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1.
Front Public Health ; 12: 1364664, 2024.
Article in English | MEDLINE | ID: mdl-38699424

ABSTRACT

Asymptomatic long-term carriers of Shigatoxin producing Escherichia coli (STEC) are regarded as potential source of STEC-transmission. The prevention of outbreaks via onward spread of STEC is a public health priority. Accordingly, health authorities are imposing far-reaching restrictions on asymptomatic STEC carriers in many countries. Various STEC strains may cause severe hemorrhagic colitis complicated by life-threatening hemolytic uremic syndrome (HUS), while many endemic strains have never been associated with HUS. Even though antibiotics are generally discouraged in acute diarrheal STEC infection, decolonization with short-course azithromycin appears effective and safe in long-term shedders of various pathogenic strains. However, most endemic STEC-strains have a low pathogenicity and would most likely neither warrant antibiotic decolonization therapy nor justify social exclusion policies. A risk-adapted individualized strategy might strongly attenuate the socio-economic burden and has recently been proposed by national health authorities in some European countries. This, however, mandates clarification of strain-specific pathogenicity, of the risk of human-to-human infection as well as scientific evidence of social restrictions. Moreover, placebo-controlled prospective interventions on efficacy and safety of, e.g., azithromycin for decolonization in asymptomatic long-term STEC-carriers are reasonable. In the present community case study, we report new observations in long-term shedding of various STEC strains and review the current evidence in favor of risk-adjusted concepts.


Subject(s)
Anti-Bacterial Agents , Azithromycin , Escherichia coli Infections , Shiga-Toxigenic Escherichia coli , Humans , Escherichia coli Infections/drug therapy , Azithromycin/therapeutic use , Azithromycin/administration & dosage , Anti-Bacterial Agents/therapeutic use , Carrier State/drug therapy , Hemolytic-Uremic Syndrome/microbiology
2.
J Pers Med ; 14(3)2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38540998

ABSTRACT

Background: Lymphoceles are amongst the most common complications following kidney transplantation. Therefore, effective strategies to prevent their development are needed. The ligation of lymphatic vessels has proven to be a successful concept for that purpose. However, whether electrocauterization or suture ligation is more effective is unclear. Methods: We conducted a meta-analysis using a random effects model with the log risk ratio as the primary outcome measure. Additionally, an analysis using a random effects model with the raw mean difference in lymphatic sealing time between suture ligation and electrocauterization was performed. Adequate studies were found in a literature search conducted in PubMed, CENTRAL and Web of Science as well as from independent sources. Results: A total of 8 studies including 601 patients were included in the analysis. The estimated average log risk ratio based on the random effects model was µ = -0.374 (95% CI: -0.949 to 0.201), which did not differ significantly from zero (z = -1.28, p = 0.2). The lymphatic sealing time was 7.28 (95% CI:1.25-13.3) minutes shorter in the electrocauterization group. Conclusions: We conclude that neither technique is superior for the purpose of lymphocele prevention post kidney transplantation, and secondary criteria like time savings, cost and surgeons' preference should be considered in the decision for an optimal outcome.

3.
Rheumatol Int ; 44(2): 263-271, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37747561

ABSTRACT

To investigate clinical symptoms and genetic variants in patients from the German anti-IL-1 registry for autoinflammatory orphan diseases (GARROD) between 2013 and 2022. Multicentre, retrospective analysis of demographic, clinical and genetic data of patients with autoinflammatory diseases (AID) who received anti-IL-1 targeted therapy. The cohort comprised 152 patients with familial Mediterranean fever (FMF; n = 71), cryopyrin-associated periodic syndromes (CAPS; n = 43), TNF-receptor associated periodic syndrome (TRAPS; n = 19), mevalonate kinase deficiency (MKD; n = 3) and unclassified AID (uAID; n = 16). Inflammatory attacks started in 61.2% of the patients before the age of 18 years. The delay between the first AID attack and anti-IL-1 therapy was 17.8 years. Monogenetic AIDs were diagnosed by clinical symptoms. Genetic analyses confirmed the diagnosis in 87.3% of patients with FMF, 65.2% with CAPS and 94.8% with TRAPS. Among this group, heterozygous MEFV variants and variants of unknown significance (VUS) were detected in 22.5% of patients with FMF, 51.2% with CAPS and 47.4% with TRAPS. Patients with VUS were older at disease onset which is consistent with a milder phenotype. Twenty-four patients had secondary AA amyloidosis (AA) at initiation of anti-IL-1 therapy. The mean age of these patients was 16.4 years at their first attack and 44.9 years at the time of AA diagnosis. Turkish-Armenian ancestry correlated with MEFV variants and higher FMF disease activity compared to German ancestry. Molecular genetic analyses should substantiate the clinical diagnosis of a monogenetic AID. Our data support the concept of variable penetrance of VUS which can be associated with late-onset AID.


Subject(s)
Amyloidosis , Familial Mediterranean Fever , Hereditary Autoinflammatory Diseases , Humans , Adolescent , Retrospective Studies , Hereditary Autoinflammatory Diseases/diagnosis , Hereditary Autoinflammatory Diseases/drug therapy , Hereditary Autoinflammatory Diseases/genetics , Fever/diagnosis , Familial Mediterranean Fever/diagnosis , Familial Mediterranean Fever/drug therapy , Familial Mediterranean Fever/genetics , Registries , Pyrin/genetics , Serum Amyloid A Protein
4.
Transplantation ; 2023 Dec 11.
Article in English | MEDLINE | ID: mdl-38073036

ABSTRACT

BACKGROUND: Whenever the kidney standard allocation (SA) algorithms according to the Eurotransplant (ET) Kidney Allocation System or the Eurotransplant Senior Program fail, rescue allocation (RA) is initiated. There are 2 procedurally different modes of RA: recipient oriented extended allocation (REAL) and competitive rescue allocation (CRA). The objective of this study was to evaluate the association of patient survival and graft failure with RA mode and whether or not it varied across the different ET countries. METHODS: The ET database was retrospectively analyzed for donor and recipient clinical and demographic characteristics in association with graft outcomes of deceased donor renal transplantation (DDRT) across all ET countries and centers from 2014 to 2021 using Cox proportional hazards methods. RESULTS: Seventeen thousand six hundred seventy-nine renal transplantations were included (SA 15 658 [89%], REAL 860 [4.9%], and CRA 1161 [6.6%]). In CRA, donors were older, cold ischemia times were longer, and HLA matches were worse in comparison with REAL and especially SA. Multivariable analyses showed comparable graft and recipient survival between SA and REAL; however, CRA was associated with shorter graft survival. Germany performed 76% of all DDRTs after REAL and CRA and the latter mode reduced waiting times by up to 2.9 y. CONCLUSIONS: REAL and CRA are used differently in the ET countries according to national donor rates. Both RA schemes optimize graft utilization, lead to acceptable outcomes, and help to stabilize national DDRT programs, especially in Germany.

5.
Arthritis Rheumatol ; 75(5): 760-767, 2023 05.
Article in English | MEDLINE | ID: mdl-36409567

ABSTRACT

OBJECTIVE: To examine concentrations of circulating antibodies targeting C3a and C5a complement receptors in antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) and analyze their association with disease activity. METHODS: Concentrations of antibodies against C3a and C5a complement receptors (anti-C3aR and anti-C5aR) and plasma complement fragments C3a and C5a were determined in patients with AAV (n = 110; granulomatosis with polyangiitis [GPA; n = 82] or microscopic polyangiitis [MPA; n = 28]), systemic lupus erythematosus (SLE) patients as disease controls (n = 36), and healthy donors (n = 220). C3aR and C5aR expression by circulating neutrophils, monocytes, and T cells was analyzed using flow cytometry. Clinical data were assessed at time of serum sampling and during follow-up for 60 months. RESULTS: In AAV, anti-C3aR and anti-C5aR antibodies were decreased (P = 0.0026 and P ≤ 0.0001, respectively). In remission, anti-C3aR antibody concentrations rose to values comparable to healthy donors, whereas anti-C5aR antibody concentrations did not. In GPA, anti-C5a and anti-C5aR antibody concentrations inversely correlated with each other (r = -0.6831, P = 0.0127). In newly diagnosed GPA, decreased concentrations of anti-C5aR antibodies but not anti-C3aR antibodies were associated with disease activity (P = 0.0009). Moreover, low anti-C5aR antibodies were associated with relapse in GPA (hazard ratio 3.54, P = 0.0009) and MPA (hazard ratio 4.41, P = 0.0041). The frequency of C5aR-expressing cells within T cell populations was increased in GPA (P = 0.0021 for CD4+ T cells; P = 0.0118 for CD8+ T cells), but not in MPA. CONCLUSION: Low concentrations of anti-C5aR antibodies reflect disease activity and are associated with an increased risk for relapse in AAV.


Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Microscopic Polyangiitis , Humans , Antibodies, Antineutrophil Cytoplasmic , Receptors, Complement/metabolism , Recurrence , Complement C5a
6.
Clin Transplant ; 36(3): e14554, 2022 03.
Article in English | MEDLINE | ID: mdl-34862985

ABSTRACT

BACKGROUND: The shortage of organs for transplantation remains a global problem. The retransplantation of a previously transplanted kidney might be a possibility to expand the pool of donors. We provide our experience with the successful reuse of transplanted kidneys in the Eurotransplant region. METHODS: A query in the Eurotransplant database was performed between January 1, 1995 and December 31, 2015, to find kidney donors who themselves had previously received a kidney graft. RESULTS: Nine out of a total of 68,554 allocated kidneys had previously been transplanted. Four of these kidneys were transplanted once again. The mean interval between the first transplant and retransplantation was 1689±1682 days (SD; range 55-5,333 days). At the time of the first transplantation the mean serum creatinine of the donors was 1.0 mg/dl (.6-1.3 mg/dl) and at the second transplantation 1.4 mg/dl (.8-1.5 mg/dl). The mean graft survival in the first recipient was 50 months (2-110 months) and in the second recipient 111 months (40-215 months). CONCLUSION: Transplantation of a previously transplanted kidney may successfully be performed with well-preserved graft function and long-term graft survival, even if the first transplantation was performed a long time ago. Such organs should be considered even for younger recipients in carefully selected cases.


Subject(s)
Kidney Transplantation , Tissue and Organ Procurement , Graft Survival , Humans , Kidney , Tissue Donors
7.
Transpl Immunol ; 69: 101449, 2021 12.
Article in English | MEDLINE | ID: mdl-34391884

ABSTRACT

BACKGROUND: Patients awaiting kidney transplantation are regularly screened for HLA-antibodies, but there is scarce data about the optimal interval. METHODS: Results from Complement-dependent cytotoxicity testing (CDC) for waitlisted patients were reviewed for increases in panel reactive antibodies (PRA) by at least 10%-points. Clinical records were screened for historic immunizing events and possible trigger factors preceding the PRA-increase. Additionally, non-pretransplanted men tested negative for HLA antibodies by solid-phase assays (SPA) out of their first two samples on the waiting list ("non-immunized men") were evaluated for detection of HLA antibodies by SPA during their further stay on the waiting list. RESULTS: 15,360 samples from 1928 patients tested by CDC were analyzed for changes in PRA. PRA-increases occurred most frequently in patients waitlisted recently for retransplantation (annual incidence 6%). Removal of previous transplants, severe infections and/or reduced immunosuppression triggered 65% of PRA-increases during the first year after waitlisting. Transfusions accounted for 55% of PRA-increases in later years. Leucocyte-reduced red blood cell units not only boosted historic antibodies, but even induced primary immunization. In the second part of the study, 6780 samples tested by SPA from 703 non-immunized men were evaluated for development of HLA-antibodies. Only 9 men (1.3%) turned HLA antibody-positive (annual incidence 0.4%). CONCLUSION: A uniform screening interval does not fit all: Frequencies should be highest in patients newly waitlisted for re-transplant and lowest in non-immunized men. Transfused patients should be monitored closely for development of HLA-antibodies even if leukoreduced products are used.


Subject(s)
Kidney Transplantation , HLA Antigens , Histocompatibility Testing , Humans , Immunosuppression Therapy , Isoantibodies , Male , Waiting Lists
8.
Clin Nephrol ; 96(6): 337-347, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34402785

ABSTRACT

BACKGROUND: The prevalence of chronic kidney disease (CKD) requiring dialysis therapy is increasing globally. Survival and mortality data of these patients in Germany are fragmentary since the nationwide registry was terminated in 2006. OBJECTIVE: The objective of this study was to analyze the survival, causes of death, and co-morbidities of dialysis patients in a German population cohort as well as to assess the factors influencing mortality in these patients. MATERIALS AND METHODS: We included adult, prevalent chronic dialysis patients from the German population who underwent hemodialysis and peritoneal dialysis at our centers between 2014 and 2018. We compared the characteristics of living and deceased patients and assessed survival. Patients with and without diabetes mellitus were also examined, and their co-morbidities were analyzed. RESULTS: Of the 425 patients included in our study (m/f: 235/190), 182 died within the observation period. Mean survival of patients with coronary artery disease (CAD) (n = 217), peripheral artery disease (PAD) (n = 128), and cardiorenal syndrome (CRS) (n = 99) was significantly reduced compared to patients without the disease (CAD: 4.2 vs. 6.4 years; PAD: 4.3 vs. 6.5 years; CRS: 3.7 vs. 7.3 years, p < 0.001, respectively). Patients with diabetes mellitus (n = 110) showed no reduced survival compared to patients without the disease (n = 315) (4.8 vs. 4.9 years, p = 0.421). Diastolic blood pressure (DBP) and C-reactive protein (CRP) levels were associated with dialysis time in linear regression analysis (DBP: R = 0.029, p < 0,001; CRP: R = 0.085, p < 0.001). CONCLUSION: Our results provide novel data regarding German CKD patients requiring dialysis and factors influencing mortality, which could serve as a useful reference for further studies.


Subject(s)
Nephrology , Peritoneal Dialysis , Adult , Humans , Peritoneal Dialysis/adverse effects , Prospective Studies , Renal Dialysis , Risk Factors
9.
Zentralbl Chir ; 146(4): 413-416, 2021 Aug.
Article in German | MEDLINE | ID: mdl-33882615

ABSTRACT

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.


Subject(s)
Kidney Transplantation , Academic Medical Centers , Humans , Minimally Invasive Surgical Procedures
11.
PLoS One ; 16(4): e0246118, 2021.
Article in English | MEDLINE | ID: mdl-33861738

ABSTRACT

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.


Subject(s)
Cytomegalovirus Infections/genetics , Interferon-gamma/genetics , Interleukin-10/genetics , Interleukin-1/genetics , Toll-Like Receptor 4/genetics , Tumor Necrosis Factor-alpha/genetics , Adult , Aged , Antiviral Agents/therapeutic use , Cytomegalovirus/isolation & purification , Cytomegalovirus Infections/etiology , Cytomegalovirus Infections/prevention & control , Female , Humans , Kidney Transplantation/adverse effects , Male , Middle Aged , Polymorphism, Single Nucleotide , Prospective Studies , Valganciclovir/therapeutic use
13.
Front Immunol ; 11: 1886, 2020.
Article in English | MEDLINE | ID: mdl-32983110

ABSTRACT

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, P < 0.001) or donor-specific HLA antibodies (DSA, HR=7.39, P < 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.


Subject(s)
Delayed Graft Function/immunology , Graft Rejection/immunology , HLA Antigens/immunology , Isoantibodies/blood , Kidney Transplantation/adverse effects , Adult , Aged , Biomarkers/blood , Delayed Graft Function/blood , Delayed Graft Function/diagnosis , Delayed Graft Function/mortality , Europe , Female , Graft Rejection/blood , Graft Rejection/diagnosis , Graft Rejection/mortality , Graft Survival , Humans , Kidney Transplantation/mortality , Male , Middle Aged , Prospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome
14.
Transpl Int ; 33(6): 617-631, 2020 06.
Article in English | MEDLINE | ID: mdl-31903658

ABSTRACT

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.


Subject(s)
Kidney Transplantation , Tissue and Organ Procurement , Graft Survival , Humans , Kidney , Retrospective Studies , Tissue Donors , Treatment Outcome
15.
Orphanet J Rare Dis ; 14(1): 260, 2019 11 15.
Article in English | MEDLINE | ID: mdl-31730475

ABSTRACT

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.


Subject(s)
Purpura, Thrombotic Thrombocytopenic/epidemiology , Adult , Female , Germany , Hospitals/statistics & numerical data , Humans , Incidence , Logistic Models , Male
16.
Clin J Am Soc Nephrol ; 14(7): 1056-1066, 2019 07 05.
Article in English | MEDLINE | ID: mdl-31213508

ABSTRACT

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; P<0.001) and 1.59 for deceased donation (95% CI, 1.21 to 2.11; P=0.001). ABO-incompatible transplantation was associated with worse graft survival (hazard ratio, 2.09; 95% CI, 1.33 to 3.27; P=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.


Subject(s)
HLA Antigens/immunology , Isoantibodies/blood , Kidney Transplantation , Living Donors , Tissue Donors , ABO Blood-Group System/immunology , Adult , Aged , Blood Group Incompatibility , Female , Graft Survival , Humans , Male , Middle Aged
17.
Kidney Int ; 94(6): 1177-1188, 2018 12.
Article in English | MEDLINE | ID: mdl-30385041

ABSTRACT

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 m2, G1 ≤15 ml/min/1.73 m2). 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.


Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/complications , Glomerulonephritis/immunology , Kidney Failure, Chronic/diagnosis , Aged , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/immunology , Antibodies, Antineutrophil Cytoplasmic , Biopsy , Cohort Studies , Disease Progression , Female , Glomerular Filtration Rate , Glomerulonephritis/pathology , Glomerulonephritis/physiopathology , Humans , Kidney Failure, Chronic/pathology , Kidney Failure, Chronic/physiopathology , Kidney Glomerulus/immunology , Kidney Glomerulus/pathology , Kidney Glomerulus/physiopathology , Male , Middle Aged , Prognosis , Prospective Studies , Risk Assessment/methods
18.
Ultrasound Int Open ; 4(4): E142-E148, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30370402

ABSTRACT

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.

19.
Case Rep Transplant ; 2018: 3757382, 2018.
Article in English | MEDLINE | ID: mdl-30147982

ABSTRACT

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.

20.
Nephron Extra ; 8(1): 1-10, 2018.
Article in English | MEDLINE | ID: mdl-29849535

ABSTRACT

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, t0), 3-5 days (t3-5), 10-17 days (t10-17), and after 1 year of follow-up (t365). 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 t0 and increased to 27 ± 26 mL/min (t3-5), 57 ± 20 mL/min (t10-17), and 84 ± 16 mL/min (t365). Albuminuria and tubular proteinuria (α1- and ß2-microglobulin) decreased during follow-up; the urinary α1-microglobulin concentration in patients who required HD was significantly higher than that in patients not requiring HD (t0: 186 ± 51 vs. 45 ± 26 mg/g creatinine; t3-5: 87 ± 14 vs. 32 ± 16 mg/g creatinine; t10-17: 63 ± 18 vs. 28 ± 12 mg/g creatinine; p < 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.

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