All clinical laboratories now report a measure of estimated glomerular filtration rate (eGFR) when they report serum creatinine. There are several eGFR formulae now available. The original ones were developed from data obtained in the Modification of Diet in Renal Disease (MDRD) Study. Since this study did not include many non-Caucasian or diabetic patients, and was based on subjects with fairly advanced renal failure, the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation was subsequently developed on the basis of data from several clinical trials including a much broader range of patients, and is more applicable to patients with normal or near-normal renal function. These estimating equations use serum creatinine along with some combination of age, sex, race, and body size as surrogates for the non-GFR determinants of serum creatinine. Subsequently, other formulae using measures of cystatin C, instead of or in addition to creatinine, have been used by some laboratories. Cystatin C may have advantages over creatinine for GFR estimation because its non-GFR determinants are less affected by race and muscle mass. Use of cystatin C and creatinine together may allow more accurate GFR estimates, but such equations are not in common use. Regardless of which formula is used, there are many patients who are reported to have an eGFR of less than 60 mL/min/1.73 m2, and thus are labelled as having stage 3 CKD (see Table 4.1). Do they really have a disease?

The staging system for CKD was developed to aid clinicians in the management of patients with kidney disease by identifying those with the most severe disease who are at greatest risk for progression and complications. Using current definitions, the prevalence of CKD in the United States during the interval from 1999 to 2006 was 11.5%, and the prevalence of CKD in people 70 years and older in the United States was approximately 45% (Levey, 2009). This is a very large percentage of elderly persons now being labelled with a disease.

The association between older age and lower eGFR in cross-sectional studies has traditionally been thought to be due to a natural aging process, with GFR typically declining at a rate of about 1 mL/min/year after the age of 40 years (Lindeman and Goldman, 1986). However, the observation that some individuals followed longitudinally do not lose kidney function as they age suggests that involutional changes due to aging alone do not completely explain the lower eGFR seen in elderly patients in cross-sectional studies. Moreover, lower eGFR values are associated with kidney as well as cardiovascular disease in older as well as younger individuals, suggesting that decreased eGFR in the elderly is evidence of disease. Similarly, the increased risk for individuals with albuminuria in older as well as younger adults suggests that albuminuria is also indicative of a disease in patients regardless of age (Hallan et al., 2012).