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Roles of renal ammonia metabolism other than in acid–base homeostasis

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Abstract

The importance of renal ammonia metabolism in acid–base homeostasis is well known. However, the effects of renal ammonia metabolism other than in acid–base homeostasis are not as widely recognized. First, ammonia differs from almost all other solutes in the urine in that it does not result from arterial delivery. Instead, ammonia is produced by the kidney, and only a portion of the ammonia produced is excreted in the urine, with the remainder returned to the systemic circulation through the renal veins. In normal individuals, systemic ammonia addition is metabolized efficiently by the liver, but in patients with either acute or chronic liver disease, conditions that increase the addition of ammonia of renal origin to the systemic circulation can result in precipitation and/or worsening of hyperammonemia. Second, ammonia appears to serve as an intrarenal paracrine signaling molecule. Hypokalemia increases proximal tubule ammonia production and secretion as well as reabsorption in the thick ascending limb of the loop of Henle, thereby increasing delivery to the renal interstitium and the collecting duct. In the collecting duct, ammonia decreases potassium secretion and stimulates potassium reabsorption, thereby decreasing urinary potassium excretion and enabling feedback correction of the initiating hypokalemia. Finally, the stimulation of renal ammonia metabolism by hypokalemia may contribute to the development of metabolic alkalosis, which in turn can stimulate NaCl reabsorption and contribute to the intravascular volume expansion, increased blood pressure and diuretic resistance that can develop with hypokalemia. The evidence supporting these novel non-acid–base roles of renal ammonia metabolism is discussed in this review.

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Notes

  1. Ammonia can exist in two molecular forms, NH3 (free ammonia) and NH4 + (ammonium cation). Throughout this review, “ammonia” refers to the combination of both molecules; “NH3” refers specifically to the molecular form of NH3; “NH4 +” refers specifically to the molecular form NH4 +.

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Acknowledgments

Generation and publication of this review was supported by funds from the NIH (R01–DK045788 and R01–DK107798).

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  1. Division of Nephrology, Hypertension and Renal Transplantation, University of Florida College of Medicine, PO Box 100224, Gainesville, FL, 32610-0224, USA

    I. David Weiner

  2. Nephrology and Hypertension Section, North Florida/South Georgia Veterans Health System, Gainesville, FL, USA

    I. David Weiner

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Weiner, I.D. Roles of renal ammonia metabolism other than in acid–base homeostasis. Pediatr Nephrol 32, 933–942 (2017). https://doi.org/10.1007/s00467-016-3401-x

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