Chronic Renal Insufficiency Cohort Study (CRIC): Overview and Summary of Selected Findings

Abstract

The Chronic Renal Insufficiency Cohort (CRIC) Study is a United States multicenter, prospective study of racially and ethnically diverse patients with CKD. Although the original aims of the study were to identify novel predictors of CKD progression and to elucidate the risk and manifestations of cardiovascular disease among nearly 4000 individuals with CKD, the CRIC Study has evolved into a national resource for investigation of a broad spectrum of CKD-related topics. The study has produced >90 published scientific articles, promoted many young investigative careers in nephrology, and fostered international collaborations focused on understanding the global burden of CKD. The third phase of the CRIC Study will complete enrollment of 1500 additional study participants in 2015 and is designed to answer questions regarding morbidity and mortality in mild-to-moderate CKD and to assess the burden of CKD in older persons. This review highlights some of the salient findings of the CRIC Study in the areas of race and ethnicity, CKD progression, CKD and cognition, and cardiovascular disease outcomes; it also outlines the ongoing and forthcoming opportunities for the global nephrology community to enhance its understanding of CKD and related complications through the study.

Keywords: chronic kidney disease; chronic renal insufficiency; cohort study.

Figure 1.

Between-group comparisons of the eGFR slope and proportion of patients free from a primary outcome event in the Chronic Renal Insufficiency Cohort Study. (A) Patients with diabetes, (B) patients without diabetes, (C) patients with diabetes, and (D) patients without diabetes. In the Chronic Renal Insufficiency Cohort (CRIC) study, the primary outcomes were the eGFR slope and a composite of end-stage renal disease or a reduction of 50% in the eGFR from baseline. Shown are mean differences in the eGFR slope for black patients in the APOL1 high-risk group versus white patients, black patients in the APOL1 low-risk group versus white patients, and black patients in the APOL1 high-risk group versus black patients in the APOL1 low-risk group, among patients with diabetes (Panel A) and among those without diabetes (Panel B). In Panels A and B, the I bars indicate 95% confidence intervals. I bars that cross above the horizontal black line indicate that the difference in eGFR is not significant. Also shown are the proportions of white patients and black patients in the APOL1 high - risk and low-risk groups who were free from the primary outcome of end-stage renal disease or a reduction of 50% in the eGFR from baseline, among patients with diabetes (Panel C) and among those without diabetes (Panel D). Reproduced from reference , with permission.

Figure 2.

Multivariable-adjusted hazard function for death according to measured (untransformed) levels of fibroblast growth factor 23. The median fibroblast growth factor 23 (FGF-23) level within the lowest FGF-23 quartile (74 relative units [RU]/ml) served as the referent value (hazard=1.0). The model was stratified by center and adjusted for age; sex; race; ethnicity; eGFR; natural log-transformed urine albumin-to-creatinine ratio; hemoglobin; serum albumin; systolic BP; body mass index; diabetes; smoking status; LDL; history of coronary artery disease, congestive heart failure, stroke, and peripheral vascular disease; use of aspirin, β-blockers, statins, and angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers; and serum calcium, phosphate, and natural log-transformed parathyroid hormone. Tick marks on the x axis indicate individual observations at corresponding levels of FGF-23. The solid black line represents the multivariable-adjusted hazard of mortality as a function of the measured (nontransformed) FGF-23 level. The dashed lines indicate the 95% confidence intervals. Reprinted from reference , with permission.

Figure 3.

Crude rates of incident heart failure per 1000 person-years of follow-up in the Chronic Renal Insufficiency Cohort Study. Event rates for NT-proBNP are shown by quintile; event rates for high sensitivity troponin T are shown for those with undetectable levels (≤3), and then by quartile among detectable levels. LLD, lower limit of detection; NT-proBNP, N-terminal pro-B-type natriuretic peptide. Reprinted from reference , with permission.

Figure 4.

Elevated circulating fibroblast growth factor 23 levels are associated with left ventricular hypertrophy in patients with CKD. (A) The distribution of FGF23 levels in baseline samples of 3070 participants who enrolled in the CRIC Study and underwent echocardiography 1 year later. The median FGF23 was 142 RU/ml. Fifty-eight participants with FGF23 of >1000 RU/ml (range, 1054–14,319 RU/ml), who were included in the analysis, are not shown here. (B) Ascending quartiles of FGF23 were associated with significantly decreased ejection fraction (P value for linear trend <0.001), but the differences between groups were modest, and the mean±SEM ejection fraction for each quartile was normal (>50%). (C) Ascending quartiles of FGF23 were associated with significantly increased mean±SEM left ventricular mass index (P value for linear trend <0.001). (D) With increasing quartiles of FGF23, the prevalence of concentric (gray) and eccentric (green) LVH increased at the expense of normal left ventricular geometry (white) and left ventricular remodeling (blue) (P<0.001). Numbers in the bars represent the percentages of prevalence for each condition. CRIC, Chronic Renal Insufficiency Cohort; FGF23, fibroblast growth factor 23; LVH, left ventricular hypertrophy; RU, relative units. Reprinted from reference , with permission.

Figure 5.

Number of funded Chronic Renal Insufficiency Cohort Study ancillary studies by type of award as of June 2015.