Beyond the Urine Anion Gap: In Support of the Direct Measurement of Urinary Ammonium.

Ammonium is a major urinary buffer that is necessary for the normal excretion of the daily acid load. Its urinary rate of excretion (UNH) may be increased several fold in the presence of extrarenal metabolic acidosis. Therefore, measurement of UNH can provide important clues about causes of metabolic acidosis. Because UNH is not commonly measured in clinical laboratories, the urinary anion gap (UAG) was proposed as its surrogate about 4 decades ago, and it is still frequently used for that purpose. Several published studies strongly suggest that UAG is not a good index of UNH and support the concept that direct measurement of UNH is an important parameter to define in clinical nephrology. Low UNH levels have recently been found to be associated with a higher risk of metabolic acidosis, loss of kidney function, and death in persons with chronic kidney disease, while surrogates like the UAG do not recapitulate this risk. In order to advance the field it is necessary for the medical community to become more familiar with UNH levels in a variety of clinical settings. Herein, we review the literature, searching for available data on UNH under normal and various pathological conditions, in an attempt to establish reference values to interpret UNH results if and when UNH measurements become available as a routine clinical test. In addition, we present original data in 2 large populations that provide further evidence that the UAG is not a good predictor of UNH. Measurement of urine NH holds promise to aid clinicians in the care of patients, and we encourage further research to determine its best diagnostic usage.