Publications by authors named "Martin Nitschke"

48 Publications

[40 Years Interdisciplinary Transplant Center at the University Medical Center Schleswig-Holstein, Campus Lübeck - Team Spirit at its Best].

Zentralbl Chir 2021 Apr 21. Epub 2021 Apr 21.

Klinik für Chirurgie, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Deutschland.

In transplantation medicine, recent decades have seen an increase in the number of interdisciplinary organ centres that can guarantee optimal care before, during and after the transplantation of solid organs. Since the foundation of our centre 40 years ago, the interdisciplinary approach between transplant surgery and nephrology has been practised at the Lübeck site, allowing a centre specialising in kidney transplantation to develop. In addition to the medical-technical aspects, an organisational and structural-infrastructural centre could be built up, which became a model for interdisciplinary transplantation centres. A high level of expertise in minimally invasive surgical techniques together with specialised transplantation nephrology form the basis for the highest possible patient satisfaction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/a-1447-0769DOI Listing
April 2021

No association of genetic variants in TLR4, TNF-α, IL10, IFN-γ, and IL37 in cytomegalovirus-positive renal allograft recipients with active CMV infection-Subanalysis of the prospective randomised VIPP study.

PLoS One 2021 16;16(4):e0246118. Epub 2021 Apr 16.

Department of Nephrology, University Clinic Frankfurt, Goethe University Frankfurt, Frankfurt, Germany.

Background: Cytomegalovirus (CMV) infection is amongst the most important factors complicating solid organ transplantation. In a large prospective randomized clinical trial, valganciclovir prophylaxis reduced the occurrence of CMV infection and disease compared with preemptive therapy in CMV-positive renal allograft recipients (VIPP study; NCT00372229). Here, we present a subanalysis of the VIPP study, investigating single nucleotide polymorphisms (SNPs) in immune-response-related genes and their association with active CMV infection, CMV disease, graft loss or death, rejection, infections, and leukopenia.

Methods: Based on literature research ten SNPs were analyzed for TLR4, three for IFN-γ, six for IL10, nine for IL37, and two for TNF-α. An asymptotic independence test (Cochran-Armitage trend test) was used to examine associations between SNPs and the occurrence of CMV infection or other negative outcomes. Statistical significance was defined as p<0.05 and Bonferroni correction for multiple testing was performed.

Results: SNPs were analyzed on 116 blood samples. No associations were found between the analyzed SNPs and the occurrence of CMV infection, rejection and leukopenia in all patients. For IL37 rs2723186, an association with CMV disease (p = 0.0499), for IL10 rs1800872, with graft loss or death (p = 0.0207) and for IL10 rs3024496, with infections (p = 0.0258) was observed in all patients, however did not hold true after correction for multiple testing.

Conclusion: The study did not reveal significant associations between the analyzed SNPs and the occurrence of negative outcomes in CMV-positive renal transplant recipients after correction for multiple testing. The results of this association analysis may be of use in guiding future research efforts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246118PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051780PMC
April 2021

Extracorporeal membrane oxygenation in ANCA-associated vasculitis.

Autoimmun Rev 2021 Jan 11;20(1):102702. Epub 2020 Nov 11.

Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, Germany. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.autrev.2020.102702DOI Listing
January 2021

Pre-transplant HLA Antibodies and Delayed Graft Function in the Current Era of Kidney Transplantation.

Front Immunol 2020 26;11:1886. Epub 2020 Aug 26.

Institute of Immunology, Heidelberg University Hospital, Heidelberg, Germany.

Delayed graft function (DGF) occurs in a significant proportion of deceased donor kidney transplant recipients and was associated with graft injury and inferior clinical outcome. The aim of the present multi-center study was to identify the immunological and non-immunological predictors of DGF and to determine its influence on outcome in the presence and absence of human leukocyte antigen (HLA) antibodies. 1,724 patients who received a deceased donor kidney transplant during 2008-2017 and on whom a pre-transplant serum sample was available were studied. Graft survival during the first 3 post-transplant years was analyzed by multivariable Cox regression. Pre-transplant predictors of DGF and influence of DGF and pre-transplant HLA antibodies on biopsy-proven rejections in the first 3 post-transplant months were determined by multivariable logistic regression. Donor age ≥50 years, simultaneous pre-transplant presence of HLA class I and II antibodies, diabetes mellitus as cause of end-stage renal disease, cold ischemia time ≥18 h, and time on dialysis >5 years were associated with increased risk of DGF, while the risk was reduced if gender of donor or recipient was female or the reason for death of donor was trauma. DGF alone doubled the risk for graft loss, more due to impaired death-censored graft than patient survival. In DGF patients, the risk of death-censored graft loss increased further if HLA antibodies (hazard ratio HR=4.75, < 0.001) or donor-specific HLA antibodies (DSA, HR=7.39, < 0.001) were present pre-transplant. In the presence of HLA antibodies or DSA, the incidence of biopsy-proven rejections, including antibody-mediated rejections, increased significantly in patients with as well as without DGF. Recipients without DGF and without biopsy-proven rejections during the first 3 months had the highest fraction of patients with good kidney function at year 1, whereas patients with both DGF and rejection showed the lowest rate of good kidney function, especially when organs from ≥65-year-old donors were used. In this new era of transplantation, besides non-immunological factors, also the pre-transplant presence of HLA class I and II antibodies increase the risk of DGF. Measures to prevent the strong negative impact of DGF on outcome are necessary, especially during organ allocation for presensitized patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2020.01886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489336PMC
April 2021

Repeated kidney re-transplantation-the Eurotransplant experience: a retrospective multicenter outcome analysis.

Transpl Int 2020 06 30;33(6):617-631. Epub 2020 Jan 30.

Department of Nephrology, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany.

In Eurotransplant kidney allocation system (ETKAS), candidates can be considered unlimitedly for repeated re-transplantation. Data on outcome and benefit are indeterminate. We performed a retrospective 15-year patient and graft outcome data analysis from 1464 recipients of a third or fourth or higher sequential deceased donor renal transplantation (DDRT) from 42 transplant centers. Repeated re-DDRT recipients were younger (mean 43.0 vs. 50.2 years) compared to first DDRT recipients. They received grafts with more favorable HLA matches (89.0% vs. 84.5%) but thereby no statistically significant improvement of patient and graft outcome was found as comparatively demonstrated in 1st DDRT. In the multivariate modeling accounting for confounding factors, mortality and graft loss after 3rd and ≥4th DDRT (P < 0.001 each) and death with functioning graft (DwFG) after 3rd DDRT (P = 0.001) were higher as compared to 1st DDRT. The incidence of primary nonfunction (PNF) was also significantly higher in re-DDRT (12.7%) than in 1st DDRT (7.1%; P < 0.001). Facing organ shortage, increasing waiting time, and considerable mortality on dialysis, we question the current policy of repeated re-DDRT. The data from this survey propose better HLA matching in first DDRT and second DDRT and careful selection of candidates, especially for ≥4th DDRT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/tri.13569DOI Listing
June 2020

Incidence of acquired thrombotic thrombocytopenic purpura in Germany: a hospital level study.

Orphanet J Rare Dis 2019 11 15;14(1):260. Epub 2019 Nov 15.

AHEAD GmbH, Agency for Health Economic Assessment and Dissemination, Lörrach, Germany.

Background: Acquired thrombotic thrombocytopenic Purpura (aTTP) is a life-threatening ultra-orphan disease with a reported annual incidence between 1.5 and 6.0 cases per million in Europe and mainly affecting otherwise young and healthy adults aged 40 years on average. The goal of this study was to assess the incidence of aTTP in Germany.

Methods: A systematic review was performed to determine the published evidence on the aTTP epidemiology in Germany. To obtain additional evidence on the proportion of aTTP cases within the national Thrombotic Microangiopathy (TMA) population a hospital-level study was performed, using a retrospective data collection approach. Diagnosis of aTTP was confirmed if ADAMTS13 level were < 10% and/or the medical records explicitly mentioned aTTP diagnosis. The aggregated hospital data were then projected to the national level using logistic regression techniques.

Results: The systematic literature search did not provide incidence estimates of aTTP in Germany. Eight centers (≈27% of the top 30 TMA hospitals) delivered data according to a predefined data collection form. On average (year 2014-2016) a total number of 172 aTTP episodes per year was projected (95% confidence interval [95%CI]: 132-212). The majority were newly diagnosed aTTP cases (n = 121; 95%CI: 105-129), and 51 were recurrent aTTP cases (95%CI: 27-84). The average annual projected incidence (year 2014-2016) of aTTP episodes was 2.10 per million inhabitants in Germany (95%CI: 1.60-2.58).

Conclusions: The determined annual incidence of newly diagnosed aTTP cases and the overall annual incidence of aTTP episodes in Germany confirm the ultra-orphan character of aTTP. An external validation against international registries (France, UK and USA) shows that our findings are quite comparable with those international incidence rates.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13023-019-1240-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858672PMC
November 2019

Preformed Donor-Specific HLA Antibodies in Living and Deceased Donor Transplantation: A Multicenter Study.

Clin J Am Soc Nephrol 2019 07 18;14(7):1056-1066. Epub 2019 Jun 18.

Department of Internal Medicine-Nephrology and.

Background And Objectives: The prognostic value of preformed donor-specific HLA antibodies (DSA), which are only detectable by sensitive methods, remains controversial for kidney transplantation.

Design, Setting, Participants, & Measurements: The outcome of 4233 consecutive kidney transplants performed between 2012 and 2015 in 18 German transplant centers was evaluated. Most centers used a stepwise pretransplant antibody screening with bead array tests and differentiation of positive samples by single antigen assays. Using these screening results, DSA against HLA-A, -B, -C, -DRB1 and -DQB1 were determined. Data on clinical outcome and possible covariates were collected retrospectively.

Results: Pretransplant DSA were associated with lower overall graft survival, with a hazard ratio of 2.53 for living donation (95% confidence interval [95% CI], 1.49 to 4.29; 0.001) and 1.59 for deceased donation (95% CI, 1.21 to 2.11; =0.001). ABO-incompatible transplantation was associated with worse graft survival (hazard ratio, 2.09; 95% CI, 1.33 to 3.27; =0.001) independent from DSA. There was no difference between DSA against class 1, class 2, or both. Stratification into DSA <3000 medium fluorescence intensity (MFI) and DSA ≥3000 MFI resulted in overlapping survival curves. Therefore, separate analyses were performed for 3-month and long-term graft survival. Although DSA <3000 MFI tended to be associated with both lower 3-month and long-term transplant survival in deceased donation, DSA ≥3000 MFI were only associated with worse long-term transplant survival in deceased donation. In living donation, only strong DSA were associated with reduced graft survival in the first 3 months, but both weak and strong DSA were associated with reduced long-term graft survival. A higher incidence of antibody-mediated rejection within 6 months was only associated with DSA ≥3000 MFI.

Conclusions: Preformed DSA were associated with an increased risk for graft loss in kidney transplantation, which was greater in living than in deceased donation. Even weak DSA <3000 MFI were associated with worse graft survival. This association was stronger in living than deceased donation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2215/CJN.13401118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6625630PMC
July 2019

Development and validation of a renal risk score in ANCA-associated glomerulonephritis.

Kidney Int 2018 12 29;94(6):1177-1188. Epub 2018 Oct 29.

Institut für Pathologie, Universitätsklinikum Hamburg Eppendorf, Hamburg, Germany.

Predicting renal outcome in antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (GN) remains a major challenge. We aimed to identify reliable predictors of end-stage renal disease (ESRD) and to develop and validate a clinicopathologic score to predict renal outcome in ANCA-associated GN. In a prospective training cohort of 115 patients, the percentage of normal glomeruli (without scarring, crescents, or necrosis within the tuft) was the strongest independent predictor of death-censored ESRD. Regression tree analysis identified predictive cutoff values for three parameters: percentage normal glomeruli (N0 >25%, N1 10 to 25%, N2 <10%), percentage tubular atrophy and interstitial fibrosis (T0 ≤25%, T1 >25%), and estimated glomerular filtration rate at the time of diagnosis (G0 >15 ml/min/1.73 m, G1 ≤15 ml/min/1.73 m). Cox regression analysis was used to assign points to each parameter (N1 = 4, N2 = 6, T1 = 2, G1 = 3 points), and the resulting risk score was used to classify predicted ESRD risk as low (0), intermediate (2 to 7), or high (8 to 11 points). The risk score accurately predicted ESRD at 36 months in the training cohort (0%, 26%, and 68%, respectively) and in an independent validation cohort of 90 patients (0%, 27%, and 78%, respectively). Here, we propose a clinically applicable renal risk score for ANCA-associated GN that highlights the importance of unaffected glomeruli as a predictor of renal outcome and allows early risk prediction of ESRD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.kint.2018.07.020DOI Listing
December 2018

Sonographic Venous Velocity Index Identifies Patients with Chronic Kidney Disease and Severe Diastolic Dysfunction.

Ultrasound Int Open 2018 Oct 25;4(4):E142-E148. Epub 2018 Oct 25.

Universitat zu Lubeck Sektion Medizin, Medical Clinic I, Lubeck, Germany.

Objective: Diagnosing cardiorenal syndrome (CRS) in patients with chronic kidney disease (CKD) continues to remain challenging in outpatient practice. In this study, we investigate whether a newly developed venous velocity ultrasound index (VVI) can differentiate between patients with CRS and patients with CKD of other cause or normal renal function (NRF).

Methods: Patients with CRS (n 30), CKD (n=30), and NRF (n=30) were included in the study. For each patient, duplex ultrasound scans of intrarenal segmental veins were retrospectively analyzed. The VVI was calculated from the renal venous doppler curve as the ratio of the maximal positive venous velocity to the maximal negative venous velocity. Patients with CRS were compared to age-matched controls with NRF and to GFR-matched controls with CKD.

Results: The GFRs of patients with CRS and those with CKD were comparable (26.4±5 and 25.6±7 ml/min/m2), as was the age in patients with CRS and NRF (6 ±12 years and 68±16 years, respectively). There was no significant difference in ejection fraction between patients with CRS and those with CKD (44.2±6.2% vs. 47.4 ±7.2), but there was a significant decrease compared to those with NRF (52.6 ±5.1, p<0.01). The VVI was significantly higher in the CRS group (0.81± 0.18) compared to the CKD group (0.18± 0.17, p<0.01) or NRF group (0.22± 0.20, p<0.01). The positive predictability of CRS was 96.4% in patients with VVI values of >0.6.

Conclusion: The newly developed VVI was useful in successfully predicting severe diastolic dysfunction (CRS) in patients with severe kidney injury in outpatient care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/a-0684-9483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6202069PMC
October 2018

Kidney Transplantation after Extended Multivisceral Resection for Pancreatic Ductal Adenocarcinoma.

Case Rep Transplant 2018 26;2018:3757382. Epub 2018 Jul 26.

Clinic for Surgery, University Clinic Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.

Long-term survival in patients with pancreatic ductal adenocarcinoma (PDAC) is limited. Consequently, solid organ transplantation in PDAC patients is usually not considered. This is the first case report of kidney transplantation (KT) in a 57-year-old female patient after extended multivisceral resection for PDAC of the distal pancreas who had developed end-stage renal disease (ESRD) due to toxic kidney damage by chemotherapy. 13,5 years after initial PDAC-operation and 3 years after KT the patient remains in a good general health condition with sufficient function of the kidney allograft without local tumor recurrence or distant metastasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2018/3757382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6083642PMC
July 2018

Proteinuria and the Clinical Course of Dobrava-Belgrade Hantavirus Infection.

Nephron Extra 2018 Jan-Apr;8(1):1-10. Epub 2018 Feb 9.

Division of Nephrology, Medical Clinic I, University of Lübeck, Lübeck, Germany.

Purpose: Human infection with Dobrava-Belgrade virus (DOBV) in Northern Germany causes a mild form of hantavirus disease predominantly characterized by acute kidney injury due to interstitial nephritis. We evaluated the largest number of DOBV-infected patients so far regarding clinical course, proteinuria, and prognostic markers.

Patients And Methods: Patients with DOBV-associated hantavirus disease admitted to the Renal Division of the University of Lübeck (Germany) between 1997 and 2012 were included in this study. Symptoms, clinical course, laboratory parameters, and urinary protein analysis were investigated at admission (baseline, t), 3-5 days (t), 10-17 days (t), and after 1 year of follow-up (t).

Results: Of the 34 patients (male/female ratio: 23/11; age: 41 ± 14 years) included in the study, 4 underwent hemodialysis (HD). Glomerular filtration rate was 17 ± 14 mL/min at t and increased to 27 ± 26 mL/min (t), 57 ± 20 mL/min (t), and 84 ± 16 mL/min (t). Albuminuria and tubular proteinuria (α- and β-microglobulin) decreased during follow-up; the urinary α-microglobulin concentration in patients who required HD was significantly higher than that in patients not requiring HD (t: 186 ± 51 vs. 45 ± 26 mg/g creatinine; t: 87 ± 14 vs. 32 ± 16 mg/g creatinine; t: 63 ± 18 vs. 28 ± 12 mg/g creatinine; < 0.001).

Conclusions: DOBV infection of inpatients in Northern Germany is associated with severe kidney injury that recovers within a few weeks and normalizes within 1 year. Tubular proteinuria is associated with the severity of kidney injury and the necessity of renal replacement therapy in these DOBV-infected patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000486322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5968261PMC
February 2018

Valganciclovir Prophylaxis Versus Preemptive Therapy in Cytomegalovirus-Positive Renal Allograft Recipients: Long-term Results After 7 Years of a Randomized Clinical Trial.

Transplantation 2018 05;102(5):876-882

Department of Internal Medicine and Nephrology, Nephrology Center of Lower Saxony, Klinikum Hann. Muenden, Hann, Muenden, Germany.

Background: The VIPP study compared valganciclovir prophylaxis with preemptive treatment regarding efficacy, safety, and long-term graft outcome in cytomegalovirus (CMV)-positive (R+) renal transplant recipients.

Methods: Multicenter, open-label, randomized clinical study with a 12-month study phase and a follow-up of up to 84 months. Patients in the prophylaxis group received 2 × 450 mg/d oral valganciclovir for 100 days adjusted to renal function. Preemptive treatment with 2 × 900 mg/d valganciclovir was initiated at a viral load of 400 CMV copies/mL or greater (polymerase chain reaction) and maintained over ≥14 days, followed by secondary prophylaxis. Patients were stratified by donor CMV IgG serostatus (donor CMV IgG positive [D+]/R+, donor CMV IgG negative [D-]/R+).

Results: The 12-month results were reported previously (Witzke et al Transplantation 2012). The intent-to-treat/safety population comprised 148 patients in the prophylaxis (61.5% D+/R+) and 151 patients in the preemptive group (52.3% D+/R+). Overall, 47% patients completed the follow-up. Significantly fewer patients in the prophylaxis compared with preemptive group experienced a CMV infection or disease up to month 84 (11.5%; 95% confidence interval [95% CI], 6.8-17.8%] vs 39.7%; 95% CI, 31.9-48.0%; P < 0.0001 and 4.7%; 95% CI, 1.9-9.5% vs 15.9%; 95% CI, 10.5-22.7%; P = 0.002). Incidences of graft loss (7.4% vs 8.6%), death (9.5% vs 11.3%), rejection (29.1% vs 28.5%), and renal function (estimated glomerular filtration rate [mean ± SD]: 58.2 ± 26.3 vs 59.9 ± 25.7 mL/min per 1.73 m) were not significantly different between prophylaxis and preemptive treatment. Tolerability was comparable between groups.

Conclusions: Prophylaxis was more effective than the preemptive approach, applying a low-intense surveillance protocol in preventing CMV infection and disease in intermediate-risk patients. Both strategies were similarly effective in preventing graft loss and death under the conditions of this long-term trial with a threshold of 400 copies/mL for initiation of anti-CMV treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TP.0000000000002024DOI Listing
May 2018

Rescue allocation and recipient oriented extended allocation in kidney transplantation-influence of the EUROTRANSPLANT allocation system on recipient selection and graft survival for initially nonaccepted organs.

Transpl Int 2017 Dec 31;30(12):1226-1233. Epub 2017 Jul 31.

Working Group NRW Transplant Physicians, Cologne, Germany.

Nonaccepted kidneys grafts enter the rescue allocation (RA) process to avoid discards. In December 2013, recipient oriented extended allocation (REAL) was introduced to improve transparency. The aim of this study was to evaluate the influence of REAL on recipients' selection and graft function compared to the formerly existing RA as well as to identify factors that influence graft outcome. Therefore, a multicenter study of 10 transplant centers in the same region in Germany was performed. All transplantations after RA or REAL from December 1, 2012, until December 31, 2014, with a follow-up time until December 31, 2015 were analyzed. 113 of 941 kidney transplantations were performed after RA or REAL (12%). With REAL, the number of refusals before transplantation had increased (12 ± 7.1 vs. 8.6 ± 8.6, P = 0.036), and cold ischemia time has decreased (13.6 ± 3.6 vs. 17.2 ± 4.8 h, P = 0.019). Recipients after REAL needed significantly more allocation points compared to RA to receive a kidney. One-year graft survival was comparable. If kidneys from the same donor were transplanted to two recipients at one center, the greater the difference in recipient age, the greater the difference in serum creatinine after 12 months (-0.019 mg/dl per year, P = 0.011) was, that is older recipients showed lower creatinine. REAL influences selection of the recipients compared to the former RA era for successful organ receipt. Graft function is comparable and seems to be influenced by recipient age.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/tri.12993DOI Listing
December 2017

The Serial Duplex Index Improves Differential Diagnosis of Acute Renal Transplant Dysfunction.

J Ultrasound Med 2017 Aug 3;36(8):1607-1615. Epub 2017 Apr 3.

Department of Internal Medicine I, Transplant Center, University of Lübeck, Lübeck, Germany.

Objectives: Renal duplex sonography represents a standard noninvasive diagnostic procedure to demonstrate morphologic changes in acute kidney transplant dysfunction. We investigated whether a newly developed serial duplex index (SDI) can differentiate between acute cellular rejection and acute vascular rejection more effectively than the established Doppler parameters of the resistive index (RI) and pulsatility index (PI) in recently transplanted patients.

Methods: Serial duplex scans of patients with histologically proven acute tubular necrosis (n = 25), acute cellular rejection (n = 28), acute vascular rejection (n = 18), and normal graft function (n = 50, partially protocol biopsied) were retrospectively analyzed. For each patient, the RI, PI, and cortex-pelvis proportion (CPP) were included from the day of biopsy (t0) and 3 to 7 days before biopsy (t-1). The sequential CPP ratio (CPP /CPP ), RI ratio (RI /RI ), and PI ratio (PI /Pi ) were determined. The SDI was calculated as: RI ratio × PI ratio/CPP ratio. The diagnostic accuracy of the SDI was compared with that of the RI and PI ratios.

Results: Selected groups were statistically comparable in all routinely determined transplant parameters. The SDI was significantly different between patients with normal graft function, acute cellular rejection, and acute vascular rejection (P < .01, analysis of variance on ranks), whereas the RI and PI ratios were only significantly different between patients with normal graft function and acute vascular rejection (P < .05, analysis of variance on ranks). The indices' ranges were defined by the 95% confidence intervals between the allograft functions.

Conclusions: The developed SDI was able to detect acute renal transplant rejection with greater sensitivity and specificity than the RI and PI ratios. Since the SDI distinguishes between acute tubular necrosis, acute cellular rejection, and acute vascular rejection, it might be a supportive tool to indicate renal biopsy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7863/ultra.16.07032DOI Listing
August 2017

Unacceptable human leucocyte antigens for organ offers in the era of organ shortage: influence on waiting time before kidney transplantation.

Nephrol Dial Transplant 2017 May;32(5):880-889

Institute of Transfusion Medicine and Transplantation Immunology, University Hospital Münster, Münster, Germany.

Background: The assignment of human leucocyte antigens (HLAs) against which antibodies are detected as unacceptable antigens (UAGs) avoids allocation of HLA- incompatible allografts. There is uncertainty as to what extent UAGs decrease the probability of receiving a kidney offer.

Methods: Kidney transplantations in 3264 patients on the waiting lists of six German transplant centres were evaluated for a period of at least 2 years. The proportion of excluded offers due to UAGs was calculated as virtual panel-reactive antibodies (vPRAs).

Results: In the common Eurotransplant Kidney Allocation Scheme, the transplant probability was unaffected by vPRAs in exploratory univariate analyses. In the multivariable model, a 1% increase in vPRA values was outweighed by an additional waiting time of 2.5 weeks. The model was confirmed using an external validation cohort of 1521 patients from seven centres. If only patients with standard risk were considered (e.g. no simultaneous transplantation of other organs), only 1.3 weeks additional waiting time was needed. In the Eurotransplant Senior Program, patients with vPRA values >50% had a strongly reduced transplant probability in the unadjusted analyses. In the multivariable model, a 1% increase in vPRA values was outweighed by an additional waiting time of 5 weeks.

Conclusions: This study demonstrates that the assignment of UAGs decreases the transplant probability in both main Eurotransplant allocation programs because of insufficient compensatory mechanisms. At present, for immunized patients, a prolonged waiting time has to be weighed against the increased immunologic risk due to donor-specific antibodies not assigned as UAGs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ndt/gfw462DOI Listing
May 2017

Hemoadsorption in Infection-Associated Rhabdomyolysis.

Ther Apher Dial 2016 Oct 17;20(5):531-533. Epub 2016 Mar 17.

University of Lübeck, Medical Clinic 1, Lübeck, Germany.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1744-9987.12410DOI Listing
October 2016

Clinical and Laboratory Consequences of Platelet Transfusion in Shiga Toxin-Mediated Hemolytic Uremic Syndrome.

Transfus Med Rev 2017 01 21;31(1):51-55. Epub 2016 Jun 21.

Department of Nephrology and Hypertension, Hanover Medical School, Hanover, Germany.

Recent studies suggest that platelet transfusions are harmful in patients with thrombotic thrombocytopenic purpura, an entity of thrombotic microangiopathies. As the typical or Shiga toxin-producing Escherichia coli-induced hemolytic uremic syndrome (STEC-HUS) is also classified as thrombotic microangiopathy, we complement these data with an analysis of 250 patients from the German O104:H4 STEC-HUS outbreak. The effect of platelet transfusion in 44 patients who received platelet transfusions vs 206 control patients was investigated. Criteria for both groups were severe thrombocytopenia less than 50/nL, severe hemolysis with administration of packed red blood cells, and a complicated clinical course with admission to intensive care units. Readouts were clinical complications and changes in routine clinical chemistry and whole blood count. Chemistry values at admission and demographic parameters were comparable. Platelet transfusions were administered in 44 cases a median of 7 (interquartile range, 6-9) days after diarrhea onset. After platelet transfusion, we observed a transient and slight increase in inflammation parameters. No significant difference in major complications such as seizures, or requirement for ventilation or renal replacement therapy could be observed. Thrombotic events such as thrombosis or embolism were comparably rare in both groups (2.3% in platelet transfused vs 4.4% in controls, P=not significant). The mortality was not significantly different (0% vs 2.6%, P=not significant) in our study cohort, but overall in the outbreak, 6 of 711 STEC-HUS patients in Germany died of a procedural-related bleeding complications. In conclusion, platelet transfusions seem comparably safe in adult STEC-HUS patients, considering both the possible necessity for invasive procedures and potential risk for severe bleeding.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tmrv.2016.06.004DOI Listing
January 2017

Sudden hypertension in a kidney transplant recipient after a skiing accident.

Int J Surg Case Rep 2016 3;25:10-2. Epub 2016 Jun 3.

Nephrology Center Reinbek and Geesthacht, Reinbek, Germany.

Introduction: Complications after renal transplants are frequent. A well-known but less frequent complication is arteriovenous fistula formation, which can remain asymptomatic or present with hematuria, hypertension, or renal insufficiency.

Presentation Of Case: We present the case of a young, male kidney transplant recipient with newly developed hypertension due to the formation of an arteriovenous fistula a long period after the last renal biopsy.

Discussion: In our case, the sonographic evaluation showed the aliasing phenomenon, which was useful in the detection of the AVF. Superselective transcatheter embolization is considered to be the treatment of choice in such cases and has been proven to be safe and effective, even in long-term evaluations.

Conclusion: Our findings in this case highlight a rarely reported clinical presentation which physicians should be aware of when evaluating patients who have received a renal transplant.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijscr.2016.05.052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972143PMC
August 2016

High-urgency kidney transplantation in the Eurotransplant Kidney Allocation System: success or waste of organs? The Eurotransplant 15-year all-centre survey.

Nephrol Dial Transplant 2016 09 4;31(9):1515-22. Epub 2016 Feb 4.

Department of Vascular Surgery, Universitätsklinikum Düsseldorf, D-40225 Düsseldorf, Germany.

Background: In the Eurotransplant Kidney Allocation System (ETKAS), transplant candidates can be considered for high-urgency (HU) status in case of life-threatening inability to undergo renal replacement therapy. Data on the outcomes of HU transplantation are sparse and the benefit is controversial.

Methods: We systematically analysed data from 898 ET HU kidney transplant recipients from 61 transplant centres between 1996 and 2010 and investigated the 5-year patient and graft outcomes and differences between relevant subgroups.

Results: Kidney recipients with an HU status were younger (median 43 versus 55 years) and spent less time on the waiting list compared with non-HU recipients (34 versus 54 months). They received grafts with significantly more mismatches (mean 3.79 versus 2.42; P < 0.001) and the percentage of retransplantations was remarkably higher (37.5 versus 16.7%). Patient survival (P = 0.0053) and death with a functioning graft (DwFG; P < 0.0001) after HU transplantation were significantly worse than in non-HU recipients, whereas graft outcome was comparable (P = 0.094). Analysis according to the different HU indications revealed that recipients listed HU because of an imminent lack of access for dialysis had a significantly worse patient survival (P = 0.0053) and DwFG (P = 0.0462) compared with recipients with psychological problems and suicidality because of dialysis. In addition, retransplantation had a negative impact on patient and graft outcome.

Conclusions: Facing organ shortages, increasing wait times and considerable mortality on dialysis, we question the current policy of HU allocation and propose more restrictive criteria with regard to individuals with vascular complications or repeated retransplantations in order to support patients on the non-HU waiting list with a much better long-term prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ndt/gfv446DOI Listing
September 2016

Management of Food-Related Diarrhea Outbreak in the Emergency Department: Lessons Learned from the German STEC O104:H4 Epidemic.

Biomed Res Int 2015 11;2015:480680. Epub 2015 Oct 11.

Department of Internal Medicine I, University Hospital of Schleswig-Holstein, Campus Lübeck, 23560 Lübeck, Germany.

Emergency department (ED) management of the German STEC O104:H4 outbreak in 2011 was not limited to patients being truly infected with STEC. In parallel to spread of alarming news in public media, patients suffering from diarrhea due to other reasons fearfully presented, equally. We retrospectively characterized these two cohorts for anamnestic, clinical, and laboratory findings at their first ED contact. From 15th of May to July 2011, 302 adult patients with diarrheal complaint presented at the EDs of two tertiary hospitals in Lubeck, northern Germany. Fecal testing for STEC was obtained in 245 (81%) patients: 105 were STEC-positive and 140 were STEC-negative. Anamnestic characteristics (defecation rate, visible bloody diarrhea, and lower abdominal pain), abdominal tenderness, and some laboratory findings were significantly different between both cohorts but not reliable to exclude STEC. In >90% of STEC-positive patients diarrheal symptoms had started in May, reflecting the retrospective nationwide peak of infections, whereas the majority of STEC-negative patients became symptomatic in June 2011. During the German STEC O104:H4 outbreak a definite distinction at initial ED contact between STEC-positive versus STEC-negative patients by clinical judgment alone was not reliable. Fecal testing in the ED, however, might survey the outbreak of foodborne infections with the utmost precision.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2015/480680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4619827PMC
August 2016

Hypertension and mild chronic kidney disease persist following severe haemolytic uraemic syndrome caused by Shiga toxin-producing Escherichia coli O104:H4 in adults.

Nephrol Dial Transplant 2016 Jan 14;31(1):95-103. Epub 2015 Jul 14.

Department of Internal Medicine I, University of Lübeck, Lübeck, Germany.

Background: Shiga toxin-producing, enteroaggregative Escherichia coli was responsible for the 2011 outbreak of haemolytic uraemic syndrome (HUS). The present single-centre, observational study describes the 1-year course of the disease with an emphasis on kidney function. Outcome data after 1 year are associated with treatment and patient characteristics at onset of HUS.

Methods: Patients were treated according to a standardized approach of supportive care, including a limited number of plasmapheresis. On top of this treatment, patients with severe HUS (n = 35) received eculizumab, a humanized anti-C5 monoclonal antibody inhibiting terminal complement activation. The per-protocol decision--to start or omit an extended therapy with eculizumab accompanied by azithromycin--separated the patients into two groups and marked Day 0 of the prospective study. Standardized visits assessed the patients' well-being, kidney function, neurological symptoms, haematological changes and blood pressure.

Results: Fifty-six patients were regularly seen during the follow-up. All patients had survived without end-stage renal disease. Young(er) age alleviated restoring kidney function after acute kidney injury even in severe HUS. After 1 year, kidney function was affected with proteinuria [26.7%; 95% confidence interval (CI) 13.8-39.6], increased serum creatinine (4.4%, CI 0.0-10.4), increased cystatin C (46.7%, CI 32.1-61.3) and reduced (<90 mL/min) estimated glomerular filtration rate (46.7%, CI 32.1-61.3). Nine of the 36 patients without previous hypertension developed de novo hypertension (25%, CI 10.9-39.1). All these patients had severe HUS.

Conclusions: Although shiga toxin-producing Escherichia coli (STEC)-HUS induced by O104:H4 was a life-threatening acute disease, follow-up showed a good recovery of organ function in all patients. Whereas kidney function recovered even after longer duration of dialysis, chronic hypertension developed after severe HUS with neurological symptoms and could not be prevented by the extended therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ndt/gfv255DOI Listing
January 2016

[Cytomegalovirus after renal transplantation - diagnosis, prevention and treatment].

Dtsch Med Wochenschr 2015 Apr 16;140(8):612-5. Epub 2015 Apr 16.

Klinik für Nephrologie, Universitätsklinikum Essen, Universität Duisburg-Essen.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0041-100777DOI Listing
April 2015

Treatment of bullous pemphigoid with adjuvant immunoadsorption: a case series.

J Am Acad Dermatol 2014 Nov 15;71(5):1018-20. Epub 2014 Oct 15.

Department of Dermatology, University of Lübeck, Germany; Comprehensive Center for Inflammatory Medicine, University of Lübeck, Germany.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaad.2014.06.014DOI Listing
November 2014

Intranasal angiotensin II in humans reduces blood pressure when angiotensin II type 1 receptors are blocked.

Hypertension 2014 Apr 13;63(4):762-7. Epub 2014 Jan 13.

Medizinische Klinik I, Universität zu Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany.

Intranasal administration of angiotensin II (ANGII) affects blood pressure in a mode different from intravenously administered ANGII via a direct access to the brain bypassing the blood-brain barrier. This clinical study investigated blood pressure regulation after intranasal ANGII administration in healthy humans, whereas systemic, blood-mediated effects of ANGII were specifically blocked. In a balanced crossover design, men (n=8) and women (n=8) were intranasally administered ANGII (400 μg) or placebo after ANGII type 1 receptors had been blocked by pretreatment with valsartan (80 mg; 12 and 6 hours before intranasal administration). Plasma levels of ANGII, aldosterone, renin, vasopressin, and norepinephrine were measured; blood pressure and heart rate were recorded continuously. Intranasal ANGII acutely decreased blood pressure without altering the heart rate. Plasma levels of vasopressin and norepinephrine remained unaffected. Plasma ANGII levels were increased throughout the recording period. Aldosterone levels increased despite the peripheral ANGII type 1 receptor blockade, indicating an aldosterone escape phenomenon. In conclusion, intranasal ANGII reduces blood pressure in the presence of selective ANGII type 1 receptor blockade. Intranasal ANGII administration represents a useful approach for unraveling the role of this peptide in blood pressure regulation in humans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/HYPERTENSIONAHA.113.02860DOI Listing
April 2014

Serological evidence of asymptomatic infections during Escherichia coli O104:H4 outbreak in Germany in 2011.

PLoS One 2013 9;8(9):e73052. Epub 2013 Sep 9.

Robert Koch Institute, Berlin, Germany.

Introduction: The largest known outbreak caused by a rare hybrid strain of Shiga toxin-producing E.coli (STEC) and enteroaggregative E. coli (EAEC) (E.coli O104:H4) of serotype O104:H4 occurred in Germany in 2011. Fenugreek sprouts acted as a transmission vehicle and were widely consumed in the outbreak area at the time of the epidemic. In total 3,842 people developed a clinical illness caused by this strain; however the rates of asymptomatic infections remain unclear. We aimed to develop a serological assay for detection of E.coli O104 LPS specific antibodies and to establish the post-outbreak levels of seropositivity among people with documented exposure to contaminated sprouts.

Results And Discussion: Developed serological assays (ELISA with 84% sensitivity, 63% specificity and Western Blot with 100% sensitivity, 82.5% specificity) identified 33% (16/49) level of asymptomatic infection. Relatively small sample size and a significant time- lapse between the onset of symptoms and serum samples collection (appr. 8 weeks) might explain the assay variability. No association was found between clinical or demographic characteristics and assay positivity. Larger studies are needed to understand the complexity of human immune response and factors influencing development of clinical symptoms. Development of intra-outbreak research plans will substantially aid the conduct of more thorough scientific investigation during an outbreak period.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0073052PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3767767PMC
June 2014

Risk factors for development of hemolytic uremic syndrome in a cohort of adult patients with STEC 0104:H4 infection.

PLoS One 2013 22;8(3):e59209. Epub 2013 Mar 22.

Department of Medicine I (Gastroenterology and Hepatology, Infectious Diseases and Tropical Medicine), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

The outbreak of Shiga toxin producing E.coli O104:H4 in northern Germany in 2011 was one of the largest worldwide and involved mainly adults. Post-diarrheal hemolytic uremic syndrome (HUS) occurred in 22% of STEC positive patients. This study's aim was to assess risk factors for HUS in STEC-infected patients and to develop a score from routine hospital parameters to estimate patient risks for developing HUS. In a cohort analysis, adult patients with STEC infection were included in five participating hospitals in northern Germany between May and July 2011. Clinical data were obtained from questionnaires and medical records, laboratory data were extracted from hospitals' electronic data systems. HUS was defined as thrombocytopenia, hemolytic anemia and acute renal dysfunction. Random forests and multivariate logistic regression were used to identify risk factors for HUS and develop a score using the estimated coefficients as weights. Among 259 adults with STEC infection, vomiting (OR 3.48,95%CI 1.88-6.53), visible blood in stools (OR 3.91,95%CI1.20-16.01), age above 75 years (OR 3.27, 95%CI 1.12-9.70) and elevated leukocyte counts (OR 1.20, 95%CI 1.10-1.31, per 1000 cells/mm(3)) were identified as independent risk factors for HUS. A score using these variables has an area under the ROC curve of 0.74 (95%CI 0.68-0.80). Vomiting, visible blood in stools, higher leukocyte counts, and higher age indicate increased risk for developing HUS. A score using these variables might help to identify high risk patients who potentially benefit from aggressive pre-emptive treatment to prevent or mitigate the devastating consequences of HUS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0059209PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3606481PMC
September 2013

Allogenic submandibular gland transplantation following hematopoietic stem cell transplantation.

J Craniomaxillofac Surg 2013 Dec 4;41(8):764-9. Epub 2013 Feb 4.

Department of Maxillofacial Surgery (Medical Director: Prof. Dr. Dr. Peter Sieg), University of Luebeck, Germany. Electronic address:

Background: Autologous submandibular gland transfer for treatment of progressive dry eye symptoms requires a functionally intact submandibular gland. In cases of total function loss of both lacrimal and submandibular glands this procedure has to be modified. Here we report on the first two cases of the allogenic transplantation of a submandibular gland to treat patients suffering from complete functional loss of both glands due to graft-versus-host disease (GvHD) following stem cell transplantation.

Methods: We carried out allogenic transplantation of the submandibular gland of the matched former stem cell donor to the temporal fossa of the stem cell recipient suffering from GvHD-induced dry eye. The treatment was carried out in two male patients who showed complete donor chimerism to the stem cell donors, so that no immunosuppressive therapy was applied.

Results: Postoperative clinical assessment of the patients revealed primary success of the procedure. The ocular surface showed improvement of lubrication and reduction of inflammatory signs. In the long-term follow-up sialoscintigraphy revealed lower tracer activity than expected and secretion of saliva-tears decreased.

Conclusion: Even though the so-called total donor chimerism was assessed allogenic transplantation of the submandibular gland following GvHD-induced dry eye showed signs of organ rejection and therefore initial immunosuppressive therapy after allogenic transplantation has to be considered.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcms.2013.01.015DOI Listing
December 2013

Duration of fecal shedding of Shiga toxin-producing Escherichia coli O104:H4 in patients infected during the 2011 outbreak in Germany: a multicenter study.

Clin Infect Dis 2013 Apr 8;56(8):1132-40. Epub 2013 Jan 8.

Institute for Medical Microbiology and Hospital Epidemiology, Department of Nephrology, Hannover Medical School, Germany.

Background: In May-July 2011, Germany experienced a large food-borne outbreak of Shiga toxin 2-producing Escherichia coli (STEC O104:H4) with 3842 cases, including 855 cases with hemolytic uremic syndrome (HUS) and 53 deaths.

Methods: A multicenter study was initiated in 5 university hospitals to determine pathogen shedding duration. Diagnostics comprised culture on selective media, toxin enzyme-linked immunosorbent assay, and polymerase chain reaction. Results were correlated with clinical and epidemiologic findings. Testing for pathogen excretion was continued after discharge of the patient.

Results: A total of 321 patients (104 male, 217 female) were included (median age, 40 years [range, 1-89 days]). Median delay from onset of symptoms to hospitalization was 4 days (range, 0-17 days). Two hundred nine patients presented with HUS. The estimate for the median duration of shedding was 17-18 days. Some patients remained STEC O104:H4 positive until the end of the observation time (maximum observed shedding duration: 157 days). There was no significant influence of sex on shedding duration. Patients presenting with HUS had a significantly shortened shedding duration (median, 13-14 days) compared to non-HUS patients (median, 33-34 days). Antimicrobial treatment was also significantly associated with reduced shedding duration. Children (age≤15 years) had longer shedding durations than adults (median, 35-41 vs 14-15 days).

Conclusions: STEC O104:H4 is usually eliminated from the human gut after 1 month, but may sometimes be excreted for several months. Proper follow-up of infected patients is important to avoid further pathogen spread.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/cis1218DOI Listing
April 2013