Recent Advances in Understanding Renal Ammonia Metabolism and Transport

I. David Weiner; Jill W. Verlander

Disclosures

Curr Opin Nephrol Hypertens. 2016;25(5):436-443. 

In This Article

Lithium and Ammonia Excretion

Chronic lithium administration is another common clinical condition for which new information regarding ammonia metabolism is available. Acute lithium administration is well known to increase urine pH. Urine pH, however, does not necessarily correlate with net acid or ammonia excretion. A recent study,[17] examining people treated chronically with lithium, showed increased basal rates of urinary ammonia excretion and an intact, if not increased, ability to increase ammonia excretion following acid loading (Fig. 2). Identical findings were observed in an animal model, and this increased ammonia excretion correlated with increased expression of the ammonia transporter, Rhcg.[17] Ammonia excretion requires parallel H+ and NH3 secretion in the collecting duct, and chronic lithium administration is known to increase the number of acid-secreting intercalated cells and the expression of H+-ATPase.[18,19] Thus, not only does chronic lithium therapy not routinely induce distal renal tubular acidosis (RTA), but is also actually associated with enhanced renal net acid excretion. The findings also emphasize the importance of not assuming that changes in urine pH predict changes in net acid excretion.

Figure 2.

Effect of lithium therapy on urinary ammonia excretion in response to an acute acid load in humans. (Top panel) Urinary ammonia excretion, expressed as mmol per mmol creatinine, at baseline, and following an acute acid load. Baseline urinary ammonia excretion was significantly higher in lithium-treated participants than in control participants. An acute acid load, induced by oral ammonium chloride loading, resulted in significant increases in urinary ammonia excretion in both groups at each time point. However, at each time point, urinary ammonia excretion was significantly greater in lithium-treated participants than in control participants. (Bottom panel) Changes in urinary ammonia excretion relative to baseline urinary ammonia excretion rates. An acute acid load resulted in significant increases in ammonia excretion relative to baseline excretion in both groups. *P<0.05 versus baseline; # P<0.05 versus control at same time point. Reproduced with permission [17].

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