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Renal Ammonia Metabolism and Transport

  1. I. David Weiner1,2,
  2. Jill W. Verlander2

Published Online: 1 JAN 2013

DOI: 10.1002/cphy.c120010

Comprehensive Physiology

Comprehensive Physiology

How to Cite

Weiner, I. D. and Verlander, J. W. 2013. Renal Ammonia Metabolism and Transport. Comprehensive Physiology. 3:201–220.

Author Information

  1. 1

    Nephrology and Hypertension Section, NF/SGVHS, Gainesville, Florida

  2. 2

    Division of Nephrology, Hypertension and Transplantation, University of Florida College of Medicine, Gainesville, Florida

Publication History

  1. Published Online: 1 JAN 2013

Abstract

Renal ammonia metabolism and transport mediates a central role in acid-base homeostasis. In contrast to most renal solutes, the majority of renal ammonia excretion derives from intrarenal production, not from glomerular filtration. Renal ammoniagenesis predominantly results from glutamine metabolism, which produces 2 NH4+ and 2 HCO3 for each glutamine metabolized. The proximal tubule is the primary site for ammoniagenesis, but there is evidence for ammoniagenesis by most renal epithelial cells. Ammonia produced in the kidney is either excreted into the urine or returned to the systemic circulation through the renal veins. Ammonia excreted in the urine promotes acid excretion; ammonia returned to the systemic circulation is metabolized in the liver in a HCO3-consuming process, resulting in no net benefit to acid-base homeostasis. Highly regulated ammonia transport by renal epithelial cells determines the proportion of ammonia excreted in the urine versus returned to the systemic circulation. The traditional paradigm of ammonia transport involving passive NH3 diffusion, protonation in the lumen and NH4+ trapping due to an inability to cross plasma membranes is being replaced by the recognition of limited plasma membrane NH3 permeability in combination with the presence of specific NH3-transporting and NH4+-transporting proteins in specific renal epithelial cells. Ammonia production and transport are regulated by a variety of factors, including extracellular pH and K+, and by several hormones, such as mineralocorticoids, glucocorticoids and angiotensin II. This coordinated process of regulated ammonia production and transport is critical for the effective maintenance of acid-base homeostasis. © 2013 American Physiological Society. Compr Physiol 3:201-220, 2013.