Urinary chitinase 3-like protein 1 for early diagnosis of acute kidney injury : a prospective cohort study in adult critically ill patients

Background: Acute kidney injury (AKI) occurs frequently and adversely affects patient and kidney outcomes, especially when its severity increases from stage 1 to stages 2 or 3. Early interventions may counteract such deterioration, but this requires early detection. Our aim was to evaluate whether the novel renal damage biomarker urinary chitinase 3-like protein 1 (UCHI3L1) can detect AKI stage >= 2 more early than serum creatinine and urine output, using the respective Kidney Disease vertical bar Improving Global Outcomes (KDIGO) criteria for definition and classification of AKI, and compare this to urinary neutrophil gelatinase-associated lipocalin (UNGAL). Methods: This was a translational single-center, prospective cohort study at the 22-bed surgical and 14-bed medical intensive care units (ICU) of Ghent University Hospital. We enrolled 181 severely ill adult patients who did not yet have AKI stage >= 2 based on the KDIGO criteria at time of enrollment. The concentration of creatinine (serum, urine) and CHI3L1 (serum, urine) was measured at least daily, and urine output hourly, in the period from enrollment till ICU discharge with a maximum of 7 ICU-days. The concentration of UNGAL was measured at enrollment. The primary endpoint was the development of AKI stage >= 2 within 12 h after enrollment. Results: After enrollment, 21 (12 %) patients developed AKI stage >= 2 within the next 7 days, with 6 (3 %) of them reaching this condition within the first 12 h. The enrollment concentration of UCHI3L1 predicted the occurrence of AKI stage >= 2 within the next 12 h with a good AUC-ROC of 0.792 (95 % CI: 0.726-0.849). This performance was similar to that of UNGAL (AUC-ROC of 0.748 (95 % CI: 0.678-0.810)). Also, the samples collected in the 24-h time frame preceding diagnosis of the 1st episode of AKI stage >= 2 had a 2.0 times higher (95 % CI: 1.3-3.1) estimated marginal mean of UCHI3L1 than controls. We further found that increasing UCHI3L1 concentrations were associated with increasing AKI severity. Conclusions: In this pilot study we found that UCHI3L1 was a good biomarker for prediction of AKI stage >= 2 in adult ICU patients

Genetic Linkage Between the Collagen Type VII Gene COL7A1 and Pretibial Epidermolysis Bullosa with Lichenoid Features

Pretibial epidermolysis bullosa is a rare form of dominant dystrophic epidermolysis bullosa. The disease was diagnosed after considerable delay in a large Belgian family and was remarkable for its late age at onset and its misleading clinical presentation in the proband, which strongly resembled keratosis lichenoides chronica. Both recessively and dominantly inherited forms of dystrophic epidermolysis bullosa have been shown to be linked to the collagen type VII gene, COL7A1. Two-point linkage analysis with two intragenic polymorphisms (PvuII, AluI) in COL7A1 was performed. Strong genetic linkage between the disease in this family and COL7AI was demonstrated by a lod score of 44.5 (theta = 0) for the AluI polymorphism. The observed intrafamilial variability of clinical phenotypes contradicts the presently proposed classification of dominantly inherited dystrophic epidermolysis bullosa

Urinary cell cycle arrest biomarkers and chitinase 3-like protein 1 (CHI3L1) to detect acute kidney injury in the critically ill : a post hoc laboratory analysis on the FINNAKI cohort

Background Acute kidney injury (AKI) is a frequently occurring syndrome in critically ill patients and is associated with worse outcomes. Biomarkers allow early identification and therapy of AKI which may improve outcomes. Urine chitinase 3-like protein 1 (uCHI3L1) was recently identified as a promising urinary biomarker for AKI. In this multicenter study, we evaluated the diagnostic performance for AKI stage 2 or greater of uCHI3L1 in comparison with the urinary cell cycle arrest biomarkers urinary tissue inhibitor of metalloproteinases-2 (TIMP-2)center dot insulin-like growth factor-binding protein 7 (IGFBP7) measured by NephroCheck Risk (R). Methods Post hoc laboratory study of the prospective observational FINNAKI study. Of this cohort, we included patients with stored admission urine samples and availability of serum creatinine at day 1 of admission. Patients who already had AKI stage 2 or 3 at ICU admission were excluded. AKI was defined and staged according to the KDIGO definition and staging system. The primary endpoint was AKI stage 2 or 3 at day 1. Biomarker performance was assessed by the area under the curve of the receiver operating characteristic curve (AUC). We assessed individual performance and different combinations of urine biomarkers. Results Of 660 included patients, 49 (7.4%) had AKI stages 2-3 at day 1. All urine biomarkers were increased at admission in AKI patients. All biomarkers and most combinations had AUCs <0.700. The combination uCHI3L1 center dot TIMP-2 was best with a fair AUC of 0.706 (0.670, 0.718). uCHI3L1 had a positive likelihood ratio (LR) of 2.25 which was comparable to that of the NephroCheck Risk (R) cutoff of 2.0, while the negative LR of 0.53 was comparable to that of the NephroCheck Risk (R) cutoff of 0.3. Conclusions We found that uCHI3L1 and NephroCheck Risk (R) had a comparable diagnostic performance for diagnosis of AKI stage 2 or greater within a 24-h period in this multicenter FINNAKI cohort. In contrast to initial discovery and validation studies, the diagnostic performance was poor. Possible explanations for this observation are differences in patient populations, proportion of emergency admissions, proportion of functional AKI, rate of developing AKI, and observation periods for diagnosis of AKI.Peer reviewe

EPTRI Belgian Joint Research Unit : harmonisation and concertation of paediatric research in Belgium to ensure better and safer healthcare for children

We want to put the excellent translational paediatric research in Belgium on the ESFRI national roadmap in order to participate in the European Paediatric Translational Research Infrastructure (EPTRI) project. Therefore, we are in the preparatory phase to form a Belgian national EPTRI Joint Research Unit (JRU). Academic research organisations and hospitals from both regions, Flanders and Wallonia are currently involved. The Belgian JRU partners will gather complementary scientific and technological competencies in the different EPTRI thematic research platforms: 1. Paediatric medicines discovery: with different types of “in vitro” paediatric models, placental and umbilical cord and 3D organoid cell cultures from paediatric samples and juvenile animal models such as the rabbit BPD model, juvenile Göttingen minipig, juvenile conventional pig model and developmental zebrafish model; 2. Paediatric biomarkers and biosamples: identification, characterisation and validation of the biomarkers used as prognostic tools, safety markers and diagnostic tools in paediatric diseases; 3. Developmental pharmacology: including PK (bioavaibility/bioequivalence) studies, Population PKPD analysis and PK/PD modelling; 4. Paediatric medicines formulations and medical devices: including regulatory knowledge of paediatric medical devices. The partners will ensure a strong liaison with other RI’s such as the BBMRI-ERIC for paediatric biobanking and the IMI conect4children network paediatric clinical trials. We propose an integrated paediatric research system that links together EPTRI Belgium with landmark RIs, conect4children and the many paediatric clinical research networks and institutions that provide services to paediatric research. This integrated system can provide: expertise, experienced facilities and practical support for pre-clinical and clinical paediatric research in Belgium and Europe. Sharing understanding of patients’ needs and concerted efforts in paediatric research will further enhance the health of children

The European Paediatric Clinical Trials Network conect4children : activities of the Belgium National Network and its progression

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Polymorphisms in the ficolin 1 gene (FCN1) are associated with susceptibility to the development of rheumatoid arthritis

Objectives. We investigated the possible association of rheumatoid arthritis (RA) with single nucleotide polymorphisms (SNP) within the ficolin (FCN) genes. Two SNPs in the FCN1 gene, four SNPs in the FCN2 gene and one SNP in the FCN3 gene were studied. Methods. The SNPs within the FCN genes were detected by an experimental INNO-LiPA methodology (Innogenetics, Belgium) in a population consisting of 338 RA patients and 595 controls. The significant SNPs were further evaluated in two subpopulations and related to carriage of the human leukocyte antigen-shared epitope (HLA-SE), rheumatoid factor (RF) and the presence of anti-citrullinated protein/peptide antibodies (ACPA). Results. Two SNPs in the FCN1 gene were significantly associated with RA: the A allele rs2989727 was significantly increased in RA patients (67%) compared with controls (60%) (P = 0.002). Also, the frequency of the G allele of rs1071583 was increased in RA patients (68%) compared with controls (61%) (P = 0.003). Analysis of agreement between SNPs suggested strong linkage between rs2989727 and rs1071583. Carriage of a FCN1 SNP was independent of carriage of the HLA-SE, RF status and ACPA positivity. Conclusions. We describe two linked SNPs in the FCN1 gene that are associated with the development of RA