Lutz Liefeldt

Charité Universitätsmedizin Berlin, Berlín, Berlin, Germany

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Publications (83)322.57 Total impact

  • Transplantation Proceedings 10/2015; 47(8):2346-2350. DOI:10.1016/j.transproceed.2015.09.002 · 0.98 Impact Factor
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    ABSTRACT: Allocation: Accordingly, organ allocation policies in this population were adjusted in several countries. The European Senior Program is the most prominent example, where elderly patients (≥65years) receive elderly (≥65years) donor organs with acceptable results. Immunosenescence: Because of age-dependent changes in the immune response and higher susceptibility to immunosuppressant side effects, outcomes in elderly patients are different compared to younger kidney transplant recipients. However, elderly patients do reject, especially poorly matched elderly donor organs. This warrants tailored immunosuppressive regimes with regard to the age-related changes of the immune system. Side effects: Rejection therapies may have detrimental side effects in the seniors and are frequently leading to over-immunosuppression (malignancy and infections) in long-term therapy. It is hypothesized that after initial graft adaptation elderly patients may benefit from less immunosuppression in order to lower cancer risk and reduce infection rates and cardiovascular comorbidities. Lack of data: Current evidence on recommended standard immunosuppressive therapy was mainly derived from trials, where elderly patients were excluded or only a minority. In order to improve immunosuppressive therapy in elderly transplant recipients, current immunosuppressive regimes have to be re-investigated in this growing population. Up to date, only a few well-designed prospective studies were performed in elderly populations and demonstrate the need for effective immunosuppression in the first months after transplantation. Conclusion: It is evident that novel treatment strategies and adequately powered prospective clinical trials are needed to establish time-adapted immunosuppressive regimens according to the needs of this vulnerable group of kidney transplant recipients.
    Transplantation reviews (Orlando, Fla.) 09/2015; DOI:10.1016/j.trre.2015.08.001 · 3.82 Impact Factor
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    ABSTRACT: Current immunosuppressive combination therapy provides excellent prevention of T-cell-mediated rejection following renal transplantation; however, antibody-mediated rejection remains of high concern and accounts for a large number of long-term allograft losses. The recent development of protocol biopsies resulted in the definition of subclinical rejection (SCR), showing histologic evidence for rejection but unremarkable clinical course. This review describes the current knowledge and evidence of pharmacotherapy to treat kidney allograft rejections and covers SCR treatment options. Each substance is analyzed with regard to its classical indication and further discussed for the treatment of other forms of rejection. Despite a lack of randomized trials, early acute T-cell-mediated rejection can be treated effectively in most cases without graft loss. The necessity to treat SCR is currently unclear. Due to a lack of effective therapies, new treatment approaches for antibody-mediated rejection are an urgent medical need to improve long-term outcomes. Future research should aim to better define pathophysiology and histology, stratify risk, and develop rational treatment strategies from randomized controlled trials, in order to establish the value of novel therapies in the arsenal of rejection pharmacotherapy. However, the effective prevention of rejection with minimal side effects still remains the goal in immunosuppression.
    Expert Opinion on Pharmacotherapy 08/2015; 16(11):1627-48. DOI:10.1517/14656566.2015.1056734 · 3.53 Impact Factor
  • Hans-Hellmut Neumayer · Klemens Budde · Lutz Liefeldt ·

    Transplantation 07/2014; 98(8). DOI:10.1097/TP.0000000000000296 · 3.83 Impact Factor
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    ABSTRACT: Background: It is unclear if the severity or the timing of acute cellular rejection (ACR) defined by Banff classification 2009 is associated with graft survival. Methods: Borderline changes, TCMR I (interstitial rejection), and TCMR II/III (vascular rejection) were defined as low, moderate, and high ACR severity, respectively. Approximately 270 patients who had at least one episode of ACR were enrolled, 270 biopsies were chosen which showed the highest ACR severity of each patient and were negative for donor-specific antibodies (DSA), C4d, and microcirculation changes (MC). Six months were used as the cutoff to define early and late ACR; 370 patients without biopsy posttransplantation were recruited in the control group. Results: Up to 8-year posttransplantation, death-censored graft survival (DCGS) rates of control, borderline, TCMR I, and TCMR II/III groups were 97.6%, 93.3%, 79.6%, and 73.6% (log rank test, P<0.001); the control group had significantly higher DCGS rate than the three ACR groups (each pairwise comparison yields P<0.05). The DCGS rate of late ACR was significantly lower compared with early ACR (63.6% vs. 87.4%, P<0.001). Intimal arteritis (Banff v-lesion) was an independent histologic risk factor correlated with long-term graft loss regardless of the timing of ACR. The v-lesions with minimal or high-grade tubulitis displayed similar graft survival (72.7% vs. 72.9%, P=0.96). Conclusion: All types of ACR affect long-term graft survival. Vascular or late ACR predict poorer graft survival; the extent of tubulointerstitial inflammation (TI) is of no prognostic significance for vascular rejection.
    Transplantation 06/2014; 97(11):1146-1154. DOI:10.1097/01.TP.0000441094.32217.05 · 3.83 Impact Factor

  • Nieren- und Hochdruckkrankheiten 01/2014; 43(07):297-309. DOI:10.5414/NHX01585
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    ABSTRACT: Currently, no international standard for the pre-transplant evaluation of living donor renal function exists. Following a standardized questionnaire on current practice in all Eurotransplant (ET) centers, we compared a new CT-based technique to measure renal cortex volume with our standard of DTPA-clearance combined with MAG3-scintigraphy (DTPAxMAG3) and with creatinine-based methods in 167 consecutive living kidney donors. Most ET centers use creatinine-clearance (64%) to measure total renal function and radioistopic methods (82%) to assess split renal function. Before transplantation, CT-measured total cortex volume (r=0.67; p<0.001) and estimated GFR using the Cockcroft-Gault formula [eGFR(CG)] (r=0.55; p<0.001) showed the strongest correlation with DTPA-clearance. In contrast, the correlation between DTPA-clearance and creatinine clearance was weak (r=0.21; p=0.02). A strong correlation was observed between CT-measured split cortex volume and MAG3-measured split renal function (r=0.93; p<0.001). A strong correlation was also found between pre-transplant split renal function assessed by eGFR(CG) together with cortex volume measurement and post-transplant eGFR(CG) of both, the donor (r=0.83; p<0.001) and the recipient (r=0.75; p<0.001). In conclusion CT-based assessment of renal cortex volume bears the potential to substitute existing methods to assess pre-transplant living donor split renal function. This article is protected by copyright. All rights reserved.
    Transplant International 09/2013; 26(12). DOI:10.1111/tri.12195 · 2.60 Impact Factor
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    ABSTRACT: In a 6-month prospective, openlabel, multicenter study, 128 de novo kidney transplant patients receiving cyclosporine (CsA) and steroids were randomized to an intensified regimen of enteric-coated mycophenolate sodium (EC-MPS) or to a standard EC-MPS regimen to Week 6 posttransplant, after which the regimen was identical. In a follow-up study to Month 12 post-transplant (49 intensified regimen, 52 standard regimen), the reduced rate of BPAR observed at Month 6 (intensified regimen 3.2%, standard regimen 16.9%, p = 0.016) was maintained at Month 12 (4.8% vs. 18.5%, p = 0.026). Estimated GFR (Cockcroft-Gault) at Month 12 was comparable in the intensified group (mean (SD) 54.8 (22.9) ml/min) vs. the standard group (mean (SD) 57.5 (23.6) ml/min, p = 0.83). The incidence of adverse events and serious adverse events at Month 12 was similar in both treatment groups, although adverse events with a suspected relation to study drug were reported in 69.8% and 50.8% of patients in the intensified and standard regimen groups, respectively (p = 0.032). Infections and hematological parameters were similar between groups. In conclusion, an early regimen of intensified EC-MPS with CsA and steroids achieves a low rate of BPAR over the first year after kidney transplantation with similar renal function to a standard regimen, and without a clinically relevant impact on safety.
    Clinical nephrology 04/2013; 79(6). DOI:10.5414/CN107908 · 1.13 Impact Factor
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    ABSTRACT: Purpose: To compare current technology multislice computed tomography angiography (CTA) with magnetic resonance angiography (MRA) in the pre-operative evaluation of vascular anatomy of living renal transplant donors. Methods and materials: Two hundred and thirty-six kidneys were included in the CTA and MRA analysis. Renal vasculature was evaluated independently by two readers in each modality with a delay of 4 weeks between reading sessions. Surgical correlation on the operated side was available in all patients. The reference standard was defined by surgical correlation and consensus reading of both modalities. Results: Detection rate of CTA for arteries was 99.1 and 95.0 % for reader 1 and reader 2, respectively. Detection rate of MRA for arteries was 95.0/94.3 %. Most of the undetected arteries were ≤ 1 mm diameter (reader 1: 2 of 3 in CTA and 9 of 16 in MRA; reader 2: 11 of 16 in CTA, and 8 of 18 in MRA). Detection rates for arteries ≥ 2 mm for reader 1/reader 2 were 99.7/98.7 % in CTA and 99.1/97.8 % in MRA, respectively. Detection rates for veins were 99.6/97.4 % in CTA and 97.8/96.9 % in MRA, respectively. Both readers misdiagnosed between 0 and 1 non-present arteries and between 2 and 3 non-present veins in both modalities. Conclusions: Modern multislice CT and MRI scanners allow highly accurate evaluation of the vascular anatomy, especially for vessels of ≥ 2 mm diameter. CTA may provide slightly better depiction of very small arteries; however, this may be reader-dependent. Additional factors affecting the choice of imaging modality should include local availability, cost, and the desire to avoid ionizing radiation in healthy transplant donors.
    World Journal of Urology 01/2013; 31(4). DOI:10.1007/s00345-012-1022-y · 2.67 Impact Factor
  • D. Schmidt · P. Glander · K. Budde · H. H. Neumayer · L. Liefeldt ·

    Transplantation 11/2012; 94(10S):918. DOI:10.1097/00007890-201211271-01808 · 3.83 Impact Factor
  • L. Liefeldt · P. Glander · Y. Lan · D. Schmidt · C. Heine · K. Budde · H. H. Neumayer ·

    Transplantation 11/2012; 94(10S):922. DOI:10.1097/00007890-201211271-01818 · 3.83 Impact Factor
  • P. Glander · L. Liefeldt · P. Hambach · M. Mai · K. Budde · H. H. Neumayer ·

    Transplantation 11/2012; 94(10S):1191. DOI:10.1097/00007890-201211271-02363 · 3.83 Impact Factor
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    ABSTRACT: Virtual Panel Reactive Antibodies (vPRA) has been implemented to gauge sensitization worldwide. It is unclear how it associates with long-term outcomes, and its correlation with peak (pPRA) or actual (aPRA) has not been studied. We retrospectively reviewed data from 18-65 year-old kidney-only transplant patients during 1.1.1996-31.7.2011 in our centre. PRAs were calculated based on solid-phase techniques. Of the 726 qualified cases, regardless of the PRA type, sensitized patients (PRA>5%) had more females and previous transplant. Highly sensitized (HS, PRA>50%) had longer waiting time, lower transplant rate, less living donor, more delayed graft function and acute rejection. The conformity between vPRA and pPRA in HS were 75%, 57% between pPRA and aPRA. Forty-three percent (61/142) patients whose pPRA was >5% had no detectable aPRA and maintained similar outcomes as sensitized patients. Multivariate analysis showed consistently lower death-censored graft survival in HS defined by vPRA [HR 2.086 (95% CI 1.078-4.037), P<0.05] and pPRA [HR 2.139 (95% CI 1.024-4.487), P<0.05]. Both vPRA and pPRA provided reliable way estimating sensitization and predicting long-term graft survival, while aPRA might underestimate true sensitization. vPRA might be the most objective parameter to gauge sensitization. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Transplantation 11/2012; 94(10S):1076. DOI:10.1097/00007890-201211271-02132 · 3.83 Impact Factor
  • K. Wu · B. Rudolph · L. Huber · D. Schmidt · L. Liefeldt · P. Glander · H. H. Neumayer · K. Budde ·

    Transplantation 11/2012; 94(10S):1044. DOI:10.1097/00007890-201211271-02066 · 3.83 Impact Factor
  • Source
    L Liefeldt · P Glander · S Brakemeier · K Budde ·

    American Journal of Transplantation 09/2012; 12(9):2563. DOI:10.1111/j.1600-6143.2012.04158.x · 5.68 Impact Factor
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    ABSTRACT: Introduction: Sirolimus is a powerful antiproliferative immunosuppressive drug approved for the prevention of kidney allograft rejection. By its unique mechanism of action, sirolimus provides a multitude of clinical potential and has been used effectively in different drug combinations. Extensive experience has been gained regarding the best timing of its application, side effect profile and potential benefits and limitations compared with other immunosuppressive drugs. Areas covered: The authors evaluate the recent experience with sirolimus in kidney transplantation. Pivotal randomized controlled trials were used to provide an overview with special attention to pharmacokinetic and dynamic aspects of sirolimus, its current clinical use as well as perspectives for its future role. Expert opinion: Sirolimus enriches the possibilities of immunosuppressive therapies after renal transplantation. Beneficial effects toward kidney function by allowing CNI sparing, lower incidence of malignancies and less viral infections have been suggested. Sirolimus should be used cautiously in de novo patients for reasons of wound healing. An early conversion to a sirolimus-based CNI-free regimen has shown promising results, whereas late conversion is more challenging. Finally, sirolimus-associated side effects are causing tolerability concerns and frequent discontinuations. Future research should aim to better define the therapeutic window and those patients most likely to benefit.
    Expert Opinion on Drug Metabolism &amp Toxicology 08/2012; 8(10):1337-56. DOI:10.1517/17425255.2012.719874 · 2.83 Impact Factor
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    ABSTRACT: Sensitization is generally referred to as the development of alloantibodies, specifically anti-human leukocyte antigen (HLA) immunoglobulin G (IgG) antibodies, most commonly caused by pregnancy, blood transfusion or a previous transplant. Despite being a well known phenomenon, there has not been a general consensus on its definition, monitoring or management. Today, 25% of the patients waitlisted for kidney transplant in the US have a panel reactive antibody (PRA) of >10% while, in the Eurotransplant zone, 14% have a PRA of >5%. Sensitized patients have more difficulty in finding a well HLA-matched donor, and have a higher risk of experiencing longer waiting times, more rejection episodes and eventually inferior long-term graft or patient survival. We review the currently available strategies in identifying and managing highly sensitized patients undergoing renal transplantation. We discuss the progress and limitations in laboratory techniques to elaborate on challenges in defining sensitized patients. The main management options (i.e. the Acceptable Mismatch Program, donor exchange programmes and the desensitization approach) and their mechanisms, related policies, advantages and outcomes, as well as medications and methods being investigated, are updated. In addition, particular emphasis is given to sensitization prevention, a practice that is neglected with our increasing ability to suppress the immune system.
    Drugs 07/2012; 72(10):1335-54. DOI:10.2165/11631110-000000000-00000 · 4.34 Impact Factor
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    ABSTRACT: Objective: To test the effect of surgeon experience on donor and recipient outcomes after laparoscopic living donor nephrectomy (LLDN). Results of a LLDN expert were compared with those of an LLDN novice. Patients and methods: Between October 2008 and October 2010 the last 20 cases of a series of 130 consecutive LLDNs, performed by an expert (EXP) were compared with the first 20 cases of an LLDN novice (NOV). Donor and recipient outcomes were evaluated. The novice was mentored by the expert during his initial four LLDN cases. Results: Donor and recipient demographics were not different between the two surgeon groups. Total operating time and warm ischaemia time during LLDN was significantly longer in the NOV group compared with the EXP group (273 min vs 147 min and 213 s vs 162 s, respectively). The incidence of donor complications was low in both groups. Length of hospital stay among donors did not differ between groups. Although delayed graft function, rejection rates and postoperative serum creatinine levels indicated slightly poorer recipient outcomes in the NOV group, differences did not reach statistical significance. Conclusions: Mentoring by an experienced urological laparoscopist may help an LLDN novice to generate acceptable donor and recipient outcomes. Whether or not prolonged operating times and warm ischaemia times during the early phase of an LLDN experience are risk factors for impaired graft function needs further evaluation.
    BJU International 07/2012; 111(1). DOI:10.1111/j.1464-410X.2012.11348.x · 3.53 Impact Factor
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    ABSTRACT: Evaluation of vascular variants is crucial for donor assessment prior to living kidney transplantation. Both contrast-enhanced (CE) magnetic resonance angiography (MRA) and multislice computed tomography (MSCT) are currently used for imaging living kidney donors. Aim of this study was the comparison of the accuracy of MSCT angiography and CE-MRA for the assessment of renal vascular anatomy. Prospective study at a university transplant center including 65 potential living kidney donors. Pre-operative imaging by MSCT angiography and CE-MRA was correlated with the findings of laparoscopic donor nephrectomy in 48 donors. MSCT detected significantly more patients and more kidneys with accessory arteries than CE-MRA (p < 0.05). MSCT and CE-MRA performed similarly in identifying venous and ureteral abnormalities. The overall sensitivity, specificity, and accuracy for identifying accessory arteries were 85%/97%/94% for MSCT and 54%/97%/85% for CE-MRA. The sensitivity, specificity, and accuracy for the identification of supernumerary veins were 67%/95%/92% for MSCT and 67%/98%/94% for CE-MRA, respectively. We found MSCT angiography to be more sensitive and accurate than CE-MRA in the detection of supernumerary arteries prior to living donor nephrectomy.
    Clinical Transplantation 07/2012; 26(4):E412-7. DOI:10.1111/j.1399-0012.2012.01680.x · 1.52 Impact Factor
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    ABSTRACT: Donor-specific HLA antibodies (DSA) have a negative impact on kidney graft survival. Therefore, we analyzed the occurrence of DSA and antibody-mediated rejection (AMR) in patients from two prospective randomized trials in our center. At 3-4.5 months posttransplant 127 patients were randomized to continue cyclosporine or converted to everolimus therapy. The presence of DSA was prospectively assessed using Luminex assays. AMR was defined according to the Banff 2009 classification. Antibody screening was available in 126 patients with a median follow-up of 1059 days. Seven out of 65 (10.8%) patients on cyclosporine developed DSA after a median of 991 days. In comparison, 14/61 patients (23.0%) randomized to everolimus developed DSA after 551 days (log-rank: p = 0.048). Eight patients on everolimus compared to two patients on cyclosporine developed AMR (log-rank: p = 0.036). Four of 10 patients with AMR-all in the everolimus group-lost their graft. A multivariate regression model revealed everolimus, >3 mismatches and living donor as significant risk factors for DSA. Acute rejection within the first year, >3 mismatches, everolimus and living donor were independent risk factors for AMR. This single center analysis demonstrates for the first time that everolimus-based immunosuppression is associated with an increased risk for the development of DSA and AMR.
    American Journal of Transplantation 02/2012; 12(5):1192-8. DOI:10.1111/j.1600-6143.2011.03961.x · 5.68 Impact Factor

Publication Stats

1k Citations
322.57 Total Impact Points


  • 2005-2015
    • Charité Universitätsmedizin Berlin
      • Department of Nephrology
      Berlín, Berlin, Germany
  • 2002-2004
    • Humboldt-Universität zu Berlin
      • Department of Biology
      Berlín, Berlin, Germany
  • 1998-2001
    • Freie Universität Berlin
      • • Institute of Pharmacology and Toxicology
      • • Division of Clinical Pharmacy
      Berlin, Land Berlin, Germany
  • 1995
    • Max-Delbrück-Centrum für Molekulare Medizin
      Berlín, Berlin, Germany