3 research outputs found
Trophic Transfer of Contaminants in a Changing Arctic Marine Food Web: Cumberland Sound, Nunavut, Canada
Contaminant dynamics in arctic marine food webs may be
impacted
by current climate-induced food web changes including increases in
transient/subarctic species. We quantified food web organochlorine
transfer in the Cumberland Sound (Nunavut, Canada) arctic marine food
web in the presence of transient species using species-specific biomagnification
factors (BMFs), trophic magnification factors (TMFs), and a multifactor
model that included δ<sup>15</sup>N-derived trophic position
and species habitat range (transient versus resident), and also considered
δ<sup>13</sup>C-derived carbon source, thermoregulatory group,
and season. Transient/subarctic species relative to residents had
higher prey-to-predator BMFs of biomagnifying contaminants (1.4 to
62 for harp seal, Greenland shark, and narwhal versus 1.1 to 20 for
ringed seal, arctic skate, and beluga whale, respectively). For contaminants
that biomagnified in a transient-and-resident food web and a resident-only
food web scenario, TMFs were higher in the former (2.3 to 10.1) versus
the latter (1.7 to 4.0). Transient/subarctic species have higher tissue
contaminant levels and greater BMFs likely due to higher energetic
requirements associated with long-distance movements or consumption
of more contaminated prey in regions outside of Cumberland Sound.
These results demonstrate that, in addition to climate change-related
long-range transport/deposition/revolatilization changes, increasing
numbers of transient/subarctic animals may alter food web contaminant
dynamics
Perfluoroalkyl Acids in the Atlantic and Canadian Arctic Oceans
We report here on the spatial distribution of C<sub>4</sub>, C<sub>6</sub>, and C<sub>8</sub> perfluoroalkyl sulfonates, C<sub>6</sub>–C<sub>14</sub> perfluoroalkyl carboxylates, and perfluorooctanesulfonamide
in the Atlantic and Arctic Oceans, including previously unstudied
coastal waters of North and South America, and the Canadian Arctic
Archipelago. Perfluorooctanoate (PFOA) and perfluorooctanesulfonate
(PFOS) were typically the dominant perfluoroalkyl acids (PFAAs) in
Atlantic water. In the midnorthwest Atlantic/Gulf Stream, sum PFAA
concentrations (∑PFAAs) were low (77–190 pg/L) but increased
rapidly upon crossing into U.S. coastal water (up to 5800 pg/L near
Rhode Island). ∑PFAAs in the northeast Atlantic were highest
north of the Canary Islands (280–980 pg/L) and decreased with
latitude. In the South Atlantic, concentrations increased near Rio
de la Plata (Argentina/Uruguay; 350–540 pg/L ∑PFAAs),
possibly attributable to insecticides containing <i>N</i>-ethyl perfluorooctanesulfonamide, or proximity to Montevideo and
Buenos Aires. In all other southern hemisphere locations, ∑PFAAs
were <210 pg/L. PFOA/PFOS ratios were typically ≥1 in the
northern hemisphere, ∼1 near the equator, and ≤1 in
the southern hemisphere. In the Canadian Arctic, ∑PFAAs ranged
from 40 to 250 pg/L, with perfluoroheptanoate, PFOA, and PFOS among the PFAAs detected at the highest concentrations. PFOA/PFOS ratios (typically ≫1) decreased from Baffin Bay to the Amundsen Gulf, possibly attributable to increased atmospheric inputs. These data help validate global emissions models and contribute to understanding of long-range transport pathways and sources of PFAAs to remote regions
Efficacy and safety of sparsentan versus irbesartan in patients with IgA nephropathy (PROTECT): 2-year results from a randomised, active-controlled, phase 3 trial
Background
Sparsentan, a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist, significantly reduced proteinuria versus irbesartan, an angiotensin II receptor blocker, at 36 weeks (primary endpoint) in patients with immunoglobulin A nephropathy in the phase 3 PROTECT trial's previously reported interim analysis. Here, we report kidney function and outcomes over 110 weeks from the double-blind final analysis.
Methods
PROTECT, a double-blind, randomised, active-controlled, phase 3 study, was done across 134 clinical practice sites in 18 countries throughout the Americas, Asia, and Europe. Patients aged 18 years or older with biopsy-proven primary IgA nephropathy and proteinuria of at least 1·0 g per day despite maximised renin–angiotensin system inhibition for at least 12 weeks were randomly assigned (1:1) to receive sparsentan (target dose 400 mg oral sparsentan once daily) or irbesartan (target dose 300 mg oral irbesartan once daily) based on a permuted-block randomisation method. The primary endpoint was proteinuria change between treatment groups at 36 weeks. Secondary endpoints included rate of change (slope) of the estimated glomerular filtration rate (eGFR), changes in proteinuria, a composite of kidney failure (confirmed 40% eGFR reduction, end-stage kidney disease, or all-cause mortality), and safety and tolerability up to 110 weeks from randomisation. Secondary efficacy outcomes were assessed in the full analysis set and safety was assessed in the safety set, both of which were defined as all patients who were randomly assigned and received at least one dose of randomly assigned study drug. This trial is registered with ClinicalTrials.gov, NCT03762850.
Findings
Between Dec 20, 2018, and May 26, 2021, 203 patients were randomly assigned to the sparsentan group and 203 to the irbesartan group. One patient from each group did not receive the study drug and was excluded from the efficacy and safety analyses (282 [70%] of 404 included patients were male and 272 [67%] were White) . Patients in the sparsentan group had a slower rate of eGFR decline than those in the irbesartan group. eGFR chronic 2-year slope (weeks 6–110) was −2·7 mL/min per 1·73 m2 per year versus −3·8 mL/min per 1·73 m2 per year (difference 1·1 mL/min per 1·73 m2 per year, 95% CI 0·1 to 2·1; p=0·037); total 2-year slope (day 1–week 110) was −2·9 mL/min per 1·73 m2 per year versus −3·9 mL/min per 1·73 m2 per year (difference 1·0 mL/min per 1·73 m2 per year, 95% CI −0·03 to 1·94; p=0·058). The significant reduction in proteinuria at 36 weeks with sparsentan was maintained throughout the study period; at 110 weeks, proteinuria, as determined by the change from baseline in urine protein-to-creatinine ratio, was 40% lower in the sparsentan group than in the irbesartan group (−42·8%, 95% CI −49·8 to −35·0, with sparsentan versus −4·4%, −15·8 to 8·7, with irbesartan; geometric least-squares mean ratio 0·60, 95% CI 0·50 to 0·72). The composite kidney failure endpoint was reached by 18 (9%) of 202 patients in the sparsentan group versus 26 (13%) of 202 patients in the irbesartan group (relative risk 0·7, 95% CI 0·4 to 1·2). Treatment-emergent adverse events were well balanced between sparsentan and irbesartan, with no new safety signals.
Interpretation
Over 110 weeks, treatment with sparsentan versus maximally titrated irbesartan in patients with IgA nephropathy resulted in significant reductions in proteinuria and preservation of kidney function.</p