Kidney Week

Abstract: TH-PO099

Effect of 3% Saline and Furosemide on Biomarkers of Kidney Injury and Renal Tubular Function and GFR in Healthy Subjects: A Randomized Controlled Trial

Session Information

• AKI: Biomarkers, Drugs, Onco-Nephrology
  November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 102 AKI: Clinical, Outcomes, and Trials

Authors

• Mose, Frank H., Hospital Unit West Jutland, Holstebro, Denmark

Frank H. Mose,

• Vrist, Marie Houmaa, Hospital Unit West Jutland, Holstebro, Denmark

Marie Houmaa Vrist,

• Bech, Jesper N., Hospital Unit West Jutland, Holstebro, Denmark

Jesper N. Bech,

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 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 GFR, fractional excretion of sodium (FE_Na), urinary chloride excretion (u-Cl), urinary excretions of aquaporin-2 (u-AQP2), 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 diet and fluid 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 NGAL was absent when furosemide was given simultaneously, and the responses in NGAL were not significantly different from placebo control. Furosemide changed responses in 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. 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.

Funding

• Government Support - Non-U.S.