Related Experiment Video
Updated: Mar 14, 2026
Assessment of Kidney Function in Mouse Models of Glomerular Disease
Published on: June 30, 2018
Estimated glomerular filtration rate and urine biomarkers in patients with single-ventricle Fontan circulation
Alexander R Opotowsky1,2, Fernando R Baraona3, Finnian R Mc Causland2
1Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts, USA.
Insights
Adults with Fontan circulation show impaired kidney function, with lower glomerular filtration rate (GFR) and elevated urinary kidney injury biomarkers. Lower GFR and tubular injury indicate a higher risk of adverse outcomes in Fontan patients.
Area of Science:
- Cardiology
- Nephrology
- Pediatric Cardiology
Background:
- Fontan circulation is characterized by lifelong venous congestion and limited cardiac output.
- Potential for impaired kidney function and injury in adults with Fontan physiology is not well-defined.
Purpose of the Study:
- To determine if adults with Fontan circulation have reduced glomerular filtration rate (GFR).
- To assess for elevated urinary biomarkers of kidney injury in Fontan patients.
- To correlate kidney function and injury markers with clinical outcomes.
Main Methods:
- Measured serum cystatin C and creatinine for GFR estimation in 70 Fontan patients and 20 controls.
- Assessed urinary biomarkers: creatinine, albumin, KIM-1, NGAL, and NAG, normalized to urine creatinine.
- Utilized survival analysis to compare outcomes based on GFR and urinary biomarker levels.
Main Results:
- Fontan patients exhibited significantly lower cystatin C GFR compared to controls (114.2 vs 136.3 mL/min/1.73 m²).
- Elevated urinary albumin-to-creatinine ratio (ACR), KIM-1, and NAG were observed in Fontan patients.
- Lower cystatin C GFR and higher KIM-1/NAG levels were associated with an increased risk of non-elective cardiovascular hospitalization or death.
Conclusions:
- Fontan circulation is associated with reduced estimated GFR and evidence of glomerular and tubular kidney injury.
- Impaired cystatin C GFR and tubular injury markers predict adverse outcomes in adults with Fontan physiology.
Objectives:
To define whether adults with a Fontan circulation, who have lifelong venous congestion and limited cardiac output, have impaired glomerular filtration rate (GFR) or elevated urinary biomarkers of kidney injury.
Methods:
We measured circulating cystatin C and creatinine (n=70) and urinary creatinine, albumin, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL) and N-acetyl glucosaminidase (NAG) (n=59) in ambulatory adult Fontan patients and 20 age-matched and sex-matched controls. Urinary biomarkers were normalised to urine creatinine concentration. Survival free from non-elective cardiovascular hospitalisation was compared by estimated GFR and urinary biomarker levels using survival analysis.
Results:
Cystatin C GFR was lower in the Fontan group compared with controls (114.2±22.8 vs 136.3±12.8 mL/min/1.73 m2, p<0.0001); GFR<90 mL/min/1.73 m2 in 14.3% vs 0% of controls. Albumin-to-creatinine ratio (ACR), KIM-1 and NAG were elevated compared with controls; ACR=23.2 (7.6-38.3) vs 3.6 (2.5-5.7) mg/g, p<0.0001; NAG=1.8 (1.1-2.6) vs 1.1 (0.9-1.6) U/g, p=0.02; KIM-1=0.91 (0.52-1.45) vs 0.33 (0.24-0.74) ng/mg, p=0.001. Microalbuminuria, ACR>30 mg/g, was present in 33.9% of the Fontan patients but in none of the controls. Over median 707 (IQR 371-942)-day follow-up, 31.4% of patients had a clinical event. Higher KIM-1 and NAG were associated with higher risk of non-elective hospitalisation or death (HR/+1 SD=2.1, 95% CI 1.3 to 3.3, p=0.002; HR/+1 SD=1.6, 95% CI 1.05 to 2.4, p=0.03, respectively); cystatin C GFR was associated with risk of the outcome (HR/+1 SD=0.66, 95% CI 0.48 to 0.90, p=0.009) but creatinine-based GFR was not (HR/+1 SD=0.91, 95% CI 0.61 to 1.38, p=0.66). Neither ACR nor NGAL was associated with events.
Conclusions:
The Fontan circulation is commonly associated with reduced estimated GFR and evidence for glomerular and tubular injury. Those with lower cystatin C GFR and tubular injury are at increased risk of adverse outcomes.
Related Concept Videos
01:25Drug Dosing in Renal Diseases: Measurement of Glomerular Filtration Rate
01:28Drug Dosing in Renal Diseases: Estimation of Glomerular Filtration Rate Based on Serum Creatinine Concentration
01:28Glomerular Filtration Rate and its Regulation
GFR regulation involves two primary intrinsic controls: the myogenic and tubuloglomerular feedback mechanisms.
The myogenic...
01:02Renal Drug Excretion: Glomerular Filtration
Drugs gain access to the kidney via the renal artery, which progressively branches off into afferent arterioles....
01:23Renal Clearance
Renal clearance refers to the volume of plasma cleared of a specific substance, such as creatinine, per unit of time. To measure clearance, urine samples are collected over a 24-hour period during each bladder voiding, followed by a single blood sample at the...
01:29Physiology of the Genitourinary System I: Renal Blood Flow and Glomerular Filtration