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- Pattaro, Cristian, et al.
(författare)
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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
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- Krawczyk, M., et al.
(författare)
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Liver Transplantation for Hepatic Trauma: A Study From the European Liver Transplant Registry
- 2016
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Ingår i: Transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 0041-1337. ; 100:11, s. 2372-2381
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Tidskriftsartikel (refereegranskat)abstract
- Background. Liver transplantation is the most extreme form of surgical management of patients with hepatic trauma, with very limited literature data supporting its use. The aim of this study was to assess the results of liver transplantation for hepatic trauma. Methods. This retrospective analysis based on European Liver Transplant Registry comprised data of 73 recipients of liver transplantation for hepatic trauma performed in 37 centers in the period between 1987 and 2013. Mortality and graft loss rates at 90 days were set as primary and secondary outcome measures, respectively. Results. Mortality and graft loss rates at 90 days were 42.5% and 46.6%, respectively. Regarding general variables, cross-clamping without extracorporeal veno-venous bypass was the only independent risk factor for both mortality (P = 0.031) and graft loss (P = 0.034). Regarding more detailed factors, grade of liver trauma exceeding IV increased the risk ofmortality (P = 0.005) and graft loss (P = 0.018). Moreover, a tendency above the level of significance was observed for the negative impact of injury severity score (ISS) onmortality (P = 0.071). The optimal cutoff for ISS was 33, with sensitivity of 60.0%, specificity of 80.0%, positive predictive value of 75.0%, and negative predictive value of 66.7%. Conclusions. Liver transplantation seems to be justified in selected patients with otherwise fatal severe liver injuries, particularly in whom cross-clamping without extracorporeal bypass can be omitted. The ISS cutoff less than 33 may be useful in the selection process.
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- Coggi, D, et al.
(författare)
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Relationship between Circulating PCSK9 and Markers of Subclinical Atherosclerosis-The IMPROVE Study
- 2021
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Ingår i: Biomedicines. - : MDPI AG. - 2227-9059. ; 9:7
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Tidskriftsartikel (refereegranskat)abstract
- (1) Background and purpose: circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) is one of the key regulators of cholesterol metabolism. Despite this, its role as a player in atherosclerosis development is still matter of debate. Here, we investigated the relationships between this protein and several markers of subclinical atherosclerosis. (2) Methods: the IMPROVE study enrolled 3703 European subjects (54–79 years; 48% men; with ≥3 vascular risk factors), asymptomatic for cardiovascular diseases. PCSK9 levels were measured by ELISA. B-mode ultrasound was used to measure markers of carotid subclinical atherosclerosis. (3) Results: in the crude analysis, PCSK9 levels were associated with several baseline measures of carotid intima-media thickness (cIMT) (all p < 0.0001); with cIMT change over time (Fastest-IMTmax-progr) (p = 0.01); with inter-adventitia common carotid artery diameter (ICCAD) (p < 0.0001); and with the echolucency (Grey Scale Median; GSM) of both carotid plaque and plaque-free common carotid IMT (both p < 0.0001). However, after adjustment for age, sex, latitude, and pharmacological treatment, all the afore-mentioned correlations were no longer statistically significant. The lack of correlation was also observed after stratification for sex, latitude, and pharmacological treatments. (4) Conclusions: in subjects who are asymptomatic for cardiovascular diseases, PCSK9 plasma levels do not correlate with vascular damage and/or subclinical atherosclerosis of extracranial carotid arteries.
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