Looking for a better creatinine.

نویسندگان

  • Jeffrey W Meeusen
  • John C Lieske
چکیده

Our kidneys maintain a constant internal environment and circulatory volume through a combination of filtration, selective reabsorption and secretion, and production of several key hormones. Young, healthy individuals filter 100 L of blood each day; however, their kidneys then reabsorb most of this for a mean urine output of only 1.5 L/day. This filtration process is necessary to eliminate byproducts of ongoing metabolism (so-called uremic toxins). Indeed, a minimum amount of kidney function is essential for life, and one can demonstrate increased morbidity and mortality when the glomerular filtration rate (GFR) chronically dips low enough. Thus, GFR is widely considered the single most important and useful indicator of overall kidney function. It is possible to directly measure GFR by administration of small molecules that are freely filtered by the kidneys and neither metabolized, secreted, nor reabsorbed. Examples include inulin, iothalamate, and iohexol, for which the renal clearance of these molecules equals GFR. However, protocols that use these exogenous agents to measure GFR require some combination of intravenous or subcutaneous administration of the marker, multiple blood draws, and carefully timed urine collections. Thus, direct measurement of GFR is not practical for most routine situations. For these reasons, several methods of GFR estimation have been developed on the basis of endogenous molecules. The best example is creatinine, a byproduct of muscle metabolism that is freely filtered, produced in a relatively consistent manner, and not reabsorbed. Although some creatinine is secreted, this amount is usually small enough that creatinine remains a useful marker of GFR. A bigger problem, however, is that muscle mass (and consequently serum creatinine) varies widely between individuals. Thus, although serum creatinine goes up as GFR goes down, the GFR for a given serum creatinine can vary widely between individuals. For example, a “normal” serum creatinine of 1.0 mg/dL (88 mol/L) can reflect a GFR range of 20 – 150 mL min 1 (1.73 m) , depending on the individual’s age, sex, and ethnicity (Fig. 1). In 1976, Cockcroft and Gault made a seminal observation in a cohort of men when they reported that 24-h creatinine production varied in a predictable way with age and weight (1). This work yielded the Cockroft– Gault equation, still widely used today. Although this equation is a helpful tool, certainly better than use of serum creatinine alone, the Cockcroft–Gault equation yields only an estimate of creatinine clearance and not GFR. In 1999, Levey and colleagues took another seminal leap forward by relating GFR to serum creatinine and demographic factors (2 ). Within the large population of patients with previously diagnosed chronic kidney disease (CKD) that were studied, sex, race, and age were the most important variables that influenced serum creatinine correlations with GFR measured by iothalamate clearance. Hence, these variables were incorporated into the first estimated GFR (eGFR) tool, the widely used Modification of Diet in Renal Disease (MDRD) equation. Although the MDRD equation works very well for patients with CKD, the population in whom it was developed, it works less well for other groups. In particular, the MDRD equation underestimates GFR in healthy individuals (3). Therefore, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was subsequently developed by use of a mixed population of individuals with (approximately 70%) and without (approximately 30%) CKD. In general, the CKD-EPI equation does estimate GFR more accurately in healthy individuals, albeit at the expense of some loss in accuracy for those with CKD. The Achilles heel of any creatinine-based GFR estimate is the influence of muscle mass on creatinine production. Consequently, a search for alternative serum markers of GFR has gained increasing momentum. Cystatin C is a 13-kDa cysteine protease inhibitor produced at a constant rate by most nucleated cells. Because cystatin C is freely filtered into the urine, it has attracted great attention as a potential serum marker of GFR. Indeed, serum cystatin C concentrations have a much tighter relationship with measured GFR than serum creatinine (Fig. 1). Perhaps most importantly, cystatin C outperforms creatinine as an indicator of GFR in the 1 Division of Clinical Core Laboratory Services, Department of Laboratory Medicine and Pathology, 2 Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, MN. * Address correspondence to this author at: 200 1st St. SW, Rochester, MN 55905. Fax 507-266-9315; e-mail [email protected]. Received February 11, 2014; accepted February 14, 2014. Previously published online at DOI: 10.1373/clinchem.2013.220764 © 2014 American Association for Clinical Chemistry 3 Nonstandard abbreviations: GFR, glomerular filtration rate; CKD, chronic kidney disease; eGFR, estimated GFR; MDRD, Modification of Diet in Renal Disease; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; KDIGO, Kidney Disease/Improving Global Outcomes. Clinical Chemistry 60:8 1036–1039 (2014) Perspective

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عنوان ژورنال:
  • Clinical chemistry

دوره 60 8  شماره 

صفحات  -

تاریخ انتشار 2014