Methodological issues in studying the epidemiology of mild tions as they relate to (1) defining the prevalence of mild to moderate chronic renal insufficiency. There is increasing to moderate CRI, (2) examining mild to moderate CRI interest in studying the epidemiology of subjects with mild to as an outcome, and (3) examining mild to moderate CRI moderate chronic renal insufficiency (CRI), defined as reduced as an exposure (Table 1). glomerular filtration rate (GFR) not requiring renal replacement therapy. This review discusses some of the methodologi-Glomerular filtration rate, serum creatinine cal challenges presented by the epidemiological study of mild to moderate CRI that have not been adequately addressed in concentration and creatinine clearance the literature. Issues that relate to defining the prevalence of Glomerular filtration rate (GFR) is generally accepted CRI include between-laboratory differences in serum creatias the best overall index of renal function. Gold standard nine (S Cr ) assays, within-person measurement errors in S Cr , and measures of GFR include inulin and iothalamate cleardifferences in S Cr in different demographic groups that are independent of GFR. Issues that relate to examining CRI as an ance. As discussed later, there is substantial day-to-day outcome include the choice between a "slope" or "threshold" variation in measured GFR. Conceptually, it is the averanalysis. Issues that relate to examining CRI as an exposure age GFR over days to weeks that defines the severity of include the choice of renal function measure (for example, CRI since it is presumably this average GFR that best S Cr vs. estimated GFR) in multivariable analysis, whether to predicts adverse outcomes (for example, degree of anenormalize renal function to body surface area or other body size parameters, potential effect modification of the association mia, blood pressure elevation).
between CRI and the outcome and the complex relation be-However, given its simplicity, low cost, and widespread tween CRI, adverse outcomes, potential confounders and interuse, serum creatinine has been relied upon as the princimediary variables. As we enter an era of more intensive study pal indicator of renal function in epidemiological studies, of mild to moderate CRI, recognition of these potential pitfalls and will likely remain so for the foreseeable future.
should guide researchers toward improving the quality of epidemiological research in this field.