Search

BackgroundPediatric kidney transplantations are rarely performed, and there is limited knowledge about the diversity in current clinical practices across Europe. This study aims to explore the utility of clinical snapshot studies in identifying these disparities, establishing a foundation for future snapshot studies and standardization efforts.MethodsA pilot clinical snapshot study was conducted, with invitations extended to all 109 pediatric kidney transplant centres in Europe. Each participating centre provided pre-, peri-, and postoperative data concerning their most recent thirty transplantations. The primary outcomes encompassed the evaluation of disparities in donor-recipient selection, surgical techniques, post-operative drainage procedures, and immunosuppressive therapy protocols. Secondary outcomes involved the analysis of rejection rates, incidence of infections, and graft survival.ResultsThe study involved 439 patients from fifteen centres (14%) in twelve countries, with varying transplant volumes (range 1–29 transplantations per year) and follow-up periods. Significant differences were found among centres in terms of donor types, cold and warm ischemia time, pre-emptive transplant rates, and kidney transplant drainage methods. The rate of living donors varied between 3% and 90% and the median duration of cold ischemia ranged was 770 min after deceased donation and 147 min after living donation. Basiliximab was the dominant induction therapy, yet steroid withdrawal varied widely. Infection, rejection, and graft survival rates also varied significantly between centres.ConclusionThis study revealed substantial variation in clinical practices among European centres performing pediatric kidney transplantations. These findings could serve as a stimulus for international dialogue and collaboration.

Author(s): Aleksandra Zurowska [sup.1] [sup.2] , Magdalena Drozynska-Duklas [sup.1] , Rezan Topaloglu [sup.3] , Antonia Bouts [sup.4] , Olivia Boyer [sup.5] [sup.6] , Mohan Shenoy [sup.7] , Marina Vivarelli [sup.8] [...], Background There is paucity of information on rituximab-associated hypogammaglobulinemia (HGG) and its potential infectious consequences in children treated for idiopathic nephrotic syndrome (INS). Methods A survey was distributed by the European Society Pediatric Nephrology to its members. It addressed the screening and management practices of pediatric nephrology units for recognizing and treating RTX-associated HGG and its morbidity and mortality. Eighty-four centers which had treated an overall 1328 INS children with RTX responded. Results The majority of centers administered several courses of RTX and continued concomitant immunosuppressive therapy. Sixty-five percent of centers routinely screened children for HGG prior to RTX infusion, 59% during, and 52% following RTX treatment. Forty-seven percent had observed HGG prior to RTX administration, 61% during and 47% >9 months following treatment in 121, 210, and 128 subjects respectively. Thirty-three severe infections were reported among the cohort of 1328 RTX-treated subjects, of whom 3 children died. HGG had been recognized in 30/33 (80%) of them. Conclusions HGG in steroid-dependent/frequently relapsing nephrotic syndrome (SDNS/FRNS) children is probably multifactorial and can be observed prior to RTX administration in children with SDNS/FRNS. Persistent HGG lasting >9 months from RTX infusion is not uncommon and may increase the risk of severe infections in this cohort. We advocate for the obligatory screening for HGG in children with SDNS/FRNS prior to, during, and following RTX treatment. Further research is necessary to identify risk factors for developing both HGG and severe infections before recommendations are made for its optimal management. Graphical abstract

Metastatic and recurrent cervical cancer is difficult to treat with limited options following platinum-based chemotherapy. Tisotumab vedotin (TV) is an antibody drug conjugate (ADC) targeted at a tissue factor (TF), which is a cell surface protein that is upregulated in the majority of cervical cancers. Prior clinical trials have demonstrated efficacy of TV in metastatic and recurrent cervical cancer with an objective response rate of 24–26 % with an 8.3 month duration of response. In this case series, we present 3 patients with recurrent or progressive cervical cancer of three different histologies (squamous cell, adenocarcinoma, and human papillomavirus (HPV)-independent gastric type carcinomas). We demonstrate a 100 % complete response rate with average time of complete response of 4.33 months. The duration of response was not reached as none of our patients had a confirmed progression at the time of writing this manuscript, but the mean time since the initiation of treatment was 6.1 months. In concordance with the clinical trials, our patients tolerated TV well although the grade 3 ocular toxicities were higher in our patients compared to prior data. This case series presents data confirming the efficacy and tolerability of TV in patients with recurrent cervical cancer, including an HPV-independent gastric type cervical cancer.

Author(s): Gilles Tourlamain [sup.1] , Mandy Keijzer-Veen [sup.2] , Antonia Bouts [sup.3] , Karlien Cransberg [sup.4] , Huib de Jong [sup.4] , Rani De Pauw [sup.1] , Karen Vanderstraeten [sup.1] [...], Background Catch-up growth after pediatric kidney transplantation (kTx) is usually insufficient to reach normal adult height. We aimed to analyze the effect of pre-transplant recombinant human growth hormone (rhGH) and corticosteroid withdrawal on linear growth in the first year after kidney transplantation and identify factors associated with final height (FH). Methods Patients who underwent kTx between 1996 and 2018 at below 18 years old in five Belgian and Dutch centers were included. We analyzed the differences between height Z-scores at kTx and 1 year post-transplant ([DELTA] height Z-score) in children with and without corticosteroids at 1 year (CS + /CS -) and with and without rhGH treatment before kTx (rhGH + /rhGH -). Univariable and multivariable linear regression analysis was applied to identify factors associated with height Z-score at 1 year post-kTx, [DELTA] height Z-score, and FH Z-score. Results A total of 177 patients were included, with median age 9.3 years at kTx. Median height Z-scores pre-kTx and 1 year later in the CS - /rhGH -, CS + /rhGH -, CS - /rhGH +, and CS + /rhGH + groups were - 1.42/ - 0.80, - 0.90/ - 0.62, - 1.35/ - 1.20, and - 1.30/ - 1.60 (p = 0.001). CS use 1 year post-kTx was the only factor associated with [DELTA] height (p = 0.003) on multivariable analysis. CS use at 1 year was the only variable associated with FH (p = 0.014) in children with pre-transplant height Z-score below - 1 (n = 52). Conclusions Increase in height Z-score in the first year post-kTx was highest in the CS - /rhGH - group and lowest in the CS + /rhGH + group. The use of corticosteroids at 1 year post-kTx is associated with catch-up growth and in children with pre-transplant height Z-score below - 1 also with final height. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information

Author(s): Floor Veltkamp [sup.1] , Arend Bökenkamp [sup.1] [sup.2] , Jeroen Slaats [sup.3] , Henrike Hamer [sup.3] , Antonia H. M. Bouts [sup.1] Author Affiliations: (1) grid.7177.6, 0000000084992262, Department of [...], Background In pediatric patients treated with levamisole to prevent relapses of idiopathic nephrotic syndrome (INS), a transient and non-progressive rise in creatinine levels has been observed. It has been suggested that levamisole affects tubular secretion of creatinine. However, other potential mechanisms - nephrotoxicity and interference with the analytical assay for creatinine - have never been thoroughly investigated. Methods In three steroid-sensitive nephrotic syndrome (SSNS) patients with elevated plasma creatinine levels, treated with levamisole 2.5 mg/kg every other day, serum cystatin C was determined. The glomerular filtration rate (GFR) was estimated using the full age spectrum for creatinine and the full age spectrum for cystatin C equations. Interference of levamisole with the enzymatic creatinine assay was tested using spare human plasma of different creatinine concentrations spiked with levamisole (4, 20, and 100 [micro]M). Results Three patients who received levamisole with elevated plasma creatinine levels had normal serum cystatin C levels and corresponding estimated GFR. There was no assay interference. Conclusion Levamisole increases plasma creatinine levels, which is most probably due to impaired tubular secretion of creatinine since there was no assay interference and patients had normal eGFR based on serum cystatin C. However, interference of metabolites of levamisole could not be excluded. To monitor GFR, cystatin C in addition to creatinine should be used and be measured before and during levamisole use.

Author(s): Marloes A. H. M. Michels [sup.1] , Kioa L. Wijnsma [sup.1] , Roel A. J. Kurvers [sup.2] , Dineke Westra [sup.1] , Michiel F. Schreuder [sup.1] , Joanna A. [...], Background C3 glomerulopathy (C3G) is a rare kidney disorder characterized by predominant glomerular depositions of complement C3. C3G can be subdivided into dense deposit disease (DDD) and C3 glomerulonephritis (C3GN). This study describes the long-term follow-up with extensive complement analysis of 29 Dutch children with C3G. Methods Twenty-nine C3G patients (19 DDD, 10 C3GN) diagnosed between 1992 and 2014 were included. Clinical and laboratory findings were collected at presentation and during follow-up. Specialized assays were used to detect rare variants in complement genes and measure complement-directed autoantibodies and biomarkers in blood. Results DDD patients presented with lower estimated glomerular filtration rate (eGFR). C3 nephritic factors (C3NeFs) were detected in 20 patients and remained detectable over time despite immunosuppressive treatment. At presentation, low serum C3 levels were detected in 84% of all patients. During follow-up, in about 50% of patients, all of them C3NeF-positive, C3 levels remained low. Linear mixed model analysis showed that C3GN patients had higher soluble C5b-9 (sC5b-9) and lower properdin levels compared to DDD patients. With a median follow-up of 52 months, an overall benign outcome was observed with only six patients with eGFR below 90 ml/min/1.73 m.sup.2 at last follow-up. Conclusions We extensively described clinical and laboratory findings including complement features of an exclusively pediatric C3G cohort. Outcome was relatively benign, persistent low C3 correlated with C3NeF presence, and C3GN was associated with higher sC5b-9 and lower properdin levels. Prospective studies are needed to further elucidate the pathogenic mechanisms underlying C3G and guide personalized medicine with complement therapeutics. Graphical abstract

Abstract Background Parental donor kidney transplantation is the most common treatment option for children and adolescents with kidney failure. Emerging data from observational studies have reported improved short- and medium-term allograft outcomes in recipients of paternal compared to maternal donors. The INCEPTION study aims to identify potential differences in immunological compatibility between maternal and paternal donor kidneys and ascertain how this affects kidney allograft outcomes in children and adolescents with kidney failure. Methods This longitudinal observational study will recruit kidney transplant recipients aged ≤18 years who have received a parental donor kidney transplant across 4 countries (Australia, New Zealand, United Kingdom and the Netherlands) between 1990 and 2020. High resolution human leukocyte antigen (HLA) typing of both recipients and corresponding parental donors will be undertaken, to provide an in-depth assessment of immunological compatibility. The primary outcome is a composite of de novo donor-specific anti-HLA antibody (DSA), biopsy-proven acute rejection or allograft loss up to 60-months post-transplantation. Secondary outcomes are de novo DSA, biopsy-proven acute rejection, acute or chronic antibody mediated rejection or Chronic Allograft Damage Index (CADI) score of > 1 on allograft biopsy post-transplant, allograft function, proteinuria and allograft loss. Using principal component analysis and Cox proportional hazards regression modelling, we will determine the associations between defined sets of immunological and clinical parameters that may identify risk stratification for the primary and secondary outcome measures among young people accepting a parental donor kidney for transplantation. This study design will allow us to specifically investigate the relative importance of accepting a maternal compared to paternal donor, for families deciding on the best option for donation. Discussion The INCEPTION study findings will explore potentially differential immunological risks of maternal and paternal donor kidneys for transplantation among children and adolescents. Our study will provide the evidence base underpinning the selection of parental donor in order to achieve the best projected long-term kidney transplant and overall health outcomes for children and adolescents, a recognized vulnerable population. Trial registration The INCEPTION study has been registered with the Australian New Zealand Clinical Trials Registry, with the trial registration number of ACTRN12620000911998 (14th September 2020).

BackgroundExercise is an effective strategy for the prevention and regression of hepatic steatosis in patients with non-alcoholic fatty liver disease (NAFLD), but it is unclear whether it can reduce advanced stages of NAFLD, i.e., steatohepatitis and liver fibrosis. Furthermore, it is not evident which modality of exercise is optimal to improve/attenuate NAFLD.ObjectivesThe aim is to systematically review evidence for the effect of aerobic exercise (AE) on NAFLD, in particular non-alcoholic steatohepatitis (NASH) and liver fibrosis.MethodsA systematic literature search was conducted in Medline and Embase. Studies were screened and included according to predefined criteria, data were extracted, and the quality was assessed by Cochrane risk of bias tools by two researchers independently according to the protocol registered in the PROSPERO database (CRD42021270059). Meta-analyses were performed using a bivariate random-effects model when there were at least three randomized intervention studies (RCTs) with similar intervention modalities and outcome.ResultsThe systematic review process resulted in an inclusion a total of 24 studies, 18 RCTs and six non-RCTs, encompassing 1014 patients with NAFLD diagnosed by histological or radiological findings. Studies were grouped based on the type of AE: moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT). A total of twelve meta-analyses were conducted. Compared to controls, MICT resulted in a mean difference (MD) in the NAFLD biomarkers alanine transaminase (ALT) and aspartate aminotransferase (AST) of -3.59 (CI: -5.60, -1.59, p

Author(s): Karen Vanderstraeten [sup.1] , Rani De Pauw [sup.1] , Noël Knops [sup.2] , Antonia Bouts [sup.3] , Karlien Cransberg [sup.4] , Amina El Amouri [sup.1] , Ann Raes [sup.1] [...], Background Hyperparathyroidism persists in up to 50% of pediatric kidney transplant recipients. The aims of this study were to describe the evolution of parathyroid hormone (PTH) in the first year after transplantation and to identify factors associated with hyperparathyroidism. Methods This retrospective study included children who underwent kidney transplantation at the University Hospitals of Ghent, Leuven, Rotterdam, or Amsterdam. Data from 149 patients were collected before and up to 12 months after transplantation. Severe hyperparathyroidism was defined as PTH 2-fold above the reference value. Factors associated with hyperparathyroidism and severe hyperparathyroidism were identified using multivariate logistic regression analysis. Results Before transplantation, 97 out of 137 patients (71%) had hyperparathyroidism. The probability of hyperparathyroidism and severe hyperparathyroidism declined from 0.49 and 0.17 to 0.29 and 0.09 at 3 and 12 months after transplantation, respectively. BMI SDS ([beta]: 0.509; p = 0.011; 95% CI: 1.122-2.468), eGFR ([beta]: - 0.227; p = 0.030; 95% CI: 0.649-0.978), and pre-transplant hyperparathyroidism ([beta]: 1.149; p = 0.039; 95% CI: 1.062-9.369) were associated with hyperparathyroidism 12 months after transplantation. Pre-transplant hyperparathyroidism ([beta]: 2.115; p = 0.044; 95% CI: 1.055-65.084), defined as intact parathormone (iPTH) levels > 65 ng/l (6.9 pmol/l) or 1-84 PTH > 58 ng/l (6.2 pmol/l), was associated with severe hyperparathyroidism at 3 months. Only eGFR ([beta]: - 0.488; p = 0.010; 95% CI: 0.425-0.888) was inversely associated with severe hyperparathyroidism at 9 months after transplantation. Conclusions Allograft function remains the main determinant of severe hyperparathyroidism after transplantation. Our findings emphasize the importance of BMI and pre-transplant PTH control.

Abstract Background Echocardiography is the most frequently used non -invasive diagnostic tool to evaluate cardiac anatomy and function in domestic species but increasingly also in non -domestic species, especially since cardiac disease is being recognized as an important cause of death in captive primates. The purpose of this cross -sectional study was to investigate the feasibility of transthoracic echocardiography in healthy squirrel monkeys as well as to provide species specific normal values for standard echocardiographic measurements. A secondary aim was to determine plasma and serum levels of the cardiac biomarkers, N -terminal pro -brain natriuretic peptide (NT -proBNP) and cardiac troponin T (cTnT). Furthermore, a commercial, non -invasive, smartphone -based ECG (AliveCor Vet TM) monitoring device was used to evaluate the heart rate and rhythm and to diagnose possible arrhythmias. Results In this study, transthoracic echocardiography of 14 squirrel monkeys was performed in right and left lateral recumbency. Similar standard right parasternal and left apical images were obtained as in dogs and cats and normal values for routine two -dimensional, time motion mode and Doppler mode measurements were generated. Thirteen animals were considered healthy and one squirrel monkey was identified with significant aortic dilation and regurgitation and consequently values obtained from this animal were not used when species specific normal values were calculated. NT -ProBNP and cTnT concentrations were available for 7 of the 13 healthy monkeys with NT -proBNP concentrations below detection limit in all animals and a mean cTnT concentration of 0.049 ng/mL. Electrocardiography was performed in all squirrel monkeys. The mean heart rate was 172 bpm. Frequent supraventricular premature beats were diagnosed in the squirrel monkey suffering from significant aortic dilation and regurgitation. Conclusion This study presents echocardiographic normal values and additional cardiovascular data in anaesthetised Saimiri monkeys, fundamental from both the perspective of zoo animal health care as well as scientific research, since the squirrel monkey is often used as an animal model for human disease.

Author(s): Lilach C. Regev [sup.1] , Antonia H.M. Bouts [sup.2] , Jaap W. Groothoff [sup.2] , Joanna A.E. van Wijk [sup.2] , Michiel van Wijk [sup.3] , Paul van der [...]