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- Uhlin, F., et al.
(författare)
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Endopeptidase Cleavage of Anti-Glomerular Basement Membrane Antibodies in vivo in Severe Kidney Disease: An Open-Label Phase 2a Study
- 2022
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Ingår i: Journal of the American Society of Nephrology. - : Ovid Technologies (Wolters Kluwer Health). - 1046-6673 .- 1533-3450. ; 33:4, s. 829-838
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Tidskriftsartikel (refereegranskat)abstract
- Background The prognosis for kidney survival is poor in patients presenting with circulating anti-glomerular basement membrane (GBM) antibodies and severe kidney injury. It is unknown if treat-ment with an endopeptidase that cleaves circulating and kidney bound IgG can alter the prognosis.& nbsp;Methods An investigator-driven phase 2a one-arm study (EudraCT 2016-004082-39) was performed in 17 hospitals in five European countries. A single dose of 0.25 mg/kg of imlifidase was given to 15 adults with circulating anti-GBM antibodies and an eGFR < 15 ml/min per 1.73m(2). All patients received standard treatment with cyclophosphamide and corticosteroids, but plasma exchange only if autoantibodies rebounded. The primary outcomes were safety and dialysis independency at 6 months.& nbsp;Results At inclusion, ten patients were dialysis dependent and the other five had eGFR levels between 7 and 14 ml/min per 1.73m(2). The median age was 61 years (range 19-77), six were women, and six were also positive for anti-neutrophil cytoplasmic antibodies. Then 6 hours after imlifidase infusion, all patients had anti-GBM antibodies levels below the reference range of a prespecified assay. At 6 months 67% (ten out of 15) were dialysis independent. This is significantly higher compared with 18% (nine out of 50) in a historical control cohort (P < 0.001, Fisher's exact test). Eight serious adverse events (including one death) were reported, none assessed as probably or possibly related to the study drug.& nbsp;Conclusions In this pilot study, the use of imlifidase was associated with a better outcome compared with earlier publications, without major safety issues, but the findings need to be confirmed in a randomized controlled trial.
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- Orme, L. C., et al.
(författare)
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Climatic impacts on an Arctic lake since 1300 AD : a multi-proxy lake sediment reconstruction from Prins Karls Forland, Svalbard
- 2023
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Ingår i: Journal of Paleolimnology. - : Springer Science and Business Media LLC. - 0921-2728 .- 1573-0417. ; 69:3, s. 249-266
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Tidskriftsartikel (refereegranskat)abstract
- On the remote Arctic archipelago of Svalbard, there is increasing evidence of environmental impacts from climate change. The analysis of lake sedimentary records can be used to assess how strongly these recent changes have altered lake ecosystems. Sediments deposited during the last millennium from Lake Blokkvatnet, Prins Karls Forland, were analysed using a multiproxy approach, including stable isotope and X-ray fluorescence analysis. The results were interpreted as reflecting variability of (1) soil organic matter inwash, and potentially catchment and lake primary production, and (2) catchment weathering and erosion. Organic content began increasing after 1920 AD to the present, likely in response to warming. Earlier peaks of a similar magnitude occurred on three occasions since 1300 AD, with evidence indicating that these may have coincided with multidecadal-scale periods with higher temperatures, reduced sea ice and negative phases of the North Atlantic Oscillation. Catchment weathering and fluvial erosion began to increase around 1800 AD and peaked during the early twentieth century, potentially due to rising temperatures in autumn and winter causing increased liquid water availability. The records suggest that similar levels of erosion and weathering occurred between approximately 1300 and 1600 AD, spanning the transition from the Medieval Climate Anomaly to the Little Ice Age.
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