A METHOD TO EVALUATE RENAL AMMONIAGENESIS IN-VIVO

A reduced rate of excretion of ammonium (NH4+) can be due to either a low rate of production and/or a low transfer of NH4+ to the urine. At present, there is no way to obtain a measure of the rate of production of NH4+ in vivo without invasive techniques. Hence, our purpose was t o develop a non-invasive test to reflect this rate in vivo. Conditions were selected so that there would be a wide range in the rate of prod uction of NH4+ in the kidney. Initial experiments were performed in do gs because both the rate of production and excretion of NH4+ could be measured directly. The rate of excretion of NH4+ in normal dogs on the ir usual diet varied over a wide range and was not directly related to its rate of production. Nevertheless, 59% of the NH4+ produced was ex creted when the pH of urine was <6 or when the rate of flow of urine w as high (after administering a loop diuretic). To produce a urine with a low pH and high flow rate in humans, a loop diuretic (20 mg of furo semide) and a mineralocorticoid (200 mu g of fludrocortisone) were giv en. The pH of urine fell to 5.1 and the rate of urine flow rose to 8 m l/min; the rate of excretion of NH4+ rose from 21 to 33 mu mol/min whe n the urine flow rate rose. Both the rise in the rate of excretion of NH4+ during this diuresis, the data in dogs, as well as data obtained by others in humans using invasive techniques, suggest that the rate o f excretion of NH4+ after administration of a loop diuretic could prov ide a reasonable, non-invasive, semi-quantitative estimate of the rate of production of NH4+ in vivo. When interpreted in conjunction with a chronic acid load to evaluate the capacity to increase the rate of am moniagenesis, disorders of urine acidification might be diagnosed at a n earlier stage.