Looking for a Better Creatinine

Abstract

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)3 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 …