Kidney International

Journal Information
ISSN / EISSN : 0085-2538 / 1523-1755
Current Publisher: Elsevier BV (10.1016)
Former Publisher: Wiley (10.1046) | Springer Science and Business Media LLC (10.1038)
Total articles ≅ 24,575
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Latest articles in this journal

, Michael G. Shlipak, Michael Cheung,
Published: 1 May 2021
Kidney International, Volume 99; doi:10.1016/j.kint.2021.02.009

Amaury Dujardin, Marine Lorent, Yohann Foucher, Christophe Legendre, Clarisse Kerleau, , Magali Giral, Gilles Blancho, Julien Branchereau, Diego Cantarovich, et al.
Published: 1 May 2021
Kidney International, Volume 99, pp 1189-1201; doi:10.1016/j.kint.2020.08.010

The publisher has not yet granted permission to display this abstract.
Rio P. Juni, Rushd Al-Shama, Diederik W.D. Kuster, Jolanda van der Velden, Henrike M. Hamer, Marc G. Vervloet, Etto C. Eringa, Pieter Koolwijk,
Published: 1 May 2021
Kidney International, Volume 99, pp 1088-1101; doi:10.1016/j.kint.2020.12.013

Abstract:
Chronic kidney disease (CKD) promotes development of cardiac abnormalities and is highly prevalent in patients with heart failure, particularly in those with preserved ejection fraction. CKD is associated with endothelial dysfunction, however, whether CKD can induce impairment of endothelium-to-cardiomyocyte crosstalk leading to impairment of cardiomyocyte function is not known. The sodium-glucose co-transporter 2 inhibitor, empagliflozin, reduced cardiovascular events in diabetic patients with or without CKD, suggesting its potential as a new treatment for heart failure with preserved ejection fraction. We hypothesized that uremic serum from patients with CKD would impair endothelial control of cardiomyocyte relaxation and contraction, and that empagliflozin would protect against this effect. Using a co-culture system of human cardiac microvascular endothelial cells with adult rat ventricular cardiomyocytes to measure cardiomyocyte relaxation and contraction, we showed that serum from patients with CKD impaired endothelial enhancement of cardiomyocyte function which was rescued by empagliflozin. Exposure to uremic serum reduced human cardiac microvascular endothelial cell nitric oxide bioavailability, and increased mitochondrial reactive oxygen species and 3-nitrotyrosine levels, indicating nitric oxide scavenging by reactive oxygen species. Empagliflozin attenuated uremic serum-induced generation of endothelial mitochondrial reactive oxygen species, leading to restoration of nitric oxide production and endothelium-mediated enhancement of nitric oxide levels in cardiomyocytes, an effect largely independent of sodium-hydrogen exchanger-1. Thus, empagliflozin restores the beneficial effect of cardiac microvascular endothelial cells on cardiomyocyte function by reducing mitochondrial oxidative damage, leading to reduced reactive oxygen species accumulation and increased endothelial nitric oxide bioavailability.
Stan R. Ursem, Annemieke C. Heijboer, Patrick C. D’Haese, Geert J. Behets, Etienne Cavalier, Marc G. Vervloet,
Published: 1 May 2021
Kidney International, Volume 99, pp 1173-1178; doi:10.1016/j.kint.2020.12.024

The publisher has not yet granted permission to display this abstract.
Published: 1 May 2021
Kidney International, Volume 99, pp 1057-1059; doi:10.1016/j.kint.2020.12.035

Published: 1 May 2021
Kidney International, Volume 99; doi:10.1016/s0085-2538(21)00304-5

Kathleen M. Hill Gallant, Elizabeth R. Stremke, Laurie L. Trevino, Ranjani N. Moorthi, Simit Doshi, Meryl E. Wastney, Nozomi Hisada, Jotaro Sato, Yoshitaka Ogita, Naohisa Fujii, et al.
Published: 1 May 2021
Kidney International, Volume 99, pp 1225-1233; doi:10.1016/j.kint.2020.09.035

Abstract:
The treatment of hyperphosphatemia remains challenging in patients receiving hemodialysis. This phase 1b study assessed safety and efficacy of EOS789, a novel pan-inhibitor of phosphate transport (NaPi-2b, PiT-1, PiT-2) on intestinal phosphate absorption in patients receiving intermittent hemodialysis therapy. Two cross-over, randomized order studies of identical design (ten patients each) compared daily EOS789 50 mg to placebo with meals and daily EOS789 100 mg vs EOS789 100 mg plus 1600 mg sevelamer with meals. Patients ate a controlled diet of 900 mg phosphate daily for two weeks and began EOS789 on day four. On day ten, a phosphate absorption testing protocol was performed during the intradialytic period. Intestinal fractional phosphate absorption was determined by kinetic modeling of serum data following oral and intravenous doses of 33Phosphate (33P). The results demonstrated no study drug related serious adverse events. Fractional phosphate absorption was 0.53 (95% confidence interval: 0.39,0.67) for placebo vs. 0.49 (0.35,0.63) for 50 mg EOS789; and 0.40 (0.29,0.50) for 100 mg EOS789 vs. 0.36 (0.26,0.47) for 100 mg EOS789 plus 1600 mg sevelamer (all not significantly different). The fractional phosphate absorption trended lower in six patients who completed both studies with EOS789 100 mg compared with placebo. Thus, in this phase 1b study, EOS789 was safe and well tolerated. Importantly, the use of 33P as a sensitive and direct measure of intestinal phosphate absorption allows specific testing of drug efficacy. The effectiveness of EOS789 needs to be evaluated in future phase 2 and phase 3 studies.
, John Asplin, Ignacio Granja, Luojing Chen, Daiana Spataru, Tong Tong Wu, Marc Grynpas, David A. Bushinsky
Published: 1 May 2021
Kidney International, Volume 99, pp 1118-1126; doi:10.1016/j.kint.2020.12.023

The publisher has not yet granted permission to display this abstract.
, Harald Mischak, Joachim Beige, ,
Published: 1 May 2021
Kidney International, Volume 99, pp 1240-1241; doi:10.1016/j.kint.2021.02.008

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