Estimated glomerular filtration rate and urine biomarkers in patients with single-ventricle Fontan circulation. Issue 6 (26th September 2016) - Opotowsky, Alexander R
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 m 2, p<0.0001); GFR<90 mL/min/1.73 m 2 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.