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Cited by 30Renal function and acid-base balanceIon Transport and Channel RegulationPotassium and Related Disorders

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

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Weiner, I. David·2017·Pediatric Nephrology
DOI 10.1007/s00467-016-3401-xPMC PMC5107182
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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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  • The loss of RHBG may contribute to the ability of fruit bats to efficiently excrete excess potassium and efficiently reabsorb scarce sodium.

    “Since ammonium inhibits potassium secretion and sodium reabsorption33, the loss of the ammonium secreting RHBG may contribute to the ability of fruit bats to efficiently excrete excess potassium and efficiently reabsorb scarce sodium34.”

    From A genomics approach reveals insights into the importance of gene losses for mammalian adaptations (2018) · cites this paper as [33]

    The section “Intrarenal roles of ammonia other than acid-base homeostasis” (page not provided) reports that ammonia inhibits collecting-duct potassium secretion and sodium reabsorption, supporting the proposed physiological mechanism. It does not address RHBG loss in fruit bats or show that such loss improves their potassium excretion or sodium reabsorption. (LLM, conf=0.85)

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Authors
Weiner, I. D.
Affiliations
University of Florida Health (US)
Corresponding author
Weiner, I. David
ORCID
Weiner, I. David
Venue
Pediatric Nephrology
Publisher
Springer Science and Business Media LLC
Published
2016-05-12
Volume
32
Issue
6
Pages
933-942
ISSN
  • 0931-041X (ISSN-L)
  • 1432-198X
DOI
10.1007/s00467-016-3401-x
PMC
PMC5107182
OpenAlex
W2376738307
Cited by
30
References
0
Citations by year
2026: 6 · 2025: 3 · 2024: 6 · 2023: 3 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 2 · 2018: 3 · 2017: 2 · 2016: 1
FWCI
0.32
Type
journal article
Language
en
Open access
Licence
Locations
  • Pediatric Nephrology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK045788, R01-DK107798)
Topics
  • Health Sciences › Medicine › Nephrology › Renal function and acid-base balance
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Potassium and Related Disorders
Keywords
hyperammonemia, liver disease, hypokalemia, paracrine signaling, thick ascending limb of Henle's loop, collecting duct, potassium reabsorption, potassium secretion, metabolic alkalosis, NaCl reabsorption, diuretic resistance, acid-base balance
MeSH terms
Acid-Base Equilibrium, Ammonia, Humans, Hypokalemia, Kidney Tubules, Collecting, Kidney Tubules, Proximal, Liver, Liver Cirrhosis, Potassium, Sodium Chloride, Hyperammonemia, Renal Elimination

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