Rapid and Highly Accurate Prediction of Poor Loop Diuretic Natriuretic Response in Patients With Heart Failure

Abstract

Background Removal of excess sodium and fluid is a primary therapeutic objective in acute decompensated heart failure (ADHF) and commonly monitored with fluid balance and weight loss. However, these parameters are frequently inaccurate or not collected and require a delay of several hours after diuretic administration before they are available. Accessible tools for rapid and accurate prediction of diuretic response are needed. Methods and Results Based on well-established renal physiologic principles an equation was derived to predict net sodium output using a spot urine sample obtained one or two hours following loop diuretic administration. This equation was then prospectively validated in 50 ADHF patients using meticulously obtained timed 6-hour urine collections to quantitate loop diuretic induced cumulative sodium output. Poor natriuretic response was defined as a cumulative sodium output of <50 mmol, a threshold that would result in a positive sodium balance with twice-daily diuretic dosing. Following a median dose of 3 mg (2–4 mg) of intravenous bumetanide, 40% of the population had a poor natriuretic response. The correlation between measured and predicted sodium output was excellent (r=0.91, p<0.0001). Poor natriuretic response could be accurately predicted with the sodium prediction equation (AUC=0.95, 95% CI 0.89–1.0, p<0.0001). Clinically recorded net fluid output had a weaker correlation (r=0.66, p<0.001) and lesser ability to predict poor natriuretic response (AUC=0.76, 95% CI 0.63–0.89, p=0.002). Conclusions In patients being treated for ADHF, poor natriuretic response can be predicted soon after diuretic administration with excellent accuracy using a spot urine sample.

Markers of diuretic resistance in emergency department patients with acute heart failure

“…A formula was recently derived to quantify the relationship between early measures of urinary sodium and 6-h natriuresis [10]. However, these patients were enrolled a median of 4 days after hospital admission and would not be reflective of the more acute, early diuresis seen in an ED AHF population.…”

The use of diuretics in heart failure with congestion — a position statement from the Heart Failure Association of the European Society of Cardiology

“…As the objective of diuretic therapy is to get rid of excessive sodium (and accompanying water), the measurement of urinary sodium content has recently experienced a renewed interest as an indicator for diuretic response . In addition to measuring sodium in a continuous urinary collection, a spot urine sample 1–2 h following loop diuretic administration has recently demonstrated an excellent correlation with total urine sodium output in a 6 h urine collection . This strategy might allow the clinician to determine loop diuretic response in a systematic and timely fashion, potentially allowing for more timely adjustments in therapy.…”

“…Afterwards, determination of urinary spot sodium content allows the clinician to interpret diuretic response, thereby generating the opportunity to intervene if sodium content is low. In the face of congestion with volume overload, a spot urine sodium content of < 50–70 mEq/L after 2 h, and/or an hourly urine output < 100–150 mL during the first 6 h, generally identifies a patient with an insufficient diuretic response . In patients who produce sufficient urinary volumes following a first intravenous loop diuretic administration, urinary sodium is almost universally high.…”

Serum Chloride and Sodium Interplay in Patients With Acute Myocardial Infarction and Heart Failure With Reduced Ejection Fraction

“…36,37 These agents block the sodium/potassium/chloride cotransporter in the thick ascending limb of Henle loop, which is relatively impermeable to water. This interference of loop diuretics with renal capacity to concentrate urine may result in the production of relatively hypotonic urine (≈120 mmol/L of urinary sodium) 38 and, therefore, offer a relative protection against hyponatremia because sodium will thereafter be reabsorbed in the distal tubule. However, loop diuretics do not protect against hypochloremia because, contrary to sodium, chloride will not be distally reabsorbed.…”