The difference between cystatin C- and creatinine-based eGFR is associated with adverse cardiovascular outcome in patients with chronic kidney disease

Background and aims: Decreased kidney function is an important risk factor for cardiovascular disease (CVD). However, assessing risk of CVD may be difficult when there is a gap between creatinine- and cystatin C-based estimated glomerular filtration rate (eGFR). We studied the association of the difference in eGFRs with major adverse cardiovascular events (MACE) in patients with chronic kidney disease (CKD). Methods: This prospective cohort study was conducted in 2076 patients with CKD stages based on the KDIGO guideline (eGFR categories of G1: >= 90; G 2: 60-89; G3: 30-59; G4: 15-29; G5: <15 mL/min/1.73 m(2) without kidney replacement therapy). The difference in eGFR (eGFR(diff)) was calculated by subtracting the cystatin Cbased eGFR (eGFR(cys)) from the creatinine-based eGFR (eGFR(creat)). The primary outcome was MACE, defined as non-fatal acute myocardial infarction and unstable angina, stroke, congestive heart failure, symptomatic arrhythmia, and cardiac death. Results: During a median follow-up of 4.1 years, MACE occurred in 147 patients (incidence rate, 15.0 per 1000 patient-years). When patients were categorized into baseline eGFR(diff) tertiles, the highest tertile was associated with a significantly higher risk of MACE (hazard ratio, 2.12; 95% confidence interval [CI], 1.28-3.51) than the lowest tertile when adjusted for eGFR(creat), eGFR(cys), or eGFR based on both creatinine and cystatin C. Patients in the highest tertile had more baseline coronary artery calcification (CAC) than those in the lowest tertile (odds ratio [OR], 1.38; 95% CI, 1.03-1.86). In addition, 978 patients had data for both baseline and follow-up CAC at year 4. In this subgroup, baseline eGFR(diff) was significantly associated with accelerated CAC progression (>= 50/year) (OR, 1.03; 95% CI, 1.01-1.05). Conclusions: A large positive difference between eGFR(creat) and eGFR(cys) was associated with a higher risk of MACE and faster CAC progression in patients with CKD. Therefore, careful monitoring of CVD is needed for patients with a higher eGFR(diff).

Automated summary

In this study, a large positive difference between eGFR based on creatinine and cystatin C was found to be associated with a higher risk of major adverse cardiovascular events (MACE) and accelerated coronary artery calcification (CAC) progression in patients with chronic kidney disease (CKD). Therefore, careful monitoring of cardiovascular diseases is recommended for patients with a higher eGFR difference.