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BACKGROUND: After kidney transplantation non-adherence and inadequate self-management undermine clinical outcomes and quality of life. Both have been demonstrated to be substantial in all age groups. However, interventions promoting adherence and self-management among kidney transplant recipients that have proven to be effective are scarce. In this study we aim to develop and test an intervention to optimize adherence and self-management. In this article we describe the background and design of the trial entitled 'promoting Medication AdheRence and Self-management among kidney transplant recipients' (MARS-trial)'. METHODS/DESIGN: This is a single-center, parallel arm randomized controlled trial. Nonadherent kidney transplant recipients aged 12 years or older are eligible for inclusion. Patients will be randomly assigned to either the experimental or a control group. The control group will receive care-as-usual. The experimental group will receive care-as-usual plus the MARS-intervention. The MARS-intervention is an outreaching intervention, based on the principles of (multi) systemic therapy which means involving the social network. A standardized intervention protocol is used for consistency but we will tailor the behavior change techniques used to the specific needs and determinants o

Het ‘Nierteam aan Huis’ (NTAH) project is in de periode van 2016-2018 uitgevoerd. NTAH is een voorlichtingsprogramma voor patiënten met terminale nierinsufficiëntie en wordt gegeven bij de patiënten thuis. De patiënt en hun sociale netwerk worden voorgelicht over terminale nierinsufficiëntie en de behandelvormen hiervan door daarin getrainde voorlichters. Dit project toonde aan dat deze unieke vorm van voorlichting in verschillende regio’s in Nederland implementeerbaar is met goede resultaten op effectiviteit en kwaliteit. Bovendien bleek uit onze analyse dat NTAH bijzonder kosteneffectief is. Om deze reden bevelen wij aan om de thuisvoorlichting landelijk in te voeren en financieel mogelijk te maken. ACHTERGROND EN DOEL Het project is gebaseerd op twee voorgaande gecontroleerde studies in de regio Rotterdam. Deze studies leidden tot een betere kennis over behandelmogelijkheden bij patiënten en hun sociale omgeving en tot een betere communicatie. Ook werden meer patiënten getransplanteerd met een nier van een levende donor vergeleken met patiënten die deze thuisvoorlichting niet kregen. In 2016 werd er een plan opgesteld om NTAH in andere regio’s in de praktijk te brengen. In de periode 2016-2018 werd intensief samengewerkt met acht deelnemende ziekenhuizen: AMC, OLVG, Erasmus MC, Maasstad Ziekenhuis, Radboud UMC, Jeroen Bosch Ziekenhuis, UMCG en het ZGT. Het project had als doel (1) om de thuisvoorlichting in andere regio’s dan Rotterdam in praktijk te brengen met behoud van kwaliteit en resultaten en (2) om NTAH in de verzekerbare zorg op te nemen. BEVINDINGEN Het project werd volgens plan uitgevoerd in alle acht ziekenhuizen voor wat betreft het contracteren van de ziekenhuizen, het aanstellen van personeel, het trainen van de voorlichters en het organiseren van intervisie- en supervisiebijeenkomsten. Tussen 2016-2018 werden er 768 patiënten bereikt en 303 voorlichtingen gegeven. Zowel patiënten als hun genodigden voor de thuisvoorlichting ontwikkelden een signif, Het ‘Nierteam aan Huis’ (NTAH) project is in de periode van 2016-2018 uitgevoerd. NTAH is een voorlichtingsprogramma voor patiënten met terminale nierinsufficiëntie en wordt gegeven bij de patiënten thuis. De patiënt en hun sociale netwerk worden voorgelicht over terminale nierinsufficiëntie en de behandelvormen hiervan door daarin getrainde voorlichters. Dit project toonde aan dat deze unieke vorm van voorlichting in verschillende regio’s in Nederland implementeerbaar is met goede resultaten op effectiviteit en kwaliteit. Bovendien bleek uit onze analyse dat NTAH bijzonder kosteneffectief is. Om deze reden bevelen wij aan om de thuisvoorlichting landelijk in te voeren en financieel mogelijk te maken.

Background: Living donor kidney transplantation (LDKT) is the preferred treatment for patients with end-stage renal disease and unspecified living kidney donation is morally justified. Despite the excellent outcomes of LDKT, unspecified kidney donation (UKD) is limited to a minority of European countries due to legal constraints and moral objections. Consequently, there are significant variations in practice and approach between countries and the contribution of UKD is undervalued. Where UKD is accepted as routine, an increasing number of patients in the kidney exchange programme are successfully transplanted when a 'chain' of transplants is triggered by a single unspecified donor. By expanding the shared living donor pool, the benefit of LDKT is extended to patients who do not have their own living donor because a recipient on the national transplant list always completes the chain. Is there a moral imperative to increase the scope of UKD and how could this be achieved? Methods: An examination of the literature and individual country practices was performed to identify the limitations on UKD in Europe and recommend strategies to increase transplant opportunities. Results: Primary limitations to UKD, key players and their roles and responsibilities were identified. Conclusions: Raising awareness to encourage the public to volunteer to donate is appropriate and desirable to increase UKD. Recommendations are made to provide a framework for increasing awareness and engagement in UKD. The public, healthcare professionals, policy makers and society and religious leaders have a role to play in creating an environment for change.

Background. Age criteria for kidney transplantation have been liberalized over the years resulting in more waitlisted elderly patients. What are the prospects of elderly patients on the waiting list? Methods. Between 2000 and 2013, 2622 patients had been waitlisted. Waiting time was defined as the period between dialysis onset and being delisted. Patients were categorized according to age upon listing: <25; 25-44; 45-54; 55-64; and >64 years. Furthermore, the influence of ABO blood type and panel reactive antibodies on outflow patterns was studied. Results. At the end of observation (November 2017), 1957 (75%) patients had been transplanted, 333 (13%) had been delisted without a transplantation, 271 (10%) had died, and 61 (2%) were still waiting. When comparing the age categories, outflow patterns were completely different. The percentage of patients transplanted decreased with increasing age, while the percentage of patients that had been delisted or had died increased with increasing age, especially in the population without living donor. Within 6 years, 93% of the population <25 years had received a (primarily living) donor kidney. In the populations >55 years, 39% received a living donor kidney, while >50% of patients without a living donor had been delisted/died. Multivariable analysis showed that the influence of age, ABO blood type, and panel reactive antibodies on outflow patterns was significant, but the magnitude of the influence of the latter 2 was only modest compared with that of age. Conclusions. "Elderly" (not only >64 y but even 55-64 y) received a living donor kidney transplantation less often. Moreover, they cannot bear the waiting time for a deceased donor kidney, resulting in delisting without a transplant in more than half the population of patients without a living donor. Promoting living donor kidney transplantation is the only modification that improves transplantation and decreases delisting/death on the waiting list in this population.

Introduction Living donor kidney transplantation (LDKT) is the optimal treatment for most patients with end-stage renal disease (ESRD). However, there are numerous patients who cannot find a living kidney donor. Randomised controlled trials have shown that homebased education for patients with ESRD and their family/ friends leads to four times more LDKTs. This educational intervention is currently being implemented in eight hospitals in the Netherlands. Supervision and quality assessment are being employed to maintain the quality of the intervention. In this study, we aim to: (1) conduct a cost-effectiveness analysis of the educational programme and its quality assurance system; (2) investigate the relationship between the quality of the implementation of the intervention and the outcomes knowledge, communication and LDKT activities; and (3) investigate policy implications. Methods and design Patients with ESRD who do not have a living kidney donor are eligible to receive the home-based educational intervention. This is carried out by allied health transplantation professionals and psychologists across eight hospitals in the Netherlands. The cost-effectiveness analysis will be conducted with a Markov model. Cost data will be obtained from the literature. We will obtain the quality of life data from the patients who participate in the educational programme. Questionnaires on knowledge and communication will be used to measure the outcomes of the pr

Background: Optimal self-management in kidney transplant recipients is essential for patient and graft survival, reducing comorbidity and health care costs while improving the quality of life. However, there are few effective interventions aimed at providing self-management support after kidney transplantation. Objective: This study aims to systematically develop a nurse-led, self-management (support) intervention for kidney transplant recipients. Methods: The Intervention Mapping protocol was used to develop an intervention that incorporates kidney transplant recipients' and nurses' needs, and theories as well as evidence-based methods. The needs of recipients and nurses were assessed by reviewing the literature, conducting focus groups, individual interviews, and observations (step 1). Based on the needs assessment, Self-Regulation Theory, and the "5A's" model, change objectives were formulated (step 2). Evidence-based methods to achieve these objectives were selected and subsequently translated into practical implementation strategies (step 3). Then, program materials and protocols were developed accordingly (step 4). The implementation to test the feasibility and acceptability was scheduled for 2015-2017 (step 5). The last step of Intervention Mapping, evaluation of the intervention, falls outside the scope of this paper (step 6). Results: The intervention was developed to optimize self-management (support) after kidney transplantation and targeted both kidney transplant recipients and nurse practitioners who delivered the intervention. The intervention was clustered into four 15-minute sessions that were combined with regular appointments at the outpatient clinic. Nurses received a training syllabus and were trained in communic

BACKGROUND T cell depleting antibody therapy with rabbit anti-thymocyte globulin (rATG) is the treatment of choice for glucocorticoid-resistant acute kidney allograft rejection (AR) and is used as first-line therapy in severe AR. Almost all studies investigating the effectiveness of rATG for this indication were conducted at the time when cyclosporine A and azathioprine were the standard of care. Here, the long-term outcome of rATG for AR in patients using the current standard immunosuppressive therapy (i.e., tacrolimus and

Background: The benefits of live donor kidney transplantation must be balanced against the potential harm to the donor. Well-designed prospective studies are needed to study the long-term consequences of kidney donation. Methods: The "LOng-term follow-up after liVE kidney donation" (LOVE) study is a single center longitudinal cohort study on long-term consequences after living kidney donation. We will study individuals who have donated a kidney from 1981 through 2010 in the Erasmus University Medical Center in Rotterdam, The Netherlands. In this time period, 1092 individuals donated a kidney and contact information is available for all individuals. Each participating donor will be matched (1:4) to non-donors derived from the population-based cohort studies of the Rotterdam Study and the Study of Health in Pomerania. Matching will be based on baseline age, gender, BMI, ethnicity, kidney function, blood pressure, pre-existing co-morbidity, smoking, the use of alcohol and highest education degree. Follow-up data is collected on kidney function, kidney-related comorbidity, mortality, quality of life and psychological outcomes in all participants. Discussion: This study will provide evidence on the long-term consequences of live kidney donation for the donor compared to matched non-donors and evaluate the current donor eligibility criteria. Trial registration: Dutch Trial Register NTR3795.

Objectives: Living donor kidney transplantation offers advantages to the patient, however involves risks to the donor. To optimize donors' mental health after donation, we studied the influence of psychological factors on this outcome. Potential predictors were based on models of Lazarus () and Ursin and Eriksen () that describe predictors of mental health mediated by stress. Design: Prospective design. Methods: Living kidney donors (n = 151) were interviewed before donation and completed questionnaires 2.5 months before and 3 and 12 months post-donation. Using multilevel regression models, we examined whether appraisals, expectations, knowledge, social support, coping, life events, and sociodemographic characteristics predicted psychological symptoms and well-being and whether these relationships were mediated by stress. Results: A greater increase in psychological symptoms over time was found among donors without a partner. Younger age, lack of social support, expectations of interpersonal benefit, lower appraisals of manageability, and an avoidant coping style were related to more psychological symptoms at all time points. The latter three were mediated by stress. No religious affiliation, unemployment, history of psychological problems, less social support, expectations of negative health consequences, and less positive appraisals were related to lower well-being at all time points. Conclusions: This study

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The impact of living kidney donation on donors' mental health has not been sufficiently nor comprehensively studied. Earlier studies demonstrated that mental health did not change in the majority of donors, however they often lacked a suitable control group and/or had other methodological limitations. Consequently, it remains unclear whether changes in mental health found among a minority of donors reflect normal fluctuations. In this study we matched 135 donors with individuals from the general Dutch population on gender and baseline mental health and compared changes in mental health over time. Mental health was measured using the Brief Symptom Inventory and Mental Health Continuum Short Form. Primary analyses compared baseline and 6 months follow-up. Secondary analyses compared baseline and 9 (controls) or 15 months (donors) follow-up. Primary multilevel regression analyses showed that there was no change in psychological complaints (p = 0.20) and wellbeing (p = 0.10) over time and donors and controls did not differ from one another in changes in psychological complaints (p = 0.48) and wellbeing (p = 0.85). Secondary analyses also revealed no difference in changes between the groups. We concluded that changes in mental health in the short term after donation do not significantly differ from normal fluctuations found in the Dutch general population.

Background: In order to make a well-considered decision and give informed consent about renal replacement therapy, potential living kidney donors and recipients should have sufficient understanding of the options and risks. Purpose: We aimed to explore knowledge about Dialysis & Transplantation (DT) and Living Donation (LD) among prospective living kidney donors and recipients. Methods: Eighty-five donors and 81 recipients completed the Rotterdam Renal Replacement Knowledge-Test (R3K-T) 1 day before surgery. The questionnaire was available in various languages. Results: Recipients knew significantly more about DT than donors (p < 0.001); donors knew more about LD than recipients (p < 0.001). A minority of donors (15 %) and recipients (17 %) had a score that was comparable to the knowledge level of the naïve general population. Recipients and donors knew less about DT and LD if their native language was not Dutch. In addition, recipients knew less about DT if they were undergoing pre-emptive transplantation. Conclusions: We conclude that recipients and donors retain different information. The decision to undergo living donation appears to be not always based on full knowledge of the risks. We recommend that professionals assess knowledge of prospective donors and recipients during the education process using the R3K-T, and extra attention is required for non-native speakers.

Summary: Memory B cells play a pivotal role in alloreactivity in kidney transplantation. Follicular T helper (Tfh) cells play an important role in the differentiation of B cells into immunoglobulin-producing plasmablasts [through interleukin (IL)-21]. It is unclear to what extent this T cell subset regulates humoral alloreactivity in kidney transplant patients, therefore we investigated the absolute numbers and function of peripheral Tfh cells (CD4POSCXCR5POS T cells) in patients before and after transplantation. In addition, we studied their relationship with the presence of donor-specific anti-human leucocyte antigen (HLA) antibodies (DSA), and the presence of Tfh cells in rejection biopsies. After transplantation peripheral Tfh cell numbers remained stable

Background. Nonadherence to medication is a common problem after kidney transplantation. The aim of this study was to explore attitudes towards medication, adherence, and the relationship with clinical outcomes. Method. Kidney recipients participated in a Q-methodological study 6 weeks after transplantation. As a measure of medication adherence, respondents completed the Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS©-interview). Moreover, the intrapatient variability in the pharmacokinetics of tacrolimus was calculated, which measures stability of drug intake. Data on graft survival was retrieved from patient records up to 2 years after transplantation. Results. 113 renal transplant recipients (19–75 years old) participated in the study. Results revealed three attitudes towards medication adherence—attitude 1: “confident and accurate,” attitude 2: “concerned and vigilant,” and attitude 3: “appearance oriented and assertive.” We found association of attitudes with intrapatient variability in pharmacokinetics of tacrolimus, but not with self-reported nonadherence or graft survival. However, self-reported nonadherence immediately after transplantation was associated with lower two-year graft survival. Conclusion. These preliminary findings suggest that nonadherence shortly after kidney transplantation may be a risk factor for lower graft survival in the years to follow. The attitudes to medication were not a risk factor.

Background: The major challenge in ABO-incompatible transplantation is to minimize antibody-mediated rejection. Effective reduction of the anti-ABO blood group antibodies at the time of transplantation has made ABO-incompatible kidney transplantation a growing practice in our hospital and in centers worldwide. ABO antibodies result from contact with A- and B-like antigens in the intestines via nutrients and bacteria. We demonstrate a patient with fulminant antibody-mediated rejection late after ABO-incompatible kidney transplantation, whose anti-A antibody titers rose dramatically following Serratia marcescens sepsis. Case presentation. A 58-year-old woman underwent an ABO-incompatible kidney transplantation for end-stage renal disease secondary to autosomal dominant polycystic kidney disease. It concerned a blood group A1 to O donation. Pre-desensitization titers were 64 for anti-blood group A IgM and 32 for anti-blood group A IgG titers. Desensitization treatment consisted of rituximab, tacrolimus, mycophenolate mofetil, corticosteroids, immunoadsorption and intravenous immunoglobulines. She was readmitted to our hospital 11 weeks after transplantation for S. marcescens urosepsis. Her anti-A IgM titer rose to >5000 and she developed a fulminant antibody-mediated rejection.We hypothesized that the (overwhelming) presence in the blood of S. marcescens stimulated anti-A antibody formation, as S. marcescens might share epitopes with blood group A antigen. Unfortunately we could not demonstrate interaction between blood group A and S. marcescens in incubation experiments. Conclusion: Two features of this post-transplant course are remarkably different from other reports of acute rejection in ABO-incompatible kidney transplantation: first, the late occurrence 12 weeks after kidney transplantation and second, the very high anti-A IgM titers (>5000), suggesting recent boosting of anti-A antibody formation by S. marcescens.

Urological complications after kidney transplantation are mostly related to the ureteroneocystostomy, often requiring interventions with additional costs, morbidity and mortality. Our aim was to assess risk factors for urological complications in deceased donor kidney transplantation. Between January 2000 and December 2011, 566 kidney transplantations were performed with deceased donor kidneys. Recipients were divided in a group with, and a group without urological complications, defined as the need for a percutaneous nephrostomy catheter or surgical revision of the ureteroneocystostomy. Univariate and multivariate analyses were performed. Univariate analysis showed increased number of male donors (p = 0.041), male recipients (p = 0.002), pre-emptively transplanted recipients (p = 0.007), and arterial reconstructions (p = 0.004) in the group with urological complications. Less urological complications occurred in recipients on hemodialysis (p = 0.005). More overall surgical interventions (p<0.001), surgical site infections (p = 0.042), urinary tract infections (p<0.001) and lymphoceles (p<0.001) occurred in the group with urological complications. Multivariate analysis showed that male recipients (p = 0.010) and arterial reconstructions (p = 0.019) were independent risk factors. No difference was found between both groups in patient or graft survival. In conclusion, recipient male gender and arterial reconstruction are independent risk factors for urological complications after deceased donor kidney transplantation. Nevertheless, graft and recipient survival is not different between both groups.

Background: There is no single model available to predict the long term survival for patients starting renal replacement therapy (RRT). The available models either predict survival on dialysis until transplantation, survival on the transplant waiting list, or survival after transplantation. The aim of this study was to develop a model that includes dialysis survival and survival after an eventual transplantation. Methods. From the Dutch renal replacement registry, patients of 16 years of age or older were included if they started RRT between 1995 and 2005, still underwent RRT at baseline (90 days after the start of RRT) and were not registered at a non-renal organ transplant waiting list (N = 13868). A prediction model of 10-year patient survival after baseline was developed through multivariate Cox regression analysis, in one half of the research group. Age at start, sex, primary renal disease (PRD) and therapy at baseline were included as possible predictors. A sensitivity analysis has been performed to determine whether listing on the transplant waiting list should be added. The predictive performance of the model was internally validated. Calibration and discrimination were computed in the other half of the research group. Another sensitivity analysis was to assess whether the outcomes differed if the model was developed and tested in two geographical regions, which were less similar than the original development and validation group. No external validation has been performed. Results: Survival probabilities were influenced by age, sex, PRD and therapy at baseline (p < 0.001). The calibration and discrimination both showed very reasonable results for the prediction model (C-index = 0.720 and calibration slope for the prognostic index = 1.025, for the 10 year survival). Adding registration on the waiting list for renal transplantation as a predictor did not improve the discriminative power of the model and was therefore not included in the model. Conclusions: Wit

Cytomegalovirus (CMV) infection has been implicated in accelerated T cell ageing. End-stage renal disease (ESRD) patients have a severely immunologically aged T cell compartment but also a high prevalence of CMV infection. We investigated whether CMV infection contributes to T cell ageing in ESRD patients. We determined the thymic output by the T cell receptor excision circle (TREC) content and percentage of CD31+ naïve T cells. The proliferative history of the T cell compartment by determination of the relative telomere length (RTL) and the T cell differentiation status was determined by immunophenotyping. It appeared that CMV infection did not affect thymic output but reduced RTL of CD8+ T cells in ESRD patients. Moreover, increased T cell differentiation was observed with higher percentages of CD57+ and CD28null CD4+ and CD8+ memory T cells. These CD28null T cells had significantly shorter telomeres compared to CD28+ T cells. Therefore we concluded that CMV infection does not affect the decreased thymic output but increases T cell differentiation as observed in ESRD-related premature T cell ageing.

BACKGROUND: There has been discussion regarding the psychologic functioning of living donors who donate their kidney to an unrelated and unknown patient ("unspecified living donors"). This is the first prospective study to investigate group- and individual-level changes in psychologic functioning among a large group of unspecified donors. METHODS: Forty-nine medically and psychologically screened unspecified living kidney donors completed the Symptom Checklist before and after donation. RESULTS: Group-level analysis showed that overall psychologic symptoms increased after donation (P=0.007); the means remained within the average range of the normal population. Individual-level analysis showed that 33 donors showed no statistically significant change, 3 donors showed a statistically significant decrease, and 13 donors showed a statistically significant increase in psychologic symptoms. Two of the latter donors showed a clinically significant increase. CONCLUSIONS: We found more increases in psychologic symptoms than decreases, particularly if follow-up time was longer. However, for almost all donors, these increases were not clinically significant and the clinically significant changes found are comparable with natural fluctuations in psychologic symptoms in the general population. Possibly, the donors underreported their psychologic symptoms before donation to pass the screening. Due to the low level of predonation symptoms reported, regression to the mean could also explain the results. Although we found that changes were not associated with donation-related factors, it is possible that other donation-related factors or other life events not measured have an influence on psychologic functioning. Therefore, further research is needed to investigate whether the fluctuations are related to the donation process.Copyright

Due to their immunomodulatory properties, mesenchymal stem cells (MSC) are interesting candidates for cellular therapy for autoimmune disorders, graft-versus-host disease and allograft rejection. MSC inhibit the proliferation of effector T cells and induce T cells with a regulatory phenotype. So far it is unknown whether human MSC-induced CD4+CD25+CD127-forkhead box P3 (FoxP3)+ T cells are functional and whether they originate from effector T cells or represent expanded natural regulatory T cells (nTreg). Perirenal adipose-tissue derived MSC (ASC) obtained from kidney donors induced a 2·1-fold increase in the percentage of CD25+CD127-FoxP3+ cells within the CD4+ T cell population from allostimulated CD25-/dim cells. Interleukin (IL)-2 receptor blocking prevented this induction. The ASC-induced T cells (iTreg) inhibited effector cell proliferation as effectively as nTreg. The vast majority of cells within the iTreg fraction had a methylated FOXP3 gene Treg-specific demethylated region (TSDR) indicating that they were not of nTreg origin. In conclusion, ASC induce Treg from effector T cells. These iTreg have immunosuppressive capacities comparable to those of nTreg. Their induction is IL-2 pathway-dependent. The dual effect of MSC of inhibiting immune cell proliferation while generating de-novo immunosuppressive cells emphasizes their potential as cellular immunotherapeutic agent.

Objectives: Reducing the incidence of delayed graft function after transplant with donation after cardiac death donor renal allografts would facilitate managing recipients during their first weeks after a transplant. To reduce this incidence, in most studies, induction therapy with depleting anti-T-lymphocyte antibodies is coupled with a reduction of the dosage of the calcineurin inhibitor. The separate effect of anti-T-cell therapy on the incidence and duration of delayed graft function is therefore difficult to assess. Patients and Methods: We performed a randomized study to evaluate the effect of a single intraoperative high-dose of anti-T-lymphocyte immunoglobulin (ATG)-Fresenius (9 mg/kg body weight) on the incidence of delayed graft function. Eligible adult recipients of a first donation after cardiac death donor renal allograft were randomly assigned to ATG-Fresenius or no induction therapy. Maintenance immunosuppression consisted of tacrolimus, in an unadjusted dose, mycophenolate mofetil, and steroids. Results: The study was prematurely terminated because of a lower-than-anticipated inclusion rate. Baseline characteristics were comparable in the ATG-Fresenius group (n=28) and the control group (n=24). Twenty-two patients in the ATG-Fresenius group (79%) had delayed graft function, compared with 13 in the control group (54%; P =.06). Allograft and patient survival were comparable in both groups. Serious adverse events occurred more frequently in the ATG-Fresenius group than they did in the control group (57% vs 29%; P <.05). Conclusions: Intraoperative administration of a single high-dose of ATG-Fresenius in donation after cardiac death donor renal allograft recipients, followed by triple immunosuppression with an unadjusted tacrolimus dose, seems ineffective to reduce the incidence of delayed graft function. Moreover, this was associated with a higher rate of serious adverse events (EudraCT-number, 2007-000210-36.)

Background: End-stage renal disease (ESRD) patients treated with renal replacement therapy (RRT) have premature immunologically aged T cells which may underlie uremia-associated immune dysfunction. The aim of this study was to investigate whether uremia was able to induce premature ageing of the T cell compartment. For this purpose, we examined the degree of premature immunological T cell ageing by examining the T cell differentiation status, thymic output via T cell receptor excision circle (TREC) content and proliferative history via relative telomere length in ESRD patients not on RRT.Results: Compared to healthy controls, these patients already had a lower TREC content and an increased T cell differentiation accompanied by shorter telomeres. RRT was able to enhance CD8 + T cell differentiation and to reduce CD8 + T cell telomere length in young dialysis patients. An increased differentiation status of memory CD4 + T cells was also noted in young dialysis patients.Conclusion: Based on these results we can conclude that uremia already causes premature immunological ageing of the T cell system and RRT further increases immunological ageing of the CD8 + T cell compartment in particular in young ESRD patients.

Background: End-stage renal disease (ESRD) patients treated with renal replacement therapy (RRT) have premature immunologically aged T cells which may underlie uremia-associated immune dysfunction. The aim of this study was to investigate whether uremia was able to induce premature ageing of the T cell compartment. For this purpose, we examined the degree of premature immunological T cell ageing by examining the T cell differentiation status, thymic output via T cell receptor excision circle (TREC) content and proliferative history via relative telomere length in ESRD patients not on RRT.Results: Compared to healthy controls, these patients already had a lower TREC content and an increased T cell differentiation accompanied by shorter telomeres. RRT was able to enhance CD8 + T cell differentiation and to reduce CD8 + T cell telomere length in young dialysis patients. An increased differentiation status of memory CD4 + T cells was also noted in young dialysis patients.Conclusion: Based on these results we can conclude that uremia already causes premature immunological ageing of the T cell system and RRT further increases immunological ageing of the CD8 + T cell compartment in particular in young ESRD patients.

Introduction: Across Europe, transplant centers vary in the set of psychosocial screening criteria/guidelines used for the selection of eligible living donors. Our aim was to explore whether a common framework underlies this variation in screening criteria and, based on this framework, to develop a consensus on the essential elements of psychosocial screening of living liver and kidney donors. In order to do so, a research question was set out to define a conceptual framework of the concept ‘Psychosocial’ in the context of screening living organ donors in Europe. We formulated the following research question: Which psychosocial screening criteria are most commonly reported and considered as most important or effective in selecting eligible kidney and liver donors? Method: Concept mapping methodology was used to create a visual representation of the complex topic ‘Psychosocial’ in the context of screening living organ donors in Europe, in which underlying concepts, the relative importance of these concepts and the interplay between different concepts are organized. Initial psychosocial screening criteria (N=83) were derived from an extensive systematic literature review on guidelines, protocols and consensus statements on psychosocial screening practices, complemented by group brainstorm sessions. These criteria were then sorted and rated for their importance and effectiveness by 26 project participants. The data were analyzed using the Concept System Core© Software, which provided us with graphical depictions (concept maps) illustrating the view of project participants on these screening criteria. Pattern Matches and Go-Zones showed us the highlycommon, important and effective criteria. Results: The concept map procedure resulted in six clusters of psychosocial screening criteria: (1) Motivation and decision making (2) Personal resources (3) Psychopathology (4) Social resources (5) Ethical and Legal factors (6) Information and risk processing. Bivariate rating of th

Terminal kidney patients are faced with lower quality of life, restricted diets and higher morbidity and mortality rates while waiting for deceased donor kidney transplantation. Fortunately, living kidney donation has proven to be a better treatment alternative (e.g. in terms of waiting time and graft survival rates). We observed an inequality in the number of living kidney transplantations performed between the non-European and the European patients in our c

Background: Living donor kidney transplantation (LDKT) is the most successful form of renal replacement therapy in terms of wait time and survival rates. However, we observed a significant inequality in the number of LDKT performed between the Dutch and the non-Dutch patients. The objective of this study is to adapt, implement and test an educational home-based intervention to contribute to the reduction of this inequality. Our aim is to establish this through guided communication together with the social network of the patients in an attempt that well-informed decisions regarding renal replacement therapy can be made: Multisystemic Engagement & Nephrology. This manuscript is a detailed description of the Kidney Team At Home-study protocol. Methods and design. All patients (>18 yrs) that are referred to the pre-transplantation outpatient clinic are eligible to participate in the study. Patients will be randomly assigned to either an experimental or a control group. The control group will continue to receive standard care. The experimental group will receive standard care plus a home-based educational intervention. The intervention consists of two sessions at the patient's home, an initial session with the patient and a second session for which individuals from their social network are invited to take part. Based on the literature and behavioural change theories we hypothesize that reducing hurdles in knowledge, risk perception, subjective norm, self-efficacy, and communication contribute to well-informed decision making and reducing inequality in accessing LDKT programs. A change in these factors is consequently our primary outcome-measure. Based on power calculations, we aim to include 160 patients over a period of two years. Discussion. If we are able to show that this home-based group educational intervention contributes to 1) achieving well-informed decision regarding treatment and 2) reducing the inequality in LDKT, the quality of life of patients will be impro

This paper studies participation of unspecified donors in kidney exchange through simultaneous domino paired donation (DPD) and non-simultaneous extended altruistic donor (NEAD) chains. It extends existing research by investigating the termination of chains, the possibility of transplantation across the blood type barrier, and the impact of incentives in multi-center exchanges. Furthermore, it looks into the effect of various configuration parameters such as the time interval between exchanges. Our analysis is based on a simulation study that uses data of all 438 patient-donor pairs and 109 unspecified donors who were screened at Dutch transplant centers between 2003 and 2011. Because multi-center coordination may raise incentive issues, special attention is paid to individually rational implementation. We find that chains are best terminated when no further segment is part of an optimal exchange within 3 months. Transplantation across the blood type barrier allows for longer continuation of chains, more transplants and more equity among patient groups. NEAD chains perform slightly better than DPD chains, provided that the renege rate is sufficiently low. Additional substantial gains are due to national individually rational coordination. Particularly highly sensitized and blood type O patients benefit. Appropriate timing of ex-changes can further improve these results.

Organ transplant recipients frequently suffer from toxicity or from lack of efficacy of immunosuppressive drugs, which can be attributed to individual variations in drug sensitivity. This problem can be resolved by applying pharmacodynamic monitoring that focuses on measuring the biological effects of drugs. Here we discuss the new technique called phospho-specific flow cytometry to monitor the activity of intracellular immune signaling pathways at the single-cell level in whole blood samples. Through this tool the efficacy of immunosuppressive medication can be assessed, novel targets can be identified, and differences in drug sensitivity between cells and patients can be clarified.

We screened 1,200 living heart, lung, liver, and kidney transplant recipients for hepatitis E virus infection by reverse transcription PCR. In 12 (1%) patients, hepatitis E virus infection was identified; in 11 patients, chronic infection developed. This immunocompromised population is at risk for hepatitis E virus infection.

Experimental studies have established the use of mesenchymal stem cells (MSC) as a candidate immunosuppre+ssive thera+py. MSC exert their immunomodulatory function through the inhibition of CD4+ and CD8+ T cell proliferation. It is unknown whether MSC impair the immunosuppressive function of reg

Background. Non-adherence to the post-transplant regime is a common problem in kidney transplant patients and may lead to rejection or even graft failure. This study investigated attitudes towards the post-transplant regime of immunosuppressive medication among the ever growing population of elderly kidney recipients.Methods. Q methodology was used to explore attitude profiles. Participants (> 65 years) were asked to rank-order opinion statements on issues associated with (non-)adherence. The rankings were subject to by-person factor analysis, and the resulting factors were interpreted and described as attitudes.Results. Twenty-six elderly renal transplant recipients participated in the study. All passed the Mini-Mental S

Introduction: There is currently a lack of validated or standardized measures to test the level of knowledge among renal patients regarding kidney disease and available treatment options. We conducted a pilot study to develop a questionnaire measuring knowledge of kidney disease, dialysis and transplantation options. The main aim of this study was to develop such an instrument for further use in research and practice. Method: An initial 61 item pool was generating by searching the literature and consulting experts in this area for additional items. This questionnaire was completed by 182 renal disease patients from 4 dialysis centers in the Rotterdam municipality. A factor analysis was conducted using the maximum likelihood factor method followed by direct oblimin rotation to obtain variance explained by each factor. Questions that loaded ≥ .30 on a factor were included. Results: Twenty-seven patients (24%) were in the pre-RRT phase, 60 (54%) were undergoing haemodialysis, 16 (14%) were undergoing peritoneal dialysis, and 9 (8%) had a graft failure. Forty (36%) were female and 72 (64%) were male. Age range 19-87 (median = 59). A factor analysi

Background. Transplantation is the only treatment offering long-term benefit to patients with chronic kidney failure. Live donor nephrectomy is performed on healthy individuals who do not receive direct therapeutic benefit of the procedure themselves. In order to guarantee the donor's safety, it is important to optimise the surgical approach. Recently we demonstrated the benefit of laparoscopic nephrectomy experienced by the donor. However, this method is characterised by higher in hospital costs, longer operating times and it requires a well-trained surgeon. The hand-assisted retroperitoneoscopic technique may be an alternative to a complete laparoscopic, transperitoneal approach. The peritoneum remains intact and the risk of visceral injuries is reduced. Hand-assistance results in a faster procedure and a significantly reduced operating time. The feasibility of this method has been demonstrated recently, but as to date there are no data available advocating the use of one technique above the other. Methods/design. The HARP-trial is a multi-centre randomised controlled, single-blind trial. The study compares the hand-assisted retroperitoneoscopic approach with standard laparoscopic donor nephrectomy. The objective is to determine the best approach for live donor nephrectomy to optimise donor's safety and comfort while reducing donation related costs. Discussion. This study will contribute to the evidence on any benefits of hand-assisted retroperitoneoscopic versus standard laparoscopic donor nephrectomy. Trial Registration. Dutch Trial Register NTR1433.

BACKGROUND. Young adult renal transplant recipients may display patterns of behavior that affect graft survival. The present study aimed to identify young adults at risk for nonadherent behavior by investigating their attitudes about posttransplant health lifestyle. METHOD. A Q-methodological study was conducted. Participants were asked to rank-order statements on issues potentially associated with (non)adherence. Factor analysis was applied to uncover patterns in the ranking of statements. The resulting factors represent attitudes and are described using a composite ranking of the statements. As a first test of discriminated validity, a different group of 34 young renal transplant patients was asked how well the factor descriptions fitted them. RESULTS. Twenty-six young renal transplant recipients (18-25 years) participated in the study. They were remarkably willing to discuss sensitive issues when confronted with statements on cards. Four distinct attitude profiles concerning posttransplant health lifestyle were found among these young adults: (a) concerned and controlled, (b) appearance orientated, (c) opinionated and independent, and (d) easy going and pliable. In a follow-up analysis, self-categorization proved to discriminate well between the four attitude profiles in 67% of the respondents. CONCLUSIONS. Using Q-methodology, four attitude profiles about posttransplant health lifestyle were uncovered. Self-categorization on these attitudes seems feasible and may be a useful screening aid to identify young adults at risk for nonadherence.

Patients with end-stage kidney disease, whether or not on renal replacement therapy, have an impaired immune system. This is clinically manifested by a large percentage of patients unresponsive to the standard vaccination procedure for hepatitis B virus (HBV). In this study, the immune response to HBV vaccination is related to the in vitro function of monocyte-derived dendritic cells (moDC). We demonstrate that mature moDC from nonresponders to HBV vaccination have a less mature phenotype, compared to responders and healthy volunteers, although this did not affect their allostimulatory capacity. However, proliferation of autologous T cells in the presence of tetanus toxoid and candida antigen was decreased in non-responders. Also, HLA-matched CD4+ hsp65-specific human T-cell clones showed markedly decreased proliferation in the group of non-responders. Our results indicate that impairment of moDC to stimulate antigen-specific T cells provides an explanation for the clinical immunodeficiency of patients with end-stage kidney disease.

Background. Dendritic cells (DCs) are antigen-presenting cells that are pivotal for the initiation of the primary immune response. Patients with chronic kidney disease (CKD) with or without chronic intermittent haemodialysis (CIHD) show an impaired immune response. Dysfunction of DCs may underlie this phenomenon. Methods. In this study, several different functions of monocyte-derived DCs (moDC) of patients with CKD class IV-V (glomerular filtration rate <30 ml/min) and patients on CIHD were studied in vitro and compared with age- and sex-matched healthy volunteers. Results. We demonstrate that, independent of the maturation stimulus used, mature moDC from both groups of patients did not acquire the same level of terminal differentiation as moDC from controls, as shown by analysis of cell surface markers and the relative high macropinocytosis activity of moDC. The stimulation of allogeneic T-cells by immature moDC and mature moDC did not differ between patients and controls. However, in the presence of immature moDC or antigen-loaded maturated moDC from patients, less proliferation of autologous T-cells was observed in response to recall antigens. There was no difference between moDC from controls and patients in their ability to activate naive T-cells and to differentiate them into Th1 and Th2 cells. Conclusions. These results show that the terminal differentiation of moDC in patients with severe CKD is impaired. This impairment is not restricted to one maturation stimulus and is independent of treatment with haemodialysis.

DOELSTELLING Nierdonatie bij leven levert medisch en maatschappelijk gezien veel voordelen op, maar toch willen of kunnen niet alle nierpatiënten op de wachtlijst en/of hun naasten zich opgeven voor het nierdonatie bij leven programma. De doelstelling van het project ‘Nierdonatie bij leven: psychologische en ethische aspecten’ is het verkrijgen van meer inzicht in de kennis en acceptatie van nierdonatie bij leven. Het gaat hierbij om kennis en acceptatie onder proefpersonen die daadwerkelijk in aanmerking komen voor nierdonatie/ transplantatie bij leven, dat wil zeggen (1) patiënten met eindfase nierfalen op de wachtlijst voor een niertransplantatie en (2) de mensen uit hun omgeving; de potentiële donoren. Het benaderen van deze groepen is de strategie om uit te vinden of, en onder welke voorwaarden, uitbreiding van het nierdonatie bij leven programma praktisch haalbaar en ethisch verdedigbaar is. VRAAGSTELLINGEN Het project omvat twee vraagstellingen. De eerste vraagstelling is: wat zijn de psychologische barrières voor nierdonatie bij leven voor patiënten op de wachtlijst, en de mensen uit hun omgeving? De tweede vraagstelling luidt: wat zijn de morele argumenten om de patiënt en de mensen uit de omgeving van de patiënt (de potentiële donoren) al dan niet actief te benaderen over nierdonatie bij leven? In andere woorden; in hoeverre zijn interventies ethisch verdedigbaar? OPZET PATIËNTEN EN (POTENTIËLE) DONOREN Wij hebben allereerst de groep patiënten die op de wachtlijst voor niertransplantatie staat benaderd (regio Erasmus MC). Aan de patiënt vragen wij toestemming om ook de potentiële donoren uit zijn of haar omgeving te benaderen. Indien beiden hiermee instemmen, vindt het interview met deze potentiële donor plaats. Voor deze studie hebben we tevens een controlegroep benaderd. In de controlegroep zitten patiënten en donoren die nog geen familietransplantatie hebben ondergaan, maar die wel al hebben besloten door te gaan met de donatie bij leven procedure en di, PURPOSE Living kidney donation offers many advantages, both from a medical and societal point of view. However, there is a group of patients that cannot or will not make use of the living kidney donation program. The purpose of the study ‘Living Kidney donation: psychological and ethical aspects’ is to gain insight into the knowledge and acceptance of this form of kidney transplantation. The group we investigate is the group that actually is eligible for living kidney donation / transplantation, namely (1) patients with end stage renal disease on the transplantation waiting list and (2) the persons in their close environment, the potential donors. Investigating these groups is the strategy to find out if, and under what circumstances, expansion of the living kidney donation program is feasible and ethically acceptable. RESEARCH QUESTIONS The project comprises two research questions. The first research question is: what are the psychological barriers for living kidney donation for the patients and the people in their close environment? The second research question is: what are the moral arguments to deal or actively or passively with the persons in the close environment of the patients who are the potential donors? In other words, to what extent are interventions morally acceptable? DESIGN PATIENTS We have approached the group of patients on the waiting list for a kidney transplant (region of the Erasmus University Medical Center). We asked the patients for permission to approach individuals in their personal environment, the potential donors. If both (patient and relative of patient) agreed on this, we interviewed these potential donors as well. We also included a control group in our study. This group consists of patients and their actual donors who have planned to undergo living kidney donation/transplantation in the near future and had already made arrangements together with their clinicians. INTERVIEW All participants in our study were interviewed by means of a

OBJECTIVES: To determine the best approach for live donor nephrectomy to minimise discomfort to the donor and to provide good graft function. DESIGN: Single blind, randomised controlled trial. SETTING: Two university medical centres, the Netherlands. PARTICIPANTS: 100 living kidney donors. INTERVENTIONS: Participants were randomly assigned to either laparoscopic donor nephrectomy or to mini incision muscle splitting open donor nephrectomy. MAIN OUTCOME MEASURES: The primary outcome was physical fatigue using the multidimensional fatigue inventory 20 (MFI-20). Secondary outcomes were physical function using the SF-36, hospital stay after surgery, pain, operating times, recipient graft function, and graft survival. RESULTS: Conversions did not occur. Compared with mini incision open donor nephrectomy, laparoscopic donor nephrectomy resulted in longer skin to skin time (median 221 v 164 minutes, P < 0.001), longer warm ischaemia time (6 v 3 minutes, P < 0.001), less blood loss (100 v 240 ml, P < 0.001), and a similar number of complications (intraoperatively 12% v 6%, P = 0.49, postoperatively both 6%). After laparoscopic nephrectomy, donors required less morphine (16 v 25 mg, P = 0.005) and shorter hospital stay (3 v 4 days, P = 0.003). During one year's follow-up mean physical fatigue was less (difference - 1.3, 95% confidence interval - 2.4 to - 0.1) and physical function was better (difference 6.2, 2.0 to 10.3) after laparoscopic nephrectomy. Function of the graft and graft survival rate of the recipient at one year censored for death did not differ (100% after laparoscopic nephrectomy and 98% after open nephrectomy). CONCLUSIONS: Laparoscopic donor nephrectomy results in a better quality of life compared with mini incision open donor nephrectomy but equal saf

The effects of immunosuppressive agents on T cell function have been well characterized but virtually nothing is known about the effects of renal transplantation on human dendritic cells (DCs). With the use of flow cytometry, we studied the kinetics of myeloid and plasmacytoid DCs in peripheral blood of 24 kidney allograft recipients before and after transplantation, and in 23 donors before and after kidney donation. All patients were treated with tacrolimus, mycophenolate mofetil and prednisone. Surgery resulted in a strong decline in the number of myeloid and plasmacytoid DCs, both in kidney donors and in their recipients. However, in donors this effect was transient, as the numbers of both DC subsets had normalized completely by the third postoperative month. In contrast, the recovery of myeloid DC counts in kidney transplant recipients was only incomplete at the end of the 3-month follow-up, despite tapering of immunosuppression. The seven patients who required additional immunosuppressive treatment because of acute rejection experienced an even more marked decrease in DC counts in the early postoperative period compared with patients who remained rejection-free. Surgical procedures markedly affect th

We have previously suggested that the in vitro donor-specific cytotoxic T-lymphocyte precursor (CTLp) assay can guide us to identify patients in which the immunosuppressive load can be tapered. In a clinical trial we had observed that a low (<10/10(6) PBMC) frequency of these CTLp was predictive for an uneventful rejection-free clinical course in patients that were converted from calcineurin inhibitors to mycophenolate mofetil or azathiopine. In the present prospective study in 81 stable kidney transplant recipients, already converted from calcineurin inhibitors, we measured CTLp frequencies and reduced the immunosuppressive load on a routine basis when CTLp were <10/10(6) PBMC. Donor-specific cytotoxicity could not be measured in 50/81 patients, while their reactivity against third-party lymphocytes was not impaired. These 50 patients were tapered in their immunosuppression. Only in one patient, who had stopped all his medication, was a rejection episode diagnosed. We conclude that in patients with a low donor-specific CTLp frequency it is safe to reduce the immunosuppression.

PURPOSE: To determine the most cost-effective strategy for preoperative imaging performed in potential living renal donors. MATERIALS AND METHODS: In a decision-analytic model, the societal cost-effectiveness of digital subtraction angiography (DSA), gadolinium-enhanced magnetic resonance (MR) angiography, contrast material-enhanced spiral computed tomographic (CT) angiography, and combinations of these imaging techniques was evaluated. Outcome measures included lifetime cost, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. A base-case analysis was performed with a 40-year-old female donor and a 40-year-old female recipient. RESULTS: For the donor, MR angiography (24.05 QALYs and 9,000 dollars) dominated all strategies except for MR angiography with CT angiography, which had an incremental ratio of 245,000 dollars per QALY. For the recipient, DSA and DSA with MR angiography yielded similar results (10.46 QALYs and 179,000 dollars) and dominated all other strategies. When results for donor and recipient were combined, DSA dominated all other strategies (34.51 QALYs and 188,000 dollars). If DSA was associated with a 99% specificity or less for detection of renal disease, MR angiography with CT angiography was superior (34.47 QALYs and 190,000 dollars). CONCLUSION: For preoperative imaging in a potential renal donor, DSA is the most cost-effective strategy if it has a specificity greater than 99% for detection of renal disease; otherwise, MR angiography with CT angiography is the most cost-effective strategy.

The extent of graft damage after ischemia-reperfusion reflects the balance between deleterious events and protective factors. Heme oxygenase-1 (HO-1) and vascular endothelial growth factor (VEGF) may contribute to cytoprotection by their anti-inflammatory and antiapoptotic properties. For investigating whether HO-1 and VEGF play a role in the adaptive response to ischemia-reperfusion injury after renal transplantation, kidney biopsies were analyzed from living (n = 45) and cadaveric (n = 16) donors, obtained at three time points: at the end of cold storage T(-1), after warm ischemia T(0), and after reperfusion T(+1). The mRNA expression levels of HO-1, VEGF(165), Bcl-2, Bax, and hypoxia inducible factor-1alpha were quantified by real-time reverse transcriptase-PCR, and the HO-1 and VEGF proteins were analyzed by immunohistochemistry. Cadaveric donor kidneys presented higher mRNA expression levels of hypoxia inducible factor-1alpha. In contrast, mRNA expression levels of HO-1, VEGF(165), and Bcl-2 were significantly lower in kidneys from cadaveric donors. Overall, a significant correlation was observed between mRNA expression of Bcl-2 and VEGF(165), between Bcl-2 and HO-1, and between HO-1 and VEGF(165). Moreover, protein expression of HO-1 and VEGF was detected in the same anatomical kidney compartments (glomerulus, arteries, and distal tubules). Renal function at the first week posttransplantation (analyzed by serum creatinine levels) showed a significant correlation with both HO-1 and VEGF mRNA expression, reinforcing the protective role of both genes in the early events of transplantation. It is concluded that the lower expression of HO-1, VEGF(165), and Bcl-2 in cadaveric donor kidneys can reflect a defective adaptation against ischemia-reperfusion injury that may affect their function in the short term.

Left ventricular (LV) hypertrophy leads to diastolic dysfunction. Standard Doppler transmitral and pulmonary vein (PV) flow velocity measurements are preload dependent. New techniques such as mitral annulus velocity by Doppler tissue imaging (DTI) and LV inflow propagation velocity measured from color M-mode have been proposed as relatively preload-independent measurements of diastolic function. These parameters were studied before and after hemodialysis (HD) with ultrafiltration to test their potential advantage for LV diastolic function assessment in HD patients. Ten patients (seven with LV hypertrophy) underwent Doppler echocardiography 1 h before, 1 h after, and 1 d after HD. Early (E) and atrial (A) peak transmitral flow velocities, peak PV systolic (s) and diastolic (d) flow velocities, peak e and a mitral annulus velocities in DTI, and early diastolic LV flow propagation velocity (V(p)) were measured. In all patients, the E/A ratio after HD (0.54; 0.37 to 1.02) was lower (P < 0.01) than before HD (0.77; 0.60 to 1.34). E decreased (P < 0.01), whereas A did not. PV s/d after HD (2.15; 1.08 to 3.90) was higher (P < 0.01) than before HD (1.80; 1.25 to 2.68). Tissue e/a after HD (0.40; 0.26 to 0.96) was lower (P < 0.01) than before HD (0.56; 0.40 to 1.05). Tissue e decreased (P < 0.02), whereas a did not. V(p) after HD (30 cm/s; 16 to 47 cm/s) was lower (P < 0.01) than before HD (45 cm/s; 32 to 60 cm/s). Twenty-four hours after the initial measurements values for E/A (0.59; 0.37 to 1.23), PV s/d (1.85; 1.07 to 3.38), e/a (0.41; 0.27 to 1.06), and V(p) (28 cm/s; 23 to 33 cm/s) were similar as those taken 1 h after HD. It is concluded that, even when using the newer Doppler techniques DTI and color M-mode, pseudonormalization, which was due to volume overload before HD, resulted in underestimation of the degree of diastolic dysfunction. Therefore, the advantage of these techniques over conventional parameters for the assessment of LV diastolic function in HD patient

Uncertainty exists regarding the necessity of continuing triple therapy consisting of mycophenolate mofetil (MMF), cyclosporine (CsA), and prednisone (Pred) after kidney transplantation (RTx). At 6 mo after RTx, 212 patients were randomized to stop CsA (n = 63), stop Pred (n = 76), or continue triple drug therapy (n = 73). The MMF dose was 1000 mg twice daily, target CsA trough levels were 150 ng/ml, and Pred dose was 0.10 mg/kg per d. Follow-up was until 24 mo after RTx. Biopsy-proven acute rejection occurred in 14 (22%) of 63 patients after CsA withdrawal compared with 3 (4%) of 76 in the Pred withdrawal group (P = 0.001) and 1 (1.4%) of 73 in the control group (P = 0.0001). Biopsy-proven chronic rejection was present in one patient in the control group, in nine patients after CsA withdrawal (P = 0.006 versus control group); and in four patients after discontinuation of Pred (NS). Graft loss occurred in two versus one patient after CsA or Pred withdrawal, respectively, and in two patients in the control group (NS). Patients who successfully withdrew CsA had a significantly lower serum creatinine during follow-up. Pred withdrawal resulted in a reduction in mean arterial pressure, and the total cholesterol/HDL ratio increased. In conclusion, rapid CsA withdrawal at 6 mo after RTx results in a significantly increased incidence of biopsy-proven acute and chronic rejection. Pred withdrawal was safe and resulted in a reduction in mean arterial pressure. However, patient and graft survival and renal function 2 yr after RTx were not different among groups.