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The effective calcineurin inhibitor (CNI) tacrolimus (Tac) is an integral part of the standard immunosuppressive regimen after renal transplantation (RTx). However, as a potent CNI it has nephrotoxic potential leading to impaired renal function in some cases. Therefore, it is of high clinical impact to identify factors which can predict who is endangered to develop CNI toxicity. We hypothesized that the Tac metabolism rate expressed as the blood concentration normalized by the dose (C/D ratio) is such a simple predictor. Therefore, we analyzed the impact of the C/D ratio on kidney function after RTx. Renal function was analyzed 1, 2, 3, 6, 12 and 24 months after RTx in 248 patients with an immunosuppressive regimen including basiliximab, tacrolimus, mycophenolate mofetil and prednisolone. According to keep the approach simple, patients were split into three C/D groups: fast, intermediate and slow metabolizers. Notably, compared with slow metabolizers fast metabolizers of Tac showed significantly lower estimated glomerular filtration rate (eGFR) values at all the time points analyzed. Moreover, fast metabolizers underwent more indication renal biopsies (p = 0.006) which revealed a higher incidence of CNI nephrotoxicity (p = 0.015) and BK nephropathy (p = 0.024) in this group. We herein identified the C/D ratio as an easy calculable risk factor for the development of CNI nephrotoxicity and BK nephropathy after RTx. We propose that the simple C/D ratio should be taken into account early in patient's risk management strategies.

Fast metabolism of immediate-release tacrolimus (IR-Tac) is associated with decreased kidney function after renal transplantation (RTx) compared to slow metabolizers. We hypothesized, by analogy, that fast metabolism of extended-release tacrolimus (ER-Tac) is associated with worse renal function. We analyzed data from patients who underwent RTx at three different transplant centers between 2007 and 2016 and received an initial immunosuppressive regimen with ER-Tac, mycophenolate, and a corticosteroid. Three months after RTx, a Tac concentration to dose ratio (C/D ratio) < 1.0 ng/ml · 1/mL defined fast ER-Tac metabolism and ≥ 1.0 ng/ml · 1/mL slow metabolism. Renal function (estimated glomerular filtration rate, eGFR), first acute rejection (AR), conversion from ER-Tac, graft and patient survival were observed up to 60-months. 610 RTx patients were divided into 192 fast and 418 slow ER-Tac metabolizers. Fast metabolizers showed a decreased eGFR at all time points compared to slow metabolizers. The fast metabolizer group included more patients who were switched from ER-Tac (p < 0.001). First AR occurred more frequently (p = 0.008) in fast metabolizers, while graft and patient survival rates did not differ between groups (p = 0.529 and p = 0.366, respectively). Calculation of the ER-Tac C/D ratio early after RTx may facilitate individualization of immunosuppression and help identify patients at risk for an unfavorable outcome.

BK polyomavirus (BKPyV) and cytomegalovirus (CMV) are the main viral pathogens affecting the graft and recipient outcome after allogenic kidney transplantation. It has recently been found that infection with both viruses has a greater impact on kidney graft function than a single infection. We retrospectively analyzed a cohort of 723 recipients who received kidney transplantation between 2007 and 2015 after living and postmortal donation for differences in risk and outcome parameters regarding BKPyV (DNAemia) and CMV (CMV DNAemia) co-infection compared to sole viremias and to patients without viremia. Of all kidney allograft recipients in our cohort, 8.2% developed co-infection with BKPyV DNAemia and CMV DNAemia, 15.1% showed BKPyV viremia alone and 25.2% sole CMV DNAemia. Acute rejection was closely linked with co-infection (multivariable analysis, p = 0.001). Despite the fact that the estimated glomerular filtration rate of patients with co-infection was noticeably reduced compared to patients with BKV or CMV infection alone, transplant survival and patient survival were not significantly reduced. Co-infection with BKPyV and CMV in kidney transplanted patients is significantly associated with inferior allograft function. Since co-infection is strongly associated with acute rejection, co-infected individuals should be considered a risk collective.

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.

Given the gap between patients in need of a renal transplantation (RTx) and organs available, transplantation centers increasingly accept organs of suboptimal quality, e.g. from donors with acute kidney injury (AKI). To determine the outcome of kidney transplants from deceased donors with AKI (defined as ≥ AKIN stage 1), all 107 patients who received a RTx from donors with AKI between August 2004 and July 2014 at our center were compared to their respective consecutively transplanted patients receiving kidneys from donors without AKI. 5-year patient and graft survival, frequencies of delayed graft function (DGF), acute rejections and glomerular filtration rate (eGFR, CKD-EPI) were assessed. Patient survival was similar in both groups, whereas death-censored and overall graft survival were decreased in AKI kidney recipients. AKI kidney recipients showed higher frequencies of DGF and had a reduced eGFR at 7 days, three months and one and three years after RTx. However, mortality was noticeably lower compared to waiting list candidates. Rejection-free survival was similar between groups. In our cohort, both short-term and long-term renal function was inferior in recipients of AKI kidneys, while patient survival was similar. Our data indicates that recipients of donor AKI kidneys should be carefully selected and additional factors impairing short- and long-term outcome should be minimized to prevent further deterioration of graft function.

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.

Aims The European Senior Program (ESP) aims to avoid waiting list competition between younger and elderly patients applying for renal transplantation. By listing patients ≥65 years on a separate waiting list and locally allocating of grafts ≥65 years exclusively to this cohort, waiting and cold ischemia times are predicted to be shortened, potentially resulting in improved kidney transplantation outcomes. This study compared a historic cohort of renal transplant recipients being simultaneously listed on the general and the ESP waiting lists with a collective exclusively listed on the ESP list in terms of surrogates of the transplantation outcome. Methods Total 151 eligible patients ≥ 65 years from Münster transplant Center, Germany, between 1999 and 2014 were included. Graft function, graft and patient survival were compared using surrogate markers of short- and long-term graft function. Patients were grouped according to their time of transplantation. Results Recipients and donors in the newESP (nESP) cohort were significantly older (69.6 ± 3.5 years vs 67.1 ± 2 years, p<0.05; 72.0 ± 5.0 years vs 70.3 ± 5.0 years, p = 0.039), had significantly shorter dialysis vintage (19.6 ± 21.7 months vs 60.2 ± 28.1 months, p<0.001) and suffered from significantly more comorbidities (2.2 ± 0.9 vs 1.8 ± 0.8, p = 0.009) than the historic cohort (HC). Five-year death-censored graft survival was better than in the HC, but 5-year graft and patient survival were better in the ESP cohort. After 2005, cold ischemia time between groups was comparable. nESP grafts showed more primary function and significantly better long-term graft function 18 months after transplantation and onwards. Conclusion nESP recipients received significantly older grafts, but experienced significantly shorter time on dialysis. Cold ischemia times were comparable, but graft function in the nESP cohort was significantly better in the long term.

The 'weekend effect' describes increased adverse outcomes after weekend hospitalization. We examined weekend-weekday differences in the outcome of 580 patients following renal transplantation (RTx, brain dead donors) between January 2007 and December 2014 at our center. 3-year patient and graft survival, incidence of delayed graft function (DGF), acute rejections and estimated glomerular filtration rate (eGFR, CKD-EPI) at 1 year as well as surgical complications were assessed. Of all 580 transplants, 416 (71.7%) were performed on weekdays (Monday-Friday) and 164 (28.3%) on weekends (Saturday-Sunday). 3-year patient and graft survival, frequencies of DGF, acute rejections and 1-year eGFR as well as length of hospital stay were similar between RTx patients transplanted on weekdays or weekends, respectively. However, a noticeable difference was detected with regard to surgical complications which were more frequent in RTx patients transplanted on weekends. All results remained consistent across all definitions of weekend status. Our results suggest that weekend transplant status does not affect functional short-term and long-term outcomes after RTx. The standardized protocols and operationalized processes applied in RTx might contribute to this finding and may provide a model for other medical procedures that are performed on weekends to improve efficiency and outcomes. The higher rate of surgical complications after weekend RTx needs further elaboration to fully assess the presence of a weekend effect in RTx.

Fast tacrolimus metabolism is linked to inferior outcomes such as rejection and lower renal function after kidney transplantation. Renal calcineurin-inhibitor toxicity is a common adverse effect of tacrolimus therapy. The present contribution hypothesized that tacrolimus-induced nephrotoxicity is related to a low concentration/dose (C/D) ratio. We analyzed renal tubular epithelial cell cultures and 55 consecutive kidney transplant biopsy samples with tacrolimus-induced toxicity, the C/D ratio, C0, C2, and C4 Tac levels, pulse wave velocity analyses, and sublingual endothelial glycocalyx dimensions in the selected kidney transplant patients. A low C/D ratio (C/D ratio < 1.05 ng/mL×1/mg) was linked with higher C2 tacrolimus blood concentrations (19.2 ± 8.7 µg/L vs. 12.2 ± 5.2 µg/L respectively; p = 0.001) and higher degrees of nephrotoxicity despite comparable trough levels (6.3 ± 2.4 µg/L vs. 6.6 ± 2.2 µg/L respectively; p = 0.669). However, the tacrolimus metabolism rate did not affect the pulse wave velocity or glycocalyx in patients. In renal tubular epithelial cells exposed to tacrolimus according to a fast metabolism pharmacokinetic profile it led to reduced viability and increased Fn14 expression. We conclude from our data that the C/D ratio may be an appropriate tool for identifying patients at risk of developing calcineurin-inhibitor toxicity.

Immunosuppression is the major risk factor for BK virus nephropathy (BKVN) after renal transplantation (RTx). As the individual tacrolimus (Tac) metabolism rate correlates with Tac side effects, we hypothesized that Tac metabolism might also influence the BKV infection risk. In this case-control study RTx patients with BK viremia within 4 years after RTx (BKV group) were compared with a BKV negative control group. The Tac metabolism rate expressed as the blood concentration normalized by the daily dose (C/D ratio) was applied to assess the Tac metabolism rate. BK viremia was detected in 86 patients after a median time of 6 (0–36) months after RTx. BKV positive patients showed lower Tac C/D ratios at 1, 3 and 6 months after RTx and were classified as fast Tac metabolizers. 8 of 86 patients with BK viremia had histologically proven BKN and a higher median maximum viral load than BKV patients without BKN (441,000 vs. 18,572 copies/mL). We conclude from our data that fast Tac metabolism (C/D ratio <1.05) is associated with BK viremia after RTx. Calculation of the Tac C/D ratio early after RTx, may assist transplant clinicians to identify patients at risk and to choose the optimal immunosuppressive regimen.