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

Autor: Mose FH; Holstebro Hospital, Hospital Unit West, Holstebro, Denmark. frchri@rm.dk.; University Clinic in Nephrology and Hypertension, Aarhus University, Aarhus, Denmark. frchri@rm.dk., Jörgensen AN; Holstebro Hospital, Hospital Unit West, Holstebro, Denmark.; University Clinic in Nephrology and Hypertension, Aarhus University, Aarhus, Denmark., Vrist MH; Holstebro Hospital, Hospital Unit West, Holstebro, Denmark.; University Clinic in Nephrology and Hypertension, Aarhus University, Aarhus, Denmark., Ekelöf NP; Department of Anaesthesiology, Holstebro Hospital, Hospital Unit West, Holstebro, Denmark., Pedersen EB; Holstebro Hospital, Hospital Unit West, Holstebro, Denmark.; University Clinic in Nephrology and Hypertension, Aarhus University, Aarhus, Denmark., Bech JN; Holstebro Hospital, Hospital Unit West, Holstebro, Denmark.; University Clinic in Nephrology and Hypertension, Aarhus University, Aarhus, Denmark.
Jazyk: angličtina
Zdroj: BMC nephrology [BMC Nephrol] 2019 Jun 03; Vol. 20 (1), pp. 200. Date of Electronic Publication: 2019 Jun 03.
DOI: 10.1186/s12882-019-1342-x
Abstrakt: 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).
Databáze: MEDLINE
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