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- Schultheiss, U. T., et al.
(författare)
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Thyroid function, renal events and mortality in chronic kidney disease patients: the German Chronic Kidney Disease study
- 2021
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Ingår i: Clinical Kidney Journal. - : Oxford University Press (OUP). - 2048-8505 .- 2048-8513. ; 14:3, s. 959-968
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Tidskriftsartikel (refereegranskat)abstract
- Background. Hypothyroidism and low free triiodothyronine (FT3) syndrome [low FT3 levels with normal thyroid-stimulating hormone (TSH)] have been associated with reduced kidney function cross-sectionally in chronic kidney disease (CKD) patients with severely reduced estimated glomerular filtration rate (eGFR) or end-stage kidney disease (ESKD). Results on the prospective effects of impaired thyroid function on renal events and mortality for patients with severely reduced eGFR or from population-based cohorts are conflicting. Here we evaluated the association between thyroid and kidney function with eGFR (cross-sectionally) as well as renal events and mortality (prospectively) in a large, prospective cohort of CKD patients with mild to moderately reduced kidney function. Methods. Thyroid markers were measured among CKD patients from the German Chronic Kidney Disease study. Incident renal endpoints (combined ESKD, acute kidney injury and renal death) and all-cause mortality were abstracted from hospital records and death certificates. Time to first event analysis of complete data from baseline to the 4-year follow-up (median follow-up time 4.04years) of 4600 patients was conducted. Multivariable linear regression and Cox proportional hazards models were fitted for single and combined continuous thyroid markers [TSH, free thyroxine (FT4), FT3] and thyroid status. Results. Cross-sectionally, the presence of low-FT3 syndrome showed a significant inverse association with eGFR and continuous FT3 levels alone showed a significant positive association with eGFR; in combination with FT4 and TSH, FT3 levels also showed a positive association and FT4 levels showed a negative association with eGFR. Prospectively, higher FT4 and lower FT3 levels were significantly associated with a higher risk of all-cause mortality (N-events=297). Per picomole per litre higher FT3 levels the risk of reaching the composite renal endpoint was 0.73-fold lower (95% confidence interval 0.65-0.82; N-events=615). Compared with euthyroid patients, patients with low-FT3 syndrome had a 2.2-fold higher risk and patients with hypothyroidism had a 1.6-fold higher risk of experiencing the composite renal endpoint. Conclusions. Patients with mild to moderate CKD suffering from thyroid function abnormalities are at an increased risk of adverse renal events and all-cause mortality over time.
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- Rouse, Ian, et al.
(författare)
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First principles characterisation of bio-nano interface
- 2021
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Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; :24
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Tidskriftsartikel (refereegranskat)abstract
- Nanomaterials possess a wide range of potential applications due to their novel properties and exceptionally high activity as a result of their large surface to volume ratios compared to bulk matter. The active surface may present both advantage and risk when the nanomaterials interact with living organisms. As the overall biological impact of nanomaterials is triggered and mediated by interactions at the bio-nano interface, an ability to predict those from the atomistic descriptors, especially before the material is produced, can present enormous advantage for the development of nanotechnology. Fast screening of nanomaterials and their variations for specific biological effects can be enabled using computational materials modelling. The challenge lies in the range of scales that needs to be crossed from the material-specific atomistic representation to the relevant length scales covering typical biomolecules (proteins and lipids). In this work, we present a systematic multiscale approach that allows one to evaluate crucial interactions at the bionano interface from the first principles without any prior information about the material and thus establish links between the details of the nanomaterials structure to protein-nanoparticle interactions. As an example, an advanced computational characterization of titanium dioxide nanoparticles (6 different surfaces of rutile and anatase polymorphs) has been performed. We computed characteristics of the titanium dioxide interface with water using density functional theory for electronic density, used these parameters to derive an atomistic force field, and calculated adsorption energies for essential biomolecules on the surface of titania nanoparticles via direct atomistic simulations and coarse-grained molecular dynamics. Hydration energies, as well as adsorption energies for a set of 40 blood proteins are reported.
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- Schlosser, Pascal, et al.
(författare)
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Genetic studies of paired metabolomes reveal enzymatic and transport processes at the interface of plasma and urine
- 2023
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Ingår i: Nature Genetics. - 1546-1718. ; 55:6, s. 995-1008
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Tidskriftsartikel (refereegranskat)abstract
- The kidneys operate at the interface of plasma and urine by clearing molecular waste products while retaining valuable solutes. Genetic studies of paired plasma and urine metabolomes may identify underlying processes. We conducted genome-wide studies of 1,916 plasma and urine metabolites and detected 1,299 significant associations. Associations with 40% of implicated metabolites would have been missed by studying plasma alone. We detected urine-specific findings that provide information about metabolite reabsorption in the kidney, such as aquaporin (AQP)-7-mediated glycerol transport, and different metabolomic footprints of kidney-expressed proteins in plasma and urine that are consistent with their localization and function, including the transporters NaDC3 (SLC13A3) and ASBT (SLC10A2). Shared genetic determinants of 7,073 metabolite-disease combinations represent a resource to better understand metabolic diseases and revealed connections of dipeptidase 1 with circulating digestive enzymes and with hypertension. Extending genetic studies of the metabolome beyond plasma yields unique insights into processes at the interface of body compartments.
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- Winitzki, D., et al.
(författare)
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Educational Attainment Is Associated With Kidney and Cardiovascular Outcomes in the German CKD (GCKD) Cohort
- 2022
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Ingår i: Kidney International Reports. - : Elsevier BV. - 2468-0249. ; 7:5, s. 1004-1015
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Prospective data on impact of educational attainment on prognosis in patients with chronic kidney disease (CKD) are scarce. We investigated the association between educational attainment and all-cause mortality, major adverse cardiovascular (CV) events (MACEs), kidney failure requiring dialysis, and CKD etiology. Methods: Participants (N = 5095, aged 18–74 years) of the ongoing multicenter German Chronic Kidney Disease (GCKD) cohort, enrolled on the basis of an estimated glomerular filtration rate (eGFR) of 30 to 60 ml/min (stages G3, A1–A3) or overt proteinuria (stages G1–G2, A3), were divided into 3 categories according to their educational attainment and were followed for 6.5 years. Results: Participants with low educational attainment (vs. high) had a higher risk for mortality (hazard ratio [HR] 1.48, 95% CI: 1.16–1.90), MACE (HR 1.37, 95% CI: 1.02–1.83), and kidney failure (HR 1.54, 95% CI: 1.15–2.05). Mediators between low educational attainment and mortality were smoking, CV disease (CVD) at baseline, low income, higher body mass index, and higher serum levels of CRP, high-density lipoprotein cholesterol, uric acid, NGAL, BAP, NT-proBNP, OPN, H-FABP, and urea. Low educational attainment was positively associated with diabetic nephropathy (odds ratio [OR] 1.65, 95% CI: 1.36–2.0) and CKD subsequent to acute kidney injury (OR 1.56, 95% CI: 1.03–2.35), but negatively associated with IgA nephropathy (OR 0.68, 95% CI: 0.52–0.90). Conclusion: Low educational attainment is associated with adverse outcomes and CKD etiology. Lifestyle habits and biomarkers mediate associations between low educational attainment and mortality. Recognition of the role of educational attainment and the associated health-relevant risk factors is important to optimize the care of patients with CKD and improve prognosis. © 2022 International Society of Nephrology
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