The approach to cardiovascular risk assessment before renal transplantation is still controversial. Therefore, we evaluated and compared the prognostic value of myocardial perfusion scintigraphy (MPS) and dobutamine stress echocardiography (DSE) in patients with end-stage renal disease (ESRD) who are candidates for kidney transplantation (KTx). METHODS:We prospectively enrolled 356 ESRD clinical transplantations for review, only patients (NCT01064674) admitted to our transplant center between August 2009 and July 2012. Cardiovascular risk assessment at the time of listing was based on the Münster Cardiovascular Risk Stratification Score (MCRSS), additionally including evaluation by DSE and MPS in all ESRD patients. Coronary angiography was conducted in patients at high risk according to the MCRSS and in those where noninvasive stress testing revealed stress-induced ischemia or wall motion abnormalities. RESULTS:During long-term follow-up until October 2020, 2.43 cardiovascular events/100 person-years (nonfatal stroke, nonfatal myocardial infarction, and cardiovascular death) occurred, and the overall patient survival was 71.9%. Mild perfusion deficits identified by MPS, unlike wall motion abnormalities detected by DSE, showed incremental prognostic value for event-free survival in patients with low MCRSS risk. CONCLUSION:We therefore propose a modified MCRSS-based approach including MPS as a reasonable risk stratification approach for cardiovascular risk assessment of ESRD patients applying for KTx.

Introduction:The German health care system lacks data on surgical complications and self-reported outcomes (SROs) of living donors. The prospective German Living Kidney Donor Registry, SOLKID-GNR aims to improve the assessment of donors' medical and psychosocial risks. Methods:Data were collected before (PRE) and 3 months after (POST) living kidney donation from transplantation centers (TCs) and donors via SROs. We reported perioperative complication rates for different surgical techniques and correlated them with donors' SROs. Datasets of 1020 donors from 30 German TCs were analyzed. Results:Donor nephrectomy procedures included laparoscopic (57.9%), retroperitoneoscopic (21.4%), open retroperitoneal (16.0%), or open abdominal nephrectomy (4.7%). Perioperative complications reported by TCs ranged from 9.8% (retroperitoneoscopic) to 17.1% (open abdominal), whereas those reported by donors ranged from 12.2% (open retroperitoneal) to 15.0% (open abdominal). Donors were discharged sooner and returned to work earlier after minimally invasive surgery; however, had comparable quality-of-life (QoL) after donation. The physical component summary (PCS) scores of the Short Form-12 (SF-12) were similar between the 4 surgical methods postdonation; however, they were lower in donors with TC- or self-reported complications than in those without. The mental component summary (MCS) scores of the SF-12 were lower in case of self-reported complications only. Despite 12.5% of self-reported complications, 96.4% expressed a willingness to donate again, and 94.1% felt well-informed. Conclusion:Although the surgical technique does not directly affect donors' QoL shortly after donation, minimally invasive procedures result in shorter hospital stays and a quicker return to work. Self-reported complications have a greater impact on mental QoL than those documented by transplant centers, highlighting the importance of subjective experiences during recovery.

Background We previously reported excellent efficacy and improved safety aspects of rapid steroid withdrawal (RSWD) in the randomized controlled 1-year "Harmony" trial with 587 predominantly deceased-donor kidney transplant recipients randomized either to basiliximab or rabbit antithymocyte globulin induction therapy and compared with standard immunosuppressive therapy consisting of basiliximab, low tacrolimus once daily, mycophenolate mofetil and corticosteroids. Methods The 5-year post-trial follow-up (FU) data were obtained in an observational manner at a 3- and a 5-year visit only for those Harmony patients who consented to participate and covered clinical events that occurred from the second year onwards. Results Biopsy-proven acute rejection and death-censored graft loss rates remained low and independent of RSWD. Rapid steroid withdrawal was an independent positive factor for patient survival (adjusted hazard ratio 0.554, 95% confidence interval 0.314-0.976; P = .041). The reduced incidence of post-transplantation diabetes mellitus in RSWD patients during the original 1-year study period was not compensated by later incidences during FU. Incidences of other important outcome parameters such as opportunistic infections, malignancies, cardiovascular morbidity/risk factors, donor-specific antibody formation or kidney function did not differ during FU period. Conclusions With all the limitations of a post-trial FU study, the Harmony FU data confirm excellent efficacy and beneficial safety aspects of RSWD under modern immunosuppressive therapy over the course of 5 years after kidney transplantation in an immunologically low-risk, elderly population of Caucasian kidney transplant recipients.

Background The selection of data elements is a decisive task within the development of a health registry. Having the right metadata is crucial for answering the particular research questions. Furthermore, the set of data elements determines the registries' readiness of interoperability and data reusability to a major extent. Six health registries shared and published their metadata within a German funding initiative. As one step in the direction of a common set of data elements, a selection of those metadata was evaluated with regard to their appropriateness for a broader usage.Methods Each registry was asked to contribute a 10%-selection of their data elements to an evaluation sample. The survey was set up with the online survey tool ,,LimeSurvey Cloud". The registries and an accompanying project participated in the survey with one vote for each project. The data elements were offered in content groups along with the question of whether the data element is appropriate for health registries on a broader scale. The question could be answered using a Likert scale with five options. Furthermore, "no answer" was allowed. The level of agreement was assessed using weighted Cohen's kappa and Kendall's coefficient of concordance.Results The evaluation sample consisted of 269 data elements. With a grade of "perhaps recommendable" or higher in the mean, 169 data elements were selected. These data elements belong preferably to groups' demography, education/occupation, medication, and nutrition. Half of the registries lost significance compared with their percentage of data elements in the evaluation sample, one remained stable. The level of concordance was adequate.Conclusions The survey revealed a set of 169 data elements recommended for health registries. When developing a registry, this set could be valuable help in selecting the metadata appropriate to answer the registry's research questions. However, due to the high specificity of research questions, data elements beyond this set will be needed to cover the whole range of interests of a register. A broader discussion and subsequent surveys are needed to establish a common set of data elements on an international scale.

Background: Although kidney transplantation is the best treatment for both sexes with end-stage renal disease, there are sex-specific differences that begin as early as the access to kidney transplantation. Objective: Presentation of sex-specific biological differences and psychosocial factors in relation to kidney transplantation. Material and methodLiterature search and discussion of basic research studies. Results: Women with terminal kidney failure are less likely to receive a kidney transplant, although their expected lifetime gain after transplantation does not differ from that of male recipients. Sex plays a role on both the organ and recipient sides, whereby immunological, infectious, and follow-up aspects must be considered. Conclusion: Sex differences exist in the context of kidney transplantation and also during follow-up. The reasons for this are manifold and include lifestyle, risk behavior, adherence to treatment, social aspects and biological factors, such as sex hormones.

The Eurotransplant Senior Program (ESP) has expedited the chance for elderly patients with kidney failure to receive a timely transplant. This current study evaluated survival parameters of kidneys donated after brain death with or without matching for HLA-DR antigens. This cohort study evaluated the period within ESP with paired allocation of 675 kidneys from donors 65 years and older to transplant candidates 65 years and older, the first kidney to 341 patients within the Eurotransplant Senior DR-compatible Program and 334 contralateral kidneys without (ESP) HLADR antigen matching. We used Kaplan-Meier estimates and competing risk analysis to assess all cause mortality and kidney graft failure, respectively. The log-rank test and Cox proportional hazards regression were used for comparisons. Within ESP, matching for HLA-DR antigens was associated with a significantly lower five-year risk of mortality (hazard ratio 0.71; 95% confidence interval 0.530.95) and significantly lower cause-specific hazards for kidney graft failure and return to dialysis at one year (0.55; 0.35-0.87) and five years (0.73; 0.53-0.99) post-transplant. Allocation based on HLA-DR matching resulted in longer cold ischemia (mean difference 1.00 hours; 95% confidence interval: 0.32-1.68) and kidney offers with a significantly shorter median dialysis vintage of 2.4 versus 4.1 yrs. in ESP without matching. Thus, our allocation based on HLA-DR matching improved five-year patient and kidney allograft survival. Hence, our paired allocation study suggests a superior outcome of HLA-DR matching in the context of old-for-old kidney transplantation.

BackgroundStudies prospectively monitoring de novo donor-specific antibodies (dnDSAs) and their clinical impact are sparse. This substudy of ATHENA was initiated to evaluate the effect of everolimus (EVR) or mycophenolic acid (MPA) in combination with reduced calcineurin inhibitor (CNI, tacrolimus [TAC] or cyclosporine [CsA]) on the formation of human leukocyte antibodies (HLA), including dnDSA, and the impact on clinical outcomes in kidney transplant (KTx) recipients.MethodsAll eligible patients were randomized 1:1:1 to receive either EVR + TAC, EVR + CsA or MPA + TAC, with basiliximab induction plus steroids after transplantation up to Month 12. The incidence of dnDSA by treatment group and the association with clinical events were evaluated descriptively as an exploratory objective in the intent-to-treat (ITT) and per-protocol (PP) populations with at least one antibody assessment.ResultsOverall, none of the patients in the EVR + TAC group had either dnDSA or antibody mediated rejection (PP or ITT population) and only one patient with dnDSA in the TAC + MPA group had antibody mediated rejection.ConclusionThe EVR regimen was comparable to MPA regimen with an extremely low incidence of dnDSA over 1 year of treatment.

BackgroundNon-human leukocyte antigen (non-HLA) antibodies including antibodies targeting Angiotensin II type 1 (AT1R) and Endothelin-1 type A (ETAR) receptors represent a topic of interest in kidney transplantation (KTx). This exploratory substudy evaluated the impact of everolimus (EVR) or mycophenolic acid (MPA) in combination with tacrolimus (TAC) or cyclosporine A (CsA) in patients with preformed non-HLA antibodies, potentially associated rejections and/or their impact on renal function over 1 year.MethodsAll eligible patients were randomized (1:1:1) before transplantation to receive either EVR/TAC, EVR/CsA, or MPA/TAC regimen. The effect of these regimens on the formation of non-HLA antibodies within one year post de novo KTx and the association with clinical events was evaluated descriptively in randomized (n = 268) population.ResultsAt Month 12, in EVR/TAC group, higher incidence of patients negative for AT1R- and ETAR-antibodies (82.2% and 76.7%, respectively) was noted, whereas the incidence of AT1R- and ETAR-antibodies positivity (28.1% and 34.7%, respectively) was higher in the MPA/TAC group. Non-HLA antibodies had no influence on clinical outcomes in any treatment group and no graft loss or death was reported.ConclusionsThe studied combinations of immunosuppressants were safe with no influence on clinical outcomes and suggested minimal exposure of calcineurin inhibitors for better patient management.Clinical Trial Registrationhttps://clinicaltrials.gov/ (NCT01843348; EudraCT number: 2011-005238-21).

Obwohl die Nierentransplantation die beste Behandlung beider Geschlechter für Nierenerkrankungen im Endstadium ist, gibt es geschlechtsspezifische Unterschiede, die schon beim Zugang zur Nierentransplantation beginnen. Darstellung geschlechtsspezifischer biologischer Unterschiede und psychosozialer Faktoren in Bezug auf eine Nierentransplantation. Literaturrecherche und Diskussion von Grundlagenarbeiten. Frauen mit einer terminalen Niereninsuffizienz haben eine geringere Wahrscheinlichkeit, nierentransplantiert zu werden, obwohl sich ihr zu erwartender Zugewinn an Lebenszeit nach einer Transplantation nicht von demjenigen männlicher Empfänger unterscheidet. Das Geschlecht spielt organ- und empfänger:innenseitig eine Rolle, wobei immunologische, infektiologische und Aspekte der Nachsorge zu berücksichtigen sind. Es existieren geschlechtsspezifische Unterschiede sowohl vor einer Nierentransplantation als auch in der Nachsorge. Die Ursachen dafür sind vielfältig und beinhalten unter anderem Lebensstil, Risikoverhalten, Therapieadhärenz, soziale Aspekte und biologische Faktoren wie Sexualhormone.

Secondary use, the reuse of medical patient data stored during routine care in the hospital's electronic medical records (EMR) for research purpose is common, especially for registers and pragmatic trials. Often the medical data items are copied manually from the EMR into the used research database. This process is time consuming and error prone. In the "Safety of the Living Kidney Donor - The German National Register" (SOLKID-GNR), laboratory results gathered during control check-ups of the living donors before and after the transplantation are to be transferred from the EMR into the electronic data capture system REDCap of the register. In this work, we present our approach of realizing an automated transfer of time-dependent laboratory results from the EMR of the University Hospital of Münster to REDCap. A challenge lies in the multi-center structure of SOLKID-GNR. The participating transplant centers are using different EMR systems, which requires a flexible architecture design. In addition, we aimed to support reuse of the implementation for other research settings with other medical data items of interest.

Abstract BACKGROUND AND AIMS In contrast to slow tacrolimus (Tac) metabolism, fast metabolism is associated with a more rapid decline in renal function [1–3]. Because the pharmacokinetics of LCP-Tac (LCPT) differ from those of immediate-release Tac (IR-Tac), we hypothesized that the estimated glomerular filtration rate (eGFR) of fast metabolizers, in particular, would be improved by switching from IR-Tac to LCPT. METHOD We included renal allograft recipients receiving a de novo immunosuppression with IR-Tac, mycophenolate and prednisolone. A Tac concentration-to-dose ratio (C/D ratio, surrogate for bioavailability) <1.05 ng/mL*1/mg defined fast metabolizers and ≥ 1.05 ng/mL*1/mg slow metabolizers one months after renal transplantation (RTx). All patients were switched to LCPT 1 month after transplantation or later. During a 3-year follow-up, Tac doses, C/D ratios, eGFR, infection and rejection rates were compared between the metabolizer groups. RESULTS Fast metabolizers (n = 58) were switched to LCPT earlier than slow metabolizers (n = 22) after RTx (2.0 (1.0–253.1 versus 13.2 (1.2–172.8 months, P = .005). Tac doses were decreased by ∼65% in both groups after 12 months of conversion to LCPT. C/D ratios at 12 months increased from 0.66 (0.24–2.10) to 1.74 (0.42–5.43) (+163%) in fast and from 1.15 (0.32–3.60) to 2.75 (1.08–5.90) (+139%) in slow metabolizers. Fast metabolizers showed significant recovery of mean eGFR as early as one month after conversion (48.5 ± 17.6 versus 41.5 ± 17.0 mL/min/1.73 m²; P = .032) and at all subsequent time points. Conversion to LCPT did not result in relevant eGFR changes in slow metabolizers. Infection and rejection rates were low and did not differ between the groups before and after conversion. CONCLUSION Switching to LCPT increases the Tac bioavailability. This was associated with a significant recovery of renal function in fast metabolizers. Conversion to LCPT is safe and beneficial early after RTx.

Fast tacrolimus (Tac) metabolism is associated with a more rapid decline of renal function after renal transplantation (RTx). Because the pharmacokinetics of LCP-Tac (LCPT) and immediate-release Tac (IR-Tac) differ, we hypothesized that switching from IR-Tac to LCPT in kidney transplant recipients would improve the estimated glomerular filtration rate (eGFR), particularly in fast metabolizers. For proof of concept, we performed a pilot study including RTx patients who received de novo immunosuppression with IR-Tac. A Tac concentration-to-dose ratio (C/D ratio) < 1.05 ng/mL·1/mg defined fast metabolizers and ≥1.05 ng/mL·1/mg slow metabolizers one month after RTx. Patients were switched to LCPT ≥ 1 month after transplantation and followed for 3 years. Fast metabolizers (n = 58) were switched to LCPT earlier than slow metabolizers (n = 22) after RTx (2.0 (1.0–253.1) vs. 13.2 (1.2–172.8) months, p = 0.005). Twelve months after the conversion to LCPT, Tac doses were reduced by about 65% in both groups. The C/D ratios at 12 months had increased from 0.66 (0.24–2.10) to 1.74 (0.42–5.43) in fast and from 1.15 (0.32–3.60) to 2.75 (1.08–5.90) in slow metabolizers. Fast metabolizers showed noticeable recovery of mean eGFR already one month after the conversion (48.5 ± 17.6 vs. 41.5 ± 17.0 mL/min/1.73 m², p = 0.032) and at all subsequent time points, whereas the eGFR in slow metabolizers remained stable. Switching to LCPT increased Tac bioavailability, C/D ratio, and was associated with a noticeable recovery of renal function in fast metabolizers. Conversion to LCPT is safe and beneficial early after RTx.

The outcome after living kidney donation was assumed to be comparable to that of the general population. However, recent register studies reveal negative changes in kidney function, quality of life and fatigue. Avoiding methodological issues of previous studies, the Safety of the Living Kidney Donor (SoLKiD) cohort study analyzed the outcome of donors in a multicenter and interdisciplinary fashion. Donor data were collected pre-donation and two-, six- and 12-months post-donation in 20 German transplantation centers. Primary parameters were kidney function, quality of life, and fatigue. Secondary endpoints were blood pressure, hemoglobin, hemoglobin A1c, body mass index, depression and somatization. Parameters were analyzed with non-parametric statistical tests and a mixed model regression for changes in time, their clinical relevance and interaction encompassing 336 donors with mean age of 52 years. Most of the physical secondary parameters, depression, and quality of life showed little or no changes and regained their pre-donation level. Kidney function decreased significantly with a 37% loss of glomerular filtration rate and an increase of donors with chronic kidney disease stage 3 from 1.5% pre-donation to about 50%. Donors consistently showed increased fatigue and somatization. Mental fatigue increased from 10.6% to 28.1%. The main influencing factors for decreased kidney function and increased fatigue were their respective pre-donation levels, and donor age for kidney function and subject stress level in fatigue. Thus, our study showed that a significant number of donors developed clinically relevant changes in physical and mental health and emphasizes the urgent need to inform potential donors about these risks.

Observational research benefits from a rich methodological foundation of registry development and operation published in international and national guidelines. Metadata management is an essential part of registry implementation based on concepts of data elements and value sets. The metadata from six German registries revealed vastly divergent interpretations of the concept of data elements. The different perspectives of research questions, data acquisition and data storage were all represented in the registries' catalogs of data elements. Consequently, the whole life cycle of a registry needs to be accompanied by a catalog of data elements, which has to be continuously adapted to the changing perspectives. A standard for the representation of those metadata is still missing. The FAIR Guiding Principles introduce important methodological requirements, but the tools for their fulfillment in respect to the management of metadata are still in its infancy.

Kidney transplant (KTx) recipients are a high-risk population for osteoporotic fractures. We herein aim to identify the role of pre-transplant parathyroidectomy (PTX) and other modifiable factors associated with osteoporotic fractures in KTx recipients. We conducted a retrospective study involving 711 adult patients (4608 patient-years) who were transplanted at our center between January 2007 and June 2015. Clinical data were extracted from patients’ electronic medical records. Different laboratory and clinical parameters for mineral bone disease (MBD) and osteoporosis, including medication, were evaluated. We chose fracture events unrelated to malignancies or adequate trauma as the primary endpoint. Osteoporotic fractures occurred in 47 (6.6%) patients (median 36.7 months, IQR 45.9) after KTx (fracture incidence of 10 per 1000 person-years). Prior to KTx, subtotal PTX was performed in 116 patients (16.3%, median time 4.2 years before KTx, IQR 5.0). Of the patients with fracture (n = 47), only one (2.2%) patient had previously undergone PTX. After adjusting for the known fracture risk factors MBD and osteoporosis, PTX remained a protective factor against fractures (HR 0.134, CI 0.018–0.991, p = 0.049). We observed a reduced risk for pathological fractures in KTx patients who underwent PTX, independent from elevated parathyroid hormone at the time of KTx or afterwards.

The prognostic significance of suPAR in various kidney diseases has recently been demonstrated. Its role in transplantation-specific outcomes is still largely unknown. Therefore, we prospectively investigated the prognostic relevance of suPAR in patients before and one year after kidney transplantation (KTx). We included 100 patients who had received a kidney transplantation between 2013 and 2015. The plasma concentration of suPAR was measured by ELISA assay. In recipients of living donations (LD), pre-transplant suPAR levels were significantly lower than those of recipients of deceased donations (DD). After KTx, suPAR levels significantly declined in LD and DD recipients, without a detectable difference between both groups any more. Higher suPAR levels in recipients one year after KTx were associated with a more severe eGFR loss in the following three years in multivariable cox-regression (n = 82, p = 0.021). suPAR-levels above 6212 pg/ml one year after KTx are associated with eGFR loss > 30%, which occurred almost twice as fast as in patients with suPAR ≤ 6212 pg/ml (p < 0.001). Hence, suPAR level at one year mark might be a risk indicator of increased eGFR loss.