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Objective: Two grafts were lost in our centre due to peracute rejection. Both were females who had children from their living kidney donor 20 years before transplantation. Although PRA (panel reactive antibodies) and crossmatch (XM) before transplantation were negative, we suspected a previous immunisation, which was not detected with conventional CDC techniques. DST boosts the potential recipient with HLA molecules from the donor to reveal the presence of B cells producing low levels of anti-donor Abs. Previously immunised recipients should display an easily detectable antibody titer with CDC technique following DST, while DST should not induce anti-donor Abs in non-immunised patients. The pitfall is that DST might actually induce an antibody response in previously nonimmunised recipients. Goal: Identify a method to detect previous immunisation in at-risk patients with CDC negative XM. Methods: All female transplant candidates with a negative CDC XM and children from their potential donors were regarded to have an immunological risk. They received a total of 3 DST from their potential donor and were treated with azathioprin or MMF. Before each DST and after the final DST a CDC XM was performed. Samples before and after DST were analysed with Flow Cytometric crossmatch (FCXM) in 16 of 21 transplant candidates. Results: 21 immunologically at-risk transplant candidates received DST. 12 remained CDC XM-negative and were transplanted. No graft loss was observed due to rejection. From the 9 candidates who developed anti-donor Abs (detected by CDC), 4 had a positive FCXM before DST indicating that they had been previously immunised due to pregnancy. These 4 patients developed high PRA as well. Importantly, 2 of the 9 were FCXM negative before DST implying that they had not be sensitised by pregnancy; in these cases, immunisation was likely caused by DST. In the remaining 3 candidates, no FCXM was done. Summary: At least 2 of 21 patients were immunised de novo by DST. The presence of anti donor Abs could have been detected in 4 of 21 candidates by FCXM avoiding the necessity of DST and preventing high PRA. Conclusions: DST is potentially harmful and can wrongly immunise transplant candidates. FCXM in potentially immunised CDC XM negative transplant candidates is safe and identifies patients at-risk for hyper- and peracute-rejection. [ABSTRACT FROM AUTHOR]

Objective: The detection of C4d along peritubular capillaries in dysfunctioning kidney grafts with histological signs of acute rejection typically indicates a humoral mediated rejection episode. In these grafts, C4d has been established as a significant independent predictor of poor graft survival. However, only very little is known about the clinical significance of C4d deposits in grafts with normal histology. Aim: To evaluate one year graft function and survival of C4d positive kidney transplants lacking histological signs of cellular or humoral rejection. Methods: Retrospective analysis of all renal allograft biopsies performed at the University Hospital in Basel from 1993 to 2003. Inclusion criteria (index biopsy): Focal or diffuse positivity for C4d along peritubular capillaries in the absence of any morphological signs of acute cellular or humoral rejection including Banff 'borderline' changes. Two patient groups were defined and compared: (1) Patients who were treated with anti-rejection therapy or an increase in maintenance immunosuppression subsequent to the index biopsy (intervention group; IG). (2) Patients with no therapeutic intervention (standard group; SG) subsequent to the index biopsy. Results: 22 biopsies/patients, 17 in the SG and 5 in the IG met the inclusion criteria. Both groups were similar with regard of demographic and pretransplant data. 21/22 grafts showed focal, 1/22 diffuse C4d positivity. Time from transplantation to index biopsy (days): SG 1,645 ± 1,606, IG 718 ± 1,558; p = NS. Serum creatinine at index biopsy (µmol/l): SG 226 ± 69, IG 216 ± 100; p = NS. Serum creatinine after one year (µmol/l): SG 204 ± 75, IG 143 ± 28; p = NS. Delta creatinine between index biopsy and one year afterwards (µmol/l): SG - 10 ± 64, IG - 96 ± 114; p = NS. One year patient survival: SG 100%, IG 80%; p = NS. One year graft survival: SG 82.5%, IG 80%; p = NS. None of the grafts were lost due to acute rejection. Conclusions: (1) C4d accumulation along peritubular capillaries in grafts lacking any histological signs of cellular or humoral rejection is not associated with rapid deterioration of graft function or graft loss. (2) Patients treated with increased immunosuppression showed a trend towards improved longterm graft function. These pilot data indicate that C4d deposits in grafts with normal histology may also detrimentally impact graft function longterm, although less dramatic than in grafts with histological signs of acute rejection. Larger prospective studies with patient follow-up for several years are required to further elucidate the role of C4d deposits in grafts with normal histology. [ABSTRACT FROM AUTHOR]

Background: At the time of transplantation (Tx), especially in preemptive transplantation, there is often some residual renal function, which is almost always lost during the course of transplantation. We report the first case with a significant recovery of renal function of the native kidneys eight years after transplantation. Case: A 13-year-old girl underwent preemptive cadaveric renal transplantation after a 5 year course of membranous nephropathy (MN) which was non responsive to immunosuppressive therapy. The maintenance immunosuppression (IS) consisted of cyclosporine (Cya), azathioprine (Aza) and prednisolone. In spite of three rejection episodes treated with steroid pulses, the IS switched from Cya to tacrolimus (Tac) and a recurrence of MN in the renal graft the course was favourable with a creatinine baseline of 130 µmol/l. Six years after Tx a diffuse large B-cell Non Hodgkin's Lymphoma of the small intestine was diagnosed. Tumour resection, chemotherapy with CHOP and CD20 antibody therapy resulted in complete remission. Tac and Aza was stopped. Because of an increasing proteinuria (circa 1.5 to 2.5 gram per day) a biopsy was performed and confirmed the recurrence of MN in the graft. Mycophenolate mofetil was added to prednisolone. 2 years after the diagnosis of the lymphoma creatinine increased (150 µmol/l), probably due to postrenal obstruction. A double-J catheter was inserted. One year later creatinine baseline was between 150 to 200 µmol/l (clearance 40 ml/min), the proteinuria about 5 gram per day. The patient complaint about pain in the region of the graft. Surprisingly, duplex-ultrasound revealed no perfusion of the graft. This result was confirmed by MR-angiography and nuclear renal-scintigraphy. However, the native kidneys showed a functional activity in both examinations in spite of cystic degeneration. Surgical exploration showed a deeply blue renal graft. Histologically, terminal stage of vascular rejection including the ureter was seen. 8 months after graft-nephrectomy the creatinine is 160 µmol/l (Cl 38 ml/min) and proteinuria about 10 gram per day. Comment: First, it remains unknown when the native kidneys recovered function. Second, spontaneous remission seems to be very unlikely. However, we do not know which factors were involved in the process of recovery. In the case of a partial remission of MN in the native kidneys, a positive effect of CyA, Tac or the CD-20 antibody rituximab may be discussed. Third, without an additionally biopsy of the native kidneys it will remain uncertain -- in spite of high clinical probability -- if MN of the native kidneys is currently still present and to which degree the MN is responsible for the high amount of proteinuria. [ABSTRACT FROM AUTHOR]

Presents an abstract of the study "Influence of Non Inherited Maternal Antigens (NIMA) on Graft Survival in Renal Transplantation From Parental Donors."

Objective: Even though light to moderate alcohol use might have beneficial effects on health, severe alcohol use is recognized as a major public health concern. Alcohol use has been studied to some extent in solid organ transplant populations, yet, very limited evidence has bee published on alcohol use and its correlates in the renal transplant population. The aim of this study was therefore to determine the prevalence and correlates of alcohol use in renal transplant recipients. Methods: This cross-sectional study is a secondary analysis of the Supporting Medication Adherence in Renal Transplantation (SMART) study. 284 patients were included in this analysis, 58.1% male, mean age: 54.02 y. (SD: 13.34); median years post transplantation 7 (IQR 3-11). The prevalence and frequency of alcohol use as well as the quantity of alcohol consumed were assessed by patient self-report using structured questionnaires. Patients were classified as being at low risk, moderate risk or severe risk based on WHO criteria. Selected psychosocial and behavioral correlates of alcohol use were explored to compare those patients consuming alcohol and those not given the small proportion of patients at risk. Results: 52.8% of the study participants reported to use alcohol. Of the 284 patients included in the analysis, 280 were drinking at low and 3 at moderate risk. However, 1 of the participants drinking at low risk according to WHO criteria was identified as binge drinker. Statistically significant correlates of alcohol use found in univariate analysis were, among others, male gender, current smoking, employment and higher education. In logistic regression analysis, male gender and paid work were found to increase the likelihood of consuming alcohol. Conclusions: Patterns of alcohol use and correlates are comparable to the general population. Severe alcohol use is less prevalent in renal transplant recipients compared to heart and liver transplantation (9% and 6%, respectively), where alcohol is known as an etiological factor in a proportion of patients with end-stage heart or liver disease. [ABSTRACT FROM AUTHOR]

Objective: A positive T-cell complement dependent cytotoxicity (CDC) XM is still a contraindication for transplantation. We describe a patient with 96% panel reactive Abs (PRA) and repeated positive Tand B-cell CDC XM. Additional techniques allowed us to diagnose the presence of non HLA specific Abs which were responsible for the positivity of all CDC assays. Case: A 66-years-old male dialysis patient with diabetic nephropathy was put on the kidney waiting list. He had 96% CDC PRA and was tested XM positive with all potential donors. Because there was no immunization in his medical history, we suspected non HLA specific Abs as the cause of the positive CDC XM and therefore performed additional tests: CDC auto XM: T and B cell positive CDC auto XM IgM depleted: T and B cell negative Flow Cytometry (FC) HLA Flow PRA beads IgG and IgM: class I and II negative FC T2 Kd human cells (HLA-neg) XM: IgG = negative, IgM = 93% positive These results proved that the Abs responsible for the positive CDC XM were of IgM type and directed against non HLA. From the negative results in the flow PRA assays we confirmed that the potential graft recipient had no HLA Abs. Moreover we demonstrated a binding of the patients Abs to a human cell line which does not express any HLA antigens. Therefore he was transplanted with a cadaveric kidney without regard of his CDC XM. Eight months after transplantation he has a creatinine of 148µmol/l and experienced no graft rejection. Conclusions: Patients with high CDC PRA without history of immunization should be tested further to determine whether non-HLA Abs cause a positive CDC result. Having demonstrated the absence of HLA Abs, the patient can be transplanted in spite of a 'positive' CDC XM. [ABSTRACT FROM AUTHOR]

Objective: Nonadherence with immunosuppressive regimen (NAH) is a major risk factor for poor outcome after renal transplantation (RTX). The aim of this study was to test the effectiveness of a 3 months educational-behavioral intervention aimed at remediating non-adherence in non-adherent RTX as assessed by electronic event monitoring. Methods: This randomized controlled trial (RCT) included 18 non-adherent renal transplant recipients (21.4% f. - age 45.6 ± 1.2 y) identified during a 3 months run-in period measuring NAH using Electronic Event Monitoring (EEM) and using an algorithm to classify patient as NA. NAH patients were randomly assigned to either intervention (IG, N = 6) or enhanced usual care group (EUC, N = 12). NAH was assessed by EEM in both the IG and EUC groups. After the 3 months intervention period, a 6 months follow-up was done. EUC implied usual care and notification of treating physician about NAH as well as severe depression or suicidal ideation if applicable. The 3 months intervention included one home visit and 3 follow-up telephone calls on a monthly basis by a nurse who used behavioral, educational and social support interventions for remediation of NAH. EEM out-prints allowed detailed feedback to patients concerning their individual medication taking dynamics in the IG. Results: EEM parameters improved from baseline until after 3 months intervention in the IG (N = 5) compared to EUC (N = 9) (see figure 1 and 2). The figures only show taking and timing adherence, and indicate the level of NA for being at risk. A generalized estimating equation type logistic regression using a binary sequence of daily EEM events (dose taken or not) showed that at the end of the 3 months intervention period the IG showed 36% lower non-adherence compared with the enhanced usual care group (β = -0.4512, p = 0.0836, two-tailed). At 9 months (after 6 months follow-up) no significant difference between the groups (β = 0.0253, p = 0.95, two-tailed) was found indicating a wean out effect when the intervention was stopped. Conclusions: The findings of this RCT suggest that it was feasible to remediate non-adherence with the immunosuppressive regimen, providing a possible pathway to improve clinical outcome in RTX. [ABSTRACT FROM AUTHOR]

Objective: BKVN is diagnosed in 1 to 10% after kidney transplantation (Tx) and leads to graft loss in up to 80%. Risk factors are rejections, rejection therapy, antilymphocyte antibodies, mycophenolate mofetil and tacrolimus. There is no accepted standard therapy. We report on the first case of sirolimus associated BKVN leading to graft failure and describe our experience with IVIG in this case. Results: Case: A 63-year-old man underwent living kidney transplantation due to analgesic nephropathy. Induction therapy consisted of basiliximab, maintenance immunosuppression (IS) of sirolimus, mycophenolate mofetil and prednisolone. The patient experienced no rejection and from day 7 creatinine baseline was 120 µmol/l. Two months after Tx urine and plasma samples revealed decoy-cells (502/10 HPF) and a positive BKV-PCR (85.660 C/ml, 4.93 log10), respectively. In spite of increasing creatinine values (150 µmol/l), two graft biopsies (Bx) showed neither signs of BKVN nor rejection. Therefore IS was reduced, but BKV-PCR increased to 6 log10 and creatinine to 200 µmol/l. A third graft Bx showed severe BKVN and severe interstitial rejection. In assumption of a steroid resistent rejection sirolimus was switched to cyclosporine and antithymocyte globulin (ATG) was applied. Because of a persistent high viral load and a further increase in creatinine (400 µmol/l) an additional graft Bx was performed, showing still severe BKVN. The interstitial infiltrate with tubulitis was interpreted as BKVN associated nephritis. Reduction and switch of the IS to azathioprin-prednisolone and two courses of IVIG (2 mg/kg) were not effective. 10 months after Tx graft function is marginal (creatinine 700 µmol/l). Conclusions: Sirolimus associated BKVN may result in renal graft failure. Treatment with IVIG showed no effect in a case of advanced BKVN and severe rejection. It is not clear, if IVIG could be a therapeutic option in an earlier stage of BKVN. [ABSTRACT FROM AUTHOR]

Objective: Laparoscopic- (LDN) and retroperitoneoscopic (RDN) donor nephrectomy have become favored procedures in living donor transplantation. They provide a benefit for the donor but only limited data are available about their impact on recipient's outcome. The aim of the study was to determine the impact of LDN and RDN compared with grafts harvested by open donor nephrectomy (ODN) on recipient outcome. Methods: Living donor transplantations performed between February 1998 and October 2003 were analyzed retrospectively. The recipient outcome was evaluated in terms of allograft function, incidence of rejections and of surgical complications rate 30 days after transplantation. Creatinine levels were measured 7, 30 and 90 days after transplantation. Results: 148 patients were analyzed (50ODN, 48LDN, 50RDN). No differences were noted in the surgical outcome and complications except of warm ischemia time that was higher in LDN (P = 0.0014 ODN vs LDN, NS ODN vs RDN and LDN vs RDN). The in-hospital stay was shorter in RDN patients (P = 0.02 ODN vs RDN, 0.05 LDN vs RDN, NS ODN vs LDN). Thirty days after transplantation the incidences of rejections were comparable between the three groups (P = NS). The incidence of delayed graft function was higher in the RDN group (P = 0.043 LDN vs RDN, 0.039 ODN vs RDN). No statistically significant difference was found in creatinine levels at 1 (ODN 136 ± 49, LDN 124 ± 37, RDN 139 ± 49µmol/l) and 3 months (ODN 154 ± 62, LDN 154 ± 99, RDN 158 ± 52µmol/l) after transplantation. Conclusions: Minimally invasive nephrectomy has no negative impact on recipient's outcome. The minimally invasive techniques provide a benefit for the donor, are safe for the recipient and are therefore the method of choice. These new minimal invasive approaches could make living donor transplantation more attractive which is desirable in times of organ shortage. [ABSTRACT FROM AUTHOR]

Objective: Calcineurin-inhibitor free immunosuppression with sirolimus is a new promising strategy in kidney transplantation to avoid nephrotoxicity. The aim of our ongoing study was to show that a calcineurin-inhibitor free regimen can be an effective and safe alternative in de novo, normal risk renal transplantation. Methods: 6-months, prospective, randomized, open label single center study. Normal immunological risk patients (n=100) were consecutively randomized either to a regimen with sirolimus or cyclosporin A. Additional immunosuppressive therapy consisted in both groups of mycophenolate mofetyl (MMF, trough level >2µg/ml) and steroids. An induction therapy with Basiliximab was started after 58 patients. Protocol biopsy were performed in every patients after 3 and 6 months. Results: Preliminary data of the first 100 patients in an intention- to-treat analysis. Demographic and clinical baseline characteristic did not differ within the two arms. Conclusions: Despite of a significant higher rejection and withdrawal rate, no negative impact on graft function was observed with a calcineurin free immunosuppressive regimen 6 months posttransplant. In contrast to previous reports we could not observe a better graft function in the sirolimus group after 6 months. Treatment with sirolimus and MMF was associated with a high drop out rate, marked erythrocyte microcytosis without persistent anemia and high triglyceride values. [ABSTRACT FROM AUTHOR]