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Effect of 3% saline and furosemide on biomarkers of kidney injury and renal tubular function and GFR in healthy subjects – a randomized controlled trial

BACKGROUND: Chloride is speculated to have nephrotoxic properties. In healthy subjects we tested the hypothesis that acute chloride loading with 3% saline would induce kidney injury, which could be prevented with the loop-diuretic furosemide. METHODS: The study was designed as a randomized, placebo-...

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Autores principales: Mose, F. H., Jörgensen, A. N., Vrist, M. H., Ekelöf, N. P., Pedersen, E. B., Bech, J. N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6545674/
https://www.ncbi.nlm.nih.gov/pubmed/31159750
http://dx.doi.org/10.1186/s12882-019-1342-x
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author Mose, F. H.
Jörgensen, A. N.
Vrist, M. H.
Ekelöf, N. P.
Pedersen, E. B.
Bech, J. N.
author_facet Mose, F. H.
Jörgensen, A. N.
Vrist, M. H.
Ekelöf, N. P.
Pedersen, E. B.
Bech, J. N.
author_sort Mose, F. H.
collection PubMed
description BACKGROUND: Chloride is speculated to have nephrotoxic properties. In healthy subjects we tested the hypothesis that acute chloride loading with 3% saline would induce kidney injury, which could be prevented with the loop-diuretic furosemide. METHODS: The study was designed as a randomized, placebo-controlled, crossover study. Subjects were given 3% saline accompanied by either placebo or furosemide. Before, during and after infusion of 3% saline we measured glomerular filtration rate (GFR), fractional excretion of sodium (FE(Na)), urinary chloride excretion (u-Cl), urinary excretions of aquaporin-2 (u-AQP2) and epithelial sodium channels (u-ENaC(γ)), neutrophil gelatinase-associated lipocalin (u-NGAL) and kidney injury molecule-1 (u-KIM-1) as marker of kidney injury and vasoactive hormones: renin (PRC), angiotensin II (p-AngII), aldosterone (p-Aldo) and arginine vasopressin (p-AVP). Four days prior to each of the two examinations subjects were given a standardized fluid and diet intake. RESULTS: After 3% saline infusion u-NGAL and KIM-1 excretion increased slightly (u-NGAL: 17 ± 24 during placebo vs. -7 ± 23 ng/min during furosemide, p = 0.039, u-KIM-1: 0.21 ± 0.23 vs − 0.06 ± 0.14 ng/ml, p <  0.001). The increase in u-NGAL was absent when furosemide was given simultaneously, and the responses in u-NGAL were not significantly different from placebo control. Furosemide changed responses in u-KIM-1 where a delayed increase was observed. GFR was increased by 3% saline but decreased when furosemide accompanied the infusion. U-Na, FE(Na), u-Cl, and u-osmolality increased in response to saline, and the increase was markedly pronounced when furosemide was added. FE(K) decreased slightly during 3% saline infusion, but simultaneously furosemide increased FE(K). U-AQP2 increased after 3% saline and placebo, and the response was further increased by furosemide. U-ENaC(γ) decreased to the same extent after 3% saline infusion in the two groups. 3% saline significantly reduced PRC, p-AngII and p-Aldo, and responses were attenuated by furosemide. p-AVP was increased by 3% saline, with a larger increase during furosemide. CONCLUSION: This study shows minor increases in markers of kidney injury after 3% saline infusion Furosemide abolished the increase in NGAL and postponed the increase in u-KIM-1. The clinical importance of these findings needs further investigation. TRIAL REGISTRATION: (EU Clinical trials register number: 2015–002585-23, registered on 5th November 2015)
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spelling pubmed-65456742019-06-06 Effect of 3% saline and furosemide on biomarkers of kidney injury and renal tubular function and GFR in healthy subjects – a randomized controlled trial Mose, F. H. Jörgensen, A. N. Vrist, M. H. Ekelöf, N. P. Pedersen, E. B. Bech, J. N. BMC Nephrol Research Article BACKGROUND: Chloride is speculated to have nephrotoxic properties. In healthy subjects we tested the hypothesis that acute chloride loading with 3% saline would induce kidney injury, which could be prevented with the loop-diuretic furosemide. METHODS: The study was designed as a randomized, placebo-controlled, crossover study. Subjects were given 3% saline accompanied by either placebo or furosemide. Before, during and after infusion of 3% saline we measured glomerular filtration rate (GFR), fractional excretion of sodium (FE(Na)), urinary chloride excretion (u-Cl), urinary excretions of aquaporin-2 (u-AQP2) and epithelial sodium channels (u-ENaC(γ)), neutrophil gelatinase-associated lipocalin (u-NGAL) and kidney injury molecule-1 (u-KIM-1) as marker of kidney injury and vasoactive hormones: renin (PRC), angiotensin II (p-AngII), aldosterone (p-Aldo) and arginine vasopressin (p-AVP). Four days prior to each of the two examinations subjects were given a standardized fluid and diet intake. RESULTS: After 3% saline infusion u-NGAL and KIM-1 excretion increased slightly (u-NGAL: 17 ± 24 during placebo vs. -7 ± 23 ng/min during furosemide, p = 0.039, u-KIM-1: 0.21 ± 0.23 vs − 0.06 ± 0.14 ng/ml, p <  0.001). The increase in u-NGAL was absent when furosemide was given simultaneously, and the responses in u-NGAL were not significantly different from placebo control. Furosemide changed responses in u-KIM-1 where a delayed increase was observed. GFR was increased by 3% saline but decreased when furosemide accompanied the infusion. U-Na, FE(Na), u-Cl, and u-osmolality increased in response to saline, and the increase was markedly pronounced when furosemide was added. FE(K) decreased slightly during 3% saline infusion, but simultaneously furosemide increased FE(K). U-AQP2 increased after 3% saline and placebo, and the response was further increased by furosemide. U-ENaC(γ) decreased to the same extent after 3% saline infusion in the two groups. 3% saline significantly reduced PRC, p-AngII and p-Aldo, and responses were attenuated by furosemide. p-AVP was increased by 3% saline, with a larger increase during furosemide. CONCLUSION: This study shows minor increases in markers of kidney injury after 3% saline infusion Furosemide abolished the increase in NGAL and postponed the increase in u-KIM-1. The clinical importance of these findings needs further investigation. TRIAL REGISTRATION: (EU Clinical trials register number: 2015–002585-23, registered on 5th November 2015) BioMed Central 2019-06-03 /pmc/articles/PMC6545674/ /pubmed/31159750 http://dx.doi.org/10.1186/s12882-019-1342-x Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Mose, F. H.
Jörgensen, A. N.
Vrist, M. H.
Ekelöf, N. P.
Pedersen, E. B.
Bech, J. N.
Effect of 3% saline and furosemide on biomarkers of kidney injury and renal tubular function and GFR in healthy subjects – a randomized controlled trial
title Effect of 3% saline and furosemide on biomarkers of kidney injury and renal tubular function and GFR in healthy subjects – a randomized controlled trial
title_full Effect of 3% saline and furosemide on biomarkers of kidney injury and renal tubular function and GFR in healthy subjects – a randomized controlled trial
title_fullStr Effect of 3% saline and furosemide on biomarkers of kidney injury and renal tubular function and GFR in healthy subjects – a randomized controlled trial
title_full_unstemmed Effect of 3% saline and furosemide on biomarkers of kidney injury and renal tubular function and GFR in healthy subjects – a randomized controlled trial
title_short Effect of 3% saline and furosemide on biomarkers of kidney injury and renal tubular function and GFR in healthy subjects – a randomized controlled trial
title_sort effect of 3% saline and furosemide on biomarkers of kidney injury and renal tubular function and gfr in healthy subjects – a randomized controlled trial
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6545674/
https://www.ncbi.nlm.nih.gov/pubmed/31159750
http://dx.doi.org/10.1186/s12882-019-1342-x
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