Estimating Glomerular Filtration Rate From Serum Creatinine in the General Population–Reply–I
We appreciate Dr Cohen's thoughtful commentary on our article. We will address his concern that using a sex-specific upper limit of normal for serum creatinine (SCr) to define CKD would result in large-scale underdiagnosis of the disease within the geriatric community.
Our example of a 60-year-old white woman with a high-normal SCr level (1.2 mg/dL for the assay we used) showed an estimated GFR of 55 mL/min per 1.73 m2 using a CKD equation but an estimated GFR of 83 mL/min per 1.73 m2 using a healthy equation.1 Inadequate information is available to determine which equation is appropriate because both healthy and CKD populations can have normal SCr levels. Clinical context can help the clinician decide whether an SCr level near the threshold between normal and abnormal represents CKD by changing the pretest probability of CKD. However, clinical context can be limited or not available. When SCr is stable and clearly elevated (eg, 2.2 mg/dL), clinical context is unnecessary for identifying CKD because the SCr level is well outside the normal reference range, and the only disease process that leads to an elevated SCr level is a reduced GFR. Also noteworthy is that elderly adults with stable moderate reductions in estimated GFR (30-59 mL/min per 1.73 m2) have a substantially lower risk of mortality than younger persons with moderate reductions in estimated GFR.2 Elderly adults with moderate reductions in estimated GFR and high-normal SCr levels may have preserved muscle mass that is protective against mortality compared with elderly adults with low-normal SCr levels and decreased muscle mass.
When GFR is measured directly (eg, iothalamate clearance), using a single threshold of 60 mL/min per 1.73 m2 to define the lower limit of normal is questionable. If any decline in GFR is defined as disease, then the lower limit of normal based on young adults is approximately 90 mL/min per 1.73 m2.3,4 Ninety-four percent of healthy elderly (>70 years) adults have a GFR below this threshold.5 If instead one defines any GFR lower than expected for an individual's age as disease, then the lower limit of normal for a 75-year-old patient is 60 mL/min per 1.73 m2, which is too low for younger adults and too high for older adults.3-5 There is precedence for using age-specific disease thresholds in medicine (eg, pulmonary function tests). Because the age-related decline in GFR is offset by a concurrent age-related decline in muscle mass, SCr levels do not change with normal aging.4,5 When GFR is reduced more than expected with aging, a sex-specific elevated SCr level occurs.1 Using a calibrated assay,6 we recently found the upper limit of normal (97.5 percentile) for SCr to be 1.1 mg/dL instead of 1.2 mg/dL in white women and 1.3 mg/dL instead of 1.4 mg/dL in white men. We acknowledge that our data were unable to define the upper limit of normal for SCr in elderly (>70 years) and nonwhite ethnic groups.
- Andrew D. Rule, MD and
- Stephen T. Turner, MD
