Effect of 0.9% NaCl compared to plasma-lyte on biomarkers of kidney injury, sodium excretion and tubular transport proteins in patients undergoing primary uncemented hip replacement - a randomized trial

Abstract

Background: Isotonic saline (IS) is widely used to secure perioperative cardiovascular stability. However, the high amount of chloride in IS can induce hyperchloremic acidosis. Therefore, IS is suspected to increase the risk of acute kidney injury (AKI). Biomarkers may have potential as indicators.

Methods: In a double-blinded, placebo-controlled study, 38 patients undergoing primary uncemented hip replacement were randomized to IS or PlasmaLyte (PL). Infusion was given during surgery as 15 ml/kg the first hour and 5 ml/kg the following two hours. Urinary samples were collected upon admission and the day after surgery. As surgery was initiated, urine was collected over the course of 4 h. Hereafter, another urine collection proceeded until the morning. Urine was analyzed for markers of AKI neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1). Arterious and venous blood samples for measurements of pH and plasma electrolytes including chloride (p-Cl) were collected as surgery was initiated, at the end of surgery and the following morning.

Results: IS induced an increase in p-Cl (111 ± 2 mmol/L after IS and 108 ± 3 after PL, p = 0.004) and a decrease in pH (7.39 ± 0.02 after IS and 7.43 ± 0.03 after PL, p = 0.001). Urinary NGAL excretion increased in both groups (ΔNGAL: 5.5 [4.1; 11.7] μg/mmol creatinine p = 0.004 after IS vs. 5.5 [2.1;9.4] μg/mmol creatinine after PL, p < 0.001). No difference was found between the groups (p = 0.839). Similarly, urinary KIM-1 excretion increased in both groups (ΔKIM-1: IS 115.8 [74.1; 156.2] ng/mmol creatinine, p < 0.001 vs. PL 152.4 [120.1; 307.9] ng/mmol creatinine, p < 0.001). No difference between the groups (p = 0.064). FENa increased (1.08 ± 0.52% after IS and 1.66 ± 1.15% after PL, p = 0.032). ENaC excretion was different within groups (p = 0.019).

Conclusion: A significantly higher plasma chloride and a lower pH was present in the group receiving isotonic saline. However, u-NGAL and u-KIM-1 increased significantly in both groups after surgery despite absence of changes in creatinine. These results indicate that surgery induced subclinical kidney injury. Also, the IS group had a delayed sodium excretion as compared to the PL group which may indicate that IS affects renal sodium excretion differently from PL.

Trial registration: ClinicalTrials.gov Identifier: NCT02528448 , 19/08/2015.

Keywords: Acute kidney injury; Hyperchloremic acidosis; Isotonic saline; KIM-1; NGAL.

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1

Flow chart showing the participant flow through screening, inclusion and completion of the trial

Fig. 2

Effect of Isotonic saline vs. PlasmaLyte on arterial blood gas levels of chloride (a) and pH (b) in a double-blinded, placebo-controlled study of 38 patients. Blood samples were drawn before anesthesia (baseline), right after surgery (after surgery) and in the morning of the postoperative day (postoperative day). Values are shown as means ± SD. Statistics are performed with unparried t-test to test difference in response between treatments, † = p < 0.05. Paired t-test was used to test statistical significant difference from baseline, * = p < 0.05

Fig. 3

Change from baseline in urinary excretion rate of neutrophil gelatinase-associated lipocalin (NGAL) (a) and kidney injury molecule-1 (KIM-1) (b) in a double-blinded, placebo-controlled study of 38 patients. Values represent changes form baseline to surgery, post-surgery and discharge. The increase in u-NGAL and u-KIM-1 after isotonic saline and PlasmaLyte was observed in this period. Values are shown as medians with 25 and 75 percentiles in brackets. P-value represents difference from baseline, * = p < 0.05. Statistics are performed with a Wilcoxon signed rank test

Fig. 4

Effect of Isotonic saline vs. PlasmaLyte on urine output in a double-blinded, placebo-controlled study of 38 patients. Urine was collected as a 24-h urine collection (baseline) prior to surgery. As surgery was initiated urine was collected over the course of 4 h (surgery). Hereafter, another urine collection proceeded until the following morning at 8.00 am (post-surgery). Values are shown as means ± SD. Statistics are performed with unpaired t-test to test difference in response between treatments, † = p < 0.05. Paired t-test was used to test statistical significant difference from baseline, * = p < 0.05

Fig. 5

Change from baseline in urinary excretion rate of ENaCγ in a double-blinded, placebo-controlled study of 38 patients. Values represent changes form baseline to surgery, post-surgery and discharge. Values are shown as means ± SD. Data are shown as means ± SD. Statistics are performed with unpaired t-test to test difference in response between treatments, † = p < 0.05. Paired t-test was used to test statistical significant difference from baseline, * = p < 0.05

Fig. 6

Effect of Isotonic saline vs. PlasmaLyte on fractional excretion of sodium (FENa) in a double-blinded, placebo-controlled study of 38 patients. Urine was collected as a 24-h urine collection (baseline) prior to surgery. As surgery was initiated urine was collected over the course of 4 h (surgery). Hereafter, another urine collection proceeded until the following morning at 8.00 am (post-surgery). Values are shown as means ± SD Data are shown as means ± SD. Statistics are performed with unpaired t-test to test difference in response between treatments, † = p < 0.05. Paired t-test was used to test statistical significant difference from baseline, * = p < 0.05