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Estimated glomerular filtration rate and urine biomarkers in patients with single-ventricle Fontan circulation
  1. Alexander R Opotowsky1,2,
  2. Fernando R Baraona3,
  3. Finnian R Mc Causland2,
  4. Brittani Loukas1,
  5. Elizabeth Landzberg4,
  6. Michael J Landzberg1,2,
  7. Venkata Sabbisetti2,
  8. Sushrut S Waikar2
  1. 1Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts, USA
  2. 2Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
  3. 3División de Enfermedades Cardiovasculares, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
  4. 4Columbia University Medical Center, New York, New York, USA
  1. Correspondence to Alexander R Opotowsky, Boston Children's Hospital and Brigham and Women's Hospital, 300 Longwood Avenue, Department of Cardiology, Boston, MA 02115, USA; alexander.opotowsky{at}childrens.harvard.edu

Abstract

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.

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