New marker to guide decongestion therapy and evade cardiorenal syndrome,JACC

Hospitalizations for HF are frequently due to symptomatic volume expansion. Strategies to reduce volume overload reduce hospitalizations and improve quality of life. Biomarker approaches (e.g., brain natriuretic peptide [BNP]) as well as physical examination (PE) show limited sensitivity and specificity. But in many patients diuresis has to be stopped or dosage decreased due to the onset of cardiorenal syndrome. The rise of creatinine leaves the patients only partially decongested with increased morbidity.

Fractional urine excretion of uric acid (FeUa) allows accurate differentiation of hyponatremia by volume status, despite diuretic use. Elevated FeUa suggests a volume replete or hypervolemic status in the body-a condition where diuretic therapy can be safely continued. Low FeUa on the other hand may serve as a harbinger of impending acute kidney injury (AKI).

Berger et al, in a case series published in JACC report the utility of this yet unexplored marker in guiding the decongestion therapy in heart failure patients by taking an arbitrary value of >8% FeUa as a cut-off to decide the volume status of patients (Figure) in whom diuretics can be safely continued.

They showed 6 cases where determining the fluid status of patients was difficult clinically, biochemically, and even using bedside ultrasound. In each of these cases, FeUa proved to be a valuable adjunct to our clinical evaluation of patients. In their small sample, FeUa cut-off of 8% to 10% seems to represent a threshold for action, and FeUa <5% represents high risk for AKI and unlikely hypovolemia.

For example in one of their cases, a patient with heart failure and reduced ejection fraction (48%) on diurectic therapy, had atrial tachycardia and asymptomatic hyponatremia (nadir 127 mEq/l). It was unclear if he was being overtreated with diuretic agents, causing his hyponatremia, or undertreated with continued expansion of his extracellular fluid volume (ECFV). There was no clinical evidence to suggest he was hypervolemic, aside from increased SOB on bending forward (he was not orthopneic).

A fractional excretion of uric acid (FeUa) was calculated as 11%. Given his high FeUa and bedside ultrasound, intravenous (IV) furosemide was restarted. Diuretic agents were continued for 4 days with symptomatic improvement. He was able to ambulate without dyspnea, he was not SOB with bending, and his heart rate normalized gradually until his atrial tachycardia abated and was replaced with normal sinus rhythm. Serum sodium improved (peak 131 mEq/l), and diuretic agents were stopped when it down-trended; then, FeUa was 5.46% and inferior vena cava <2.1 cm with >50% collapse on ultrasound. He continues to do well as an outpatient with no recurrence of SOB or hyponatremia.

Thus the case series presents a string of clinical observations to support the hypothesis that FeUa can identify patients with hard to assess volume status that are responsive to diuresis with low risk of AKI. FeUa served as a valuable tool to guide initiation, dosing, and termination of diuretic therapy.

It has been shown that the utility of FeUa to diagnose volume expansion does not change depending on urine flow or use of loop diuretic agents (unlike FeNa), but is mostly a function of changes in ECFV. They leveraged the utility of FeUa in different ECFV states and present for the first time observations supporting the use of FeUa to direct diuretic use in congestive HF.

Source: JACC J Am Coll Cardiol Case Rep. Apr 07, 2021. Epublished DOI: 10.1016/j.jaccas.2020.12.035