Creatinine versus cystatin C to estimate glomerular filtration rate in adults with congenital heart disease: Results of the Boston Adult Congenital Heart Disease Biobank

Background: Glomerular filtration rate is a key physiologic variable with a central role in clinical decision making and a strong association with prognosis in diverse populations. Reduced estimated glomerular filtration rate (eGFR) is common among adults with congenital heart disease (ACHD).

Methods: We conducted a prospective cohort study of outpatient ACHD ≥18 years old seen in 2012-2017. Creatinine and cystatin C were measured; eGFR was calculated using either the creatinine or cystatin C Chronic Kidney Disease-Epidemiology Collaboration equation (CKD-EPI_Cr and CKD-EPI_CysC, respectively). Survival analysis was performed to define the relationship between eGFR and both all-cause mortality and a composite outcome of death or nonelective cardiovascular hospitalization.

Results: Our cohort included 911 ACHD (39 ± 14 years old, 49% female). Mean CKD-EPI_Cr and CKD-EPI_CysC were similar (101 ± 20 vs 100 ± 23 mL/min/1.73 m²), but CKD-EPI_Cr estimates were higher for patients with a Fontan circulation (n = 131, +10 ± 19 mL/min/1.73 m²). After mean follow-up of 659 days, 128 patients (14.1%) experienced the composite outcome and 31 (3.4%) died. CKD-EPI_CysC more strongly predicted all-cause mortality (eGFR <60 vs >90 mL/min/1.73 m²: CKD-EPI_CysC unadjusted HR = 20.2 [95% CI 7.6-53.1], C-statistic = 0.797; CKD-EPI_Cr unadjusted HR = 4.6 [1.7-12.7], C-statistic = 0.620). CKD-EPI_CysC independently predicted the composite outcome, whereas CKD-EPI_Cr did not (CKD-EPI_CysC adjusted HR = 3.0 [1.7-5.3]; CKD-EPI_Cr adjusted HR = 1.5 [0.8-3.1]). Patients reclassified to a lower eGFR category by CKD-EPI_CysC, compared with CKD-EPI_Cr, were at increased risk for the composite outcome (HR = 2.9 [2.0-4.3], P < .0001); those reclassified to a higher eGFR class were at lower risk (HR = 0.5 [0.3-0.9], P = .03).

Conclusions: Cystatin C-based eGFR more strongly predicts clinical events than creatinine-based eGFR in ACHD. Creatinine-based methods appear particularly questionable in the Fontan circulation.