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Hyperammonemia associated with distal renal tubular acidosis or urinary tract infection: a systematic review

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Abstract

Background

Hyperammonemia usually results from an inborn error of metabolism or from an advanced liver disease. Individual case reports suggest that both distal renal tubular acidosis and urinary tract infection may also result in hyperammonemia.

Methods

A systematic review of the literature on hyperammonemia secondary to distal renal tubular acidosis and urinary tract infection was conducted.

Results

We identified 39 reports on distal renal tubular acidosis or urinary tract infections in association with hyperammonemia published between 1980 and 2017. Hyperammonemia was detected in 13 children with distal renal tubular acidosis and in one adult patient with distal renal tubular acidosis secondary to primary hyperparathyroidism. In these patients a negative relationship was observed between circulating ammonia and bicarbonate levels (P < 0.05). In 31 patients (19 children, 12 adults), an acute urinary tract infection was complicated by acute hyperammonemia and symptoms and signs of acute neuronal dysfunction, such as an altered level of consciousness, convulsions and asterixis, often associated with signs of brain edema, such as anorexia and vomiting. Urea-splitting bacteria were isolated in 28 of the 31 cases. The urinary tract was anatomically or functionally abnormal in 30 of these patients.

Conclusions

This study reveals that both altered distal renal tubular acidification and urinary tract infection may be associated with relevant hyperammonemia in both children and adults.

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Notes

  1. “Ammonia” [2] 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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Acknowledgements

The authors would like to thank Dr. Alec Villa for his assistance in the linguistic revision.

Funding

This work was supported in part by the Fondazione Ettore Balli and the Swiss Research Network of Clinical Pediatric Hubs. Dr. Gregorio P. Milani is the current recipient of research grants from the Fondazione G. & D. de Marchi ONLUS.

Author information

Authors and Affiliations

  1. Pediatric Department of Southern Switzerland, Bellinzona, Switzerland

    Caterina M. Clericetti, Mario G. Bianchetti & Giacomo D. Simonetti

  2. Pediatric Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    Caterina M. Clericetti & Gregorio P. Milani

  3. Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy

    Gregorio P. Milani

  4. University Children’s Hospital, Inselspital – University of Bern, Bern, Switzerland

    Sebastiano A. G. Lava

  5. Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland

    Mario G. Bianchetti & Giacomo D. Simonetti

  6. Department of Internal Medicine, Ente Ospedaliero Cantonale, Mendrisio, Switzerland

    Olivier Giannini

Authors
  1. Caterina M. Clericetti
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  2. Gregorio P. Milani
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  4. Mario G. Bianchetti
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  5. Giacomo D. Simonetti
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  6. Olivier Giannini
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Contributions

GPM, SAGL and MGB conceptualized and designed the study, and drafted the article. CMC and GPM performed the literature search, extracted and analyzed the data and critically revised the manuscript. GS and OG made significant contributions in their area of expertise for data interpretation and for the revision of the article. All authors approved the final version of the manuscript as submitted.

Corresponding author

Correspondence to Mario G. Bianchetti.

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The authors declare that they have no conflict of interest.

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Clericetti, C.M., Milani, G.P., Lava, S.A.G. et al. Hyperammonemia associated with distal renal tubular acidosis or urinary tract infection: a systematic review. Pediatr Nephrol 33, 485–491 (2018). https://doi.org/10.1007/s00467-017-3829-7

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  • DOI: https://doi.org/10.1007/s00467-017-3829-7

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