Objectives To define whether adults with a Fontan circulation, who have life-long 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- and sex- matched controls. Urinary biomarkers were normalized to urine creatinine concentration. Survival free from non-elective cardiovascular hospitalization 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±12.8mL/min/1.73m2, p<0.0001); GFR<90mL/min/1.73m2 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>30mg/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 hospitalization or death (HR/+1SD=2.1, 95%CI=1.3–3.3, p=0.002; HR/+1SD=1.6, 95%CI=1.05–2.4, p=0.03, respectively); cystatin C GFR was associated with risk of the outcome (HR/+1SD=0.66, 95%CI=0.48–0.90, p=0.009) but creatinine-based GFR was not (HR/+1SD=0.91, 95%CI=0.61–1.38, p=0.66). Neither ACR nor NGAL were 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.

Background Adults with congenital heart disease (ACHD, CHD) comprise a growing, increasingly complex population. The Boston Adult Congenital Heart Disease Biobank is a program for the collection and storage of biospecimens to provide a sustainable resource for scientific biomarker investigation in ACHD. Methods We describe a protocol to collect, process and store biospecimens for adults with CHD or associated diagnoses developed based on existing literature and consultation with cardiovascular biomarker epidemiologists. The protocol involves collecting urine and ~48.5 ml of blood. A subset of the blood and urine undergoes immediate clinically relevant testing. The remaining biospecimens are processed soon after collection and stored at −80°C as aliquots of EDTA and lithium heparin plasma, serum, red cell and buffy coat pellet, and urine supernatant. Including tubes with diverse anti-coagulant and clot accelerator contents will enable flexible downstream use. Demographic and clinical data are entered into a database; data on biospecimen collection, processing and storage are managed by an enterprise laboratory information management system. Results Since implementation in 2012, we have enrolled more than 650 unique subjects (aged 18–80 years, 53.3% women); the Biobank contains over 11,000 biospecimen aliquots. The most common primary CHD diagnoses are single ventricle status-post Fontan procedure (18.8%), repaired tetralogy of Fallot with pulmonary stenosis or atresia (17.6%) and left-sided obstructive lesions (17.5%). Conclusions We describe the design and implementation of biospecimen collection, handling and storage protocols with multiple levels of quality assurance. These protocols are feasible and reflect the size and goals of the Boston ACHD Biobank.

Ammonium bifluoride is an inorganic, fluoride-containing compound found in glass and metal etching products, as well as wheel cleaners. Fluoride toxicity is a common cause of preventable poisoning and has been reported to cause life-threatening ventricular dysrhythmias. Here, we report a case of recurrent ventricular fibrillation secondary to ingestion of ammonium bifluoride. The patient presented with vomiting and coma. She was intubated for altered mental status and respiratory failure and subsequently had 5 episodes of ventricular fibrillation, each resolving with a single defibrillation. She developed metabolic acidosis and hypocalcemia, which were treated with sodium bicarbonate and calcium gluconate, respectively. During transfer to a tertiary care children's hospital, ventricular fibrillation recurred despite electrolyte correction. Hemodialysis (HD) was initiated emergently. No further dysrhythmia occurred after initiation of HD. The result of a basic urine drug screen was negative, and a comprehensive drug screen (gas chromatography and mass spectroscopy) revealed only a nonsignificant peak for diphenhydramine. Subsequent laboratory evaluation revealed an elevated serum fluoride level. Diagnostic laryngoscopy and upper endoscopy did not reveal evidence of caustic injury. She was successfully extubated on hospital day 2 and discharged from the hospital on day 4 with no neurologic sequelae. With this example, we demonstrate a potential therapeutic approach to this potentially lethal poisoning. Fluoride toxicity is typically treated with calcium. However, dysrhythmia may result from calcium-independent direct myocardial toxicity. The kinetics of fluoride are amenable to HD, and renal clearance is slow. The potential use of HD in cases of fluoride poisoning refractory to other therapies warrants further study.

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