A randomised controlled trial of succinylated gelatin (4%) fluid on urinary acute kidney injury biomarkers in cardiac surgical patients

Abstract

Background Fluid resuscitation is frequently required for cardiac surgical patients admitted to the intensive care unit. The ideal fluid of choice in regard to efficacy and safety remains uncertain. Compared with crystalloid fluid, colloid fluid may result in less positive fluid balance. However, some synthetic colloids are associated with increased risk of acute kidney injury (AKI). This study compared the effects of succinylated gelatin (4%) (GEL) with compound sodium lactate (CSL) on urinary AKI biomarkers in patients after cardiac surgery. Methods Cardiac surgical patients who required an intravenous fluid bolus of at least 500 mL postoperatively were randomly allocated to receive GEL or CSL as the resuscitation fluid of choice for the subsequent 24 h. Primary outcomes were serial urinary neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C concentrations measured at baseline, 1 h, 5 h and 24 h after enrolment, with higher concentrations indicating greater kidney injury. Secondary biomarker outcomes included urinary clusterin, α1-microglobulin and F2-isoprostanes concentrations. Differences in change of biomarker concentration between the two groups over time were compared with mixed-effects regression models. Statistical significance was set at P < 0.05. Results Forty cardiac surgical patients (n = 20 per group) with similar baseline characteristics were included. There was no significant difference in the median volume of fluid boluses administered over 24 h between the GEL (1250 mL, Q1–Q3 500–1750) and CSL group (1000 mL, Q1–Q3 500–1375) (P = 0.42). There was a significantly greater increase in urinary cystatin C (P < 0.001), clusterin (P < 0.001), α1-microglobulin (P < 0.001) and F2-isoprostanes (P = 0.020) concentrations over time in the GEL group, compared to the CSL group. Change in urinary NGAL concentration (P = 0.68) over time was not significantly different between the groups. The results were not modified by adjustment for either urinary osmolality or EuroSCORE II predicted risk of mortality. Conclusions This preliminary randomised controlled trial showed that use of succinylated gelatin (4%) for fluid resuscitation after cardiac surgery was associated with increased biomarker concentrations of renal tubular injury and dysfunction, compared to crystalloid fluid. These results generate concern that use of intravenous gelatin fluid may contribute to clinically relevant postoperative AKI. Trial registration ANZCTR.org.au, ACTRN12617001461381. Registered on 16th October, 2017, http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373619&isReview=true.

The Proximal Tubule as the Pathogenic and Therapeutic Target in Acute Kidney Injury

“…TGF is the mechanistic link between PT dysfunction, oliguria, and reduced GFR in AKI [22]. The early involvement of the PT dysfunction across a broad range of AKI is suggested by initial rises in urinary GGT, NGAL, and cystatin C. These urinary PT biomarkers and also urinary KIM-1 and mitochondrial DNA copy numbers [36, 40, 41] can be considered early markers to identify patients who are at most risk of developing subsequent rises in serum creatinine and can be used as an early AKI outcome in testing interventions in phase II trials [68] (Fig. 3).…”

The Impact of Intraoperative Hypotension on Postoperative Acute Kidney Injury, Mortality and Length of Stay following Off-Pump Coronary Artery Bypass Grafting Surgery: a single-center retrospective cohort study

“…However, evidence regarding the bene ts and harms of succinyl gelatin remains limited. Smart L [21] found that uid resuscitation after heart surgery with succinyl gelatin (4%) was related to the increase of biomarker concentration of renal tubular injury and dysfunction compared with crystalloid uid. Katona [22] similarly reported a signi cant association between gelatin administration and an increased risk for early postoperative AKI in a dose-dependent manner.…”

Comparisons of Electrolyte Balance Efficacy of Two Gelatin-Balanced Crystalloid for Surgery Patients Under General Anesthesia: A Multi-Center, Prospective, Randomized, Single-Blind, Controlled Study

“…Besides, high-dose gelatin infusion may increase the fibrinogen level. 28 According to one study, colloid-induced hemodynamic changes during fluid resuscitation are only temporary but may induce acute kidney injury 29 and coagulation disorders. 28 The incidence of these AEs increases as the cumulative dose increases.…”