Long-Term Follow-Up after Paediatric Kidney Transplantation and Influence Factors on Graft Survival: A Single-Centre Experience of 16 years

Introduction: To evaluate graft- and patient survival after paediatric kidney transplantation and detecting influence factors, which affect the post-transplant time. Materials and Methods: We analysed long-term survival rates and complications after paediatric kidney transplantation and searched for predictive parameters for graft function. Results: In 132 patients, 143 kidney transplantations were performed. Graft failure occurred in 25%. Chronic rejections were the leading cause of graft loss (42.9%). Graft survival rates were 92.2% after 1 year, 85.5% after 5 years, 71.1% after 10 years and 62.1% after 15 years. The following parameters strongly influenced graft survival: number of transplants (p = 0.014), year of transplant (p 50 min (p = 0.008), delayed graft function (p = 0.003) and deceased donation (p = 0.039). The percentage of patients who died was 5.6%. Overall patient survival rates were 99.3% after 1 year, 95.2% after 5 years, 94.2% after 10 years and 90.7% after 15 years. Various types of infections (42.9%) were the main causes of death. Conclusions: The main causes of death after kidney transplantations in paediatric recipients are malignancy and infections. To avoid vascular complications especially in young recipients (< 9 years), the cold ischemia time should be as short as possible

Long-term survival after pediatric kidney transplantation

Zusammenfassung Einleitung Die Nierentransplantation ist bei terminaler Niereninsuffizienz im Kindesalter die Behand-lungsmethode der Wahl. Dank neuer Immunsuppressiva zeigte sich in den letzten Jahren ein Rückgang der Rejektionen sowie ein verbessertes Transplantat- und Patientenüberle-ben. Methodik Kinder und Jugendliche, die von 01/1997–05/2013 an der Charité nierentransplantiert wur-den, sind retrospektiv untersucht worden. Es wurden der Langzeitverlauf und Komplikati-onen nach Nierentransplantation im Kindes- und Jugendalter erfasst sowie prädiktive Fak-toren identifiziert. Signifikanztests wurden durchgeführt, die binäre logistische Regression angewendet sowie definierte Endpunkte als Kaplan-Meier-Überlebenskurven dargestellt. Ergebnisse Es wurden 143 Nierentransplantationen bei 132 Patienten durchgeführt. Das mittlere Alter bei Transplantation betrug 11,5 ± 4,8 Jahre. Die häufigsten zur terminalen Niereninsuffizi-enz führenden Erkrankungen waren angeborene Fehlbildungen der Niere und der ableiten-den Harnwege mit 34,1% (45/123). Der Lebendspenderanteil betrug 24,5% (35/143). 9,8% (14/143) der Kinder wurden präemptiv transplantiert. Das mittlere Spenderalter lag bei 33,3 ± 19,6 Jahren. Vaskuläre Komplikationen waren mit 29,3% postoperativ die größte Gruppe. Am häufigsten wurde mit 42% eine Kombinationstherapie aus einem Glukokortikoid, My-cophenolatmofetil und Cyclosporin A angewendet. Bei 44,1% (63/143) der Kinder traten Rejektionsepisoden auf. Die mittlere Anzahl renaler Begleiterkrankungen vor Nierentrans-plantation lag bei 3,3 ± 1,4 gegenüber einem Wert von 2,5 ± 1,4 nach NTX (p < 0,001). Insgesamt traten bei 67,8% (97/143) der Kinder nach Nierentransplantation stationär the-rapiebedürftige Infektionen (davon 28,7% (41/143) Harnwegsinfektionen) auf. Ein Transplantatversagen trat bei 24,5% (35/143) der Kinder ein. Die häufigste Ursache des Transplantatverlustes war das chronische Transplantatversagen (42,9% (15/35)). Die mittlere Funktionsdauer betrug 7,1 ± 5,1 Jahre. Das 1-, 5-, 10- und 15-Jahresüberleben des Transplantates lag bei 92,2%, 85,5%, 71,1% und 62,1%. In der weiterführenden Statistik waren die Variablen Transplantationszeitraum (p = 0,005), Anzahl bioptisch gesicherte Rejektionen (p = 0,032) und Panel reaktive Antikörper nach Transplantation (p = 0,005) signifikant für die Variable des Transplantatversagens. 5,6% (8/143) der Kinder verstarben. Die mittlere Lebensdauer betrug 8,8 ± 5,0 Jahre. Das 1-, 5-, 10- und 15-Jahresüberleben lag bei 99,3%, 95,2%, 94,2% und 90,7%. Die weiter-führende Statistik zeigte für Retransplantation (p = 0,022) und lymphoproliferative Er-krankungen nach Transplantation (p = 0,002) Signifikanz in Bezug auf das Patientenüber-leben. Infektionen stellten mit 42,9% (3/7) die häufigste Todesursache dar. Schlussfolgerung Die chronische Transplantatabstoßung ist die häufigste Ursache eines Nierentransplantat-verlustes. Maligne Erkrankungen und Infektionen sind die häufigsten Todesursachen. Langzeitprobleme sind Hypertonus und kardiovaskuläre Störungen, Wachstums- und Ge-wichtsentwicklung, Harnwegsinfektionen sowie maligne Erkrankungen.Abstract Background Renal Transplantation remains the treatment of choice for children with end stage renal disease. Due to new immunosuppressive medication decreased number of rejections and improvement of transplant- and patient outcome have been seen. Methods Children and adolescent transplanted at Charité university hospital from January 1997 to May 2013 were assessed retrospectively. Long-term survival rates and complications after pediatric kidney transplantation and predictive parameters for graft function were ana- lyzed. Significance tests, Binary logistic regression and Kaplan-Meier survival curves were applied. Results 143 kidney transplantations were performed in 132 patients. The mean age at transplanta-tion was 11.5 ± 4.8 years. The main primary diagnosis causing end stage renal disease was congenital anomalies of the kidney and urinary tract (34.1% (45/123)). The percentage of living kidney donation was 24.5% (35/143). Preemptive transplantation was performed in 9.8% (14/143). The mean donor age was 33.3 ± 19.6 years. Postoperative vascular complications made the major group with 29.3%. A combined immunosuppression with Prednisone, Mycophenolatmofetil and Cyclosporine was used most often (42%). Rejections occurred in 44.1% (63/143). The mean number of diseases associated with renal end stage disease decreased from 3.3 ± 1.4 to 2.5 ± 1.4 after renal transplantation (p < 0.001). At large 67.8% (97/143) developed infections treated in hospital (most often urinary tract infection with 28.7% (41/143)). Graft failure occurred in 25% (35/143). Chronic rejections were the leading cause of graft loss (42.9% (15/35)). The mean duration of graft function was 7.1 ± 5.1 years. Graft sur-vival rates were 92.2% after 1 year, 85.5% after 5 years, 71.1% after 10 years and 62.1% after 15 years. Binary logistic regression confirmed the significance oft the following vari-ables concerning graft failure: Transplantation era (p = 0.005), rejections proved by biopsy (p = 0.032) and panel reactive antibodies after transplantation (p = 0.005). 5.6% of the patients died. The mean patient survival was 8.8 ± 5.0 years. Overall patient survival rates were 99.3% after 1 year, 95.2% after 5 years, 94.2% after 10 years and 90.7% after 15 years. Binary logistic regression showed retransplantation (p = 0.022) and Post- Transplant-Lymphoproliferative-Disorders (p = 0.002) as significant parameters for patient survival. Infections were the main causes of death with an amount of 42.9% (3/7). Conclusions The main causes of graft loss are chronic rejections. Malignancy and infections are the main causes of death. Long-term problems are hypertension, cardiovascular diseases, de-velopment of growth and weight, urinary tract infections and malignancy

Immunological Risk Factors in Paediatric Kidney Transplantation

Purpose: The aim of this study was to identify factors impacting recipient sensitization rates and paediatric renal transplant patient outcomes. Patients and Methods: For this purpose, a retrospective analysis of 143 paediatric renal transplants was carried out. This included the evaluation of patient's and donor's demographic data, HLA mismatches, immunosuppressive therapy, rejection episodes, panel reactive antibody (PRA) and post-transplant lymphoproliferative disease (PTLD). Results: The mean patient age at the point of transplant receival was 11.5 years with a mean follow up time of 9.33 +/- 5.05 years. It was noted that graft survival rates for donors over 59 years had the worst outcome. HLA match did not show statistically significant influence on graft outcome. Graft survival for more than one biopsy-proven rejection was also significantly shorter (p=0.008). PRA were found in 28% of the recipient's post-transplantation and showed association with lower graft survival rates (p<0.001). In the present study, 22.7% (5/22) of the patients with EBV infections presented a PTLD. Conclusion: In conclusion, good graft survival with reduced sensitization for future transplantations and minimize the risk of PTLD, can be ensured through a balance between donor age, HLA match and condition of the recipient should be sought. Furthermore, paediatric patients should preferably receive organs from donors between the age of 10 and 59. EBV infection could be a relevant factor for developing PTLD

General Practitioner’s Knowledge about Bariatric Surgery Is Associated with Referral Practice to Bariatric Surgery Centers

(1) Background: Patients seeking treatment for obesity and related diseases often contact general practitioners (GPs) first. The aim of this study was to evaluate GPs’ knowledge about weight loss surgery (WLS) and potential stereotypes towards obese patients. (2) Methods: For this prospective cohort study, 204 GPs in the region of the bariatric surgery center at the University Hospital Aachen were included. The participants filled out a questionnaire comprising general treatment of obese patients, stigmatization towards obese patients (1–5 points) as well as knowledge regarding WLS (1–5 points). (3) Results: The mean age of the GPs was 54 years; 41% were female. Mean score for self-reported knowledge was 3.6 points out of 5. For stigma-related items, the mean score was 3.3 points out of 5. A total of 60% of the participants recognized bariatric surgery as being useful. Knowledge about bariatric surgery significantly correlated with the number of referrals to bariatric surgery centers (p &lt; 0.001). No significant correlation was found between stigma and referral to surgery (p = 0.057). (4) Conclusions: The more GPs subjectively know about bariatric surgery, the more often they refer patients to bariatric surgery specialists—regardless of potentially present stereotypes. Therefore, GPs should be well informed about indications and opportunities of WLS

Virtual histology of cortical thickness and shared neurobiology in 6 psychiatric disorders

Importance Large-scale neuroimaging studies have revealed group differences in cortical thickness across many psychiatric disorders. The underlying neurobiology behind these differences is not well understood. Objective To determine neurobiologic correlates of group differences in cortical thickness between cases and controls in 6 disorders: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and schizophrenia. Design, Setting, and Participants Profiles of group differences in cortical thickness between cases and controls were generated using T1-weighted magnetic resonance images. Similarity between interregional profiles of cell-specific gene expression and those in the group differences in cortical thickness were investigated in each disorder. Next, principal component analysis was used to reveal a shared profile of group difference in thickness across the disorders. Analysis for gene coexpression, clustering, and enrichment for genes associated with these disorders were conducted. Data analysis was conducted between June and December 2019. The analysis included 145 cohorts across 6 psychiatric disorders drawn from the ENIGMA consortium. The numbers of cases and controls in each of the 6 disorders were as follows: ADHD: 1814 and 1602; ASD: 1748 and 1770; BD: 1547 and 3405; MDD: 2658 and 3572; OCD: 2266 and 2007; and schizophrenia: 2688 and 3244. Main Outcomes and Measures Interregional profiles of group difference in cortical thickness between cases and controls. Results A total of 12 721 cases and 15 600 controls, ranging from ages 2 to 89 years, were included in this study. Interregional profiles of group differences in cortical thickness for each of the 6 psychiatric disorders were associated with profiles of gene expression specific to pyramidal (CA1) cells, astrocytes (except for BD), and microglia (except for OCD); collectively, gene-expression profiles of the 3 cell types explain between 25% and 54% of variance in interregional profiles of group differences in cortical thickness. Principal component analysis revealed a shared profile of difference in cortical thickness across the 6 disorders (48% variance explained); interregional profile of this principal component 1 was associated with that of the pyramidal-cell gene expression (explaining 56% of interregional variation). Coexpression analyses of these genes revealed 2 clusters: (1) a prenatal cluster enriched with genes involved in neurodevelopmental (axon guidance) processes and (2) a postnatal cluster enriched with genes involved in synaptic activity and plasticity-related processes. These clusters were enriched with genes associated with all 6 psychiatric disorders. Conclusions and Relevance In this study, shared neurobiologic processes were associated with differences in cortical thickness across multiple psychiatric disorders. These processes implicate a common role of prenatal development and postnatal functioning of the cerebral cortex in these disorders