Combining creatinine and volume kinetics identifies missed cases of acute kidney injury following cardiac arrest

Abstract

IntroductionFluid resuscitation in the critically ill often results in a positive fluid balance, potentially diluting the serum creatinine concentration and delaying diagnosis of acute kidney injury (AKI).MethodsDilution during AKI was quantified by combining creatinine and volume kinetics to account for fluid type, and rates of fluid infusion and urine output. The model was refined using simulated patients receiving crystalloids or colloids under four glomerular filtration rate (GFR) change scenarios and then applied to a cohort of critically ill patients following cardiac arrest.ResultsThe creatinine concentration decreased during six hours of fluid infusion at 1 litre-per-hour in simulated patients, irrespective of fluid type or extent of change in GFR (from 0% to 67% reduction). This delayed diagnosis of AKI by 2 to 9 hours. Crystalloids reduced creatinine concentration by 11 to 19% whereas colloids reduced concentration by 36 to 43%. The greatest reduction was at the end of the infusion period. Fluid dilution alone could not explain the rapid reduction of plasma creatinine concentration observed in 39 of 49 patients after cardiac arrest. Additional loss of creatinine production could account for those changes. AKI was suggested in six patients demonstrating little change in creatinine, since a 52 ± 13% reduction in GFR was required after accounting for fluid dilution and reduced creatinine production. Increased injury biomarkers within a few hours of cardiac arrest, including urinary cystatin C and plasma and urinary Neutrophil-Gelatinase-Associated-Lipocalin (biomarker-positive, creatinine-negative patients) also indicated AKI in these patients.ConclusionsCreatinine and volume kinetics combined to quantify GFR loss, even in the absence of an increase in creatinine. The model improved disease severity estimation, and demonstrated that diagnostic delays due to dilution are minimally affected by fluid type. Creatinine sampling should be delayed at least one hour following a large fluid bolus to avoid dilution. Unchanged plasma creatinine post cardiac arrest signifies renal injury and loss of function.Trial registrationAustralian and New Zealand Clinical Trials Registry ACTRN12610001012066.

Neutrophil Gelatinase–Associated Lipocalin Combined With Delta Serum Creatinine Provides Early Risk Stratification for Adverse Outcomes After Cardiac Surgery

“…However, any increase in S Cr can only occur through a reduction in creatinine clearance (glomerular filtration rate [GFR]), an increase in creatinine production, or a reduction in apparent volume of distribution for creatinine (total body water). Sophisticated kinetic modeling suggests that the rise in S Cr following an acute reduction in GFR is relatively slow (29), with any increase likely further delayed and limited by dilution of S Cr occurring secondary to the increase in total body water typically associated with cardiac surgery or critical illness (30,31). However, rate of change in S Cr may also be subject to changes in creatinine production, a variable that remains largely unexplored in the context of cardiac surgery.…”

Effects of Serum Uric Acid on Estimated GFR in Cardiac Surgery Patients: A Pilot Study

“…However, the strengths of the study were that data were collected in a prospective manner, the lowest absolute value of SUA measured at the highest dilution time-point was used as the reference SUA (SUA 1 h ) to minimize the influence of baseline SCr, and fluid balance-adjusted creatinine was used for all calculations. Since intraoperative fluid administration affects SCr the most and results in poor performance of KeGFR at 1-8 h [25] , we mitigated this by utilizing NGAL in the 1-12 h postoperative period followed by KeGFR measurements in days 1 through 4. In the absence of a reliable method to circumvent inaccuracies related to intraoperative hemodilution, we used the values of NGAL for analyses instead of differences in pre-to postoperative concentrations.…”

Serum Creatinine Changes Associated with Critical Illness and Detection of Persistent Renal Dysfunction after AKI

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