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  1. Article ; Online: Comparison of 2 Immunosuppression Minimization Strategies in Kidney Transplantation: The ALLEGRO Trial.

    van den Born, Joost C / Meziyerh, Soufian / Vart, Priya / Bakker, Stephan J L / Berger, Stefan P / Florquin, Sandrine / de Fijter, Johan W / Gomes-Neto, António W / Idu, Mirza M / Pol, Robert A / Roelen, Dave L / van Sandwijk, Marit S / de Vries, Dorottya K / de Vries, Aiko P J / Bemelman, Frederike J / Sanders, Jan Stephan F

    Transplantation

    2024  Volume 108, Issue 2, Page(s) 556–566

    Abstract: Background: Evidence on the optimal maintenance of immunosuppressive regimen in kidney transplantation recipients is limited.: Methods: The Amsterdam, LEiden, GROningen trial is a randomized, multicenter, investigator-driven, noninferiority, open- ... ...

    Abstract Background: Evidence on the optimal maintenance of immunosuppressive regimen in kidney transplantation recipients is limited.
    Methods: The Amsterdam, LEiden, GROningen trial is a randomized, multicenter, investigator-driven, noninferiority, open-label trial in de novo kidney transplant recipients, in which 2 immunosuppression minimization strategies were compared with standard immunosuppression with basiliximab, corticosteroids, tacrolimus, and mycophenolic acid. In the minimization groups, either steroids were withdrawn from day 3, or tacrolimus exposure was reduced from 6 mo after transplantation. The primary endpoint was kidney transplant function at 24 mo.
    Results: A total of 295 participants were included in the intention-to-treat analysis. Noninferiority was shown for the primary endpoint; estimated glomerular filtration rate at 24 mo was 45.3 mL/min/1.73 m 2 in the early steroid withdrawal group, 49.0 mL/min/1.73 m 2 in the standard immunosuppression group, and 44.7 mL/min/1.73 m 2 in the tacrolimus minimization group. Participants in the early steroid withdrawal group were significantly more often treated for rejection ( P = 0.04). However, in this group, the number of participants with diabetes mellitus during follow-up and total cholesterol at 24 mo were significantly lower.
    Conclusions: Tacrolimus minimization can be considered in kidney transplant recipients who do not have an increased immunological risk. Before withdrawing steroids the risk of rejection should be weighed against the potential metabolic advantages.
    MeSH term(s) Humans ; Tacrolimus/adverse effects ; Kidney Transplantation/adverse effects ; Immunosuppressive Agents/adverse effects ; Immunosuppression Therapy ; Mycophenolic Acid/adverse effects ; Steroids ; Graft Rejection/prevention & control ; Carbazoles ; Tryptamines
    Chemical Substances Tacrolimus (WM0HAQ4WNM) ; frovatriptan (H82Q2D5WA7) ; Immunosuppressive Agents ; Mycophenolic Acid (HU9DX48N0T) ; Steroids ; Carbazoles ; Tryptamines
    Language English
    Publishing date 2024-01-19
    Publishing country United States
    Document type Randomized Controlled Trial ; Multicenter Study ; Journal Article
    ZDB-ID 208424-7
    ISSN 1534-6080 ; 0041-1337
    ISSN (online) 1534-6080
    ISSN 0041-1337
    DOI 10.1097/TP.0000000000004776
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  2. Article ; Online: Risk factors for neurocognitive impairment and the relation with structural brain abnormality in children and young adults with severe chronic kidney disease.

    Lijdsman, Sophie / Oostrom, Kim J / van Sandwijk, Marit S / Bouts, Antonia H / van Hoeck, Koen / de Jong, Huib / Oosterlaan, Jaap / Bemelman, Frederike J / Königs, Marsh / Groothoff, Jaap W

    Pediatric nephrology (Berlin, Germany)

    2022  Volume 38, Issue 6, Page(s) 1957–1969

    Abstract: Background: Severe chronic kidney disease (CKD) in children and young adults has shown to be associated with abnormal brain development, which may contribute to neurocognitive impairments. We aimed to investigate risk factors for neurocognitive ... ...

    Abstract Background: Severe chronic kidney disease (CKD) in children and young adults has shown to be associated with abnormal brain development, which may contribute to neurocognitive impairments. We aimed to investigate risk factors for neurocognitive impairment and investigate the relation with structural brain abnormalities in young severe CKD patients.
    Methods: This cross-sectional study includes 28 patients with severe CKD (eGFR < 30), aged 8-30 years (median 18.5 years), on different treatment modalities (pre-dialysis [n = 8], dialysis [n = 8], transplanted [n = 12]). We assessed neurocognitive functioning using a comprehensive test battery and brain structure by magnetic resonance imaging metrics of brain volume and white matter integrity (fractional anisotropy [FA] and mean diffusivity [MD] measured with diffusion tensor imaging). Multivariate regression and mediation analyses were performed between clinical CKD parameters, brain structure, and neurocognitive outcome.
    Results: A combination of risk factors (e.g., longer time since kidney transplantation, longer dialysis duration and late CKD onset) was significantly associated with lower intelligence and/or worse processing speed and working memory. Lower FA in a cluster of white matter tracts was associated with lower intelligence and mediated the relation between clinical risk factors and lower intelligence.
    Conclusions: Young severe CKD patients with a prolonged duration of kidney replacement therapy, either dialysis or transplantation are at particular risk for impairments in intelligence, processing speed, and working memory. Disrupted white matter integrity may importantly contribute to these neurocognitive impairments. Prospective, longitudinal studies are needed to elucidate the mechanisms involved in CKD and treatment that affect white matter integrity and neurocognitive outcome in young patients. A higher resolution version of the Graphical abstract is available as Supplementary information.
    MeSH term(s) Humans ; Child ; Young Adult ; Diffusion Tensor Imaging ; Prospective Studies ; Cross-Sectional Studies ; Brain/diagnostic imaging ; Brain/pathology ; Brain Diseases ; Renal Insufficiency, Chronic/complications ; Renal Insufficiency, Chronic/therapy ; Renal Insufficiency, Chronic/pathology ; Risk Factors
    Language English
    Publishing date 2022-11-02
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 631932-4
    ISSN 1432-198X ; 0931-041X
    ISSN (online) 1432-198X
    ISSN 0931-041X
    DOI 10.1007/s00467-022-05781-1
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  3. Article ; Online: Structural brain abnormalities in children and young adults with severe chronic kidney disease.

    Lijdsman, Sophie / Königs, Marsh / van Sandwijk, Marit S / Bouts, Antonia H / van Hoeck, Koen / de Jong, Huib / Engelen, Marc / Oosterlaan, Jaap / Bemelman, Frederike J / Oostrom, Kim J / Groothoff, Jaap W

    Pediatric nephrology (Berlin, Germany)

    2021  Volume 37, Issue 5, Page(s) 1125–1136

    Abstract: Background: The pathophysiology of neurological dysfunction in severe chronic kidney disease (CKD) in children and young adults is largely unknown. We aimed to investigate brain volumes and white matter integrity in this population and explore brain ... ...

    Abstract Background: The pathophysiology of neurological dysfunction in severe chronic kidney disease (CKD) in children and young adults is largely unknown. We aimed to investigate brain volumes and white matter integrity in this population and explore brain structure under different treatment modalities.
    Methods: This cross-sectional study includes 24 patients with severe CKD (eGFR < 30) aged 8-30 years (median = 18.5, range = 9.1-30.5) on different therapy modalities (pre-dialysis, n = 7; dialysis, n = 7; transplanted, n = 10) and 21 healthy controls matched for age, sex, and parental educational level. Neuroimaging targeted brain volume using volumetric analysis on T1 scans and white matter integrity with tract-based spatial statistics and voxel-wise regression on diffusion tensor imaging (DTI) data.
    Results: CKD patients had lower white matter integrity in a widespread cluster of primarily distal white matter tracts compared to healthy controls. Furthermore, CKD patients had smaller volume of the nucleus accumbens relative to healthy controls, while no evidence was found for abnormal volumes of gray and white matter or other subcortical structures. Longer time since successful transplantation was related to lower white matter integrity. Exploratory analyses comparing treatment subgroups suggest lower white matter integrity and smaller volume of the nucleus accumbens in dialysis and transplanted patients relative to healthy controls.
    Conclusions: Young CKD patients seem at risk for widespread disruption of white matter integrity and to some extent smaller subcortical volume (i.e., nucleus accumbens). Especially patients on dialysis therapy and patients who received a kidney transplant may be at risk for disruption of white matter integrity and smaller volume of the nucleus accumbens.
    MeSH term(s) Brain/diagnostic imaging ; Child ; Cross-Sectional Studies ; Diffusion Tensor Imaging/methods ; Female ; Humans ; Magnetic Resonance Imaging/methods ; Male ; Renal Insufficiency, Chronic/complications ; Renal Insufficiency, Chronic/therapy ; White Matter/diagnostic imaging ; Young Adult
    Language English
    Publishing date 2021-11-20
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 631932-4
    ISSN 1432-198X ; 0931-041X
    ISSN (online) 1432-198X
    ISSN 0931-041X
    DOI 10.1007/s00467-021-05276-5
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  4. Article: Complement activation and long-term graft function in ABO-incompatible kidney transplantation.

    van Sandwijk, Marit S / Klooster, Astrid / Ten Berge, Ineke Jm / Diepstra, Arjan / Florquin, Sandrine / Hoelbeek, Joris J / Bemelman, Frederike J / Sanders, Jan-Stephan

    World journal of nephrology

    2019  Volume 8, Issue 6, Page(s) 95–108

    Abstract: Background: ABO-incompatible and ABO-compatible kidney transplantation are equivalent in terms of short-term graft and patient survival. This is thought to be the result of ABO-incompatible graft accommodation, which occurs when anti-blood group ... ...

    Abstract Background: ABO-incompatible and ABO-compatible kidney transplantation are equivalent in terms of short-term graft and patient survival. This is thought to be the result of ABO-incompatible graft accommodation, which occurs when anti-blood group antibodies re-occur after transplantation but somehow do not yield their detrimental effect. The underlying mechanism is unclear, but one of the hypotheses is that this is the result of complement inhibition. Since virtually all ABO-incompatible graft biopsies are C4d positive, this complement inhibition must occur somewhere in the complement cascade after the formation of C4d has already taken place, but where exactly is unclear. It is also unclear whether complement inhibition is complete. Incomplete accommodation could explain why recent studies have shown that long-term graft function in ABO-incompatible transplantation is somewhat inferior to ABO-compatible kidney transplantation.
    Aim: To unravel the relationship between pre-transplant anti-ABO antibodies, complement activation, and long-term graft function.
    Methods: We included all 27 ABO-incompatible transplantations that were performed between 2008 and 2013 at the Academic Medical Center Amsterdam and the University Medical Center Groningen. For each ABO-incompatible transplantation, we included four ABO-compatible controls matched by age, sex, and transplantation date.
    Results: Graft and patient survival were not significantly different. The slope of kidney function during five-year follow-up was also not significantly different, but ABO-incompatible recipients did have a lower kidney function at three months (creatinine clearance 58
    Conclusion: Co-stimulation of T-cell activation by ongoing complement activation by anti-ABO antibodies may be responsible for an impaired long-term graft function in ABO-incompatible kidney transplantation.
    Language English
    Publishing date 2019-07-03
    Publishing country United States
    Document type Journal Article
    ISSN 2220-6124
    ISSN 2220-6124
    DOI 10.5527/wjn.v8.i6.95
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  5. Article: Cognitive Improvement After Kidney Transplantation Is Associated With Structural and Functional Changes on MRI.

    van Sandwijk, Marit S / Ten Berge, Ineke J M / Caan, Matthan W A / Düring, Marco / van Gool, Willem A / Majoie, Charles B L M / Mutsaerts, Henk-Jan M M / Schmand, Ben A / Schrantee, Anouk / de Sonneville, Leo M J / Bemelman, Frederike J

    Transplantation direct

    2020  Volume 6, Issue 3, Page(s) e531

    Abstract: Background: Several studies have reported improved cognitive outcomes after kidney transplantation, but most studies either did not include controls or lacked extensive neuroimaging. In addition, there is uncertainty whether kidney donation is a safe ... ...

    Abstract Background: Several studies have reported improved cognitive outcomes after kidney transplantation, but most studies either did not include controls or lacked extensive neuroimaging. In addition, there is uncertainty whether kidney donation is a safe procedure in terms of cognitive outcomes.
    Methods: We prospectively studied neurocognitive function in kidney transplant recipients. The primary outcome was change in neurocognitive function after 1 year compared with baseline, which was evaluated using the Amsterdam Neuropsychological Task battery and verbal fluency tests. Secondary outcomes included changes in depression and anxiety (measured by the Hospital Anxiety and Depression scale) and changes in fatigue (measured by the Checklist for Individual Strength). We included kidney donors to control for learning effects, socioeconomic status, and surgery. In addition, kidney transplant recipients were evaluated with MRI scans at baseline and at year 1. The MRI protocol included conventional MRI, automated volumetric measurement, diffusion tensor imaging, magnetic resonance spectroscopy, arterial spin labeling, and a resting state functional MRI.
    Results: Twenty-seven recipients and 24 donors were included. For both recipients and donors, neuropsychologic testing scores improved 1 year after transplantation (donation). Recipient improvement significantly exceeded donor improvement on tasks measuring attention and working memory. These improvements were associated with increases in white matter volume and
    Conclusions: Attention and working memory improve significantly 1 year after kidney transplantation. Learning effects do not account for these improvements because recipient improvement in these areas exceeds donor improvement and correlates with an improvement in white matter integrity after transplantation. Kidney donation appears to be a safe procedure in terms of cognitive outcomes.
    Language English
    Publishing date 2020-02-10
    Publishing country United States
    Document type Journal Article
    ISSN 2373-8731
    ISSN 2373-8731
    DOI 10.1097/TXD.0000000000000976
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  6. Article ; Online: Fatigue, anxiety, depression and quality of life in kidney transplant recipients, haemodialysis patients, patients with a haematological malignancy and healthy controls.

    van Sandwijk, Marit S / Al Arashi, Doaa / van de Hare, Fons M / van der Torren, J M Rolien / Kersten, Marie-José / Bijlsma, Joost A / Ten Berge, Ineke J M / Bemelman, Frederike J

    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association

    2018  Volume 34, Issue 5, Page(s) 833–838

    Abstract: Background: The impact of haemodialysis (HD) and kidney transplantation on quality of life (QoL) is often underestimated due to a lack of comparative studies with other patient groups.: Methods: We conducted a cross-sectional cohort study in 168 ... ...

    Abstract Background: The impact of haemodialysis (HD) and kidney transplantation on quality of life (QoL) is often underestimated due to a lack of comparative studies with other patient groups.
    Methods: We conducted a cross-sectional cohort study in 168 patients including HD patients, kidney transplant recipients (KTR), patients with a haematological malignancy either receiving chemotherapy or in remission and healthy controls. All participants completed the 36-item short form survey of health-related quality of life, the Checklist Individual Strength and the Hospital Anxiety and Depression Scale questionnaire.
    Results: HD patients and haematological patients undergoing chemotherapy were more frequently severely fatigued (53.3% and 50% of cases) compared with KTR (33.3%), haematological patients in remission (23.3%) and healthy controls (12.1%, P < 0.001). There were no significant differences in anxiety rates. HD patients and haematological patients undergoing chemotherapy were most likely to be depressed (33.3% and 25%), compared with 16.7% of KTR, 20% of haematological patients in remission and 8.6% of healthy controls (P = 0.066). KTR reported the largest positive health change (+27%, P < 0.001), but still had a lower overall QoL than healthy controls, comparable to haematological patients in remission. HD and chemotherapy patients reported the lowest QoL scores.
    Conclusions: Fatigue and depression are common in HD patients, resulting in a low QoL, comparable to haematological patients receiving chemotherapy. KTR do better, with scores similar to patients with a haematological malignancy in remission, but still have a lower QoL than healthy controls.
    MeSH term(s) Anxiety/epidemiology ; Anxiety/etiology ; Anxiety/psychology ; Cross-Sectional Studies ; Depression/epidemiology ; Depression/etiology ; Depression/psychology ; Fatigue/epidemiology ; Fatigue/etiology ; Fatigue/psychology ; Female ; Follow-Up Studies ; Hematologic Neoplasms/therapy ; Humans ; Incidence ; Kidney Transplantation/psychology ; Male ; Middle Aged ; Netherlands/epidemiology ; Quality of Life ; Renal Dialysis/psychology ; Surveys and Questionnaires ; Transplant Recipients/psychology
    Language English
    Publishing date 2018-05-21
    Publishing country England
    Document type Comparative Study ; Journal Article
    ZDB-ID 90594-x
    ISSN 1460-2385 ; 0931-0509
    ISSN (online) 1460-2385
    ISSN 0931-0509
    DOI 10.1093/ndt/gfy103
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    Zs.A 2198: Show issues Location:
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    Zs.MO 329: Show issues

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  7. Article ; Online: Cognitive Changes in Chronic Kidney Disease and After Transplantation.

    Van Sandwijk, Marit S / Ten Berge, Ineke J M / Majoie, Charles B L M / Caan, Matthan W A / De Sonneville, Leo M J / Van Gool, Willem A / Bemelman, Frederike J

    Transplantation

    2016  Volume 100, Issue 4, Page(s) 734–742

    Abstract: Cognitive impairment is very common in chronic kidney disease (CKD) and is strongly associated with increased mortality. This review article will discuss the pathophysiology of cognitive impairment in CKD, as well as the effect of dialysis and ... ...

    Abstract Cognitive impairment is very common in chronic kidney disease (CKD) and is strongly associated with increased mortality. This review article will discuss the pathophysiology of cognitive impairment in CKD, as well as the effect of dialysis and transplantation on cognitive function. In CKD, uremic toxins, hyperparathyroidism and Klotho deficiency lead to chronic inflammation, endothelial dysfunction and vascular calcifications. This results in an increased burden of cerebrovascular disease in CKD patients, who consistently have more white matter hyperintensities, microbleeds, microinfarctions and cerebral atrophy on magnetic resonance imaging scans. Hemodialysis, although beneficial in terms of uremic toxin clearance, also contributes to cognitive decline by causing rapid fluid and osmotic shifts. Decreasing the dialysate temperature and increasing total dialysis time limits these shifts and helps maintain cognitive function in hemodialysis patients. For many patients, kidney transplantation is the preferred treatment modality, because it reverses the underlying mechanisms causing cognitive impairment in CKD. These positive effects have to be balanced against the possible neurotoxicity of infections and immunosuppressive medications, especially glucocorticosteroids and calcineurin inhibitors. A limited number of studies have addressed the overall effect of transplantation on cognitive function. These have mostly found an improvement after transplantation, but have a limited applicability to daily practice because they have only included relatively young patients.
    MeSH term(s) Aged ; Animals ; Cognition ; Cognition Disorders/diagnosis ; Cognition Disorders/etiology ; Cognition Disorders/mortality ; Cognition Disorders/psychology ; Comorbidity ; Female ; Health Status ; Humans ; Kidney Transplantation/adverse effects ; Kidney Transplantation/mortality ; Kidney Transplantation/psychology ; Male ; Mental Health ; Renal Dialysis ; Renal Insufficiency, Chronic/complications ; Renal Insufficiency, Chronic/diagnosis ; Renal Insufficiency, Chronic/mortality ; Renal Insufficiency, Chronic/psychology ; Renal Insufficiency, Chronic/surgery ; Risk Assessment ; Risk Factors ; Treatment Outcome
    Language English
    Publishing date 2016-04
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 208424-7
    ISSN 1534-6080 ; 0041-1337
    ISSN (online) 1534-6080
    ISSN 0041-1337
    DOI 10.1097/TP.0000000000000968
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  8. Article: Early Steroid Withdrawal Compared With Standard Immunosuppression in Kidney Transplantation - Interim Analysis of the Amsterdam-Leiden-Groningen Randomized Controlled Trial.

    van Sandwijk, Marit S / de Vries, Aiko P J / Bakker, Stephan J L / Ten Berge, Ineke J M / Berger, Stefan P / Bouatou, Yassine R / de Fijter, Johan W / Florquin, Sandrine / Homan van der Heide, Jaap J / Idu, Mirza M / Krikke, Christina / van der Pant, Karlijn A M I / Reinders, Marlies E / Ringers, Jan / van der Weerd, Neelke C / Bemelman, Frederike J / Sanders, Jan-Stephan S

    Transplantation direct

    2018  Volume 4, Issue 6, Page(s) e354

    Abstract: Background: The optimal immunosuppressive regimen in kidney transplant recipients, delivering maximum efficacy with minimal toxicity, is unknown.: Methods: The Amsterdam, LEiden, GROningen trial is a randomized, multicenter, investigator-driven, ... ...

    Abstract Background: The optimal immunosuppressive regimen in kidney transplant recipients, delivering maximum efficacy with minimal toxicity, is unknown.
    Methods: The Amsterdam, LEiden, GROningen trial is a randomized, multicenter, investigator-driven, noninferiority, open-label trial in 305 kidney transplant recipients, in which 2 immunosuppression minimization strategies-one consisting of early steroid withdrawal, the other of tacrolimus minimization 6 months after transplantation-were compared with standard immunosuppression with basiliximab, corticosteroids, tacrolimus, and mycophenolic acid. The primary endpoint was kidney function. Secondary endpoints included death, primary nonfunction, graft failure, rejection, discontinuation of study medication, and a combined endpoint of treatment failure. An interim analysis was scheduled at 6 months, that is, just before tacrolimus minimization.
    Results: This interim analysis revealed no significant differences in Modification of Diet in Renal Disease between the early steroid withdrawal group and the standard immunosuppression groups (43.2 mL/min per 1.73 m
    Conclusions: Based on these interim results, early steroid withdrawal is a safe short-term immunosuppressive strategy. Long-term outcomes, including a comparison with tacrolimus minimization after 6 months, will be reported in the final 2-year analysis.
    Language English
    Publishing date 2018-05-15
    Publishing country United States
    Document type Journal Article
    ISSN 2373-8731
    ISSN 2373-8731
    DOI 10.1097/TXD.0000000000000794
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