Renal handling of ammonium and Acid base regulation

Renal ammonium metabolism is the primary component of net acid excretion and thereby is critical for acid-base homeostasis. Briefly, ammonium is produced from glutamine in the proximal tubule in a series of biochemical reactions that result in equimolar bicarbonate. Ammonium is predominantly secreted into the luminal fluid via the apical Na(+)/H(+) exchanger, NHE3. The thick ascending limb of the loop of Henle reabsorbs luminal ammonium, predominantly by transport of NH(4) (+) by the apical Na(+)/K(+)/2Cl(-) cotransporter, BSC1/NKCC2. This process results in renal interstitial ammonium accumulation. Finally, the collecting duct secretes ammonium from the renal interstitium into the luminal fluid. Although in past ammonium was believed to move across epithelia entirely by passive diffusion, an increasing number of studies demonstrated that specific proteins contribute to renal ammonium transport. Recent studies have yielded important new insights into the mechanisms of renal ammonium transport. In this review, we will discuss renal handling of ammonium, with particular emphasis on the transporters involved in this process.