| Abstract: | Background and objectives: All glomerular filtration rate (GFR) estimating equations have been developed from cross-sectional data. The aims of this study were to examine the concordance between use of measured GFR (mGFR) and estimated GFR (eGFR) in tracking changes in kidney function over time among patients with moderately severe chronic kidney disease.Design, setting, participants, & measurements: A retrospective cohort study of subjects who had been enrolled in the MDRD Study A and who had two or more contemporaneous assessments of mGFR and eGFR (n = 542; mGFR range, 25 to 55 ml/min per 1.73 m2) during the chronic phase (month 4 and afterwards). mGFR was based on urinary iothalamate clearance; eGFR was based on the 4-variable MDRD Study equation. Temporal changes in GFR were assessed by within-subject linear regression of time on GFR.Results: Median follow-up time for all subjects was 2.6 yr; median number of GFR measurements was six. The eGFR slope tended to underestimate measured decrements in GFR. The absolute value of the difference in mGFR and eGFR slopes was ≤2 ml/min per 1.73 m2 per yr among 58.3% of subjects; the remainder of subjects had larger absolute differences. Among the 22 variables studied, none predicted a systematic difference between mGFR slope and eGFR slope.Conclusions: Although eGFR and mGFR exhibited similar relationships to 22 baseline variables, the overall bias seen in the full cohort suggests that clinicians and researchers should exercise caution when interpreting eGFR slope as a marker of progression of kidney disease.The glomerular filtration rate (GFR) is considered the best available index of kidney function in health and disease (1). GFR can be measured by clearance techniques involving endogenous (e.g., creatinine and urea) or exogenous (e.g., inulin, iohexol, and iothalamate) filtration markers, with the latter considered to be the gold-standard approach (2). Unfortunately, clearance measurements are both cumbersome and costly; thus, in clinical practice, GFR is often estimated based upon the serum creatinine concentration. Numerous GFR estimating equations have been developed, the most widely used of which was derived from the Modification of Diet in Renal Disease (MDRD) Study (3,4).Essentially all GFR estimating equations have been developed from cross-sectional data and perform well when used to classify individuals at single points in time, particularly for levels of GFR less than 60 ml/min per 1.73 m2 (3,5–9). Ideally, these equations could also be used to monitor GFR changes over time in research and clinical practice. However, the validity of these equations for longitudinal application has not been sufficiently examined. Temporal changes in factors influencing creatinine production (e.g., muscle mass and dietary intake) and renal creatinine handling (e.g., tubular secretion), or extra-renal elimination (e.g., antibiotics) potentially further limit the accuracy of estimating equations or serum creatinine used alone as a filtration marker when applied over time (10). Understanding this potential limitation is of particular importance for two reasons: 1) the movement toward standardized reporting of estimated GFR (which may lead clinicians to draw longitudinal comparisons), and 2) the use of estimated GFR as an outcome measure in studies of preservation of kidney function.The MDRD Study is one of only a few trials that tracked decline in kidney function longitudinally in a population with chronic kidney disease (CKD) with measurement of GFR. Thus, data from this study provide a context in which to assess the longitudinal performance of GFR estimating equations. We undertook the following study: 1) to examine and characterize the correspondence between changes over time in measured GFR (mGFR) and estimated GFR (eGFR) and 2) to identify factors that may influence the relationship between longitudinal changes in mGFR and eGFR. |
