Defining incident chronic kidney disease in the research setting: The ARIC Study

Abstract

Deaths of participants and losses to follow-up pose challenges for defining outcomes in epidemiologic studies. The authors compared several definitions of incident chronic kidney disease (CKD) in terms of incidence, agreement, and risk factor associations. They used data from 14,873 participants in the community-based, multicenter, biracial Atherosclerosis Risk in Communities Study (1987-1999). The estimated glomerular filtration rate (eGFR) was based on serum creatinine at baseline and the 3- and 9-year follow-up visits. Hospitalizations were ascertained continuously. The authors compared 4 definitions of incident CKD: 1) low eGFR (<60 mL/minute/1.73 m(2)); 2) low and declining (> or =25%) eGFR; 3) an increase in serum creatinine (> or =0.4 mg/dL) at 3- or 9-year follow-ups; and 4) CKD-related hospitalization or death. From these definitions, they identified 1,086, 677, 457, and 163 cases, respectively. There was relatively good agreement among definitions 1-3, but definition 4 identified mostly different cases. Risk factor associations were consistent across definitions for hypertension and lipids. Diabetes showed weaker associations with definition 1 (incidence rate ratio = 1.5, 95% confidence interval: 1.2, 1.7) than with definition 4 (incidence rate ratio = 6.3, confidence interval: 4.4, 8.9). Associations with gender differed in direction and magnitude across definitions. Case definition can impact relative risk estimates for CKD risk factors.

Figure 1.

Follow-up and sample size by visit in the Atherosclerosis Risk in Communities Study, United States, 1987–1999. The number of participants after initial exclusions were made is represented. White bars represent the number present at the visit; striped boxes, the (cumulative) number who died prior to the visit; and black boxes, the number who were absent from the visit. For visit 1, 14,873 individuals were present; for visit 2, 13,586 were present, 1,023 had died prior, and 264 were absent; for visit 4, 11,101 were present, 2,591 had died prior, and 1,181 were absent. Visit 3 was not included in the figure, because serum creatinine measurements were not available at that time.

Figure 2.

Concordant and discordant occurrence of incident chronic kidney disease (iCKD) in the Atherosclerosis Risk in Communities Study population, United States, 1987–1999, by case definition. Definition 1 is represented by the largest, empty, outer circle; definition 2, by the inner circle with vertical lines; definition 3, by the leftmost circle with horizontal lines; and definition 4, by the 2 smallest gray circles at the top. Of the 74 hospitalization- and death-based cases who do not overlap with any other case definition, only 12 had both 3- and 9-year follow-up measures, while 60 had follow-up serum creatinine measured only at the 3-year follow-up visit, and 2 had only a 9-year follow-up measure. The 30 cases in a separate circle did not attend any follow-up visits. eGFR, estimated glomerular filtration rate.

Figure 3.

Distribution of percent change in estimated glomerular filtration rate (eGFR) from baseline to the time of incident chronic kidney disease (iCKD) in the Atherosclerosis Risk in Communities Study population, United States, 1987–1999. The change in eGFR from baseline until the time of iCKD is represented here, where a negative change reflects a decrease in eGFR, and a positive change represents an increase. Histograms represent the distribution of percent change in eGFR among those who were low eGFR (definition 1) for gray bars and creatinine rise (definition 3) iCKD cases for empty bars. The black, dashed, vertical line represents the cutoff of a 25% decline in eGFR. sCr, serum creatinine.