Phenotyping of Fontan-Associated Renal Physiology and Disease.

BACKGROUND

Kidney dysfunction is prevalent but insufficiently understood in Fontan patients. We aimed to investigate Fontan-Associated Renal Disease (FARD) through comprehensive phenotyping using biomarkers of renal function and injury, as well as ultrasound assessment of intrarenal hemodynamics.

METHODS

We prospectively collected data on serum creatinine and cystatin C levels, and 24-h urine creatinine clearance and albumin excretion in 25 Fontan patients, comparing them to healthy age- and sex-matched controls. Additionally, we measured intrarenal venous and arterial flow patterns using Doppler ultrasonography.

RESULTS

Median age was 28 (Q1-Q3: 19-35) years, with 48% female. Compared to controls, Fontan patients had similar creatinine-based eGFR (eGFRcr) (114 vs. 106 mL/min/1.73 m2; p = 0.2), lower cystatin C-based eGFR (eGFRcys) (96 vs. 106 mL/min/1.73 m2; p = 0.045), and lower 24-h urinary creatinine excretion (10.0 vs. 13.7 mmol/24 h; p < 0.001). Additionally, patients had higher 24-h urine albumin excretion (14 vs. 2 mg/24-h; p < 0.001). In patients, both eGFRcys and urine albumin correlated with age (r = -0.56 and r = 0.44, respectively; p < 0.05). Twenty--four out of 25 patients and all controls had continuous intrarenal venous flow patterns. Venous impedance and arterial renal resistance indices were higher in patients than controls (0.44 vs. 0.14 and 0.67 vs. 0.60, respectively; p < 0.05).

CONCLUSION

FARD involves a progressive decline in kidney function and glomerular injury. eGFRcr masks kidney dysfunction in Fontan patients due to reduced muscle mass. Fontan intrarenal hemodynamics demonstrate decreased venous and arterial compliance. Moreover, continuous intrarenal venous flow persists in Fontan patients.