Estimated glomerular filtration rate and urine biomarkers in patients with single-ventricle Fontan circulation.
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.



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.



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 m2in 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.



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.
Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts, USA.|Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Alexander R
AR
Opotowsky
División de Enfermedades Cardiovasculares, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
Fernando R
FR
Baraona
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Finnian R
FR
Mc Causland
Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts, USA.
Brittani
B
Loukas
Columbia University Medical Center, New York, New York, USA.
Elizabeth
E
Landzberg
Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts, USA.|Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Michael J
MJ
Landzberg
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Venkata
V
Sabbisetti
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Sushrut S
SS
Waikar
D058186:Acute Kidney Injury / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology / Q000652:urine; D000328:Adult; D000419:Albuminuria / Q000209:etiology / Q000503:physiopathology / Q000652:urine; D015415:Biomarkers / Q000652:urine; D002302:Cardiac Output; D016022:Case-Control Studies; D003326:Coronary Circulation; D003404:Creatinine / Q000652:urine; D055316:Cystatin C / Q000652:urine*; D018572:Disease-Free Survival; D005260:Female; D018729:Fontan Procedure; D005919:Glomerular Filtration Rate; D006330:Heart Defects, Congenital / Q000175:diagnosis / Q000503:physiopathology / Q000601:surgery*; D000072596:Hepatitis A Virus Cellular Receptor 1 / Q000378:metabolism; D006596:Hexosaminidases / Q000652:urine; D006760:Hospitalization; D006801:Humans; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000503:physiopathology*; D000071068:Lipocalin-2 / Q000652:urine; D008297:Male; D008954:Models, Biological; D016016:Proportional Hazards Models; D011652:Pulmonary Circulation; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D016482:Urinalysis; D055815:Young Adult
D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D003404:Creatinine; D006596:Hexosaminidases
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