Skip to main content
Top
Published in: BMC Nephrology 1/2021

Open Access 01-12-2021 | Kidney Injury | Research article

Effect of balanced crystalloids versus saline on urinary biomarkers of acute kidney injury in critically ill adults

Authors: Blake E. Funke, Karen E. Jackson, Wesley H. Self, Sean P. Collins, Christina T. Saunders, Li Wang, Jeffrey D. Blume, Nancy Wickersham, Ryan M. Brown, Jonathan D. Casey, Gordon R. Bernard, Todd W. Rice, Edward D. Siew, Matthew W. Semler, for the SMART Investigators, the Pragmatic Critical Care Research Group

Published in: BMC Nephrology | Issue 1/2021

Login to get access

Abstract

Background

Recent trials have suggested use of balanced crystalloids may decrease the incidence of major adverse kidney events compared to saline in critically ill adults. The effect of crystalloid composition on biomarkers of early acute kidney injury remains unknown.

Methods

From February 15 to July 15, 2016, we conducted an ancillary study to the Isotonic Solutions and Major Adverse Renal Events Trial (SMART) comparing the effect of balanced crystalloids versus saline on urinary levels of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) among 261 consecutively-enrolled critically ill adults admitted from the emergency department to the medical ICU. After informed consent, we collected urine 36 ± 12 h after hospital admission and measured NGAL and KIM-1 levels using commercially available ELISAs. Levels of NGAL and KIM-1 at 36 ± 12 h were compared between patients assigned to balanced crystalloids versus saline using a Mann-Whitney U test.

Results

The 131 patients (50.2%) assigned to the balanced crystalloid group and the 130 patients (49.8%) assigned to the saline group were similar at baseline. Urinary NGAL levels were significantly lower in the balanced crystalloid group (median, 39.4 ng/mg [IQR 9.9 to 133.2]) compared with the saline group (median, 64.4 ng/mg [IQR 27.6 to 339.9]) (P < 0.001). Urinary KIM-1 levels did not significantly differ between the balanced crystalloid group (median, 2.7 ng/mg [IQR 1.5 to 4.9]) and the saline group (median, 2.4 ng/mg [IQR 1.3 to 5.0]) (P = 0.36).

Conclusions

In this ancillary analysis of a clinical trial comparing balanced crystalloids to saline among critically ill adults, balanced crystalloids were associated with lower urinary concentrations of NGAL and similar urinary concentrations of KIM-1, compared with saline. These results suggest only a modest reduction in early biomarkers of acute kidney injury with use of balanced crystalloids compared with saline.

Trial registration

ClinicalTrials.​gov number: NCT02444988. Date registered: May 15, 2015.
Appendix
Available only for authorised users
Literature
1.
go back to reference Myburgh JA, Mythen MG. Resuscitation fluids. N Engl J Med. 2013;369:1243–51.CrossRef Myburgh JA, Mythen MG. Resuscitation fluids. N Engl J Med. 2013;369:1243–51.CrossRef
2.
go back to reference Finfer S, Liu B, Taylor C, et al. Resuscitation fluid use in critically ill adults: an international cross-sectional study in 391 intensive care units. Crit Care Lond Engl. 2010;14:R185.CrossRef Finfer S, Liu B, Taylor C, et al. Resuscitation fluid use in critically ill adults: an international cross-sectional study in 391 intensive care units. Crit Care Lond Engl. 2010;14:R185.CrossRef
3.
go back to reference Hammond NE, Taylor C, Finfer S, et al. Patterns of intravenous fluid resuscitation use in adult intensive care patients between 2007 and 2014: An international cross-sectional study. PLoS One. 2017;12:e0176292.CrossRef Hammond NE, Taylor C, Finfer S, et al. Patterns of intravenous fluid resuscitation use in adult intensive care patients between 2007 and 2014: An international cross-sectional study. PLoS One. 2017;12:e0176292.CrossRef
4.
go back to reference Semler MW, Self WH, Wanderer JP, et al. Balanced crystalloids versus saline in critically ill adults. N Engl J Med. 2018;378:829–39.CrossRef Semler MW, Self WH, Wanderer JP, et al. Balanced crystalloids versus saline in critically ill adults. N Engl J Med. 2018;378:829–39.CrossRef
5.
go back to reference Wilcox CS. Regulation of renal blood flow by plasma chloride. J Clin Invest. 1983;71:726–35.CrossRef Wilcox CS. Regulation of renal blood flow by plasma chloride. J Clin Invest. 1983;71:726–35.CrossRef
6.
go back to reference Zhou F, Peng Z-Y, Bishop JV, et al. Effects of fluid resuscitation with 0.9% saline versus a balanced electrolyte solution on acute kidney injury in a rat model of sepsis*. Crit Care Med. 2014;42:e270–8.CrossRef Zhou F, Peng Z-Y, Bishop JV, et al. Effects of fluid resuscitation with 0.9% saline versus a balanced electrolyte solution on acute kidney injury in a rat model of sepsis*. Crit Care Med. 2014;42:e270–8.CrossRef
7.
go back to reference Bellomo R, Ronco C, Kellum JA, et al. Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the second international consensus conference of the acute Dialysis quality initiative (ADQI) group. Crit Care Lond Engl. 2004;8:R204–12.CrossRef Bellomo R, Ronco C, Kellum JA, et al. Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the second international consensus conference of the acute Dialysis quality initiative (ADQI) group. Crit Care Lond Engl. 2004;8:R204–12.CrossRef
8.
go back to reference Chowdhury AH, Cox EF, Francis ST, et al. A randomized, controlled, double-blind crossover study on the effects of 2-L infusions of 0.9% saline and plasma-lyte® 148 on renal blood flow velocity and renal cortical tissue perfusion in healthy volunteers. Ann Surg. 2012;256:18–24.CrossRef Chowdhury AH, Cox EF, Francis ST, et al. A randomized, controlled, double-blind crossover study on the effects of 2-L infusions of 0.9% saline and plasma-lyte® 148 on renal blood flow velocity and renal cortical tissue perfusion in healthy volunteers. Ann Surg. 2012;256:18–24.CrossRef
9.
go back to reference Chowdhury AH, Cox EF, Francis ST, et al. A randomized, controlled, double-blind crossover study on the effects of 1-L infusions of 6% hydroxyethyl starch suspended in 0.9% saline (voluven) and a balanced solution (plasma volume Redibag) on blood volume, renal blood flow velocity, and renal cortical tissue perfusion in healthy volunteers. Ann Surg. 2014;259:881–7.CrossRef Chowdhury AH, Cox EF, Francis ST, et al. A randomized, controlled, double-blind crossover study on the effects of 1-L infusions of 6% hydroxyethyl starch suspended in 0.9% saline (voluven) and a balanced solution (plasma volume Redibag) on blood volume, renal blood flow velocity, and renal cortical tissue perfusion in healthy volunteers. Ann Surg. 2014;259:881–7.CrossRef
10.
go back to reference Williams EL, Hildebrand KL, McCormick SA, et al. The effect of intravenous lactated Ringer’s solution versus 0.9% sodium chloride solution on serum osmolality in human volunteers. Anesth Analg. 1999;88:999–1003.PubMed Williams EL, Hildebrand KL, McCormick SA, et al. The effect of intravenous lactated Ringer’s solution versus 0.9% sodium chloride solution on serum osmolality in human volunteers. Anesth Analg. 1999;88:999–1003.PubMed
11.
go back to reference Volta CA, Trentini A, Farabegoli L, et al. Effects of two different strategies of fluid administration on inflammatory mediators, plasma electrolytes and acid/base disorders in patients undergoing major abdominal surgery: a randomized double blind study. J Inflamm. 2013;10:29.CrossRef Volta CA, Trentini A, Farabegoli L, et al. Effects of two different strategies of fluid administration on inflammatory mediators, plasma electrolytes and acid/base disorders in patients undergoing major abdominal surgery: a randomized double blind study. J Inflamm. 2013;10:29.CrossRef
12.
go back to reference Weinberg L, Li M, Churilov L, et al. Associations of fluid amount, type, and balance and acute kidney injury in patients undergoing major surgery. Anaesth Intensive Care. 2018;46:79–87.CrossRef Weinberg L, Li M, Churilov L, et al. Associations of fluid amount, type, and balance and acute kidney injury in patients undergoing major surgery. Anaesth Intensive Care. 2018;46:79–87.CrossRef
13.
go back to reference Shaw AD, Bagshaw SM, Goldstein SL, et al. Major complications, mortality, and resource utilization after open abdominal surgery: 0.9% saline compared to plasma-Lyte. Ann Surg. 2012;255:821–9.CrossRef Shaw AD, Bagshaw SM, Goldstein SL, et al. Major complications, mortality, and resource utilization after open abdominal surgery: 0.9% saline compared to plasma-Lyte. Ann Surg. 2012;255:821–9.CrossRef
14.
go back to reference Self WH, Semler MW, Wanderer JP, et al. Balanced crystalloids versus saline in noncritically ill adults. N Engl J Med. 2018;378:819–28.CrossRef Self WH, Semler MW, Wanderer JP, et al. Balanced crystalloids versus saline in noncritically ill adults. N Engl J Med. 2018;378:819–28.CrossRef
15.
go back to reference Schmidt-Ott KM, Mori K, Li JY, et al. Dual action of neutrophil gelatinase-associated lipocalin. J Am Soc Nephrol JASN. 2007;18:407–13.CrossRef Schmidt-Ott KM, Mori K, Li JY, et al. Dual action of neutrophil gelatinase-associated lipocalin. J Am Soc Nephrol JASN. 2007;18:407–13.CrossRef
16.
go back to reference Han WK, Bailly V, Abichandani R, et al. Kidney injury Molecule-1 (KIM-1): a novel biomarker for human renal proximal tubule injury. Kidney Int. 2002;62:237–44.CrossRef Han WK, Bailly V, Abichandani R, et al. Kidney injury Molecule-1 (KIM-1): a novel biomarker for human renal proximal tubule injury. Kidney Int. 2002;62:237–44.CrossRef
17.
go back to reference Bonventre JV. Kidney injury molecule-1 (KIM-1): a urinary biomarker and much more. Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc - Eur Ren Assoc. 2009;24:3265–8. Bonventre JV. Kidney injury molecule-1 (KIM-1): a urinary biomarker and much more. Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc - Eur Ren Assoc. 2009;24:3265–8.
18.
go back to reference Semler MW, Self WH, Wang L, et al. Balanced crystalloids versus saline in the intensive care unit: study protocol for a cluster-randomized, multiple-crossover trial. Trials. 2017;18:129.CrossRef Semler MW, Self WH, Wang L, et al. Balanced crystalloids versus saline in the intensive care unit: study protocol for a cluster-randomized, multiple-crossover trial. Trials. 2017;18:129.CrossRef
19.
go back to reference Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int. 2012;2(Suppl):8. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int. 2012;2(Suppl):8.
20.
go back to reference Palevsky PM, Molitoris BA, Okusa MD, et al. Design of clinical trials in acute kidney injury: report from an NIDDK workshop on trial methodology. Clin J Am Soc Nephrol CJASN. 2012;7:844–50.CrossRef Palevsky PM, Molitoris BA, Okusa MD, et al. Design of clinical trials in acute kidney injury: report from an NIDDK workshop on trial methodology. Clin J Am Soc Nephrol CJASN. 2012;7:844–50.CrossRef
21.
go back to reference Kellum JA, Chawla LS, Keener C, et al. The effects of alternative resuscitation strategies on acute kidney injury in patients with septic shock. Am J Respir Crit Care Med. 2016;193:281–7.CrossRef Kellum JA, Chawla LS, Keener C, et al. The effects of alternative resuscitation strategies on acute kidney injury in patients with septic shock. Am J Respir Crit Care Med. 2016;193:281–7.CrossRef
22.
go back to reference Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150:604–12.CrossRef Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150:604–12.CrossRef
23.
go back to reference Knaus WA, Draper EA, Wagner DP, et al. APACHE II: a severity of disease classification system. Crit Care Med. 1985;13:818–29.CrossRef Knaus WA, Draper EA, Wagner DP, et al. APACHE II: a severity of disease classification system. Crit Care Med. 1985;13:818–29.CrossRef
24.
go back to reference Dey A, Adinarayanan S, Bidkar PU, et al. Comparison of normal saline and balanced crystalloid (plasmalyte) in patients undergoing elective craniotomy for supratentorial brain tumors: a randomized controlled trial. Neurol India. 2018;66:1338–44.CrossRef Dey A, Adinarayanan S, Bidkar PU, et al. Comparison of normal saline and balanced crystalloid (plasmalyte) in patients undergoing elective craniotomy for supratentorial brain tumors: a randomized controlled trial. Neurol India. 2018;66:1338–44.CrossRef
25.
go back to reference Mose FH, Jörgensen AN, Vrist MH, et al. Effect of 3% saline and furosemide on biomarkers of kidney injury and renal tubular function and GFR in healthy subjects - a randomized controlled trial. BMC Nephrol. 2019;20:200.CrossRef Mose FH, Jörgensen AN, Vrist MH, et al. Effect of 3% saline and furosemide on biomarkers of kidney injury and renal tubular function and GFR in healthy subjects - a randomized controlled trial. BMC Nephrol. 2019;20:200.CrossRef
26.
go back to reference Parikh CR, Coca SG, Thiessen-Philbrook H, et al. Postoperative biomarkers predict acute kidney injury and poor outcomes after adult cardiac surgery. J Am Soc Nephrol JASN. 2011;22:1748–57.CrossRef Parikh CR, Coca SG, Thiessen-Philbrook H, et al. Postoperative biomarkers predict acute kidney injury and poor outcomes after adult cardiac surgery. J Am Soc Nephrol JASN. 2011;22:1748–57.CrossRef
27.
go back to reference Parikh CR, Thiessen-Philbrook H, Garg AX, et al. Performance of kidney injury molecule-1 and liver fatty acid-binding protein and combined biomarkers of AKI after cardiac surgery. Clin J Am Soc Nephrol CJASN. 2013;8:1079–88.CrossRef Parikh CR, Thiessen-Philbrook H, Garg AX, et al. Performance of kidney injury molecule-1 and liver fatty acid-binding protein and combined biomarkers of AKI after cardiac surgery. Clin J Am Soc Nephrol CJASN. 2013;8:1079–88.CrossRef
28.
go back to reference Vaidya VS, Waikar SS, Ferguson MA, et al. Urinary biomarkers for sensitive and specific detection of acute kidney injury in humans. Clin Transl Sci. 2008;1:200–8.CrossRef Vaidya VS, Waikar SS, Ferguson MA, et al. Urinary biomarkers for sensitive and specific detection of acute kidney injury in humans. Clin Transl Sci. 2008;1:200–8.CrossRef
29.
go back to reference Haase-Fielitz A, Haase M, Devarajan P. Neutrophil gelatinase-associated lipocalin as a biomarker of acute kidney injury: a critical evaluation of current status. Ann Clin Biochem. 2014;51:335–51.CrossRef Haase-Fielitz A, Haase M, Devarajan P. Neutrophil gelatinase-associated lipocalin as a biomarker of acute kidney injury: a critical evaluation of current status. Ann Clin Biochem. 2014;51:335–51.CrossRef
30.
go back to reference Charlton JR, Portilla D, Okusa MD. A basic science view of acute kidney injury biomarkers. Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc - Eur Ren Assoc. 2014;29:1301–11. Charlton JR, Portilla D, Okusa MD. A basic science view of acute kidney injury biomarkers. Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc - Eur Ren Assoc. 2014;29:1301–11.
31.
go back to reference Pfortmueller CA, Funk G-C, Reiterer C, et al. Normal saline versus a balanced crystalloid for goal-directed perioperative fluid therapy in major abdominal surgery: a double-blind randomised controlled study. Br J Anaesth. 2018;120:274–83.CrossRef Pfortmueller CA, Funk G-C, Reiterer C, et al. Normal saline versus a balanced crystalloid for goal-directed perioperative fluid therapy in major abdominal surgery: a double-blind randomised controlled study. Br J Anaesth. 2018;120:274–83.CrossRef
32.
go back to reference Brown RM, Wang L, Coston TD, et al. Balanced crystalloids versus saline in Sepsis. A secondary analysis of the SMART clinical trial. Am J Respir Crit Care Med. 2019;200:1487–95.CrossRef Brown RM, Wang L, Coston TD, et al. Balanced crystalloids versus saline in Sepsis. A secondary analysis of the SMART clinical trial. Am J Respir Crit Care Med. 2019;200:1487–95.CrossRef
Metadata
Title
Effect of balanced crystalloids versus saline on urinary biomarkers of acute kidney injury in critically ill adults
Authors
Blake E. Funke
Karen E. Jackson
Wesley H. Self
Sean P. Collins
Christina T. Saunders
Li Wang
Jeffrey D. Blume
Nancy Wickersham
Ryan M. Brown
Jonathan D. Casey
Gordon R. Bernard
Todd W. Rice
Edward D. Siew
Matthew W. Semler
for the SMART Investigators
the Pragmatic Critical Care Research Group
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Nephrology / Issue 1/2021
Electronic ISSN: 1471-2369
DOI
https://doi.org/10.1186/s12882-021-02236-x

Other articles of this Issue 1/2021

BMC Nephrology 1/2021 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.