Lutz Liefeldt

Charité Universitätsmedizin Berlin, Berlin, Land Berlin, Germany

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Publications (60)236.64 Total impact

  • Transplantation 07/2014; · 3.78 Impact Factor
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    ABSTRACT: It is unclear if the severity or the timing of acute cellular rejection (ACR) defined by Banff classification 2009 is associated with graft survival.
    Transplantation 06/2014; 97(11):1146-1154. · 3.78 Impact Factor
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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; · 3.16 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; · 1.29 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; · 2.89 Impact Factor
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    American Journal of Transplantation 09/2012; 12(9):2563. · 6.19 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. · 2.94 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. · 4.13 Impact Factor
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    ABSTRACT: Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Laparoscopic living donor nephrectomy has evolved as the procurement method of choice for living kidney donation. Given that this is a technically challenging procedure with potential risks for the healthy donor, skills transfer from an experienced laparoscopist to a novice is critical. The present study investigates donor and recipient outcomes during a novice's early experience with this procedure. Previous training in laparoscopic renal surgery and mentoring by the expert helps the novice to generate acceptable outcomes. However, longer warm ischaemia times during the learning phase may affect short-term graft function. 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; · 3.05 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. · 1.63 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. · 6.19 Impact Factor
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    Lutz Liefeldt, Klemens Budde, Petra Glander
    Transplant International 10/2011; 24(10):e83-4. · 3.16 Impact Factor
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    ABSTRACT: Inosine 5'monophosphate dehydrogenase (IMPDH) is the rate limiting enzyme in the de novo synthesis of guanine nucleotides. The direct determination of target enzyme activity as a biomarker of mycophenolic acid (MPA) may help to estimate better the individual response to the immunosuppressant. However, the assessment of the clinical utility of this approach is limited by the diversity of the assay systems, which has not yet allowed the prospective assessment of this enzyme in larger patient cohorts. A recently validated and standardized assay allows the investigation of IMPDH activity in larger clinical studies. Although descriptive results from observational studies hold promise for a more individualized therapy in transplant medicine, more studies are needed to prospectively validate this approach.
    Clinica chimica acta; international journal of clinical chemistry 08/2011; 413(17-18):1391-7. · 2.54 Impact Factor
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    ABSTRACT: Antibody-mediated rejection (ABMR) following kidney transplantation is associated with poor allograft survival. Conventional treatment based on plasmapheresis (PPH) and the administration of intravenous immunoglobulins (IVIG) is not satisfactory. Two compounds, more specifically targeting B cells and plasma cells, may help to improve the prognosis: rituximab, a B-cell-depleting monoclonal antibody, and bortezomib, a proteasome inhibitor causing apoptosis of plasma cells. Starting in February 2009, we treated 10 consecutive patients with ABMR according to current Banff criteria with one cycle of bortezomib [1.3 mg/m(2) intravenously (i.v.), Day 1, 4, 8, 11]. This group was compared to a historical control group of patients (n = 9) treated with a fixed single dose of rituximab (500 mg i.v.). All patients received PPH (6×) and IVIG (30 g). Patients with acute ABMR additionally received methylprednisolone (3 × 500 mg i.v.). Patient survival in both groups was 100%. At 18 months after treatment, graft survival was 6/10 in the bortezomib group as compared to 1/9 functioning grafts in the rituximab group (P = 0.071). Renal function was superior in patients treated with bortezomib as compared to rituximab-treated patients (serum creatinine at 9 months: 2.5 ± 0.6 versus 5.1 ± 2.1 mg/dL, P = 0.008). Proteinuria was not different between both groups (9 months: 1.3 ± 1.0 versus 1.6 ± 1.6 g/day, P = n.s.). Treatment of ABMR with bortezomib in addition to standard therapy was partially effective, whereas treatment with a fixed dose of rituximab in addition to standard therapy with PPH and IVIG did not result in sufficient long-term graft survival. In the future, new strategies including the combination of both substances and the application of higher doses must be discussed.
    Nephrology Dialysis Transplantation 08/2011; 27(3):1246-51. · 3.37 Impact Factor
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    World Journal of Urology 08/2011; 29(4):567. · 2.89 Impact Factor
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    ABSTRACT: Systemic heparin administration during laparoscopic donor nephrectomy (LDN) may prevent microvascular thrombus formation following warm ischemia. We herein present our experience with and without systemic heparinization during LDN. We retrospectively reviewed donor complications and graft outcomes in 119 consecutive live donor kidney transplantations between January 2005 and December 2009. Systemic heparin was administered to the first 65 donors. LDN was carried out by 2 surgeons using a pure laparoscopic technique. Total operating time for LDN was significantly longer in the heparin group (202 vs. 157 min). The incidence of renal artery multiplicity was significantly higher in the heparin group. Mean warm ischemia time was 160 s, and mean hospital stay was 5 days with no differences between groups. Postoperative hemorrhage occurred in 3 donors with systemic heparinization and in 1 without heparinization. Two donors received blood transfusions, and 2 underwent laparoscopic reexploration. Three grafts were lost in the heparin group and 1 in the non-heparin group. Graft loss was due to early vascular thrombosis (n = 3) and due to acute rejection (n = 1). Overall, 1-year graft survival was 96.6%, and 1-year serum creatinine was 1.41 mg/dl (P = n. s. between groups). Abandoning systemic donor heparinization in LDN with short warm ischemia has a low complication rate without adverse effects on short- and long-term graft outcomes.
    World Journal of Urology 05/2011; 29(4):561-6. · 2.89 Impact Factor
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    ABSTRACT: Efficacy and safety of an intensified dosing (ID) regimen of enteric-coated mycophenolate sodium (EC-MPS), which achieves higher mycophenolic acid exposure early posttransplantation, were evaluated in comparison with a standard dosing (SD) regimen. In total, 128 de novo kidney transplant recipients treated with basiliximab induction, cyclosporine A, and steroids were randomized (1:1) to receive EC-MPS as SD (1440 mg/day; n=65) or ID (days 0-14: 2880 mg/day; days 15-42: 2160 mg/day; followed by 1440 mg/day; n=63). Efficacy parameters, safety, and tolerability were assessed over a 6-month study period. The primary endpoint was mean time to first occurrence of treatment failure. Mean time to treatment failure was 130 days (95% confidence interval [CI]: 81-n/a) in the ID group versus 114 days (95% CI: 15-155) in the SD group (P=0.36). Similar percentages (ID 30.2%; SD 36.9%) experienced treatment failure. Biopsy-proven acute rejection occurred in 2 (3.2%) ID versus 11 (16.9%) SD patients (P<0.001). Three (2.3%) deaths (2 SD, 1 ID) and five (3.9%) graft losses (3 SD, 2 ID) occurred. Renal function, incidence of infection, and hematologic disorders were comparable in both study cohorts. Gastrointestinal disorders occurred in 51 (81.0%) ID and 49 (75.4%) SD patients with overall similar tolerability as assessed by the Gastrointestinal Symptom Rating Scale. In this exploratory study, the EC-MPS ID regimen reduced the incidence of rejection and showed a comparable safety and tolerability profile to SD. Further examination of this approach in a larger patient cohort is now warranted to confirm these findings.
    Transplantation 02/2011; 91(7):779-85. · 3.78 Impact Factor
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    ABSTRACT: Cold ischaemic time (CIT) may negatively influence graft function, increase the risk of acute rejection, and have adverse effects on graft and patient survival. This holds true especially for expanded criteria donors. As multi-centre studies on the impact of CIT are potentially biased, we performed a retrospective single-centre analysis of both kidneys from the same deceased donor transplanted consecutively into two recipients. A retrospective analysis of 80 kidneys from 40 donors transplanted into 80 recipients between January 1989 and December 2007 was conducted. Transplantations were performed successively due to logistic reasons resulting in a longer CIT for the second transplantation. We compared the outcome of the first (Rank 1) vs. the second (Rank 2) transplantation of the same donor. Ten donors/20 kidneys were allocated in the Eurotransplant Senior Program (ESP). Overall, no significant difference was found for the number of rejections, delayed graft function (DGF), functional data (creatinine, creatinine clearance and GFR) or graft survival despite a significant difference in CIT of Rank 1 recipients (8.3 h) vs. Rank 2 recipients (14.3 h). Subgroup analysis of kidneys transplanted in the Eurotransplant Senior Program (CIT Rank 1: 7 h vs. Rank 2: 12 h) also showed no difference for all the items studied. Donor kidneys ≥65 years transplanted at Rank 2 had a higher rate of DGF when compared with kidneys from donors <65 years transplanted at Rank 1, and function was better for the young Rank 1 recipients for all the time points measured. Graft- and patient survival did not differ. We found no difference between the successively transplanted kidneys of the same donor, not even for the expanded criteria donor organs. Nevertheless, assuming a 'safe' CIT is not justified, and CIT should always be kept as short as possible.
    Nephrology Dialysis Transplantation 12/2010; 25(12):4055-61. · 3.37 Impact Factor
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    Lutz Liefeldt, Klemens Budde
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    ABSTRACT: Cardiovascular disease is the leading cause of death following renal transplantation, and renal transplant patients have a greatly increased cardiac risk compared with the general population. Death with a functioning graft caused by cardiovascular disease also represents a substantial cause of graft loss. Decreased renal function in transplant recipients is a major contributor to increased cardiac risk, both as an independent risk factor and because of its negative effects on hypertension, anemia, left ventricular hypertrophy, and dyslipidemia. Graft loss and diabetes mellitus are also significant risk factors for cardiac death. Although critical for maintaining the transplanted organs, standard immunosuppressants have toxicities that exacerbate cardiac risk. Preservation of renal function, prevention of graft loss, and reductions in cardiovascular risk factors via improvements in both patient management and immunosuppressive therapies constitute critical strategies for optimizing patient and graft survival over the long term.
    Transplant International 12/2010; 23(12):1191-204. · 3.16 Impact Factor
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    ABSTRACT: Mycophenolic acid (MPA) therapy is a fundamental component of most post-transplant immunosuppressive regimens. Side effects, however, are common and frequently necessitate dose reductions or discontinuations. Enteric-coated mycophenolate sodium (EC-MPS) is designed to improve the gastrointestinal (GI) tolerability of MPA. This review assesses the pharmacology, efficacy and safety of EC-MPS. An understanding of the use of EC-MPS in solid organ transplantation and the key trials examining the GI impact of EC-MPS versus the immediate-release mycophenolate mofetil (MMF) formulation. The article also addresses the possible impact of proton pump inhibitor therapy, and the optimal MPA dose with different concomitant immunosuppressants. Evidence from blinded trials using standard reporting measures or patient-reported outcomes has not confirmed a significant improvement in the GI symptom burden using EC-MPS. Several open-label studies, however, have consistently shown an improvement in GI tolerability with EC-MPS, which can permit restoration of the optimal MPA dose. EC-MPS has equal efficacy and possibly a different tolerability profile to MMF, thus offering a choice to physicians and their patients, particularly those experiencing MMF-related GI symptoms, diabetic patients or those in whom an MPA dose reduction is required.
    Expert Opinion on Drug Safety 11/2010; 9(6):981-94. · 2.62 Impact Factor

Publication Stats

536 Citations
236.64 Total Impact Points

Institutions

  • 2005–2012
    • Charité Universitätsmedizin Berlin
      • • Department of Nephrology
      • • Medical Department, Division of Nephrology
      Berlin, Land Berlin, Germany
  • 2011
    • Universität Heidelberg
      • Department of Nephrology
      Heidelberg, Baden-Wuerttemberg, Germany
  • 2010
    • Heinrich-Heine-Universität Düsseldorf
      • Urologische Klinik
      Düsseldorf, North Rhine-Westphalia, Germany
  • 2002–2004
    • Humboldt-Universität zu Berlin
      Berlín, Berlin, Germany