Assessing glomerular filtration rate (GFR) in critically ill patients with acute kidney injury true GFR versus urinary creatinine clearance and estimating equations

Introduction: Estimation of kidney function in critically ill patients with acute kidney injury (AKI), is important for appropriate dosing of drugs and adjustment of therapeutic strategies, but challenging due to fluctuations in kidney function, creatinine metabolism and fluid balance. Data on the agreement between estimating and gold standard methods to assess glomerular filtration rate (GFR) in early AKI are lacking. We evaluated the agreement of urinary creatinine clearance (CrCl) and three commonly used estimating equations, the Cockcroft Gault (CG), the Modification of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) equations, in comparison to GFR measured by the infusion clearance of chromium-ethylenediaminetetraacetic acid (Cr-51-EDTA), in critically ill patients with early AKI after complicated cardiac surgery. Methods: Thirty patients with early AKI were studied in the intensive care unit, 2 to 12 days after complicated cardiac surgery. The infusion clearance for Cr-51-EDTA obtained as a measure of GFR (GFR(51Cr-EDTA)) was calculated from the formula: GFR (mL/min/1.73m(2)) = (Cr-51-EDTA infusion rate x 1.73)/(arterial Cr-51-EDTA x body surface area) and compared with the urinary CrCl and the estimated GFR (eGFR) from the three estimating equations. Urine was collected in two 30-minute periods to measure urine flow and urine creatinine. Urinary CrCl was calculated from the formula: CrCl (mL/min/1.73m(2)) = (urine volume x urine creatinine x 1.73)/(serum creatinine x 30 min x body surface area). Results: The within-group error was lower for GFR(51Cr-EDTA) than the urinary CrCl method, 7.2% versus 55.0%. The between-method bias was 2.6, 11.6, 11.1 and 7.39 ml/min for eGFR(CrCl), eGFR(MDRD), eGFR(CKD-EPI) and eGFR(CG), respectively, when compared to GFR(51Cr-EDTA). The error was 103%, 68.7%, 67.7% and 68.0% for eGFR(CrCl), eGFR(MDRD), eGFR(CKD-EPI) and eGFR(CG), respectively, when compared to GFR(51Cr-EDTA). Conclusions: The study demonstrated poor precision of the commonly utilized urinary CrCl method for assessment of GFR in critically ill patients with early AKI, suggesting that this should not be used as a reference method when validating new methods for assessing kidney function in this patient population. The commonly used estimating equations perform poorly when estimating GFR, with high biases and unacceptably high errors.