Pitfalls in urinary sodium excretion

In the recent years, the increased prevalence of hypertension and cardio‐cerebrovascular accidents as a result of excessive salt intake urged the World Health Organization (WHO) to recommend sodium consumption <2 grams/day.1 The monitoring of population sodium intake is a key part of any salt reduction intervention and can be evaluated through urinary sodium excretion. Collection of 24‐hour urine is considered the gold standard for assessment of sodium intake.2 Assuming all sodium from dietary intake, about 90% is excreted in 24‐hour urine and the remaining 10% is excreted through sweat and feces, which can vary in particular conditions, such as hot climates, increased physical activity, fever, or gastrointestinal disorders. Even 24‐hour urine collection has several limitations, since it is not always suitable for patients for serial monitoring of some analytes or hormones, whose excretion can widely vary from day to day. Moreover, it can be expensive for large population‐based studies and more than 30% of collections are incomplete, for example, due to frequent urine incontinence in very elderly patients, and underestimate the real 24‐hour excretion. This problem interests not only estimation of sodium intake, but also of electrolyte disorders in patients in emergency care or in neurosurgery and can influence the evaluation of some hormones linked to the regulation of sodium and volume balance, such as renin, aldosterone, cortisol, and catecholamine. Recently, many authors proposed the use of spot urine samples to extrapolate 24‐hour excretion, but even this method has several limitations, since it represents only sodium intake in the previous hours and it is influenced by individual variability depending on salt and water ingestion, hormonal and nonhormonal factors involved in sodium concentration, hypertensive status, and related treatments.3, 4 Assessment of complete 24‐hour urine collection is more accurate measuring urinary creatinine. Previous studies constructed equations to estimate 24‐hour creatinine excretion, considering other variables, such as height, weight, age, and gender.5, 6, 7 However, the criteria used for completeness of urinary collection may be criticized, being based on interview,5 on serial collections for a 3‐5‐day period,6 or on a 24‐hour volume >250 cc.7 Moreover, these prediction equations should be assessed in different populations, considering the possible differences in the pattern of diurnal urine sodium excretion among different racial groups.8 Gerber and colleagues 9 developed an equation based on weight, age, gender, and race to estimate 24‐hour urinary creatinine excretion. Determination of incomplete collection was defined by 24‐hour creatinine content <15 mg/kg in women and <20 mg/kg in men.10 The accuracy of this equation was further confirmed by a strong correlation found comparing estimated versus measured 24‐hour creatinine excretion with muscle mass, measured by bioelectrical impedance. In a recent study, the same authors 11 evaluated whether routinely correcting measured 24‐hour urinary creatinine excretion using the ratio of estimated to measured creatinine excretion may improve interpretation of the results of 24‐hour collection, mitigating the inaccuracy due to urine undercollection. They confirmed that about 30% of cases with low 24‐hour sodium excretions was actually underestimated due to incompleteness of the urine collection and that the arithmetic adjustment of the results by the ratio of estimated to measured creatinine excretion increased the accuracy of the results. However, the study population considered only white and African American patients. Moreover, creatinine excretion is not constant, since it is influenced by many factors, such as protein intake; physical activity; pregnancy; liver, renal, and thyroid function; water intake; and treatments for hypertension or other diseases related to electrolyte unbalance.

The use and the proposal of other equations to accurately estimate 24‐hour excretion are needed to improve the correct interpretation of all the analytes measured in 24‐hour urine collection.

The determination of sodium excretion is an important tool to monitor population sodium intake as screening or among patients with high cardiovascular risk. It is important to note that genetic and epigenetic factors can influence sodium metabolism and sensitivity 3: for example, African Americans have a genetic tendency to sodium retention, predisposing to low‐renin essential hypertension. The detection of autoantibodies against angiotensin II type 1 receptors in patients with hypertension, pre‐eclampsia, and primary aldosteronism seems to be involved in the pathogenesis not only of hypertension, but also of hyperaldosteronism and related inflammatory and cardiovascular disorders.12 Several studies have evidenced increased levels of copeptin in different pathological conditions, especially in resistant hypertension and essential hypertension in adolescents, suggesting a possible pathogenetic role and a complex interplay with the renin‐angiotensin‐aldosterone system.13 Finally, some populations, especially in South‐East Asia, can present low‐renin and low‐aldosterone hypertension related to overconsumption of salt contained in foods.3

The most important way to reduce the cardiovascular risk is to evaluate all the possible factors involved, from sodium intake and other lifestyle habits to genetic predisposition and individual risk factors, such as diabetes, metabolic syndrome, hypertension, and other hormonal disorders.14 In particular, adrenal, thyroid, and renal function should always be evaluated and must be considered in the correct interpretation of sodium excretion. Many drugs, not only diuretics and other antihypertensive agents, but also treatments interfering with plasma sodium levels, such as some antidepressants, antiepileptics, antibiotics, and nonsteroidal anti‐inflammatory drugs, should be considered when evaluating sodium excretion. The evaluation of measured creatinine excretion and the adjustment of the results with the available equations are useful to overcome the problem of urine undercollection, but many other factors must always be considered for the correct interpretation of the patient's risk.

CONFLICT OF INTEREST

The authors declare no conflict of interest.