Real-time Biomechanical Modeling for Intraoperative Soft Tissue Registration

Computer assisted surgery systems intraoperatively support the surgeon by providing information on the location of hidden risk and target structures during surgery. However, soft tissue deformations make intraoperative registration (and thus intraoperative navigation) difficult. In this work, a novel, biomechanics based approach for real-time soft tissue registration from sparse intraoperative sensor data such as stereo endoscopic images is presented to overcome this problem

A unified appraisal framework for the assessment of biorefinery technologies : an approach and first steps to application

As part of the desired bio-economy, biomass will find a wide industrial application in the future, re-placing fossil resources and reducing the need of their import from insecure third countries. However, such an increased industrial application of biomass holds its own problems e.g. like an intensifying competition between food and fuel (and so an increasing competition for arable land) and sometimes other serious social problems, such as the so-called Tortilla-Crisis in Mexico in 2007. Therefore, (political) decision making within a bio-economy has not only to account for economic and ecologic aspects, but also for societal ones in the fields of human rights and justice. Moreover, the three aspects of sustainability (economics, environment, and societal aspects) are to be aligned and balanced within those decisions. A standardized assessment methodology for biorefinery technologies, acknowledging all these aspects, has not been presented in literature so far. However, the need for such a standardized assessment framework was already discussed and demanded in the literature. In the present work, a basic architecture for such an assessment methodology as well as a standardized procedure for the selection of biorefinery technologies is presented (Section 2). The methodology includes thoroughly executed technology analysis by Technology Design Assessments (data level). It concerns explicit values and ethics by the use of the triple bottom line approach of sustainability on the impact level. On the decision making level a tailor-made multi-criteria decision making method (Multi-criteria Based Benchmarking) is proposed and Advanced Radar Plots are used for transparent and easy visual comparison of different policy options. The appraisal framework proposed goes beyond the literature on bioenergy appraisal frameworks and can be used as a baseline for future research. Furthermore, first steps towards the implementation of the proposed methodology are undertaken. In this context, hydrothermal carbonization is used as an example as a promising technology in a new developing bio-economy. Based on data from lab experiments, model equations are derived using a severity approach for proper mass balancing (Section 3 and 4). With these equations the product yields of hydrothermal carbonization (of biogas digestate and wheat straw) as well as the degree of carbonization of the hydrochar produced are quantified as functions of different process parameters using a severity approach. In contrast to other studies, a logarithmic dependence on process severity was applied. Process severity itself was calculated from temperature, retention time and catalyst concentration. By these models basing on few selected reaction conditions, a wide range of process conditions can be covered and the yields for the solid, liquid, and gaseous product phase can be predicted. The equations form the necessary data input for the basic Technology Design Assessment of HTC defined within the proposed standardized appraisal framework.Im Rahmen einer angestrebten Bioökonomie soll Biomasse in Zukunft wieder eine breite industrielle Anwendung finden und dabei fossile Rohstoffe ersetzen bzw. die Notwendigkeit ihres Importes aus unsicheren Drittstaaten reduzieren. Auf der Hand liegt jedoch, dass eine breite industrielle Anwendung von Biomasse eigene, z.T. schwerwiegende gesellschaftliche Probleme nach sich zieht. So kann die Verschärfung des Wettbewerbs zwischen Nahrungsmitteln und Treibstoffen (also die direkte Konkurrenz um Ackerland) gefährliche gesellschaftspolitische Folgen haben, wie die so genannte Tortilla-Krise in Mexiko im Jahre 2007 gezeigt hat. Die politische Entscheidungsfindung muss auf dem Weg zu einer Bioökonomie somit nicht nur ökonomische und ökologische Aspekte bei der Auswahl verschiedener Biomassekonversionstechnologien berücksichtigen, sondern auch gesellschaftliche Aspekte im Bereich der Menschenrechte und allgemeiner Gerechtigkeitsgrundsätze. Darüber hinaus sind Wirtschaftlichkeit, Umwelt, und Gesellschaft bei der Entscheidungsfindung miteinander in Einklang zu bringen. Eine in diesem Zusammenhang standardisierte Bewertungsmethodik für zugehörige (politische) Entscheidungsprozesse, die all diese Aspekte berücksichtigt, fehlte bislang in der Literatur. Die Notwendigkeit eines solchen standardisierten Beurteilungsrahmens hingegen wurde in der Literatur jedoch bereits ausführlich diskutiert und eingefordert. Im Rahmen der vorliegenden Arbeit wird daher eine grundlegende Architektur für eine solche Beurteilungs- und Entscheidungsmethodik sowie ein dazugehöriges standardisiertes Vorgehen für die Auswahl von Bioraffinerie-Technologien in einer Bioökonomie vorgestellt (Sektion 2). Die Methode beinhaltet dabei die Beschreibung einer Prozedur zur Durchführung von Technologieanalysen (Technologie Design Assessments Datenebene). Die Einbeziehung expliziter Werte und Ethik erfolgt dabei durch die Einbettung des so genannten Triple-Bottom-Line Ansatzes (auf der so genannten Einflussebene). Auf der Entscheidungsebene kommt ein maßgeschneidertes multi-kriterielles Entscheidungsverfahren (Multi-criteria Based Benchmarking) zum Einsatz. Ferner werden hier so genannte Advanced Radar Plots eingesetzt, um einen einfachen und transparenten visuellen Vergleich verschiedener Entscheidungsoptionen zu ermöglichen. Der hier vorgeschlagene einheitliche Beurteilungsrahmen geht inhaltlich über die bislang in der Literatur diskutierten Ansätze hinaus und kann als Grundlage für zukünftige Forschungsarbeiten in diesem Bereich gesehen werden. Über dies hinaus präsentiert die vorliegende Arbeit erste Schritte im Hinblick auf die Anwendung der vorgeschlagenen Bewertungsmethodik. In diesem Zusammenhang werden anhand von Daten aus Laborversuchen zur hydrothermalen Karbonisierung (als vielversprechende Beispieltechnologie für eine Bioökonomie) unter Berücksichtigung verschiedener Reaktionsintensitäten (severity approach), Modellgleichungen für die Massenbilanzierung abgeleitet (Sektion 3 und 4). Mit Hilfe dieser Gleichungen können die verschiedenen Produktausbeuten der hydrothermalen Karbonisierung (von Biogasgärresten und Weizenstroh), sowie der Grad der Karbonisierung der entstehenden Biokohle als Funktion von Prozessparametern berechnet werden. Im Gegensatz zu anderen Studien wurde hier eine logarithmische Abhängigkeit von der Reaktionsintensität verwendet. Letztere wurde dabei in Abhängigkeit von der Reaktionstemperatur, der Verweildauer und der Katalysatorkonzentration berechnet. Mit den ermittelten Modellen kann eine breite Palette verschiedener Prozessbedingungen simuliert und die Ausbeute der festen, flüssigen und gasförmigen Produktphase berechnet werden. Diese Modellgleichungen bilden die Grundlage für die Durchführung eines Technology Design Assessments als Ausgangspunkt für die Anwendung der vorgeschlagenen, standardisierten Bewertungsmethode

A unified appraisal framework for the assessment of biorefinery technologies : an approach and first steps to application

As part of the desired bio-economy, biomass will find a wide industrial application in the future, re-placing fossil resources and reducing the need of their import from insecure third countries. However, such an increased industrial application of biomass holds its own problems e.g. like an intensifying competition between food and fuel (and so an increasing competition for arable land) and sometimes other serious social problems, such as the so-called Tortilla-Crisis in Mexico in 2007. Therefore, (political) decision making within a bio-economy has not only to account for economic and ecologic aspects, but also for societal ones in the fields of human rights and justice. Moreover, the three aspects of sustainability (economics, environment, and societal aspects) are to be aligned and balanced within those decisions. A standardized assessment methodology for biorefinery technologies, acknowledging all these aspects, has not been presented in literature so far. However, the need for such a standardized assessment framework was already discussed and demanded in the literature. In the present work, a basic architecture for such an assessment methodology as well as a standardized procedure for the selection of biorefinery technologies is presented (Section 2). The methodology includes thoroughly executed technology analysis by Technology Design Assessments (data level). It concerns explicit values and ethics by the use of the triple bottom line approach of sustainability on the impact level. On the decision making level a tailor-made multi-criteria decision making method (Multi-criteria Based Benchmarking) is proposed and Advanced Radar Plots are used for transparent and easy visual comparison of different policy options. The appraisal framework proposed goes beyond the literature on bioenergy appraisal frameworks and can be used as a baseline for future research. Furthermore, first steps towards the implementation of the proposed methodology are undertaken. In this context, hydrothermal carbonization is used as an example as a promising technology in a new developing bio-economy. Based on data from lab experiments, model equations are derived using a severity approach for proper mass balancing (Section 3 and 4). With these equations the product yields of hydrothermal carbonization (of biogas digestate and wheat straw) as well as the degree of carbonization of the hydrochar produced are quantified as functions of different process parameters using a severity approach. In contrast to other studies, a logarithmic dependence on process severity was applied. Process severity itself was calculated from temperature, retention time and catalyst concentration. By these models basing on few selected reaction conditions, a wide range of process conditions can be covered and the yields for the solid, liquid, and gaseous product phase can be predicted. The equations form the necessary data input for the basic Technology Design Assessment of HTC defined within the proposed standardized appraisal framework.Im Rahmen einer angestrebten Bioökonomie soll Biomasse in Zukunft wieder eine breite industrielle Anwendung finden und dabei fossile Rohstoffe ersetzen bzw. die Notwendigkeit ihres Importes aus unsicheren Drittstaaten reduzieren. Auf der Hand liegt jedoch, dass eine breite industrielle Anwendung von Biomasse eigene, z.T. schwerwiegende gesellschaftliche Probleme nach sich zieht. So kann die Verschärfung des Wettbewerbs zwischen Nahrungsmitteln und Treibstoffen (also die direkte Konkurrenz um Ackerland) gefährliche gesellschaftspolitische Folgen haben, wie die so genannte Tortilla-Krise in Mexiko im Jahre 2007 gezeigt hat. Die politische Entscheidungsfindung muss auf dem Weg zu einer Bioökonomie somit nicht nur ökonomische und ökologische Aspekte bei der Auswahl verschiedener Biomassekonversionstechnologien berücksichtigen, sondern auch gesellschaftliche Aspekte im Bereich der Menschenrechte und allgemeiner Gerechtigkeitsgrundsätze. Darüber hinaus sind Wirtschaftlichkeit, Umwelt, und Gesellschaft bei der Entscheidungsfindung miteinander in Einklang zu bringen. Eine in diesem Zusammenhang standardisierte Bewertungsmethodik für zugehörige (politische) Entscheidungsprozesse, die all diese Aspekte berücksichtigt, fehlte bislang in der Literatur. Die Notwendigkeit eines solchen standardisierten Beurteilungsrahmens hingegen wurde in der Literatur jedoch bereits ausführlich diskutiert und eingefordert. Im Rahmen der vorliegenden Arbeit wird daher eine grundlegende Architektur für eine solche Beurteilungs- und Entscheidungsmethodik sowie ein dazugehöriges standardisiertes Vorgehen für die Auswahl von Bioraffinerie-Technologien in einer Bioökonomie vorgestellt (Sektion 2). Die Methode beinhaltet dabei die Beschreibung einer Prozedur zur Durchführung von Technologieanalysen (Technologie Design Assessments Datenebene). Die Einbeziehung expliziter Werte und Ethik erfolgt dabei durch die Einbettung des so genannten Triple-Bottom-Line Ansatzes (auf der so genannten Einflussebene). Auf der Entscheidungsebene kommt ein maßgeschneidertes multi-kriterielles Entscheidungsverfahren (Multi-criteria Based Benchmarking) zum Einsatz. Ferner werden hier so genannte Advanced Radar Plots eingesetzt, um einen einfachen und transparenten visuellen Vergleich verschiedener Entscheidungsoptionen zu ermöglichen. Der hier vorgeschlagene einheitliche Beurteilungsrahmen geht inhaltlich über die bislang in der Literatur diskutierten Ansätze hinaus und kann als Grundlage für zukünftige Forschungsarbeiten in diesem Bereich gesehen werden. Über dies hinaus präsentiert die vorliegende Arbeit erste Schritte im Hinblick auf die Anwendung der vorgeschlagenen Bewertungsmethodik. In diesem Zusammenhang werden anhand von Daten aus Laborversuchen zur hydrothermalen Karbonisierung (als vielversprechende Beispieltechnologie für eine Bioökonomie) unter Berücksichtigung verschiedener Reaktionsintensitäten (severity approach), Modellgleichungen für die Massenbilanzierung abgeleitet (Sektion 3 und 4). Mit Hilfe dieser Gleichungen können die verschiedenen Produktausbeuten der hydrothermalen Karbonisierung (von Biogasgärresten und Weizenstroh), sowie der Grad der Karbonisierung der entstehenden Biokohle als Funktion von Prozessparametern berechnet werden. Im Gegensatz zu anderen Studien wurde hier eine logarithmische Abhängigkeit von der Reaktionsintensität verwendet. Letztere wurde dabei in Abhängigkeit von der Reaktionstemperatur, der Verweildauer und der Katalysatorkonzentration berechnet. Mit den ermittelten Modellen kann eine breite Palette verschiedener Prozessbedingungen simuliert und die Ausbeute der festen, flüssigen und gasförmigen Produktphase berechnet werden. Diese Modellgleichungen bilden die Grundlage für die Durchführung eines Technology Design Assessments als Ausgangspunkt für die Anwendung der vorgeschlagenen, standardisierten Bewertungsmethode

The Effects of 1 mA tACS and tRNS on Children/Adolescents and Adults: Investigating Age and Sensitivity to Sham Stimulation

The aim of this study was to investigate the effect of transcranial random noise (tRNS) and transcranial alternating current (tACS) stimulation on motor cortex excitability in healthy children and adolescents. Additionally, based on our recent results on the individual response to sham in adults, we explored this effect in the pediatric population. We included 15 children and adolescents (10-16 years) and 28 adults (20-30 years). Participants were stimulated four times with 20 Hz and 140 Hz tACS, tRNS, and sham stimulation (1 mA) for 10 minutes over the left M1HAND. Single-pulse MEPs (motor evoked potential), short-interval intracortical inhibition, and facilitation were measured by TMS before and after stimulation (baseline, 0, 30, 60 minutes). We also investigated aspects of tolerability. According to the individual MEPs response immediately after sham stimulation compared to baseline (Wilcoxon signed-rank test), subjects were regarded as responders or nonresponders to sham. We did not find a significant age effect. Regardless of age, 140 Hz tACS led to increased excitability. Incidence and intensity of side effects did not differ between age groups or type of stimulation. Analyses on responders and nonresponders to sham stimulation showed effects of 140 Hz, 20 Hz tACS, and tRNS on single-pulse MEPs only for nonresponders. In this study, children and adolescents responded to 1 mA tRNS and tACS comparably to adults regarding the modulation of motor cortex excitability. This study contributes to the findings that noninvasive brain stimulation is well tolerated in children and adolescents including tACS, which has not been studied before. Finally, our study supports a modulating role of sensitivity to sham stimulation on responsiveness to a broader stimulation and age range

study protocol for a randomised controlled trial

Background Immunosuppression with calcineurin inhibitors remains the mainstay of treatment after kidney transplantation; however, long-term use of these drugs may be associated with nephrotoxicity. In this regard, the current approach is to optimise available immunosuppressive regimens to reduce the calcineurin inhibitor dose while protecting renal function without affecting the efficacy. The ATHENA study is designed to evaluate renal function in two regimens: an everolimus and reduced calcineurin inhibitor-based regimen versus a standard treatment protocol with mycophenolic acid and tacrolimus in de novo kidney transplant recipients. Method/Design ATHENA is a 12-month, multicentre, open-label, prospective, randomised, parallel-group study in de novo kidney transplant recipients (aged 18 years or older) receiving renal allografts from deceased or living donors. Eligible patients are randomised (1:1:1) prior to transplantation to one of the following three treatment arms: everolimus (starting dose 1.5 mg/day; C0 3–8 ng/mL) with cyclosporine or everolimus (starting dose 3 mg/day; C0 3–8 ng/mL) with tacrolimus or mycophenolic acid (enteric-coated mycophenolate sodium at 1.44 g/day or mycophenolate mofetil at 2 g/day) with tacrolimus; in combination with corticosteroids. All patients receive induction therapy with basiliximab. The primary objective is to demonstrate non-inferiority of renal function (eGFR by the Nankivell formula) in one of the everolimus arms compared with the standard group at month 12 post transplantation. The key secondary objective is to assess the incidence of treatment failure, defined as biopsy-proven acute rejection, graft loss, or death, among the treatment groups. Other objectives include assessment of the individual components of treatment failure, incidence and severity of viral infections, incidence and duration of delayed graft function, incidence of indication biopsies, slow graft function and wound healing complications, and overall safety and tolerability. Exploratory objectives include evaluation of left ventricular hypertrophy assessed by the left ventricular mass index, evolution of human leukocyte antigen and non-human leukocyte antigen antibodies, and a cytomegalovirus substudy. Discussion As one of the largest European multicentre kidney transplant studies, ATHENA will determine whether a de novo everolimus-based regimen can preserve renal function versus the standard of care. This study further assesses a number of clinical issues which impact long-term outcomes post transplantation; hence, its results will have a major clinical impact

Design and rationale of the ATHENA study – A 12-month, multicentre, prospective study evaluating the outcomes of a de novo everolimus-based regimen in combination with reduced cyclosporine or tacrolimus versus a standard regimen in kidney transplant patients: study protocol for a randomised controlled trial

Background: Immunosuppression with calcineurin inhibitors remains the mainstay of treatment after kidney transplantation; however, long-term use of these drugs may be associated with nephrotoxicity. In this regard, the current approach is to optimise available immunosuppressive regimens to reduce the calcineurin inhibitor dose while protecting renal function without affecting the efficacy. The ATHENA study is designed to evaluate renal function in two regimens: an everolimus and reduced calcineurin inhibitor-based regimen versus a standard treatment protocol with mycophenolic acid and tacrolimus in de novo kidney transplant recipients. Method/Design: ATHENA is a 12-month, multicentre, open-label, prospective, randomised, parallel-group study in de novo kidney transplant recipients (aged 18 years or older) receiving renal allografts from deceased or living donors. Eligible patients are randomised (1:1:1) prior to transplantation to one of the following three treatment arms: everolimus (starting dose 1.5 mg/day; C0 3–8 ng/mL) with cyclosporine or everolimus (starting dose 3 mg/day; C0 3–8 ng/mL) with tacrolimus or mycophenolic acid (enteric-coated mycophenolate sodium at 1.44 g/day or mycophenolate mofetil at 2 g/day) with tacrolimus; in combination with corticosteroids. All patients receive induction therapy with basiliximab. The primary objective is to demonstrate non-inferiority of renal function (eGFR by the Nankivell formula) in one of the everolimus arms compared with the standard group at month 12 post transplantation. The key secondary objective is to assess the incidence of treatment failure, defined as biopsy-proven acute rejection, graft loss, or death, among the treatment groups. Other objectives include assessment of the individual components of treatment failure, incidence and severity of viral infections, incidence and duration of delayed graft function, incidence of indication biopsies, slow graft function and wound healing complications, and overall safety and tolerability. Exploratory objectives include evaluation of left ventricular hypertrophy assessed by the left ventricular mass index, evolution of human leukocyte antigen and non-human leukocyte antigen antibodies, and a cytomegalovirus substudy. Discussion: As one of the largest European multicentre kidney transplant studies, ATHENA will determine whether a de novo everolimus-based regimen can preserve renal function versus the standard of care. This study further assesses a number of clinical issues which impact long-term outcomes post transplantation; hence, its results will have a major clinical impact. Trial registration: Clinicaltrials.gov: NCT01843348 , date of registration – 18 April 2013; EUDRACT number: 2011-005238-21, date of registration – 20 March 201

Case Report: Management of a Multidrug-Resistant CMV-Strain in a Renal Transplant Recipient by High-Dose CMV-Specific Immunoglobulins, Modulation in Immunosuppression, and Induction of CMV-Specific Cellular Immunity

The management of multidrug-resistant strains of cytomegalovirus after solid organ transplantation is challenging. This case report demonstrates the successful treatment of a multidrug-resistant strain of cytomegalovirus that may represent a valuable option for problematic cases. This report illustrates the emergence of a multidrug-resistant cytomegalovirus (CMV) UL54 mutant strain in a renal transplant recipient with severe lymphopenia and thrombocytopenia. We show that the combined treatment with highdose intravenous cytomegalovirus-specific immunoglobulins (CMV-IVIG) after the switch to a mammalian target of rapamycin (mTOR)-inhibitor and cyclosporine A was a successful treatment alternative to direct antiviral treatment with high-dose ganciclovir and foscarnet. This treatment was associated with a quantitative induction of CMVspecific CD4 and CD8 T cells that showed maturation in phenotype and functionality with decreasing viral load. Our case report illustrates that high-dose CMV-IVIG and conversion of immunosuppressive drugs to mTOR inhibitors and cyclosporine A can be a successful treatment in a situation where the use of direct antiviral drugs was considered insufficient

Antigen-Specific versus Non-Antigen-Specific Immunoadsorption in ABO-Incompatible Renal Transplantation

Introduction: ABO-incompatible (ABOi) renal transplantation (RTx) from living donors is an established procedure to expand the donor pool for patients with end stage renal disease. Immunoadsorption (IA) is a standard procedure for the removal of preformed antibodies against the allograft. In this study, antigen-specific and non-antigen-specific IA in ABOi RTx were compared. Patients and Methods: 10 patients underwent antigen-specific IA (Glycosorb group) and 13 patients non-antigen-specific IA (Immunosorba group). The effects of both procedures regarding antibody reduction, number of treatments, complications, costs, as well as the allograft function and patient survival were compared between both groups. Results: Although the IgG levels were reduced equally by both procedures (p=0.82), the reduction of the IgM level was more effective in the Glycosorb group (p=0.0172). Patients in both groups required a median number of 6 IA before ABOi RTx. Allograft function at one year after AB0i RTx was similar in both groups (estimated glomerular filtration rate: 66 vs. 64 ml/min/1.73m² respectively), with a death-censored graft survival of 90.0% and 92.3% respectively. Complication rates did not differ between procedures. Due to the reuse of non-antigen-specific Immunosorba columns, costs were considerably lower in this group; however, the use of the Immunosorba-based IA was less time-efficient. Conclusion: Considering upcoming alternatives as simultaneous performance of dialysis and IA or a possible reuse of Glycosorb columns, this might become less relevant in the future

Effect of everolimus-based drug regimens on CMV-specific T-cell functionality after renal transplantation: 12-month ATHENA subcohort-study results

Post-transplant cytomegalovirus (CMV) infections and increased viral replication are associated with CMV-specific T-cell anergy. In the ATHENA-study, de-novo everolimus (EVR) with reduced-exposure tacrolimus (TAC) or cyclosporine (CyA) showed significant benefit in preventing CMV infections in renal transplant recipients as compared to standard TAC + mycophenolic acid (MPA). However, immunomodulatory mechanisms for this effect remain largely unknown. Ninety patients from the ATHENA-study completing the 12-month visit on-treatment (EVR + TAC n = 28; EVR + CyA n = 19; MPA + TAC n = 43) were included in a posthoc analysis. Total lymphocyte subpopulations were quantified. CMV-specific CD4 T cells were determined after stimulation with CMV-antigen, and cytokine-profiles and various T-cell anergy markers were analyzed using flow cytometry. While 25.6% of MPA + TAC-treated patients had CMV-infections, no such events were reported in EVR-treated patients. Absolute numbers of lymphocyte subpopulations were comparable between arms, whereas the percentage of regulatory T cells was significantly higher with EVR + CyA versus MPA + TAC (p = 0.019). Despite similar percentages of CMV-specific T cells, their median expression of CTLA-4 and PD-1 was lower with EVR + TAC (p < 0.05 for both) or EVR + CyA (p = 0.045 for CTLA-4) compared with MPA + TAC. Moreover, mean percentages of multifunctional CMV-specific T cells were higher with EVR + TAC (27.2%) and EVR + CyA (29.4%) than with MPA + TAC (19.0%). In conclusion, EVR-treated patients retained CMV-specific T-cell functionality, which may contribute to enhanced protection against CMV infections

The Tacrolimus Metabolism Rate Influences Renal Function after Kidney Transplantation

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.</p