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- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Ruilope, LM, et al.
(författare)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
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Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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| 6. |
- Fehmi, Janev, et al.
(författare)
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Contactin-1 links autoimmune neuropathy and membranous glomerulonephritis
- 2023
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 18:3 March
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Tidskriftsartikel (refereegranskat)abstract
- Membranous glomerulonephritis (MGN) is a common cause of nephrotic syndrome in adults, mediated by glomerular antibody deposition to an increasing number of newly recognised antigens. Previous case reports have suggested an association between patients with anti-contactin-1 (CNTN1)-mediated neuropathies and MGN. In an observational study we investigated the pathobiology and extent of this potential cause of MGN by examining the association of antibodies against CNTN1 with the clinical features of a cohort of 468 patients with suspected immune-mediated neuropathies, 295 with idiopathic MGN, and 256 controls. Neuronal and glomerular binding of patient IgG, serum CNTN1 antibody and protein levels, as well as immune-complex deposition were determined. We identified 15 patients with immune-mediated neuropathy and concurrent nephrotic syndrome (biopsy proven MGN in 12/12), and 4 patients with isolated MGN from an idiopathic MGN cohort, all seropositive for IgG4 CNTN1 antibodies. CNTN1-containing immune complexes were found in the renal glomeruli of patients with CNTN1 antibodies, but not in control kidneys. CNTN1 peptides were identified in glomeruli by mass spectroscopy. CNTN1 seropositive patients were largely resistant to first-line neuropathy treatments but achieved a good outcome with escalation therapies. Neurological and renal function improved in parallel with suppressed antibody titres. The reason for isolated MGN without clinical neuropathy is unclear. We show that CNTN1, found in peripheral nerves and kidney glomeruli, is a common target for autoantibody-mediated pathology and may account for between 1 and 2% of idiopathic MGN cases. Greater awareness of this cross-system syndrome should facilitate earlier diagnosis and more timely use of effective treatment.
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| 7. |
- Gray, Howard W. I., et al.
(författare)
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Comparative biogeography and the evolution of population structure for bottlenose and common dolphins in the Indian Ocean
- 2021
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Ingår i: Journal of Biogeography. - : Wiley. - 0305-0270 .- 1365-2699. ; 48:7, s. 1654-1668
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Tidskriftsartikel (refereegranskat)abstract
- Aim: In the marine environment, where there are few physical boundaries to gene flow, there is often nevertheless intraspecific diversity with consequences for effective conservation and management. Here, we compare two closely related dolphin species with a shared distribution in the Indian Ocean (IO) to better understand the biogeographic drivers of their population structure.Location: Global oceans and seas with a focus on the Indian OceanTaxon: Tursiops sp. and Delphinus sp.Methods: Bayesian, ordination, assignment, statistical and phylogenetic analyses to assess phylogeography, connectivity and population structure using microsatellite and mitochondrial DNA genetic markers.Results: Both Tursiops sp. and Delphinus sp. showed population structure across the western IO and, in each case, populations in the Arabian Sea (off India, Pakistan and Oman) were most differentiated. Comparisons with other populations worldwide revealed independent lineages in this geographic region for both genera. For T. aduncus, (for which multiple sites within the IO could be compared), Bayesian modelling best supported a scenario of expansion southwards following a bottleneck event resulting in differentiation between the northern and western IO. For Delphinus, the same pattern is even more pronounced. Populations in the Arabian Sea region of the north-western IO show genetic isolation for each of the two genera, consistent with other studies of cetacean species in this region.Main conclusions: We propose that changes in the intensity of the southwest monsoon during the climate cycles of the Pleistocene could have affected regional patterns of productivity and represent an important biogeographic driver promoting the observed patterns of differentiation and population dynamics seen in our focal species. Patterns of population genetic structure are consistent with phenotypic differences, suggesting an influence from distinct habitats and resources, and emphasising the need for effective conservation measures in this geographic region.
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| 8. |
- Mendez, Martin, et al.
(författare)
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Integrating multiple lines of evidence to better understand the evolutionary divergence of humpback dolphins along their entire distribution range : a new dolphin species in Australian waters?
- 2013
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Ingår i: Molecular Ecology. - : Wiley. - 0962-1083 .- 1365-294X. ; 22:23, s. 5936-5948
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Tidskriftsartikel (refereegranskat)abstract
- The conservation of humpback dolphins, distributed in coastal waters of the Indo-West Pacific and eastern Atlantic Oceans, has been hindered by a lack of understanding about the number of species in the genus (Sousa) and their population structure. To address this issue, we present a combined analysis of genetic and morphologic data collected from beach-cast, remote-biopsied and museum specimens from throughout the known Sousa range. We extracted genetic sequence data from 235 samples from extant populations and explored the mitochondrial control region and four nuclear introns through phylogenetic, population-level and population aggregation frameworks. In addition, 180 cranial specimens from the same geographical regions allowed comparisons of 24 morphological characters through multivariate analyses. The genetic and morphological data showed significant and concordant patterns of geographical segregation, which are typical for the kind of demographic isolation displayed by species units, across the Sousa genus distribution range. Based on our combined genetic and morphological analyses, there is convincing evidence for at least four species within the genus (S.teuszii in the Atlantic off West Africa, S.plumbea in the central and western Indian Ocean, S.chinensis in the eastern Indian and West Pacific Oceans, and a new as-yet-unnamed species off northern Australia).
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