Deterioration in Renal Function in Patients With a Fontan Circulation and Association With Mortality

Background: Renal dysfunction is a well-established risk factor in cardiovascular disease, but little is known about the prevalence and factors associated with deterioration in renal function in patients with a Fontan circulation.

Objectives: The purpose of the study was to investigate the course and factors associated with deterioration in renal function in patients with a Fontan circulation and its association with mortality.

Methods: This is a longitudinal study of patients with a Fontan circulation (n = 82), in which creatinine-based estimated glomerular filtration rate (eGFR_cr) was measured over an 11-year time period. Cystatin C and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels were measured at baseline. Renal dysfunction was defined as an eGFR <90 ml/min/1.73 m². Factors associated with annual change in eGFR_cr were investigated with linear mixed-effect models and compared with data from a healthy Dutch cohort. The primary endpoint for the survival analyses was all-cause mortality. Associations between repeated eGFR_cr levels and the primary endpoint were assessed using a joint model.

Results: The median age at baseline was 20 years (IQR: 14-27 years). Twelve percent of the cohort had renal dysfunction based on eGFR_cr and 24% based on cystatin C-based eGFR_cys. During follow-up, eGFR_cr deteriorated on average by 1.36 ml/min/1.73 m²/year, which is faster than the healthy cohort. Higher baseline NT-proBNP z-scores were associated with a more rapid decline in eGFR_cr. A larger decline in eGFR_cr was associated with all-cause mortality.

Conclusions: Declines in eGFR_cr in patients with Fontan circulation are more rapid than in healthy individuals. Higher baseline NT-proBNP z-scores are associated with a more rapid deterioration of eGFR_cr, and eGFR_cr deterioration is associated with mortality.