15 research outputs found

    Effects of rare kidney diseases on kidney failure: a longitudinal analysis of the UK National Registry of Rare Kidney Diseases (RaDaR) cohort

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    Background Individuals with rare kidney diseases account for 5–10% of people with chronic kidney disease, but constitute more than 25% of patients receiving kidney replacement therapy. The National Registry of Rare Kidney Diseases (RaDaR) gathers longitudinal data from patients with these conditions, which we used to study disease progression and outcomes of death and kidney failure. Methods People aged 0–96 years living with 28 types of rare kidney diseases were recruited from 108 UK renal care facilities. The primary outcomes were cumulative incidence of mortality and kidney failure in individuals with rare kidney diseases, which were calculated and compared with that of unselected patients with chronic kidney disease. Cumulative incidence and Kaplan–Meier survival estimates were calculated for the following outcomes: median age at kidney failure; median age at death; time from start of dialysis to death; and time from diagnosis to estimated glomerular filtration rate (eGFR) thresholds, allowing calculation of time from last eGFR of 75 mL/min per 1·73 m2 or more to first eGFR of less than 30 mL/min per 1·73 m2 (the therapeutic trial window). Findings Between Jan 18, 2010, and July 25, 2022, 27 285 participants were recruited to RaDaR. Median follow-up time from diagnosis was 9·6 years (IQR 5·9–16·7). RaDaR participants had significantly higher 5-year cumulative incidence of kidney failure than 2·81 million UK patients with all-cause chronic kidney disease (28% vs 1%; p<0·0001), but better survival rates (standardised mortality ratio 0·42 [95% CI 0·32–0·52]; p<0·0001). Median age at kidney failure, median age at death, time from start of dialysis to death, time from diagnosis to eGFR thresholds, and therapeutic trial window all varied substantially between rare diseases. Interpretation Patients with rare kidney diseases differ from the general population of individuals with chronic kidney disease: they have higher 5-year rates of kidney failure but higher survival than other patients with chronic kidney disease stages 3–5, and so are over-represented in the cohort of patients requiring kidney replacement therapy. Addressing unmet therapeutic need for patients with rare kidney diseases could have a large beneficial effect on long-term kidney replacement therapy demand. Funding RaDaR is funded by the Medical Research Council, Kidney Research UK, Kidney Care UK, and the Polycystic Kidney Disease Charity

    High-resolution alkenone sea surface temperature variability on the North Icelandic Shelf: implications for Nordic Seas palaeoclimatic development during the Holocene

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    The palaeoceanography of the northern Icelandic Shelf for the Holocene period was reconstructed from alkenone indices measured in core JR51-GC35. This contains a continuous record of Holocene sedimentation spanning 0 10.2 cal. kyr BP with a resolution of ~ 20 yr/cm. We have identified a general Holocene cooling trend that has superimposed millennial-scale oscillations of &#62;2°C. Their timing is in close agreement with the timing of glacier advances in northern Iceland. For the later half of the Holocene, the alkenone-sea surface temperature (SST) record from JR51-GC35 correlates with proxy data for the strength of NADW formation recorded in cores south of Iceland. This is interpreted as evidence of a close connection existing between north Icelandic sea surface temperatures and the North Atlantic meridonal overturning circulation. The timing of the millennial-scale SST variability in our core off North Iceland is found to be out of phase, or anti-phased, with the SST variability of a record in the eastern Nordic Seas (MD952011). This suggests that the evolution of Holocene climate in the Nordic Seas was more complex than previously proposed; and it is likely to be caused by differential responses of the Irminger and Norwegian Currents and modulated by changes in atmospheric circulation analogous to the North Atlantic Oscillation

    Persistent Near–Tropical Warmth on the Antarctic Continent During the Early Eocene Epoch

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    The warmest global climates of the past 65 million years occurred during the early Eocene epoch (about 55 to 48 million years ago), when the Equator–to–pole temperature gradients were much smaller than today and atmospheric carbon dioxide levels were in excess of one thousand parts per million by volume. Recently the early Eocene has received considerable interest because it may provide insight into the response of Earth’s climate and biosphere to the high atmospheric carbon dioxide levels that are expected in the near future as a consequence of unabated anthropogenic carbon emissions. Climatic conditions of the early Eocene ‘greenhouse world’, however, are poorly constrained in critical regions, particularly Antarctica. Here we present a well–dated record of early Eocene climate on Antarctica from an ocean sediment core recovered off the Wilkes Land coast of East Antarctica. The information from biotic climate proxies (pollen and spores) and independent organic geochemical climate proxies (indices based on branched tetraether lipids) yields quantitative, seasonal temperature reconstructions for the early Eocene greenhouse world on Antarctica. We show that the climate in lowland settings along the Wilkes Land coast (at a palaeolatitude of about 70° south) supported the growth of highly diverse, near-tropical forests characterized by mesothermal to megathermal floral elements including palms and Bombacoideae. Notably, winters were extremely mild (warmer than 10°C) and essentially frost–free despite polar darkness, which provides a critical new constraint for the validation of climate models and for understanding the response of high–latitude terrestrial ecosystems to increased carbon dioxide forcing

    Orbital Forcing of the East Antarctic Ice Sheet During the Pliocene and Early Pleistocene

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    The Pliocene and Early Pleistocene, between 5.3 and 0.8 million years ago, span a transition from a global climate state that was 2-3 °C warmer than present with limited ice sheets in the Northern Hemisphere to one that was characterized by continental-scale glaciations at both poles. Growth and decay of these ice sheets was paced by variations in the Earth\u27s orbit around the Sun. However, the nature of the influence of orbital forcing on the ice sheets is unclear, particularly in light of the absence of a strong 20,000-year precession signal in geologic records of global ice volume and sea level. Here we present a record of the rate of accumulation of iceberg-rafted debris oshore from the East Antarctic ice sheet, adjacent to the Wilkes Subglacial Basin, between 4.3 and 2.2 million years ago. We infer that maximum iceberg debris accumulation is associated with the enhanced calving of icebergs during ice-sheet margin retreat. In the warmer part of the record, between 4.3 and 3.5 million years ago, spectral analyses show a dominant periodicity of about 40,000 years. Subsequently, the powers of the 100,000-year and 20,000-year signals strengthen. We suggest that, as the Southern Ocean cooled between 3.5 and 2.5 million years ago, the development of a perennial sea-ice field limited the oceanic forcing of the ice sheet. After this threshold was crossed, substantial retreat of the East Antarctic ice sheet occurred only during austral summer insolation maxima, as controlled by the precession cycle

    Relative Sea-Level Rise Around East Antarctica During Oligocene Glaciation

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    During the middle and late Eocene (∼48-34 Myr ago), the Earth\u27s climate cooled1,2 and an ice sheet built up on Antarctica. The stepwise expansion of ice on Antarctica3,4induced crustal deformation and gravitational perturbations around the continent. Close to the ice sheet, sea level rose5,6despite an overall reduction in the mass of the ocean caused by the transfer of water to the ice sheet. Here we identify the crustal response to ice-sheet growth by forcing a glacial-hydro isostatic adjustment model7 with an Antarctic ice-sheet model. We find that the shelf areas around East Antarctica first shoaled as upper mantle material upwelled and a peripheral forebulge developed. The inner shelf subsequently subsided as lithosphere flexure extended outwards from the ice-sheet margins. Consequently the coasts experienced a progressive relative sea-level rise. Our analysis of sediment cores from the vicinity of the Antarctic ice sheet are in agreement with the spatial patterns of relative sea-level change indicated by our simulations. Our results are consistent with the suggestion8 that near-field processes such as local sea-level change influence the equilibrium state obtained by an icesheet grounding line

    Integrated Ocean Drilling Program Expedition 318 Preliminary Report Wilkes Land Glacial History Cenozoic East Antarctic Ice Sheet Evolution from Wilkes Land Margin Sediments

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    Understanding the evolution and dynamics of the Antarctic cryosphere, from its inception during the Eocene-Oligocene transition (∼34 Ma) through the significant subsequent periods of likely coupled climate and atmospheric CO2 changes, is not only of major scientific interest but also is of great importance for society. Drilling the Antarctic Wilkes Land margin was designed to provide a long-term record of the sedimentary archives along an inshore to offshore transect of Cenozoic Antarctic glaciation and its intimate relationships with global climatic and oceanographic change. The principal goals were 1. To obtain the timing and nature of the first arrival of ice at the Wilkes Land margin inferred to have occurred during the earliest Oligocene (reflecting Oligocene isotope Event 1), 2. To obtain the nature and age of the changes in the geometry of the prograda- tional wedge interpreted to correspond with large fluctuations in the extent of the East Antarctic Ice Sheet and possibly coinciding with the transition from a wet-based to a cold-based glacial regime, 3. To obtain a high-resolution record of Antarctic climate variability during the late Neogene and Quaternary, and 4. To obtain an unprecedented ultrahigh resolution (i.e., annual to decadal) Holocene record of climate variability. The Wilkes Land drilling program was developed to constrain the age, nature, and paleoenvironment of deposition of the previously only seismically inferred glacial sequences. Drilling the Wilkes Land margin has a unique advantage in that seismic Unconformity WL-U3, inferred to separate preglacial strata below from glacial strata above in the continental shelf, can be traced to the continental rise deposits, allowing sequences to be linked from shelf to rise. Integrated Ocean Drilling Program Expedition 318, carried out in January-March 2010 (Wellington, New Zealand to Hobart, Australia), occupied seven sites that recovered ∼2000 m of high-quality middle Eocene-Holocene sediments at proposed Sites WLRIS-6A, WLRIS-7A, WLRIS-4A, and WLRIS-5A (Sites U1355, U1356, U1359, and U1361) on the Wilkes Land rise and Sites WLSHE-8A, WLSHE-9A, and ADEL-01B (Sites U1358, U1360, and U1357) on the Wilkes Land shelf at water depths between ∼400 and 4000 m. Together, the cores represent ∼53 m.y. of Antarctic history. Recovered cores successfully date the inferred seismic units (WL-S4-WL-S9). The cores reveal the history of the Wilkes Land Antarctic margin from an ice-free greenhouse Antarctica, to the first cooling, to the onset and erosional consequences of the first glaciation and the subsequent dynamics of the waxing and waning ice sheets, all the way to thick, unprecedented tree ring style records with seasonal resolution of the last deglaciation that began ∼10,000 y ago. The cores also reveal details of the tectonic history of the so-called Australo-Antarctic Gulf (at 53 Ma) from the onset of the second phase of rifting between Australia and Antarctica, to ever subsiding margins and deepening, all the way to the present continental and ever widening ocean/continent configuration. Tectonic and climatic change turned the initially shallow broad subtropical Antarctic Wilkes Land shelf into a deeply subsided basin with a narrow, iceinfested margin. Thick Oligocene and notably Neogene deposits, including turbidites, contourites, and larger and smaller scaled debris mass flows witness the erosional power of the waxing and waning ice sheets and deep ocean currents. The recovered clays, silts, and sands and their microfossils also reveal the transition of subtropical ecosystems and a vegetated Antarctica into sea ice-dominated ecosystems bordered by calving glaciers

    Reorganization of Southern Ocean Plankton Ecosystem At the Onset of Antarctic Glaciation

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    The circum-Antarctic Southern Ocean is an important region for global marine food webs and carbon cycling because of sea-ice formation and its unique plankton ecosystem. However, the mechanisms underlying the installation of this distinct ecosystem and the geological timing of its development remain unknown. Here, we show, on the basis of fossil marine dinoflagellate cyst records, that a major restructuring of the Southern Ocean plankton ecosystem occurred abruptly and concomitant with the first major Antarctic glaciation in the earliest Oligocene (∼33.6 million years ago). This turnover marks a regime shift in zooplankton-phytoplankton interactions and community structure, which indicates the appearance of eutrophic and seasonally productive environments on the Antarctic margin. We conclude that earliest Oligocene cooling, ice-sheet expansion, and subsequent sea-ice formation were important drivers of biotic evolution in the Southern Ocean

    Dynamic Behaviour of the East Antarctic Ice Sheet During Pliocene Warmth

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    Warm intervals within the Pliocene epoch (5.33-2.58 million years ago) were characterized by global temperatures comparable to those predicted for the end of this century and atmospheric CO 2 concentrations similar to today. Estimates for global sea level highstands during these times imply possible retreat of the East Antarctic ice sheet, but ice-proximal evidence from the Antarctic margin is scarce. Here we present new data from Pliocene marine sediments recovered offshore of Adélie Land, East Antarctica, that reveal dynamic behaviour of the East Antarctic ice sheet in the vicinity of the low-lying Wilkes Subglacial Basin during times of past climatic warmth. Sedimentary sequences deposited between 5.3 and 3.3 million years ago indicate increases in Southern Ocean surface water productivity, associated with elevated circum-Antarctic temperatures. The geochemical provenance of detrital material deposited during these warm intervals suggests active erosion of continental bedrock from within the Wilkes Subglacial Basin, an area today buried beneath the East Antarctic ice sheet. We interpret this erosion to be associated with retreat of the ice sheet margin several hundreds of kilometres inland and conclude that the East Antarctic ice sheet was sensitive to climatic warmth during the Pliocene
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