Associations Between Characteristics of Individuals With Fontan Circulation With Blood and Urine Biomarkers of Kidney Injury and Dysfunction

Abstract

Background Fontan circulation is associated with kidney injury and dysfunction, often unappreciated until Fontan circulatory failure. We hypothesized that cystatin C‐estimated glomerular filtration rate (eGFR) would identify chronic kidney disease more frequently and that urine kidney injury biomarkers would be higher with declining Fontan physiological features. Methods and Results We enrolled 100 ambulatory individuals. Blood and urinary laboratory measurements were compared with demographics and clinically obtained data. Different eGFR equations were used for individuals aged ≥19 years and <19 years. Chronic kidney disease was defined as eGFR <90 mL/min per 1.73 m 2 . Median (25th–75th percentile) age was 19 (14–26) years, and 43% were female patients. Cystatin C eGFR detected chronic kidney disease (37%) in more patients than creatinine eGFR (11%). Cystatin C eGFR was positively associated, and skeletal muscle mass was negatively associated, with creatinine eGFR in both univariate (cystatin C eGFR β=0.44±0.12, P =0.0006; skeletal muscle mass β=−0.72±0.32, P =0.03) and multivariable analysis (cystatin C eGFR β=0.43±0.12, P =0.0005; skeletal muscle mass β=−0.69±0.29, P =0.02). Urine neutrophil gelatinase‐associated lipocalin concentration correlated with Fontan pressure ( r =0.28; P =0.04), ventricular end‐diastolic pressure ( r =0.28; P =0.04), and body fat mass ( r =0.26; P =0.03). Conclusions Cystatin C eGFR identified more kidney dysfunction, likely attributable to creatinine eGFR being confounded by skeletal muscle mass. Elevated urine neutrophil gelatinase‐associated lipocalin was associated with worse Fontan hemodynamics and higher percentage body fat, suggesting that higher venous pressure and higher adiposity are associated with ongoing kidney injury.

Noninvasive Advanced Cardiovascular Magnetic Resonance–Derived Fontan Hemodynamics Are Associated With Reduced Kidney Function But Not Albuminuria

“…Furthermore, the CKD‐EPI40 does not rely on height, which is often smaller given somatic growth restriction and incomplete catch‐up growth in patients with a Fontan circulation. 27 This enhancement in accuracy is illustrated through comparison with a recent study by Katz et al, 28 wherein the bedside Schwartz equation identified reduced kidney function in a mere 11% of patients with a Fontan circulation. In contrast, our present study, despite dealing with a marginally younger cohort (median age, 16 years versus 19 years), identified twice the number of affected patients, underscoring the tangible advantages of embracing the CKD‐EPI40 equation.…”

“… 31 Imprecision of eGFR measurements, as expressed as the IQR of the difference between measurements, is 15.4 (IQR, 14.3–16.5) mL/min per 1.73 m 2 and can also lead to discordant results between eGFR and mGFR as has commonly been reported in the literature. Furthermore, it has been suggested that creatinine‐based eGFR methods would overestimate mGFR in patients with a Fontan circulation because of its reliance on skeletal muscle mass, 28 , 29 which is known to be reduced in these patients. 32 Cystatin C–based methods have been proposed to circumvent this issue; however, the applicable equations designed for the pediatric and adolescent demographic only became available after our study's enrollment phase.…”

“…Initial findings within the Fontan population are promising, although further research is requisite to translate these findings into clinical practice. 28 …”

Correlation Between Cystatin C and the Severity of Cardiac Dysfunction in Patients with Systolic Heart Failure

“…4 Fontan circulation is associated with kidney injury and dysfunction, often unappreciated until Fontan circulatory failure. 5 It hypothesized that cystatin C-estimated glomerular filtration rate (eGFR) would identify chronic kidney disease more frequently and that urine kidney injury biomarkers would be higher with declining Fontan physiological features. 5 Cystatin C levels were associated with disease severity and prognosis in patients with pre-capillary PH.…”

“…5 It hypothesized that cystatin C-estimated glomerular filtration rate (eGFR) would identify chronic kidney disease more frequently and that urine kidney injury biomarkers would be higher with declining Fontan physiological features. 5 Cystatin C levels were associated with disease severity and prognosis in patients with pre-capillary PH. 6 A combination of high cystatin C and advanced WHO-FC identifies patients at particularly high risk of clinical deterioration.…”