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) 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 m. Factors associated with annual change in eGFR 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 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 and 24% based on cystatin C-based eGFR. During follow-up, eGFR deteriorated on average by 1.36 ml/min/1.73 m/year, which is faster than the healthy cohort. Higher baseline NT-proBNP z-scores were associated with a more rapid decline in eGFR. A larger decline in eGFR was associated with all-cause mortality.

Conclusions: Declines in eGFR 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, and eGFR deterioration is associated with mortality.