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- Bergling, Karin, et al.
(författare)
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Optimised versus standard automated peritoneal dialysis regimens pilot study (OptiStAR) : A randomised controlled crossover trial
- 2022
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Ingår i: Peritoneal Dialysis International. - : SAGE Publications. - 0896-8608. ; 42:6, s. 615-621
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Tidskriftsartikel (refereegranskat)abstract
- Background: The continuous global rise of end-stage kidney disease creates a growing demand of economically beneficial home-based kidney replacement therapies such as peritoneal dialysis (PD). However, undesirable absorption and exposure of peritoneal tissues to glucose remain major limitations of PD. Methods: We compared a reference (standard) automated PD regimen 6 × 2 L 1.36% glucose (76 mmol/L) over 9 h with a novel, theoretically glucose sparing (optimised) prescription consisting of ‘ultrafiltration cycles’ with high glucose strength (126 mmol/L) and ‘clearance cycles’ with ultra-low, physiological glucose (5 mmol/L) for approximately 40% of the treatment time. Twenty-one prevalent PD patients underwent the optimised regimen (7 × 2 L 2.27% glucose + 5 × 2 L 0.1% glucose over 8 h) and the standard regimen in a crossover fashion. Six patients were excluded from data analysis. Results: Median glucose absorption was 43 g (IQR 41–54) and 44 g (40–55) for the standard and optimised intervention, respectively (p = 1). Ultrafiltration volume, weekly Kt/V creatinine and urea were significantly improved during optimised interventions, while no difference in sodium removal was detected. Post hoc analysis showed significantly improved ultrafiltration efficiency (ml ultrafiltration per gram absorbed glucose) during optimised regimens. No adverse events were observed except one incidence of drain pain. Conclusion: Optimised treatments were feasible and well tolerated in this small pilot study. Despite no difference in absorbed glucose, results indicate possible improvements of ultrafiltration efficiency and small solute clearances by optimised regimens. Use of optimised prescriptions as glucose sparing strategy should be evaluated in larger study populations.
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- Bergling, Karin, et al.
(författare)
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Optimized vs. Standard Automated Peritoneal Dialysis Regimens (OptiStAR) : Study protocol for a randomized controlled crossover trial
- 2020
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Ingår i: Pilot and Feasibility Studies. - : Springer Science and Business Media LLC. - 2055-5784. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: It has been estimated that automated peritoneal dialysis (APD) is currently the fastest growing renal replacement therapy in the world. However, in light of the growing number of diabetic patients on peritoneal dialysis (PD), the unwanted glucose absorption during APD remains problematic. Recent results, using an extended 3-pore model of APD, indicated that large reductions in glucose absorption are possible by using optimized bi-modal treatment regimens, having "UF cycles"using a higher glucose concentration, and "Clearance cycles"using a low concentration or, preferentially, no glucose. The present study is designed to test the theoretical prediction of a lower glucose absorption using these novel regimes. Methods: This study is a randomized single-center, open-label, prospective study. Prevalent PD patients between 18 and 75 years old without known catheter problems or recent peritonitis are eligible for inclusion. Patients are allocated to a first treatment session of either standard APD (6 × 2 L 1.36% over 9 h) or optimized APD (7 × 2 L 2.27% + 5 × 2 L 0.1% over 8 h). A second treatment session using the other treatment will be performed in a crossover fashion. Samples of the dialysis fluid will be taken before and after the treatment, and the volume of the dialysate before and after the treatment will be carefully assessed. The primary endpoint is difference in glucose absorption between the optimized and standard treatment. Secondary endpoints are ultrafiltration, sodium removal, Kt/V urea, and Kt/V Creatinine. The study will be closed when a total of 20 patients have successfully completed the interventions or terminated according to interim analysis. A Monte Carlo power analysis shows that the study has 80% power to detect a difference of 10 g (in line with that of theoretical results) in glucose absorption between the two treatments in 10 patients. Discussion: The present study is the first clinical investigation of optimized bi-modal treatments proposed by recent theoretical studies. Trial registration: ClinicalTrials.gov identifier: NCT04017572. Registration date: July 12, 2019, retrospectively registered.
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- Bergling, Karin, et al.
(författare)
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Phloretin Improves Ultrafiltration and Reduces Glucose Absorption during Peritoneal Dialysis in Rats
- 2022
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Ingår i: Journal of the American Society of Nephrology. - 1046-6673. ; 33:10, s. 1857-1863
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Tidskriftsartikel (refereegranskat)abstract
- Background: Harmful glucose exposure and absorption remain major limitations of peritoneal dialysis. We previously showed that inhibition of sodium glucose cotransporter 2 did not affect glucose transport during peritoneal dialysis in rats. However, more recently we found that phlorizin, a dual blocker of sodium glucose co-transporter 1 and 2, reduces glucose diffusion in peritoneal dialysis. Therefore, either inhibiting sodium glucose co-transporter 1 or blocking facilitative glucose channels by phlorizin metabolite phloretin would reduce glucose transport in peritoneal dialysis. Methods: We tested a selective blocker of sodium glucose co-transporter 1, mizagliflozin, as well as phloretin, a non-selective blocker of facilitative glucose channels, in an anesthetized Sprague-Dawley rat model of peritoneal dialysis. Results: Intraperitoneal phloretin treatment reduced glucose absorption by more than 30% and resulted in a more than 50% higher ultrafiltration rate compared to control animals. Sodium removal and sodium clearances were similarly improved, whereas the amount of ultrafiltration per mmol sodium removed did not differ. Mizagliflozin did not influence glucose transport or osmotic water transport. Conclusions: Taken together, our present and previous results indicate that blockers of facilitative glucose channels may be a promising target for reducing glucose absorption and improving ultrafiltration efficiency in peritoneal dialysis.
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- Caporale, N., et al.
(författare)
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From cohorts to molecules: Adverse impacts of endocrine disrupting mixtures
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375:6582
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Tidskriftsartikel (refereegranskat)abstract
- Convergent evidence associates exposure to endocrine disrupting chemicals (EDCs) with major human diseases, even at regulation-compliant concentrations. This might be because humans are exposed to EDC mixtures, whereas chemical regulation is based on a risk assessment of individual compounds. Here, we developed a mixture-centered risk assessment strategy that integrates epidemiological and experimental evidence. We identified that exposure to an EDC mixture in early pregnancy is associated with language delay in offspring. At human-relevant concentrations, this mixture disrupted hormone-regulated and disease-relevant regulatory networks in human brain organoids and in the model organisms Xenopus leavis and Danio rerio, as well as behavioral responses. Reinterrogating epidemiological data, we found that up to 54% of the children had prenatal exposures above experimentally derived levels of concern, reaching, for the upper decile compared with the lowest decile of exposure, a 3.3 times higher risk of language delay. © 2022 American Association for the Advancement of Science. All rights reserved.
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- Cheng, Peifu, et al.
(författare)
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High-Performance Hemofiltration via Molecular Sieving and Ultra-Low Friction in Carbon Nanotube Capillary Membranes
- 2023
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Ingår i: Advanced Functional Materials. - 1616-301X. ; 33:50
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Tidskriftsartikel (refereegranskat)abstract
- Conventional dialyzer membranes typically comprise of unevenly distributed polydisperse, tortuous, rough pores, embedded in relatively thick ≈20–50 µm polymer layers wherein separation occurs via size exclusion as well as differences in diffusivity of the permeating species. However, transport in such polymeric pores is increasingly hindered as the molecule size approaches the pore dimension, resulting in significant retention of undesirable middle molecules (≥15–60 kDa) and uremic toxins. Enhanced removal of middle molecules is usually accompanied by high albumin loss (≈66 kDa) causing hypoalbuminemia. Here, the scalable bottom-up fabrication of wafer-scale carbon nanotube (CNT) membranes with highly aligned, low-friction, straight-channels/capillaries and narrow pore-diameter distributions (≈0.5–4.5 nm) is demonstrated, to overcome persistent challenges in hemofiltration/hemodialysis. Using fluorescein isothiocyanate (FITC)-Ficoll 70 and albumin in phosphate buffered saline (PBS) as well as in bovine blood plasma, it is shown that CNT membranes can allow for significantly higher hydraulic permeability (more than an order of magnitude when normalized to pore area) than commercial high-flux hemofiltration/hemodialysis membranes (HF 400), as well as greatly enhance removal of middle molecules while maintaining comparable albumin retention. These findings are rationalized via an N-pore transport model that highlights the critical role of molecular flexing and deformation during size-selective transport within nanoscale confinements of the CNTs. The unique transport characteristics of CNTs coupled with size-exclusion and wafer-scale fabrication offer transformative advances for hemofiltration, and the obtained insight into molecular transport can aid advancements in several other bio-systems/applications beyond hemofiltration/hemodialysis.
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| 9. |
- Dolinina, Julia, et al.
(författare)
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Clemizole and La3+ salts ameliorate angiotensin II-induced glomerular hyperpermeability in vivo
- 2021
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Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 9:10
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Tidskriftsartikel (refereegranskat)abstract
- Angiotensin II (Ang II) induces marked, dynamic increases in the permeability of the glomerular filtration barrier (GFB) in rats. After binding to its receptor, Ang II elicits Ca2+ influx into cells, mediated by TRPC5 and TRPC6 (transient receptor potential canonical type 5 and 6). Clemizole and La3+ salts have been shown to block TRPC channels in vitro, and we therefore tested their potential effect on Ang II-induced glomerular hyperpermeability. Anesthetized male Sprague-Dawley rats were infused with Ang II (80 ng kg–1min–1) alone, or together with clemizole or low-dose La3+ (activates TRPC5, blocks TRPC6) or high-dose La3+ (blocks both TRPC5 and TRPC6). Plasma and urine samples were taken during baseline and at 5 min after the start of the infusions and analyzed by high-performance size-exclusion chromatography for determination of glomerular sieving coefficients for Ficoll 10–80 Å (1–8 nm). Ang II infusion evoked glomerular hyperpermeability to large Ficolls (50–80 Å), which was ameliorated by clemizole, having no significant effect on glomerular filtration rate (GFR) or Ang II-mediated increase in mean arterial pressure (ΔMAP). In contrast, high- and low-dose La3+ significantly lowered ΔMAP and reduced Ang II-induced hyperpermeability. Combined, clemizole and low-dose La3+ were less effective at ameliorating Ang II-induced glomerular hyperpermeability than low-dose La3+ alone. In conclusion, our data show that both clemizole and La3+ are effective against Ang II-induced glomerular hyperpermeability, with differential effects on blood pressure. Further research using more specific blockers of TRPC5 and TRPC6 should be performed to reveal the underlying mechanisms.
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| 10. |
- Eriksson, Carl, 1981-, et al.
(författare)
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Real-world effectiveness of vedolizumab in inflammatory bowel disease : week 52 results from the Swedish prospective multicentre SVEAH study
- 2021
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Ingår i: Therapeutic Advances in Gastroenterology. - : Sage Publications. - 1756-283X .- 1756-2848. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prospectively and systematically collected real-world data on vedolizumab are scarce. We aimed to assess the long-term clinical effectiveness of vedolizumab in inflammatory bowel disease (IBD).Methods: This study was a prospective, observational, multicentre study. Overall, 286 patients with active IBD were included (Crohn's disease, n = 169; ulcerative colitis, n = 117). The primary outcomes were clinical response at week 12 and clinical remission at week 52, based on the Harvey Bradshaw Index and the partial Mayo Clinic score. Secondary outcomes included clinical remission at week 12, clinical response at week 52, corticosteroid-free clinical remission at week 52, changes in biochemical measures, and health-related quality of life (HRQoL).Results: At baseline, 88% of the patients were exposed to anti-TNF and 41% of the patients with Crohn's disease had undergone ⩾1 surgical resection. At week 12, clinical response was 27% and remission 47% in Crohn's disease; corresponding figures in ulcerative colitis were 52% and 34%. Clinical response, remission and corticosteroid-free remission at week 52 were 22%, 41% and 40% in Crohn's disease and 49%, 47% and 46% in ulcerative colitis, respectively. A statistically significant decrease in median faecal-calprotectin and C-reactive protein was observed at 12 and 52 weeks in patients with Crohn's disease and ulcerative colitis. The HRQoL measures Short Health Scale and EuroQol 5-Dimensions improved in both Crohn's disease and ulcerative colitis patients (p < 0.001). Clinical disease activity at baseline was inversely associated with clinical remission at week 52.Conclusion: Vedolizumab proved effective for the treatment of refractory IBD in clinical practice.
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