On first reading, the report by Spanaus et al.(1) in this issue of Clinical Chemistry might be dismissed as just another comparison of serum biomarkers of glomerular filtration rate (GFR); however, the data and conclusions should stimulate a reevaluation of the widespread professional misconception that serum creatinine is an insensitive biomarker of GFR and an affirmation of its role in the diagnosis and monitoring of renal disease.
Healthy renal function is essential for the maintenance of physiological homeostasis. It is therefore surprising that without GFR measurements the clinical manifestations of kidney failure remain largely silent until renal function is so low that the patient may be in end-stage renal disease. Early palliative treatments for kidney disease, including the suggestion that patients should be “rigidly dieted to the exclusion of strong meats and drinks”(2), were changed profoundly with the introduction of hemodialysis and renal transplantation. These clinical interventions afforded the initial impetus for clinical laboratories to provide accurate routine measurements of GFR, a momentum consolidated by the increasing prevalence of kidney disease(3) and the appreciation of kidney function in determining cardiovascular disease risk(4).
Formal measurements of GFR, particularly standard renal-clearance techniques with urine collection, are, by their very nature, invasive, time consuming, and costly. As renal function declines, however, the serum/plasma concentration of any analyte produced in the body at a relatively constant rate and removed exclusively by glomerular filtration will increase as a reciprocal function: GFR = (Ux × V)/Px, where (Ux × V) is the urine excretion rate of analyte x and Px is the plasma concentration of x (i.e., GFR ∝ 1/Px). Consequently, simple serum/plasma biomarkers for routine GFR measurement are especially attractive.
Historically, the serum urea concentration was considered a useful biomarker of …