Association of Kidney Disease Outcomes With Risk Factors for CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study

Background Various indicators of progression of chronic kidney disease (CKD) have been used as outcomes in clinical research studies. The effect of using varying measures on the association of risk factors with CKD progression has not been well characterized. Study Design Prospective cohort study. Setting & Participants The Chronic Renal Insufficiency Cohort (CRIC) Study (N = 3,939) enrolled men and women with mild to moderate CKD, 48% of whom had diabetes and 42% were self-reported black race. Predictors Age, race, sex, diabetes, baseline estimated glomerular filtration rate (eGFR), proteinuria, and other established CKD risk factors. Outcomes Death, end-stage renal disease (ESRD), and eGFR events, including: (1) eGFR halving, (2) eGFR < 15 mL/min/1.73 m2, (3) eGFR halving and <15 mL/min/1.73 m2, (4) eGFR decrease of 20 mL/min/1.73 m2, (5) eGFR halving or decrease of 20 mL/min/1.73 m2, and (6) eGFR decrease of 25% and change in CKD stage. Results Mean entry eGFR was 44.9 mL/min/1.73 m2. Annual rates of death, ESRD, and eGFR halving were 2.5%, 4.0%, and 6.1%, respectively, during an average follow-up of 5.4 years. Associations between risk factors and ESRD and eGFR events were similar across different definitions. However, these associations were substantially different from those with death. HRs for ESRD, eGFR halving, and death in the highest compared to the lowest proteinuria category were 11.83 (95% CI, 8.40-16.65), 11.19 (95% CI, 8.53-14.68), and 1.47 (95% CI, 1.10-1.96), respectively. Limitations Participants may not be representative of the entire CKD population. Conclusions Using ESRD or eGFR events, but not death, in the definition of kidney disease outcomes is appropriate in follow-up studies to identify risk factors for CKD progression. Various indicators of progression of chronic kidney disease (CKD) have been used as outcomes in clinical research studies. The effect of using varying measures on the association of risk factors with CKD progression has not been well characterized. Prospective cohort study. The Chronic Renal Insufficiency Cohort (CRIC) Study (N = 3,939) enrolled men and women with mild to moderate CKD, 48% of whom had diabetes and 42% were self-reported black race. Age, race, sex, diabetes, baseline estimated glomerular filtration rate (eGFR), proteinuria, and other established CKD risk factors. Death, end-stage renal disease (ESRD), and eGFR events, including: (1) eGFR halving, (2) eGFR < 15 mL/min/1.73 m2, (3) eGFR halving and <15 mL/min/1.73 m2, (4) eGFR decrease of 20 mL/min/1.73 m2, (5) eGFR halving or decrease of 20 mL/min/1.73 m2, and (6) eGFR decrease of 25% and change in CKD stage. Mean entry eGFR was 44.9 mL/min/1.73 m2. Annual rates of death, ESRD, and eGFR halving were 2.5%, 4.0%, and 6.1%, respectively, during an average follow-up of 5.4 years. Associations between risk factors and ESRD and eGFR events were similar across different definitions. However, these associations were substantially different from those with death. HRs for ESRD, eGFR halving, and death in the highest compared to the lowest proteinuria category were 11.83 (95% CI, 8.40-16.65), 11.19 (95% CI, 8.53-14.68), and 1.47 (95% CI, 1.10-1.96), respectively. Participants may not be representative of the entire CKD population. Using ESRD or eGFR events, but not death, in the definition of kidney disease outcomes is appropriate in follow-up studies to identify risk factors for CKD progression.