Augmented Renal Clearance in the ICU: Is It a Real Phenomenon?

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Nei AM, Kashani KB, Dierkhising R, Barreto EF: Predictors of Augmented Renal Clearance in a Heterogeneous ICU Population as Defined by Creatinine and Cystatin C.  Nephron DOI 10.1159/000507255


Several reports, going back 5–7 years, noted increased levels of an estimated glomerular filtration rate (eGFR) in a variable number of patients with severe sepsis or trauma admitted to the intensive care unit (ICU). This phenomenon became known as “augmented renal clearance” (ARC). These reports typically used eGFR formulas based on serum creatinine, developed in stable outpatients.

Nei and coworkers re-examined this phenomenon using an assessment of eGFR using both creatinine and cystatin C, believed to be a more accurate and less biased assessment of actual or measured GFR. In a retrospective review of 368 patients admitted to the ICU they found that the prevalence of ARC (as defined by an eGFR >130 mL/min/1.73 m2 regardless of age by either eGFR-creatinine, eGFR-cystatin C, or a combination of both within the first 48 h after admission) varied. The prevalence of ARC by these formulas was 3.3–7.9% depending on which formula was used. The lowest prevalence was found by the eGFR creatinine + cystatin C formula. The Charlson Comorbidity Index, major trauma, intracranial hemorrhage, older age, and a high SOFA score were predictive of ARC, so defined.

The most concerning weakness of this and other studies is the application of eGFR formulas, the accuracy, precision, and bias of which were largely evaluated in stable outpatients, not sick and unstable ICU patients, where assumptions regarding creatinine and/or cystatin C production cannot be reliably made. In addition, the ARC has not been confirmed by the assessment of measured GFR, although these values would also be subject to variation in hemodynamically unstable, critically ill subjects. Thus, ACR is not equivalent to “hyperfiltration”. Whether ARC is real or merely an artifact of measurement is uncertain and whether it should be used to modify dosage of water-soluble therapeutic agents cleared by GFR is equally in doubt, in my opinion.


Richard Glassock


Quoted Karger Article

Predictors of Augmented Renal Clearance in a Heterogeneous ICU Population as Defined by Creatinine and Cystatin C