Long-Term Outcomes in IgA Nephropathy

BACKGROUND: IgA nephropathy can progress to kidney failure, and risk assessment soon after diagnosis has advantages both for clinical management and the development of new therapeutics. We present relationships among proteinuria, eGFR slope and lifetime risks for kidney failure. METHODS: The IgA nephropathy cohort (2,299 adults, 140 children) of the UK National Registry of Rare Kidney Diseases (RaDaR) was analyzed. Patients enrolled had a biopsy-proven diagnosis of IgA nephropathy, plus proteinuria >0.5 g/day or eGFR <60 mL/min/1.73m 2 . Incident and prevalent populations were studied as well as a population representative of a typical phase 3 clinical trial cohort. Analyses of kidney survival were conducted using Kaplan-Meier and Cox regression. eGFR slope was estimated using linear mixed models with random intercept and slope. RESULTS: Median (Q1, Q3) follow-up was 5.9 (3.0, 10.5) years; 50% of patients reached kidney failure or died in the study period. Median (95% CI) kidney survival was 11.4 (10.5, 12.5) years; mean age at kidney failure/death was 48 years, and most patients progressed to kidney failure within 10-15 years. Based on eGFR and age at diagnosis, almost all patients are at risk of progression to kidney failure within their expected lifetime unless a rate of eGFR loss ≤1 ml/min/1.73m 2 /year can be maintained. Time-averaged proteinuria was significantly associated with worse kidney survival and more rapid eGFR loss in incident, prevalent, and "clinical trial" populations. 30% of patients with time-averaged proteinuria of 0.44 to <0.88 g/g and approximately 20% of patients with time-averaged proteinuria <0.44 g/g developed kidney failure within 10 years. In the "clinical trial" population each 10% decrease in time-averaged proteinuria from baseline was associated with a hazard ratio (95% CI) for kidney failure/death of 0.89 (0.87-0.92). CONCLUSIONS: Outcomes in this large IgA nephropathy cohort are generally poor with few patients expected to avoid kidney failure in their lifetime. Significantly, patients traditionally regarded as being "low-risk", with proteinuria <0.88 g/g (<100 mg/mmol), have high rates of kidney failure within 10 years

Using the surface profiles of modern ice masses to inform palaeo-glacier reconstructions

Morphometric study of modern ice masses is useful because many reconstructions of glaciers traditionally draw on their shape for guidance Here we analyse data derived from the surface profiles of 200 modern ice masses-valley glaciers icefields ice caps and ice sheets with length scales from 10(0) to 10(3) km-from different parts of the world Four profile attributes are investigated relief span and two parameters C* and C that result from using Nye s (1952) theoretical parabola as a profile descriptor C* and C respectively measure each profile s aspect ratio and steepness and are found to decrease in size and variability with span This dependence quantifies the competing influences of unconstrained spreading behaviour of ice flow and bed topography on the profile shape of ice masses which becomes more parabolic as span Increases (with C* and C tending to low values of 2 5-3 3 m(1/2)) The same data reveal coherent minimum bounds in C* and C for modern ice masses that we develop into two new methods of palaeo glacier reconstruction In the first method glacial limits are known from moraines and the bounds are used to constrain the lowest palaeo ice surface consistent with modern profiles We give an example of applying this method over a three-dimensional glacial landscape in Kamchatka In the second method we test the plausibility of existing reconstructions by comparing their C* and C against the modern minimum bounds Of the 86 published palaeo ice masses that we put to this test 88% are found to be plausible The search for other morphometric constraints will help us formalise glacier reconstructions and reduce their uncertainty and subjectiveness (C) 2010 Elsevier Ltd All rights reserve

Quantifying episodic erosion and transient storage on the western margin of the Tibetan Plateau, upper Indus River

Transient storage and erosion of valley-fills, or sediment buffering, is a fundamental but poorly quantified process that may significantly bias fluvial sediment budgets and marine archives used for paleoclimatic and tectonic reconstructions. Prolific sediment buffering is now recognized to occur within the mountainous upper Indus River and is quantified here for the first time using OSL dating, petrography, detrital zircon U-Pb geochronology, and morphometric analysis to define the timing, provenance, and volumes of prominent valley-fills. This study finds that climatically-modulated sediment buffering occurs over 103–104 yr timescales and results in biases in sediment compositions and volumes. Increased sediment storage coincides with strong phases of Summer Monsoon and Winter Westerlies precipitation over the Late Pleistocene (32–25 ka) and mid-Holocene (~8–6 ka), followed by incision and erosion with monsoon weakening. Glacial erosion and periglacial frost-cracking drive sediment production and monsoonal precipitation mediates sediment evacuation, in contrast to the arid Transhimalaya and monsoonal frontal Himalaya. Plateau interior basins, although volumetrically large, lack transport capacity and are consequently isolated from the modern Indus River drainage. Marginal plateau basins that both efficiently produce and evacuate sediment may regulate the overall compositions and volumes of exported sediment from the Himalayan rain shadow

Crustal structure of the Mid-Atlantic Ridge south of the Kane Fracture Zone from seafloor and sea surface gravity data

International audienceSeafloor and sea surface gravity data are inverted together to construct a model for the near-axis crustal structure of a slow spreading ridge. The seafloor data set offers two main advantages: it allows us to recover shorter-wavelengths signal and to constrain the value of a potential field at two different levels. The model we propose here would not have been derived from sea surface data alone. It is based on a dense sea surface gravity coverage and on 121 sea bottom gravity measurements collected in the Mid-Atlantic Ridge at Kane (MARK) area, during the Hydrosnake (1988) and Gravinaute (1993) cruises. The primary goal of the seafloor surveys was to test for the presence of a magma reservoir beneath the axial neovolcanic ridge. First, a forward two-dimensional (2-D) model of the crustal structure across the axis is fit to observed gravity anomalies, using constraints from geological and structural observations. Bouguer anomalies computed from sea bottom measurements and downward continuation of sea surface measurements both constrain the forward modeling. This forward model is the starting point of a 2-D Monte Carlo inversion of seafloor and sea surface data. In addition to the crustal thickness variations along-axis, our data document the amplitude variations of the crustal thickness and/or its density in the across-axis direction. The model resulting from our inversion exhibits several features of the crustal structure in the MARK area: (1) The presence of a low-density (Ap =-300_+ 50 kg/m 3) body beneath the neovolcanic ridge is suggested and could correspond to a magma chamber, or more probably to a highly hydrothermally fissured zone. (2) Both long-and short-wavelength gravity signals exhibit a difference between the western and eastern sides of the axial domain: the mean value and the amplitude of Bouguer anomalies are higher on the western part. This difference suggests that axial processes, in this area, are very asymmetric. (3) Abyssal hills are not associated with a single gravity signature: for instance, on the west side of the axis, one of the explored hills has no Bouguer anomaly and is interpreted as a neovolcanic ridge, whereas the others are associated with a shifted Bouguer anomaly high and are interpreted as having thinner magmatic crust. (4) The last feature of the crustal fabric we document here is the asymmetric emplacement of some deep rocks outcrops. In the MARK area, we find that "Pink Hill," a topographic high where serpentinized peridotites are outcropping, is much more serpentinized on its east flank, toward the axial valley, than on its west flank. Alteration occurring mainly by fluid circulation through faulted zones, the asymmetric serpentinization suggests that deep-origin rocks have outcropped by means of a main fault zone and are not emplaced by diapirism

Taxonomy and identification of bacteria associated with acute oak decline

© 2017, The Author(s). Acute oak decline (AOD) is a relatively newly described disorder affecting native oak species in Britain. Symptomatic trees are characterised by stem bleeds from vertical fissures, necrotic lesions in the live tissue beneath and larval galleries of the two spotted oak buprestid (Agrilus biguttatus). Several abiotic and biotic factors can be responsible for tree death, however the tissue necrosis and stem weeping is thought to be caused by a combination of bacterial species. Following investigations of the current episode of AOD which began in 2008, numerous strains belonging to several different bacteria in the family Enterobacteriaceae have been consistently isolated from symptomatic tissue. The majority of these enterobacteria were found to be novel species, subspecies and even genera, which have now been formally classified. The most frequently isolated species from symptomatic oak are Gibbsiella quercinecans, Brenneria goodwinii and Rahnella victoriana. Identification of these bacteria is difficult due to similarities in colony morphology, phenotypic profile and 16S rRNA gene sequences. Current identification relies heavily on gyrB gene amplification and sequencing, which is time consuming and laborious. However, newer techniques based on detection of single nucleotide polymorphisms show greater promise for rapid and reliable identification of the bacteria associated with AOD

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

\ua9 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: 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\ub773 m2 or more to first eGFR of less than 30 mL/min per 1\ub773 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\ub76 years (IQR 5\ub79–16\ub77). RaDaR participants had significantly higher 5-year cumulative incidence of kidney failure than 2\ub781 million UK patients with all-cause chronic kidney disease (28% vs 1%; p&lt;0\ub70001), but better survival rates (standardised mortality ratio 0\ub742 [95% CI 0\ub732–0\ub752]; p&lt;0\ub70001). 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

Carbon sequestration and biodiversity following 18 years of active tropical forest restoration

Vast areas of degraded tropical forest, combined with increasing interest in mitigating climate change and conserving biodiversity, demonstrate the potential value of restoring tropical forest. However, there is a lack of long-term studies assessing active management for restoration. Here we investigate Above-Ground Biomass (AGB), forest structure, and biodiversity, before degradation (in old-growth forest), after degradation (in abandoned agricultural savanna grassland), and within a forest that is actively being restored in Kibale National Park, Uganda. In 1995 degraded land in Kibale was protected from fire and replanted with native seedlings (39 species) at a density of 400 seedlings ha-1. Sixty-five plots (50 m × 10 m) were established in restoration areas in 2005 and 50 of these were re-measured in 2013, allowing changes to be assessed over 18 years. Degraded plots have an Above Ground Biomass (AGB) of 5.1 Mg dry mass ha-1, of which 80% is grass. By 2005 AGB of trees ≥10 cm DBH was 9.5 Mg ha-1, increasing to 40.6 Mg ha-1 by 2013, accumulating at a rate of 3.9 Mg ha-1 year-1. A total of 153 planted individuals ha-1 (38%) remained by 2013, contributing 28.9 Mg ha-1 (70%) of total AGB. Eighteen years after restoration, AGB in the plots was 12% of old-growth (419 Mg ha-1). If current accumulation rates continue restoration forest would reach old-growth AGB in a further 96 years. Biodiversity of degraded plots prior to restoration was low with no tree species and 2 seedling species per sample plot (0.05 ha). By 2005 restoration areas had an average of 3 tree and 3 seedling species per sample plot, increasing to 5 tree and 9 seedling species per plot in 2013. However, biodiversity was still significantly lower than old-growth forest, at 8 tree and 16 seedling species in an equivalent area. The results suggest that forest restoration is beneficial for AGB accumulation with planted stems storing the majority of AGB. Changes in biodiversity appear slower; possibly due to low stem turnover. Overall this restoration treatment is an effective means of restoring degraded land in the area, as can be seen from the lack of regeneration in degraded plots, which remain low-AGB and diversity, largely due to the impacts of fire and competition with grasses