliximab [Tac/Bas], 139 tacrolimus/mycophenolate mofetil [Tac/MMF], and 139 tacrolimus/MMF/steroids [triple therapy]). In the time interval from 6 months to 3 years after transplantation, the incidence of biopsy-proven acute rejection was low and similar (Tac/Bas, 2.1%; Tac/MMF, 2.2%; triple therapy, 2.2%); Most rejection episodes occurred during the first 6 months of the study. Graft survival was high (Kaplan-Meier estimates: 92.7%, 92.5%, and 92.5%), as was patient survival (93.1%, 96.4%, and 97.0%). There were 10 graft losses (n=2, 4, and 4) and 12 patient deaths (n=5, 2, and 5). Renal function was well preserved throughout the study and similar between groups. There was a trend toward improved cardiovascular risk factors in the Tac/Bas group, including reduced total and low-density lipoprotein cholesterol and lower new-onset insulin use. There were no between-group differences in the incidence or type of adverse events., Conclusion: Higher rates of acute rejection early in treatment were seen with the steroid-free regimens, but this did not translate into poorer long-term outcomes, such as graft and patient survival and renal function. A trend for a more favorable cardiovascular risk profile was observed for steroid-free immunosuppression with Tac/Bas.

In immunosuppressed patients human herpesvirus 6 (HHV-6) reactivations are common. The aim of the study was to determine to which extent HHV-6 can be found in the gastrointestinal tract in kidney transplant recipients and in patients on chronic dialysis. The HHV-6 and cytomegalovirus (CMV) examinations were performed on gastro duodenal and colon biopsy specimens obtained from 81 kidney transplant recipients and on 46 chronic dialysis patients. The HHV-6 and CMV were demonstrated by immunohistochemistry detecting both HHV-6A and HHV-6B, and CMV-specific antigens. The HHV-6B-positive cells, were found in gastroduodenal biopsy specimens from 34% of the transplant recipients and 28% of the patients on chronic dialysis, CMV-positive cells were found in specimens from 53% of the transplant recipients and 28% of the patients on chronic dialysis. The HHV-6B positive cells were found in the colonic mucosa specimens from 36% of the transplant recipients and 22% of the patients on chronic dialysis, CMV-positive cells were found in specimens from 36% of the transplant recipients and 17% of the patients on chronic dialysis. The HHV-6B positive cells were found equally often in the gastroduodenal as in the colorectal mucosa. The HHV-6B positive cells as well as CMV positive cells were simultaneously found in every fifth of transplant recipients., (© 2012 The Authors. Transplant International © 2012 European Society for Organ Transplantation.)

Background: Reliable markers for assessing the biological effect of immunosuppressive drugs and identification of transplant recipients at risk of developing rejection are not available., Methods: In a prospective multicenter study, we investigated whether posttransplant measurement of the T-cell activation marker soluble CD30 (sCD30) can be used for estimating the risk of graft loss in kidney transplant recipients. Pre- and posttransplant sera of 2322 adult deceased-donor kidney recipients were tested for serum sCD30 content using a commercial enzyme-linked immunosorbent assay., Results: sCD30 decreased posttransplant and reached a nadir on day 30. Patients with a high sCD30 of more than or equal to 40 U/mL on day 30 showed a subsequent graft survival rate after 3 years of 78.3±4.1%, significantly lower than the 90.3±1.0% rate in recipients with a low sCD30 on day 30 of less than 40 U/mL (log-rank P<0.001; Cox hazard ratio 2.02, P<0.001). Although an association was found between pre- and posttransplant sCD30 levels, patients with high sCD30 on posttransplant day 30 demonstrated significantly lower 3-year graft survival irrespective of the pretransplant level., Conclusions: Our data suggest that posttransplant measurement of sCD30 on day 30 is a predictor of subsequent graft loss in kidney transplant recipients and that sCD30 may potentially serve as an indicator for adjustment of immunosuppressive medication.

Different donor parameters and baseline biopsy have been used to assess the quality of donor organs. There is, however, no consensus which risk factors and chronic changes in the donor kidney can be accepted for transplantation. The study included 481 deceased organ donors and their 829 kidney recipients transplanted during 1995-2005. The biopsies were re-evaluated according to the Banff 97 classification. The prognostic significance of donor risk factors and Chronic Allograft Damage Index (CADI) was analyzed. We propose a new donor risk score, calculated as the count of positive risk factors from a defined set of factors in the medical history of the donor. This donor risk score predicts histological quality of the kidney, graft function, and survival. Transplantations from donors with donor risk score >4 had significantly decreased graft survival compared to those with donor risk scores 0-4; the five-yr death-censored graft survivals were 83% vs. 93%, respectively. High donor CADI score (>3) was associated with worse graft function and survival. Three-yr glomerular filtration rate declined from 82 to 49 mL/min with donor CADI increase from 0 to ≥4. Our results show that high donor risk score and CADI value reflect low functional reserve and risk for poor graft outcome., (© 2011 John Wiley & Sons A/S.)

Introduction: Expanding the criteria for deceased organ donors increases the risk of delayed graft function (DGF) and complicates kidney transplant outcome. We studied whether donor neutrophil gelatinase-associated lipocalin (NGAL), a novel biomarker for acute kidney injury, could predict DGF after transplantation., Methods: We included 99 consecutive, deceased donors and their 176 kidney recipients. For NGAL detection, donor serum and urine samples were collected before the donor operation. The samples were analyzed using a commercial enzyme-linked immunosorbent assay kit (serum) and the ARCHITECT method (urine)., Results: Mean donor serum NGAL (S-NGAL) concentration was 218 ng/mL (range 27 to 658, standard deviation (SD) 145.1) and mean donor urine NGAL (U-NGAL) concentration was 18 ng/mL (range 0 to 177, SD 27.1). Donor S-NGAL and U-NGAL concentrations correlated directly with donor plasma creatinine levels and indirectly with estimated glomerular filtration rate (eGFR) calculated using the modification of diet in renal disease equation for glomerular filtration rate. In transplantations with high (greater than the mean) donor U-NGAL concentrations, prolonged DGF lasting longer than 14 days occurred more often than in transplantations with low (less than the mean) U-NGAL concentration (23% vs. 11%, P = 0.028), and 1-year graft survival was worse (90.3% vs. 97.4%, P = 0.048). High U-NGAL concentration was also associated with significantly more histological changes in the donor kidney biopsies than the low U-NGAL concentration. In a multivariate analysis, U-NGAL, expanded criteria donor status and eGFR emerged as independent risk factors for prolonged DGF. U-NGAL concentration failed to predict DGF on the basis of receiver operating characteristic curve analysis., Conclusions: This first report on S-NGAL and U-NGAL levels in deceased donors shows that donor U-NGAL, but not donor S-NGAL, measurements give added value when evaluating the suitability of a potential deceased kidney donor.

Delayed graft function (DGF), especially long-lasting DGF, complicates kidney transplant outcome. Neutrophil gelatinase-associated lipocalin (NGAL) is an acute kidney injury marker; therefore, we tested whether urine NGAL could predict DGF, prolonged DGF (lasting over 14 days), or the quality of kidney function in transplant recipients without DGF (non-DGF). We collected urine samples from 176 recipients transplanted with deceased donor kidneys before and various days after transplantation. A total of 70 transplantations had DGF, of which 26 were prolonged. Patients who developed DGF had a significantly slower decrease in urinary NGAL compared with those without DGF, such that day 1 NGAL predicted DGF (area under the curve (AUC) 0.75) and predicted DGF in 15 of 112 cases with day 1 urine output over 1 l (AUC 0.70) and in 19 of 86 cases with a day 1 decrease in creatinine over 50 μmol/l (AUC 0.74). The urinary NGAL level on day 1 predicted prolonged DGF (AUC 0.75), which had significantly worse 1-year graft survival (73%), compared with shorter DGF (100%). In non-DGF, high day 3 NGAL (greater than the mean) was associated with significantly worse kidney function at 3 weeks compared with low NGAL, but not at 3 months and 1 year. NGAL did not correlate with long-term function in DGF. Hence, day 1 urinary NGAL predicted DGF even when it was not clinically expected early on, and importantly, it predicted prolonged DGF that led to worse graft survival.

Side effects of steroid use have led to efforts to minimize their use in transplantation. Two corticosteroid-free regimens were compared with a triple immunosuppressive therapy. Data from the original intent-to-treat (ITT) population (153 tacrolimus/basiliximab [Tac/Bas], 151 tacrolimus/MMF [Tac/MMF], and 147 tacrolimus/MMF/steroids [control]) were analyzed in a 12-month follow-up. Percentage of graft survival were 92.8%, 95.4%, and 95.9% (KM estimates 89.9%, 95.3%, 95.9%), percentage of surviving patients were 98.7%, 98.0%, and 100% (KM estimates 95.9%, 92.8%, and 100%). During months 7-12, graft loss occurred in 3 Tac/Bas, 2 Tac/MMF, and zero control patients, patient deaths in 1 Tac/Bas, 2 Tac/MMF, and zero control, and biopsy-proven acute rejection episodes in 4 Tac/Bas, 3 Tac/MMF, and zero control. Mean serum creatinine at month 12 was 141.9 +/- 69.6 microM, 144.0 +/- 82.1 microM, and 134.5 +/- 71.2 microM (ns). New-onset insulin use in previously non-diabetic patients at month 12 was 1/138, 6/127, and 4/126. Patient and graft survival as well as renal function at 12 months were not different between patient groups, despite considerably higher rates of acute rejection occurring within the first six months after transplantation in both steroid-free patient groups. Tac/Bas therapy might offer benefits in terms of a trend for a more favorable cardiovascular risk profile.

In the treatment of end-stage renal disease, kidney transplantation is the best and most cost-effective alternative with regard to both prognosis and quality of life. Problems arise from the disproportion between the number of available allografts and the patients waiting for the transplantation. There are few absolute contraindications to kidney transplantation. In the assessment of the eligibility for transplantation of patients on dialysis the most important factors include cardiovascular diseases, cancer diseases, other diseases affecting operability and life expectancy, age, excess weight and possible infections.

Aim: Cytomegalovirus (CMV) is the most common viral pathogen affecting organ transplant recipients. The objective was to determine to what extent CMV can be found in the gastrointestinal tract in kidney transplant recipients and to compare them with patients in dialysis and randomly chosen otherwise healthy patients who were referred for oesophagogastroduodenoscopy (OEGD) or colonoscopy., Patients and Methods: Biopsies for CMV examinations were obtained from 130 oesophagogastroduodenoscopies and 54 colonoscopies performed on 82 kidney transplant recipients, 49 dialysis patients with chronic end-stage kidney disease and 53 immunocompetent patients because of clinical indications. CMV was demonstrated by immunohistochemistry, both in frozen sections using a monoclonal antibody against CMV-specific antigens (pp65 matrix protein) and in paraffin sections by means of a monoclonal antibody against the delayed early protein (p52)., Results: CMV-positive cells were found in the gastroduodenal mucosa in 46 (68%) out of 82 kidney transplant recipients, in 9 (31%) of 49 dialysis patients and in 15 (45%) of 53 immunocompetent patients, in the colorectal mucosa in 7 (50%), in 6 (30%) and in 9 (45%) of the patient groups, respectively. In the transplant recipient group, 4 patients had severe and 10 patients moderate CMV infection in the gastroduodenal mucosa. CMV disease was diagnosed in two patients with severe infection and in one patient with moderate infection. All dialysis and immunocompetent patients had only moderate or mild CMV involvement., Conclusion: It appears that CMV-positive cells were present in all groups studied, suggesting that CMV-infected cells alone are not sufficient to make the diagnosis of CMV disease in the transplanted host. Moreover, the clinical symptoms and the intensity of the histologic CMV findings did not correlate with the symptoms the patients were having. In kidney transplant recipients, it emerges that CMV is activated more easily in the upper rather than in the lower gastrointestinal tract.

Background: The closely-linked genes of CD28, cytotoxic T-lymphocyte associated antigen 4 (CTLA4), inducible costimulator (ICOS), and programmed cell death 1 on chromosome 2q encode costimulatory molecules, which are regulators of the T-cell activity. The T-cell mediated immune response has a major role in allograft rejection. Hence, the variation in these genes may have an effect on graft survival and the amount of immunosuppression needed, but so far the studies have restricted solely to the CTLA4 gene., Methods: We determined 13 single nucleotide polymorphisms in CD28, CTLA4, ICOS, and PPCD1 genes in 678 adult patients who received a kidney from deceased donor. The effect of genetic variation on the outcome of renal transplantation was analyzed., Results: Two markers on the ICOS gene, rs10183087 and rs4404254, were associated with delayed graft function (odds ratio=5.8; P=0.020 and odds ratio=5.8; P=0.019, respectively). Interestingly, the same ICOS variation has been shown to regulate the expression level of ICOS. We also demonstrated an association of the ICOS polymorphism rs10932037 with the graft survival (P=0.026)., Conclusions: The present results indicate that potentially functional genetic variation in T-cell costimulatory molecule ICOS has an effect on the outcome of kidney transplantation.

Conclusions: This study found a 0.8% incidence of non-cutaneous head and neck cancer during a mean follow-up of 10 years. The benefits of successful renal transplantation clearly outweigh the observed risk of malignancy., Objective: Increased cancer incidence after organ transplantation is well documented but few studies have reported on the rate of head and neck malignancies among these patients. This study aimed to determine the incidence and specific sites of head and neck cancer in a nationwide series of renal transplant patients in Finland., Patients and Methods: Data from the National Kidney Transplant Registry and the Finnish Cancer Registry were used. A total of 2884 kidney transplant patients from the period 1964 to 1997 were followed for cancer incidence during the period from 1967 to 2003., Results: There were 113 non-lymphomatous head and neck malignancies. The standardized incidence ratio (SIR), as compared with the general population, was 13.6, with a 95% confidence interval (CI) of 11.2-16.2. The SIR was significantly elevated for cancers of the skin (47.3, 95% CI 36.3-60.7), lip (31.8, 95% CI 20.8-46.6), oral cavity (6.5, 95% CI 2.4-14.0) and thyroid (5.8, 95% CI 3.0-10.2).

Background: Cold preservation, reperfusion damage, immunosuppressive drugs, and uremia-induced acquired thrombophilias increase the risk of thrombotic complications in renal transplantation. Intragraft fibrin deposition may be associated with delayed graft function., Methods: We studied coagulation and fibrinolysis in 45 patients of a larger trial in renal transplantation: perioperative antithymocyte globulin (group A, n=15), perioperative basiliximab (group B, n=16), and conventional triple therapy (group C, n=14). Blood samples for prothrombin fragment F1+2, plasminogen activator inhibitor (PAI)-1, d-dimer, tPA antigen, tPA activity, and platelet counts were obtained simultaneously at 1 and 5 min after reperfusion from iliac artery and graft vein for calculation of transrenal changes. Because antithymocyte globulin activates coagulation and fibrinolysis, group A was analyzed separately. Groups B and C were pooled (group BC)., Results: In group BC, transrenal D-dimer release occurred at 1 min, tPA-antigen release at 1 and 5 min, and transrenal PAI-1 uptake at 5 min postreperfusion. tPA activity increased marginally only at 1 min. High graft tPA-antigen release at 5 min and D-dimer release at 1 min were associated with delayed graft function. In group A, transrenal tPA-antigen release occurred at 1 and 5 min and D-dimer release at 1 min. There were no transrenal F1+2 changes in either group., Conclusion: Although graft PAI-1 uptake inhibits tPA activity, graft releases D-dimer at early reperfusion without concomitant F1+2 release. Data suggest thrombin and fibrin formation already before cold preservation during donor care and organ retrieval. This fibrin deposition increases risk of delayed graft function.

Background: Acute rejection episodes and vascular complications are common after renal transplantation and have negative impact on the long-term patient and graft survival. We investigated whether the risks of acute rejection, thrombosis, infarction and graft loss could be predicted based on the presence of functional polymorphisms in the genes of the coagulation and endothelial inflammation cascade., Methods: The study consisted of 772 consecutive cadaver kidney transplantations from a single centre. The effects of gene polymorphisms FVL, F5R2, FII G20210A, MTHFR C677T, F13A1 V34L, TFPI P151L, PROC W380G, TNF G(-308)A, IL10 A(-592)C, IL10 A(-1082)G and IL6 C(-174)G of recipients and donors were investigated., Results: We were unable to find statistically significant associations between any of the studied polymorphisms and clinical outcomes., Conclusions: Our results indicate that high-risk renal transplant candidates cannot be identified through the routine analysis of the polymorphisms.

Background: The aim of this prospective randomized study was to examine the effect of induction immunosuppression and low initial cyclosporine (CsA) on the onset of graft function and its long-term consequences., Methods: During 1999-2001, 155 patients were randomized to single 9 mg/kg dose antithymocyte globulin (ATG)-Fresenius (group A) or two 20-mg doses of basiliximab (group B) with reduced dose CsA or conventional CsA triple therapy without induction (group C)., Results: Delayed function (DGF) was lower in group A than in groups B or C (5.7% vs. 24.1% and 15.9%, P<0.025) and need of dialysis was less in groups A and B compared to C (10.3 and 10.4 vs. 20.0 days, P<0.05). Acute rejections occurred in 11.3%, 12.1% and 20.5%, and the mean (median) time to rejection was 16 (13), 97 (46) and 101 (35) days in groups A, B, and C, respectively (P<0.005). One-and 5-year graft survivals (GS) were 98.1% and 90.6% (group A), 96.6% and 96.6% (group B), and 93.2% and 84.1% (group C). Five-year GS was significantly better in group B than in group C (P<0.05). The death censored 5-year GS in groups A, B, and C were 94.3%, 96.6%, and 90.0% (P=NS). Single high-dose ATG induction was associated with hemodynamic and pulmonary disturbances without, however, serious or long-term consequences., Conclusions: ATG induction significantly reduced DGF. Both induction regimens together with low initial CsA led to significantly less posttransplant dialysis and excellent survival. The high dose ATG was associated with significant hemodynamic and pulmonary side effects during drug infusion.

The results of 3,165 kidney transplants from deceased donors during the 3 time periods, 1986-92 (n=882), 1993-99 (n=1,107) and 2000-06 (n=1,176) were analysed and following conclusions could be made: 1. One-year patient survival improved from 93.2% to 98.1%, one-year graft survival improved from 86.1% to 95.1% and one-year death censored graft survival improved from 90.4% to 96.6%. Patient death due to cardiovascular disease decreased significantly. Despite that, patient death with a functioning graft became the main cause of graft loss after the first posttransplant year in our most recent cohort. The estimated graft half-life has improved from 9.3 to 20.4 years. 2. The rejection incidence decreased from 28.1% to 14.1%. 3. The mean donor age increased from 35.5 to 47.8 years. The proportion of donors fulfilling the UNOS criteria for extended criteria donors increased from 2.9% to 26.3%. The long-term effects of donor factors on these transplants need to be critically evaluated. 4. A good HLA match remains a sound basis for kidney allocation. Provisions should be made for highly immunized patients and those with unusually long waiting times.

The long-term effects of cytomegalovirus (CMV) infections on kidney allografts are unknown. We examined the impact of persistent intragraft CMV infection on long-term kidney allograft function and survival. CMV was diagnosed in 82/172 renal transplant recipients by antigenemia test and viral cultures. Biopsies from 48 of 82 patients taken after CMV infection and from 15 patients with no previous CMV infection detected were available for the immunohistochemical demonstration of CMV antigens and DNA hybridization in situ. Five-year follow-up data from these 63 patients were analysed. In 17 patients, CMV antigens and/or DNA persisted in the biopsy >2 months after the last positive finding in blood or urine. Patients with persistent intragraft CMV had reduced graft survival (P = 0.041) and Cox regression analysis showed persistent CMV as a risk factor for reduced graft survival (RR: 3.5). Recipients with persistent intragraft CMV had reduced creatinine clearance 1 and 2 years after transplantation (P = 0.007) and in multivariate logistic regression analyses including several potential pre- and posttransplant risk factors, persistent CMV was an independent risk factor for lower clearance at 1 and 2 years (OR: 4.4 and 4.9). Our novel findings show that persistent intragraft CMV infection was associated with reduced kidney allograft function and survival.

Cytomegalovirus (CMV) seronegative recipients of kidneys from CMV seropositive donors are at a high risk of CMV infection after transplantation since viruses in the allograft may reactivate in patients without prior immunity. We hypothesized that the genetic background of the graft has an influence on the incidence of infection. Effects of IL10, IL6 and IFNG gene polymorphisms, known to affect CMV infectivity, were investigated in 71 CMV seronegative recipients of grafts from CMV seropositive cadaver donors. Donor IL10(-1082 AA) genotype reduced the incidence of CMV infection (p=0.031) and CMV episodes in these patients tended to occur later (AA: median 83 days,, Ag/gg: median 45 days, p=0.072). In multivariate analysis, other explaining factors than the donor IL10(-1082 AA) genotype alone did not improve Cox hazard model (HR=0.3, 95% CI=0.09-0.96, p=0.043). Recipient polymorphisms did not reduce the incidence of CMV infection. We conclude that donor IL10 gene polymorphisms may influence the likelihood of CMV infection in the high risk patients investigated.

Background: The challenge in renal transplantation is to improve long-term patient and graft survival without increasing early acute rejection by minimizing immunosuppression., Methods: This multicenter, observational study investigated the effects of withdrawal of steroids or mycophenolate mofetil (MMF) from a tacrolimus-based triple regimen (tac/MMF/steroids) 3 months posttransplant at 3 years; no additional interventions or assessments were undertaken. Adult patients, included in the intent-to-treat population of the THOMAS study, participated. Patient and graft survival, adverse events, rejection episodes, and immunosuppressive and concomitant medications were assessed., Results: Data at Year 3 was available for 718 patients (triple therapy, n=237; steroid stop, n=235; MMF stop, n=246). The original randomized regimen was maintained in 45.6% of patients in the triple, 62.6% in the steroid stop, and 53.9% in the MMF stop groups. Graft survival rates were 88.1% (triple), 86.4% (steroid stop), and 85.8% (MMF stop); patient survival was 96.1%, 95.9%, and 95.7%, respectively. The incidence of biopsy-proven acute rejection was similar in all groups between Month 7 and Year 3: 1.2% (triple), 2.0% (steroid stop) and 2.0% (MMF stop). Patients in the steroid stop group had less hypertension and significantly lower mean total cholesterol and LDL-cholesterol at Year 3 compared with Month 3 (P=0.02). Median serum creatinine levels remained stable throughout the follow-up and were comparable between groups., Conclusion: Immunosuppression minimization initiated at Month 3 was maintained at Year 3 in over half of the patients. Steroid withdrawal was advantageous in reducing the cardiovascular risk factors hyperlipidemia, hypertension and diabetes mellitus. Renal function was stable in all groups.

Immunosuppression is thought to be responsible for the increased incidence of tumor development after organ transplantation. Natural history of these tumors may be more aggressive than would be expected for a similar tumor in a patient without transplant. We describe the fulminant course of small cell carcinoma, likely of prostatic origin, in a kidney transplant patient. Small cell carcinoma (SCC) and especially SCC of the prostate is an aggressive and rare type of tumor. Due to its rarity, only case reports have been published. To our knowledge, this is the first case of SCC, likely of prostatic origin, in an organ transplant recipient (OTR). The case illustrates the aggressiveness of the disease as reflected by its fulminant progression, which may have been further accentuated by the immunosuppression.

Background: C2 monitoring of cyclosporine (CsA) has been promoted as improving the results of organ transplantation. No randomized, controlled studies in de novo kidney transplant recipients are available., Methods: Between June 2003 and August 2004, 160 consecutive cadaveric kidney recipients allocated to CsA, mycophenolate and steroids were randomized to either C0 or C2 monitoring of CsA for the first 3 weeks posttransplant. Both levels were measured, keeping the other level blinded until 3 weeks. Altogether, 1451 double measurements were done. The target C0 was 200-300 microg/L and C2 1500-2000 microg/L. From the fourth week on, only C0 monitoring was used. Median follow up time was 505 days., Results: The overall 3-month rejection rate was 7.5% in Group C0 vs. 10.8% in Group C2 and the one-year graft survival rates were 92.5% vs. 94.6% (NS). Rate of delayed graft function was similar in the groups. Plasma creatinine tended to be higher in group C2 at 3 weeks, but not thereafter. During the first three weeks posttransplant, the mean CsA dose was 57%, mean C2 levels were 55%, and mean C0 levels were 98% higher in group C2 than in group C0 (P < 0.00001)., Conclusion: This pilot study showed no advantages of C2 monitoring but led to significantly higher CsA doses and blood levels than C0 monitoring.

Background: The side effects associated with corticosteroids have led to efforts to minimize their use in renal transplant patients. In this study we compared two corticosteroid-free tacrolimus-based regimens with a standard triple therapy., Methods: This was a 6-month, phase III, open-label, parallel-group, multicenter study. The total analysis set comprised 451 patients, randomized (1:1:1) to receive tacrolimus (Tac) monotherapy following basiliximab (Bas) administration (n=153), Tac/mycophenolate mofetil (MMF) (n=151), or, Tac/MMF/corticosteroids triple therapy as a control (n=147)., Results: The study was completed by 91.2% (triple therapy), 94.7% (Tac/MMF), and 82.4% (Bas/Tac) of patients. Patient baseline characteristics were similar in all groups. The incidences of biopsy-proven acute rejection were 8.2% (triple therapy), 30.5% (Tac/MMF), and 26.1% (Bas/Tac), p<0.001 (multiple test for comparison with triple therapy); Bas/Tac vs. Tac/MMF, p=ns. The incidences of corticosteroid-resistant acute rejection were 2.0%, 4.0%, and 5.2%, p=ns. Graft survival (95.9%, 96.7%, and 94.7%, p=ns) and patient survival (100%, 99.3%, and 99.3%, p=ns) were similar in all groups. Median serum creatinine at month 6 was 123.0 micromol/L (triple therapy), 134.7 micromol/L (Tac/MMF) and 135.8 micromol/L (Bas/Tac). The overall safety profiles were similar; differences (p<0.05) were reported for anaemia (24.5% vs. 12.6% vs. 14.5%), diarrhoea (12.9% vs. 17.9% vs. 5.9%), and leukopenia (7.5% vs. 18.5% vs. 5.9%) for the triple therapy, Tac/MMF, and Bas/Tac group, respectively. The incidences of new-onset diabetes mellitus were 4.6%, 7.1%, and 1.4%, respectively., Conclusion: Corticosteroid-free immunosuppression was feasible with the Bas/Tac and the Tac/MMF regimens. Both corticosteroid-free regimens were equally effective in preventing acute rejection, with the Bas/Tac therapy offering some safety benefits.

In kidney transplantation, pretransplant serum sCD30 testing has been proposed in immunological risk estimation together with anti-HLA antibodies. We evaluated the risks associated with high pretransplant serum sCD30 in well HLA-matched cadaveric kidney recipients recruited in a clinical study comparing different immunosuppressive regimens. Rejection rate was similar in 37 recipients with high pretransplant serum sCD30 compared to 117 recipients with low serum sCD30 (16% vs. 15%, P=NS). Compared to pretransplant levels, the posttransplant sCD30 levels generally decreased, also in patients with rejection, although on day 21 posttransplant, rejecting patients had significantly higher relative sCD30 than nonrejecting patients (P<0.01). However, steroid-resistant rejection was associated with increasing posttransplant sCD30 levels. High pretransplant sCD30 values were associated with tubulointerstitial rejection. There was no correlation of sCD30 with delayed graft function. Good HLA matching seems to be effective in neutralizing the negative effect of a high pretransplant serum sCD30.

We studied the role of endogenous activated protein C (APC), the major physiological anti-coagulant with concomitant anti-inflammatory properties, on ischemia/reperfusion (I/R) in 45 patients participating in a larger trial comparing three immunosuppressive protocols in cadaveric renal transplantation: perioperative anti-thymocyte globulin (ATG, Fresenius AG, Bad Homburg, Germany), perioperative basiliximab and conventional triple therapy. Blood samples for assessing plasma APC, protein C, and lactoferrin concentrations, neutrophil CD11b and L-selectin expressions and blood leukocyte differential counts were obtained preoperatively and before reperfusion from central venous cannula, complemented with simultaneous samples from iliac artery and graft vein for calculation of transrenal differences (Delta) of study parameters at 1 and 5 min after reperfusion. Unlike basiliximab or conventional therapy groups, ATG infusion induced a substantial increase in plasma APC concentration (119 [88-144]% before infusion vs. 232 [85-1246]% after infusion, p<0.001), resulting in renal graft sequestration of APC at 1 min after reperfusion (Delta=-72 [-567 to 12]%, p<0.001). Graft APC consumption was associated with transrenal reduction of neutrophil activation markers (L-selectin r=0.7, p=0.01; lactoferrin r=-0.6, p=0.02; CD11b r=-0.8, p=0.001), and with both warm (r=0.6, p=0.01) and cold ischemia time (r=0.6, p=0.02) and donor age (r=0.6, p=0.01). These findings suggest that APC has an anti-inflammatory role in I/R injury in clinical renal transplantation.

Objective: Cytomegalovirus (CMV) infection is known to cause ulcerations, erosion and mucosal haemorrhage in the gastrointestinal tract. The aim of this study was to report the CMV findings in the gastroduodenal mucosa of kidney transplantation patients and immunocompetent controls., Material and Methods: Forty-six kidney transplant patients with upper gastrointestinal symptoms and 43 immunocompetent, dyspeptic patients (controls) prospectively underwent oesophagogastroduodenoscopies (OEGDs), with biopsies from the duodenum and stomach. CMV was demonstrated by immunohistochemistry, both in frozen sections using a monoclonal antibody against CMV-specific antigens (pp65 matrix protein) and in paraffin sections by means of a monoclonal antibody against the delayed early protein (p52)., Results: CMV was detected in the gastric mucosa in 30% of the kidney transplant patients and in 9% of the controls (p<0.05) and in the duodenal mucosa in 70% and 35%, respectively (p<0.01). The total frequency of CMV findings was similar in patients who underwent OEGDs <1 year and >1 year after transplantation. CMV inclusions were found only in transplantation patients <1 year after transplantation (n=9). CMV findings, especially inclusions, in the gastric biopsies were associated with nausea and upper gastric pain. Histopathological findings in CMV-positive samples were non-specific, focal inflammation in haematoxylin-eosin-stained preparations, while CMV p52 staining showed inclusions in either the epithelial or endothelial cells., Conclusions: CMV could be detected in the gastroduodenal mucosa in 74% of kidney transplantation patients and in 40% of immunocompetent controls (p<0.01). CMV diagnostics are always recommended when gastroduodenal biopsies of kidney transplantation patients are performed.

The objective of this study was to analyze factors that are involved in the progression of renal allograft damage in the first 6 mo after transplantation. Donor and 6-mo protocol biopsies of 83 patients who received a renal transplant were classified using the Chronic Allograft Damage Index (CADI). Histologic changes were compared and correlated to clinical parameters at transplantation, at 6 mo, and annually over 2 yr. All CADI components increased significantly in the 6-mo posttransplantation period, except chronic vascular changes and the percentage of glomerulosclerosis. Total cholesterol and LDL- cholesterol at the time of biopsy correlated positively with mesangial matrix increase, and HDL cholesterol correlated negatively with vascular intima increase. High BP at biopsy was associated with tubular atrophy. Diastolic BP at biopsy correlated with 6-mo CADI (CADI-6). Patients with diastolic BP > or =85 mmHg at biopsy had a higher difference between CADI score in protocol biopsies and CADI score in donor biopsies (DeltaCADI) and higher creatinine at 1 and 2 yr. CADI in donor biopsies (CADI-0) >1 was more frequently found in older (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.01 to 1.14) and nontraumatic dead donors (OR, 3.89; 95% CI, 1.13 to 13.33). CADI-6 >3 was more frequently found in those with CADI-0 >1 (OR, 3.82; 95% CI, 1.19 to 12.21), older donors (OR, 1.05; 95% CI, 1.01 to 1.10), and number of AB mismatches (OR, 2.36; 95% CI, 1.09 to 5.10). CADI-0, CADI-6, and DeltaCADI correlated significantly with serum creatinine at hospital discharge, at 6 mo, and at 2 yr. DeltaCADI was affected by initial percentage of glomerulosclerosis (OR, 1.10; 95% CI, 1.02 to 1.19) and creatinine at hospital discharge (OR, 1.01; 95% CI, 1.00 to 1.02). Donor-related as well as nonimmunologic factors, such as hypertension and dyslipidemia, are associated with increased risk for renal allograft damage progression.

Modern immunosuppressive regimens reduce the acute rejection rate by combining a cornerstone immunosuppressant like tacrolimus or cyclosporine with adjunctive agents like corticosteroids, mycophenolate mofetil (MMF) or azathioprine, often associated with untoward side effects. A 6-month randomized study was conducted in 47 European centers. Triple therapy with tacrolimus (trough levels 5-15 ng/mL), corticosteroids (dosage 10 mg/day) and MMF (1 g/day) was administered for 3 months. From day 92, patients either continued with triple therapy (control, n = 277), or stopped steroids (n = 279), or stopped MMF (n = 277). Surrogate markers for long-term benefits were changes in lipid profiles and occurrence of hematological, gastrointestinal and infectious complications. The 6-month acute rejection incidence (biopsy-proven) was similar in all groups (17.0% vs. 15.1% vs. 14.8%, p = 0.744), although the incidence after month 3 was higher in the steroid stop group than in the two other groups. Mean reductions in total cholesterol (18.9 mg/dL [0.49 mmol/L]) and LDL-cholesterol (8.1 mg/dL [0.21 mmol/L]) between months 4 and 6 were greater in the steroid stop group (p < 0.001). Leukopenia (p = 0.0082), serious CMV infection (p = 0.024), anemia (p = NS) and diarrhea (p = NS) were less frequent in the MMF stop group. In a study population of immunologically low-risk patients' withdrawal of corticosteroids or MMF from a tacrolimus-based therapy at 3 months was feasible. A longer follow-up will be needed to confirm the expected advantages for the long-term outcome and to assess the long-term safety of this minimization of immunosuppressive therapy.

Background: Pretransplantation identification of patients at an increased risk for adverse events would allow more individualized treatment strategies possibly improving long-term outcome. We studied cytokine gene polymorphisms of kidney allograft recipients and their donors to identify factors predisposing for acute rejection (AR) and delayed graft function (DGF)., Methods: A total of 291 adult cadaver kidney recipients transplanted at a single transplantation centre between 1999 and 2002 were investigated. Recipients and donors were typed for TNF-alpha(-308G/A), TGF-beta1(codon 10T/C, codon 25C/G), IL-10(-1082G/A, -819C/T, -592C/A), IL-6(-174C/G), and IFN-gamma(+874T/A) polymorphisms using a SSP-PCR kit. An AR episode was defined based on clinical and histological findings (Banff criteria). RESULTS.: The incidence of AR was 17%. In univariate statistical analyses recipients with TNF-alpha -308AA-genotype were found to be at a significantly increased risk for rejection (odds ratio [OR] 5.0, 95% CI 3.0-8.3, P = 0.003). The association was independent from the patient-donor HLA-mismatch status. In addition, patients with IL-10 ACCACC, ATAATA, GCCATA (-1082A/G, -819C/T, -592C/A, respectively) haplotypes were predisposed to rejection (OR 1.9, 95% CI 1.1-3.1, P = 0.016). Further, the combination of recipient TGF-beta1 25GG-genotype and donor IL-10 -819T-allele was associated with rejection (OR 1.8, 95% CI 1.1-3.0, P = 0.027). These variables remained significant risk factors also in a multivariate logistic regression analysis. The incidence of DGF was 22%. The risk was increased by a donor TNF-alpha -308GA-genotype (OR 1.6, 95% CI 1.1-2.6, P = 0.040)., Conclusions: Our results confirm that cytokine gene polymorphisms influence the outcome of kidney transplantation. Our data especially identify the TNF-alpha -308AA-genotype as a factor predisposing for AR episodes.

We studied, retrospectively, the occurrence of severe gastrointestinal (GI) complications after kidney transplantation. After 1,515 consecutive adult kidney transplantations performed on 1,445 patients during 1990-1999 at our centre, 147 (10%) severe post-transplantation GI complications were found. Ten percent of the complications were fatal. The median follow-up time was 6.2 years. The main complications were gastroduodenal ulcers and colon complications. GI malignancy developed in 13 patients (0.9%). The complication rate for the first post-transplantation year was 4.8%. Delayed graft function, high age and polycystic kidney disease were risk factors. Five-year patient survival rate was significantly lower in patients with a first-year complication than in those with later or no GI complications (68% vs 88%). Graft survival with deaths censored was the same in both groups. In conclusion, severe GI complications during the first post-transplantation year remain a high risk factor also for long-term patient survival.

The waiting list (WL) history of 405 diabetic patients placed on the kidney transplantation WL for the years 1993-2000 was examined. By 31 December 2000, 295 (73 %) patients had received a transplant. Of the remaining 110 patients 53 (13 %) were still on the WL; 27 of these were temporarily withdrawn, i.e. non-active, 46 others (11 %) had died and 11 (3 %) had been permanently removed. Patient follow-up continued until the end of 2002. Although the mean total time on the WL of the non-transplanted was twice that of the transplanted patients there were no significant differences in the mean active times on the WL. The mean cumulative withdrawal time of the transplanted and those on the active WL was less than 10 % of their total time on the list, but for the patients who had died or were withdrawn on 31 December 2000 it exceeded 50 %, usually because of diabetic complications. The 5-year survival of the transplanted patients was greatly superior to that of the non-transplanted, as expected. However, the better survival of the transplanted patients is not necessarily proof of a better treatment modality but rather a consequence of the exclusion from transplantation of patients suffering from diabetic complications. It is not justified to compare the survival of transplantable and non-transplantable WL patients.

Background: Screening of donor-specific antibodies or alloantibodies after kidney transplantation has not been performed routinely. The aim of this study was to evaluate the humoral antidonor and alloresponse of immunologically low-risk recipients of cadaveric renal allografts during the first posttransplant year., Methods: Alloresponse against the donor was analyzed by means of T-cell immunoglobulin (Ig)G and IgM and B cell IgG flow cytometric crossmatch (FCXM) tests with sera from days 0, 21, 90, and 365 posttransplant. In addition, panel reactive anti-human leukocyte antigen (HLA) class I and class II antibodies (PRA I and PRA II) were analyzed using flow cytometric methods. The recipients were treated either with a low initial cyclosporine regimen with single-bolus antithymocyte globulin (ATG) or basiliximab induction or conventional cyclosporine triple therapy., Results: No significant posttransplant anti-HLA class I or class II sensitization was found in the recipients as a whole. Recipients receiving a single-bolus ATG showed significantly higher proportion of PRA I positivity in the day 21 sample compared with the other groups. Flow cytometric donor-specific T- and B-cell IgG alloresponses remained low, but the proportion of T-cell IgM crossmatch-positive recipients increased during the study. Positive T-cell IgM FCXM was found to be associated with acute rejection episodes and cytomegalovirus (CMV) infections., Conclusions: In immunologically low-risk kidney-graft recipients, positive T-cell IgM FCXM at transplantation was found to be a risk factor for rejection episodes. Conversion of T-cell IgM FCXM to positive was found to be associated with CMV infections.

Background: The authors studied the impact of neutrophil activation, detected in experimental models, on reperfusion injury in clinical renal transplantation., Methods: Forty-five patients from a larger trial comparing three immunosuppressive protocols were recruited: perioperative antithymocyte globulin (ATG) with low initial cyclosporine A (CsA) triple therapy (group A, n=15); two-dose basiliximab with low initial CsA triple therapy (group B, n=16); and conventional triple therapy (group C, n=14). Blood samples were obtained preoperatively, before reperfusion, and at 1 and 5 min after reperfusion. During reperfusion, samples were collected from the iliac artery and the graft vein for calculation of transrenal differences (Delta) of study parameters. Leukocyte differential counts, plasma lactoferrin concentration, and neutrophil CD11b and L-selectin expressions were assessed. Graft blood flow was measured at 2 and 30 min after reperfusion., Results: ATG induced neutrophil activation already before reperfusion. Thus, group A was excluded, but groups B and C were pooled for analysis of reperfusion-induced neutrophil activation. At 1 min after reperfusion, lactoferrin concentration was higher in graft vein than iliac artery, yielding Delta=15 microg/L (P<0.05). Concomitantly, Delta neutrophil count correlated with both Delta L-selectin expression (R=0.49, P=0.012) and graft blood flow at 2 min (R=0.51, P=0.007). At 5 min after reperfusion, 0.17 (-1.0-0.24)x10 cells/L neutrophils were sequestered in the graft (P<0.001). This sequestration correlated with graft blood flow at 30 min (R=0.53, P=0.005) and was stronger in patients with delayed graft function (DGF) (Delta = -0.38 [-1.45 to -0.2]) than those without (Delta = -0.12 [-0.41-0.24], P<0.001). In multiple regression analysis, sequestration was the most important parameter associated with DGF., Conclusions: Neutrophils are activated and sequestered in the reperfused graft during clinical renal transplantation. Neutrophil sequestration is a powerful independent factor explaining the incidence of DGF.

The Nordic organ exchange organization Scandiatransplant was founded in 1969. It covers a population of 24.41 million inhabitants in five countries: Denmark (5.45 million), Finland (5.19 million), Iceland (0.29 million), Norway (4.54 million), and Sweden (8.94 million). Initially, the purpose of Scandiatransplant was to establish and maintain a common waiting list for all Nordic patients with end-stage renal failure waiting for a cadaveric kidney transplant. The basis of maintaining a common Nordic waiting list was the recognition of the wide polymorphism of the human leukocyte antigen system, which demands a substantial pool of waiting patients to provide optimal histocompatibility matching between organ donor and recipient. Thus, one of the major tasks of the organization was and still is to specify rules for the exchange of kidneys between the participating transplant centers. Scandiatransplant includes the cooperation of all 10 Nordic kidney transplant centers in addition to eight immunology laboratories. Denmark has four transplant centers located in Copenhagen, Herlev, Odense, and Aarhus. Finland has one center in Helsinki. Norway has one center located in Oslo. Sweden has four kidney transplantation centers located in each of the university hospitals in Göteborg, Malmö, Stockholm, and Uppsala. The fifth Nordic country, Iceland, is participating fully in organ donation but has no individual transplant center. Organ transplantation in Icelandic patients is performed in other Nordic countries.

The cadaveric renal graft is exposed to ischaemic injury during preservation and to oxidative damage during reperfusion. Both these mechanisms are known to cause cell damage, which may impair graft function. Reperfusion injury (RPI) is mediated by reactive oxygen species (ROS). Ascorbic acid (AA) is a potent physiological extracellular scavenger of ROS. We perfused 31 renal grafts immediately before implantation with a solution of Euro-Collins containing 0.5 mg/ml of AA to diminish RPI. From every donor, the contralateral kidney served as a control. The control grafts were perfused with the same perfusion as those of the AA group, only without the AA substitution. We assessed the effect of AA by recording serum creatinine, creatinine clearance, initial graft function and early rejections. The incidence of delayed graft function (DGF) was 32% in the AA group, and 29% in the control group. Other parameters were also similar in both groups, except for the length of DGF, which showed a trend towards a shorter duration in the AA group. The pre-operative systemic AA concentration was significantly ( P=0.01) lower in the haemodialysis patients than in those on peritoneal dialysis. In conclusion, this clinical study could not demonstrate significant benefits of AA in renal transplantation.

Background: A number of institutions have reported favorable results in renal transplant patients after conversion from cyclosporine (CsA) to tacrolimus at the time of acute rejection, but no prospective, controlled study has been performed to date. Here, we report the first randomized study comparing patients whose therapy was changed at a first episode of acute rejection to tacrolimus with those who were maintained on CsA microemulsion (ME)., Methods: This 3-month, prospective, open, multicenter, parallel-group study was conducted at 15 centers in seven European countries. In total, 119 renal graft recipients experiencing a first biopsy-proven acute rejection episode while receiving CsA-ME were randomized (1:1) to start tacrolimus-based therapy (n=61) or to continue CsA-ME-based therapy (n=58)., Results: Baseline characteristics were comparable for both groups. The initial rejection episode responded to steroid treatment in 93.4% (tacrolimus) and 63.8% (CsA-ME) (P=0.001), respectively. In patients at risk, the incidence of recurrent rejection events within 3 months was significantly lower with tacrolimus therapy (5/57, 8.8%) compared with CsA-ME therapy (15/44, 34.1%) (P=0.002). Patient and graft survival were similar in both study groups 3 months after randomization. The most frequently reported adverse events were increased serum creatinine (29.5% vs. 22.4%), hypertension (24.6% vs. 22.4%), and urinary tract infection (18.0% vs. 20.7%) for tacrolimus versus CsA-ME. Tremor was more common in tacrolimus treated-patients (17.4% vs. 2.1%, P=0.011)., Conclusions: Early conversion to tacrolimus therapy benefited the resolution of acute rejection episodes and significantly reduced the risk of recurrent rejection compared with continuation of CsA-ME.

Background. Before the introduction of modern medication for ulcer disease, gastroduodenal complications were often fatal in recipients of kidney transplants. Helicobacter pylori causes gastritis and is an important risk factor for peptic ulcer disease and gastric malignancies. The aim of this study was to evaluate whether H. pylori infection influences the outcomes of kidney transplantation. [ABSTRACT FROM PUBLISHER]

Presents a study that examined the impact of immunoprophylaxis with basiliximab, an anti-CD25 monoclonal antibody, on renal transplant patients undergoing triple immunosuppresive therapies. Characterization of the disposition of basiliximab; Estimation of the duration of CD25 saturation and its relation to acute rejection events; Assessment of the immunogenicity of basiliximab.

Kidney transplant recipients are highly susceptible to life-threatening infections, including bacteremia. To determine the risk factors for bacteremia within the first month after renal transplantation we performed a non-concurrent transplant population-based case-control study involving all 1,000 consecutively operated adult patients at Helsinki University Central Hospital in 1987-93. All patients with at least 1 positive blood culture within 31 d of transplantation were defined as cases. Control patients were drawn systematically from the transplant population with no positive blood cultures within the first 31 d post-transplant. The study included 35 cases and 123 controls. The overall rate of bacteremia in the population was 3.5%. The case patients were more likely to have been on haemodialysis prior to transplantation (71% vs. 43%, p <0.05) and to have experienced acute rejection (46% vs. 20%, p<0.05) than the controls. Local infections (46% vs. 12%, p<0.05) were also more common among case patients. In the crude analysis an additive interaction of acute rejection and haemodialysis was found, with a 10% rate of bacteremia occurring if both conditions were present. The mortality rate within 2 months of follow-up was higher among case patients than among controls (14% vs. 1%, p<0.05) and they also returned more often to dialysis (23% vs. 4%, p<0.05). Bacteremia during the immediate postoperative period might still have severe outcomes measured as allograft and patient survival at 2 months post-transplant. Further evaluation will confirm whether a lower rate of bacteremia among kidney transplantation patients can be achieved if peritoneal dialysis is preferred to haemodialysis whenever possible. [ABSTRACT FROM AUTHOR]